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Sample records for acquired heterotopic ossification

  1. 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.

  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. Heterotopic ossification after hip arthroscopy

    PubMed Central

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

    2015-01-01

    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. PMID:27011859

  4. Heterotopic ossification: a systematic review.

    PubMed

    Edwards, Dafydd S; Clasper, J C

    2015-12-01

    Heterotopic ossification (HO) is the formation of mature lamellar bone in extraskeletal soft tissues. It was first described 1000 years ago in the healing of fractures, and in relation to military wounds, texts from the American Civil War and World War I refer to HO specifically. It continues to cause problems to injured service personnel; the consequences of wound and soft tissue complications in traumatic amputations pose particular problems to rehabilitation and prosthetic use. While HO is seen in rare genetic conditions, it is most prevalent after joint replacement surgery and trauma. In the civilian setting HO has been commonly described in patients after traumatic brain injuries, spinal cord injuries and burns. Militarily, as a consequence of recent operations, and the characteristic injury of blast-related amputations, a renewed interest in HO has emerged due to an increased incidence seen in casualties. The heterogeneous nature of a blast related amputation makes it difficult for a single aetiological event to be identified, although it is now accepted that blast, amputation through the zone of injury, increased injury severity and associated brain injuries are significant risk factors in HO formation. The exact cellular event leading to HO has yet to be identified, and as a consequence its prevention is restricted to the use of anti-inflammatory medication and radiation, which is often contraindicated in the acute complex military casualty. A systematic review in PubMed and the Cochrane Database identified research articles related to HO to illustrate the military problem of HO and its management, current research concepts and experimental theories regarding HO. This also served as a gap analysis providing the researchers detail of any knowledge deficit in this field, in particular to the military aspects of HO; 637 out of 7891 articles initially identified that referenced HO were relevant to this review. PMID:25015927

  5. Heterotopic ossification: a systematic review.

    PubMed

    Edwards, Dafydd S; Clasper, J C

    2015-12-01

    Heterotopic ossification (HO) is the formation of mature lamellar bone in extraskeletal soft tissues. It was first described 1000 years ago in the healing of fractures, and in relation to military wounds, texts from the American Civil War and World War I refer to HO specifically. It continues to cause problems to injured service personnel; the consequences of wound and soft tissue complications in traumatic amputations pose particular problems to rehabilitation and prosthetic use. While HO is seen in rare genetic conditions, it is most prevalent after joint replacement surgery and trauma. In the civilian setting HO has been commonly described in patients after traumatic brain injuries, spinal cord injuries and burns. Militarily, as a consequence of recent operations, and the characteristic injury of blast-related amputations, a renewed interest in HO has emerged due to an increased incidence seen in casualties. The heterogeneous nature of a blast related amputation makes it difficult for a single aetiological event to be identified, although it is now accepted that blast, amputation through the zone of injury, increased injury severity and associated brain injuries are significant risk factors in HO formation. The exact cellular event leading to HO has yet to be identified, and as a consequence its prevention is restricted to the use of anti-inflammatory medication and radiation, which is often contraindicated in the acute complex military casualty. A systematic review in PubMed and the Cochrane Database identified research articles related to HO to illustrate the military problem of HO and its management, current research concepts and experimental theories regarding HO. This also served as a gap analysis providing the researchers detail of any knowledge deficit in this field, in particular to the military aspects of HO; 637 out of 7891 articles initially identified that referenced HO were relevant to this review.

  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. Functional Outcomes of the Surgery and Rehabilitation in a Challenging Case of Heterotopic Ossification after Encephalitis

    PubMed Central

    Ekiz, T; Aslan, M Doğan; Demir, S Özbudak; Altay, M; Özgirgin, N

    2015-01-01

    ABSTRACT Heterotopic ossification is the formation of the lamellar bone where normally osseous tissue does not exist. Since heterotopic ossification can cause severe functional loss, it is a challenging condition for both clinicians and patients. Neurogenic heterotopic ossification is a rare condition after encephalitis. Likewise, in this paper, we have presented a challenging case of heterotopic ossification after viral encephalitis and functional outcomes after the management of heterotopic ossification. PMID:26426185

  8. Pharmacological treatment of heterotopic ossification following hip and acetabular surgery.

    PubMed

    Macfarlane, Robert J; Ng, Boon Han; Gamie, Zakareya; El Masry, Mohamed A; Velonis, Stylianos; Schizas, Constantin; Tsiridis, Eleftherios

    2008-04-01

    Heterotopic ossification is a common complication following total hip arthroplasty and surgery following acetabular trauma. It is associated with pain and a decreased range of movement. Prophylaxis is achieved by either non-steroidal anti-inflammatory drug treatment or localised irradiation therapy. The objective of this study was to evaluate the evidence for pharmacological agents used for the prophylaxis of heterotopic ossification following hip and acetabular surgery. The study used a comprehensive literature search to identify all major clinical studies investigating the pharmacological agents used in the prophylaxis of heterotopic ossification following hip and acetabular surgery. It was concluded that indometacin remains the 'gold standard' for heterotopic ossification prophylaxis following total hip arthroplasty and is the only drug proven to be effective against heterotopic ossification following acetabular surgery. Following total hip arthroplasty, other non-steroidal anti-inflammatory drugs, including naproxen and diclofenac, are equally as effective as indometacin and can be considered as alternative first-line treatments. Celecoxib is also of equal efficacy to indometacin and is associated with significantly fewer gastrointestinal side effects. However, serious concerns were raised over the safety of selective cyclooxygenase-2 inhibitors for the cardiovascular system and these should be used cautiously.

  9. Heterotopic Ossification Causing Radiculopathy after Lumbar Total Disc Arthroplasty.

    PubMed

    Jackson, Keith L; Hire, Justin M; Jacobs, Jeremy M; Key, Charles C; DeVine, John G

    2015-06-01

    To date, no reports have presented radiculopathy secondary to heterotopic ossification following lumbar total disc arthroplasty. The authors present a previously unpublished complication of lumbar total disk arthroplasty (TDA) secondary to heterotopic ossification (HO) in the spinal canal, and they propose a modification to the McAfee classification of HO. The patient had undergone an L5/S1 lumbar TDA two years prior due to discogenic back pain. His preoperative back pain was significantly relieved, but he developed new, atraumatic onset radiculopathy. Radiographs and a computed tomography myelogram revealed an implant malposition posteriorly with heterotopic bone formation in the canal, causing an impingement of the traversing nerve root. Revision surgery was performed with implant extraction, L5/S1 anterior lumbar interbody fusion, supplemental posterior decompression, and pedicle screw fixation. The patient tolerated the procedure well, with complete resolution of the radicular leg pain. At a two-year follow up, the patient had a solid fusion without subsidence or recurrence of heterotopic bone. This case represents a novel pattern of heterotopic ossification, and it describes a previously unreported cause for implant failure in lumbar disc replacement surgery-reinforcing the importance of proper intraoperative component positioning. We propose a modification to the existing McAfee classification of HO after TDA with the addition of Class V and VI HO. PMID:26097664

  10. Heterotopic Ossification Causing Radiculopathy after Lumbar Total Disc Arthroplasty

    PubMed Central

    Jackson, Keith L.; Jacobs, Jeremy M.; Key, Charles C.; DeVine, John G.

    2015-01-01

    To date, no reports have presented radiculopathy secondary to heterotopic ossification following lumbar total disc arthroplasty. The authors present a previously unpublished complication of lumbar total disk arthroplasty (TDA) secondary to heterotopic ossification (HO) in the spinal canal, and they propose a modification to the McAfee classification of HO. The patient had undergone an L5/S1 lumbar TDA two years prior due to discogenic back pain. His preoperative back pain was significantly relieved, but he developed new, atraumatic onset radiculopathy. Radiographs and a computed tomography myelogram revealed an implant malposition posteriorly with heterotopic bone formation in the canal, causing an impingement of the traversing nerve root. Revision surgery was performed with implant extraction, L5/S1 anterior lumbar interbody fusion, supplemental posterior decompression, and pedicle screw fixation. The patient tolerated the procedure well, with complete resolution of the radicular leg pain. At a two-year follow up, the patient had a solid fusion without subsidence or recurrence of heterotopic bone. This case represents a novel pattern of heterotopic ossification, and it describes a previously unreported cause for implant failure in lumbar disc replacement surgery-reinforcing the importance of proper intraoperative component positioning. We propose a modification to the existing McAfee classification of HO after TDA with the addition of Class V and VI HO. PMID:26097664

  11. 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.

  12. Spontaneous Knee Ankylosis through Heterotopic Ossification after Total Knee Arthroplasty

    PubMed Central

    Boulezaz, Samuel; Gibon, Emmanuel; Loriaut, Philippe; Casabianca, Laurent; Rousseau, Romain; Dallaudiere, Benjamin; Pascal-Moussellard, Hugues

    2016-01-01

    This paper reports on a case of total ankylosis of the knee after a cruciate-sacrificing cemented total knee arthroplasty (TKA). An 82-year-old female patient previously underwent primary TKA for osteoarthritis twenty years ago in our institution. She had recovered uneventfully and returned to her regular activities. There was no history of postsurgical trauma; however, she progressively lost knee range of motion. Radiographs revealed severe bridging heterotopic ossification. PMID:27119034

  13. 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

  14. Noncollagenous proteins in heterotopic ossification. Immunohistochemical analysis in 15 paraplegies.

    PubMed

    Bosse, A; Wuisman, P; Jones, D B; Schwarz, K

    1993-12-01

    We used immunohistochemical techniques to investigate the distribution pattern of osteonectin, osteocalcin, bone sialoprotein II and the small proteoglycans decorin and PG 100 during different stages of heterotopic ossification (HO) in pressure sores of paraplegic patients. All these noncollagenous proteins (NCPs) accumulated in fibroblasts and preosteoblasts, predominantly in the activity centers of early osteogenetic areas. Mature types of HO showed a more discrete expression pattern for this protein group, with weaker reactions in the narrow osteoblastic rims. Decorin was detected predominantly in the stroma of HO. Our results indicate that the NCPs are important components during the pathogenesis of HO and that fibroblasts may serve as osteoprogenitor cells.

  15. 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. PMID:27088747

  16. Progression of Heterotopic Ossification around the Elbow after Trauma

    PubMed Central

    ter Meulen, Dirk P.; Nota, Sjoerd P.F.T.; Hageman, Michiel G.J.S.; Ring, David C.

    2016-01-01

    Background: This study addresses the null hypothesis that there is no expansion of heterotopic ossification (HO) in the elbow beyond what can be seen early on. Methods: The area of HO was measured on lateral radiographs of 38 consecutive patients that had operative treatment of HO between 2000 and 2013. Measurements from radiographs obtained between 3 to 7 weeks were compared to measurements from radiographs made 3 months or more after injury. Results: There was no significant difference between the average area of HO on the first (median 2.8 square centimeters, Q1: 1.5, Q3: 5.1) and later radiographs (median of 2.8 square centimeters, Q1: 1.4, Q3: 5.0) (P = 0.99). Conclusion: According to our results the area of HO does not expand beyond what can be seen early in the disease process. PMID:27517067

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. ...

  18. Direct Mouse Trauma/Burn Model of Heterotopic Ossification.

    PubMed

    Peterson, Jonathan R; Agarwal, Shailesh; Brownley, R Cameron; Loder, Shawn J; Ranganathan, Kavitha; Cederna, Paul S; Mishina, Yuji; Wang, Stewart C; Levi, Benjamin

    2015-01-01

    Heterotopic ossification (HO) is the formation of bone outside of the skeleton which forms following major trauma, burn injuries, and orthopaedic surgical procedures. The majority of animal models used to study HO rely on the application of exogenous substances, such as bone morphogenetic protein (BMP), exogenous cell constructs, or genetic mutations in BMP signaling. While these models are useful they do not accurately reproduce the inflammatory states that cause the majority of cases of HO. Here we describe a burn/tenotomy model in mice that reliably produces focused HO. This protocol involves creating a 30% total body surface area partial thickness contact burn on the dorsal skin as well as division of the Achilles tendon at its midpoint. Relying solely on traumatic injury to induce HO at a predictable location allows for time-course study of endochondral heterotopic bone formation from intrinsic physiologic processes and environment only. This method could prove instrumental in understanding the inflammatory and osteogenic pathways involved in trauma-induced HO. Furthermore, because HO develops in a predictable location and time-course in this model, it allows for research to improve early imaging strategies and treatment modalities to prevent HO formation. PMID:26274052

  19. Treatment of heterotopic ossification through remote ATP hydrolysis.

    PubMed

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

    2014-09-24

    Heterotopic ossification (HO) is the pathologic development of ectopic bone in soft tissues because of a local or systemic inflammatory insult, such as burn injury or trauma. In HO, mesenchymal stem cells (MSCs) are inappropriately activated to undergo osteogenic differentiation. Through the correlation of in vitro assays and in vivo studies (dorsal scald burn with Achilles tenotomy), we have shown that burn injury enhances the osteogenic potential of MSCs and causes ectopic endochondral heterotopic bone formation and functional contractures through bone morphogenetic protein-mediated canonical SMAD signaling. We further demonstrated a prevention strategy for HO through adenosine triphosphate (ATP) hydrolysis at the burn site using apyrase. Burn site apyrase treatment decreased ATP, increased adenosine 3',5'-monophosphate, and decreased phosphorylation of SMAD1/5/8 in MSCs in vitro. This ATP hydrolysis also decreased HO formation and mitigated functional impairment in vivo. Similarly, selective inhibition of SMAD1/5/8 phosphorylation with LDN-193189 decreased HO formation and increased range of motion at the injury site in our burn model in vivo. Our results suggest that burn injury-exacerbated HO formation can be treated through therapeutics that target burn site ATP hydrolysis and modulation of SMAD1/5/8 phosphorylation. PMID:25253675

  20. 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.

  1. The inhibition effects of insulin on BMP2-induced muscle heterotopic ossification.

    PubMed

    Zhang, Jing; Zhao, Yannan; Hou, Xianglin; Chen, Bing; Xiao, Zhifeng; Han, Jin; Shi, Chunying; Liu, Jianzhou; Miao, Qi; Dai, Jianwu

    2014-11-01

    Bone morphogenetic proteins (BMPs) play an important role in regulating osteoblastic differentiation and bone formation. But the diffuse of BMPs into muscle tissues around bone injury sites often leads to heterotopic ossification, which has been regarded as one of major side-effects of BMP implementation in bone defect patients. It raises great demands for exploring effective methods that preventing BMP-induced heterotopic ossification while not interrupting the osteoinductive activity of BMPs for in situ bone defect repair. Here we found insulin, a positive regulator for bone regeneration, inhibited BMP2-induced muscle heterotopic ossification by suppressing the expression of bone transcription factor Osterix. By analyzing downstream molecules of insulin pathway, we found AKT/mTOR/GSK3 signaling was responsible for the inhibition of insulin on BMP2-induced ossification, and GSK3 inhibitor SB216763 attenuated BMP2-induced muscle heterotopic ossification. The data might shed light on developing effective clinical therapy for inhibiting muscle heterotopic ossification when BMPs were used bone defect repair. PMID:25132600

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

    PubMed

    Suleiman, Nergis Nina; Sandberg, Lars Johan Marcus

    2016-07-01

    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

  3. Role of altered signal transduction in heterotopic ossification and fibrodysplasia ossificans progressiva.

    PubMed

    Shore, Eileen M; Kaplan, Frederick S

    2011-06-01

    Heterotopic ossification is a pathologic condition in which bone tissue is formed outside of the skeleton, within soft tissues of the body. The extraskeletal bone that forms in these disorders is normal; the cellular mechanisms that direct cell fate decisions are dysregulated. Patients with fibrodysplasia ossificans progressiva (FOP), a rare human genetic disorder of extensive and progressive heterotopic ossification, have malformations of normal skeletal elements, identifying the causative gene mutation and its relevant signaling pathways as key regulators of skeletal development and of cell fate decisions by adult stem cells. The discovery that mildly activating mutations in ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor, is the cause of FOP has provided opportunities to identify previously unknown functions for this receptor and for BMP signaling and to develop new diagnostic and therapeutic strategies for FOP and other more common forms of heterotopic ossification, as well as tissue engineering applications.

  4. 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

  5. Heterotopic ossification prophylaxis following operative treatment of acetabular fracture.

    PubMed

    Johnson, E E; Kay, R M; Dorey, F J

    1994-08-01

    Eighty seven patients with 88 fractures were retrospectively reviewed to assess the effect of postoperative prophylaxis on the formation of heterotopic ossification (HO). Sixty eight patients with 69 acetabular fractures were followed for an average of 21 months (range, 3-98 months). The grade of HO was assessed using the Brooker classification system. Thirty four fractures had no prophylactic treatment, 30 were treated prophylactically with indomethacin, two with radiation therapy, and three with both indomethacin and radiation. Twenty (59%) of 34 untreated fractures developed HO, of which nine (26%) were Grade III or IV. Thirteen (43%) of 30 fractures treated with indomethacin developed HO, of which 5 (16%) were Grade III and none were Grade IV. Twenty one of 24 fractures were stabilized through the extended iliofemoral approach; 13 of these had no prophylaxis. Eleven of the 13 developed HO; eight were Grade III or IV (62%). Seven of eight fractures treated with indomethacin following the extended iliofemoral approach developed HO; one was Grade III (13%) and non Grade IV. There was no significant difference between 13 patients who were not treated prophylactically and 18 indomethacin treated patients stabilized through the Kocher-Langenbeck approach. Only one of 11 patients had HO (Grade I) following an ilioinguinal approach. Postoperative radiation therapy, with or without indomethacin, resulted in three patients with Grade 0 HO (all radiated 1-4 days post surgery), one with Grade II (radiated postoperative Day 8), and one with Grade III HO (significant delay in surgery with preoperative Grade III HO of the hip).(ABSTRACT TRUNCATED AT 250 WORDS)

  6. 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.

  7. Heterotopic ossification: review of histologic findings and tissue distribution in a 10-year experience.

    PubMed

    Liu, Katharine; Tripp, Sheryl; Layfield, Lester J

    2007-01-01

    Heterotopic ossification (HO) within tissues involved by a pathologic process is a well-recognized phenomenon. It is most frequently observed in atherosclerotic plaques, in soft tissue around joints, and in the central nervous system. Less frequently, carcinomas and some benign neoplasms will undergo heterotopic ossification. We performed a retrospective review of our experience with HO over a 10-year period to determine the frequency and tissue site distribution of heterotopic ossification. A computerized review of surgical pathology records of approximately 126,000 reports revealed 85 cases in which heterotopic ossification, ectopic bone or metaplastic bone was specifically mentioned in the surgical pathology diagnosis. Twenty-two cases were neoplasms of non-osseous tissues, and 63 cases were non-neoplastic lesions. Immunohistochemical staining for bone morphogenic proteins (BMP) 1, 4, and 6 was performed. Fourteen cases showed staining for BMP-1, 22 cases showed staining for BMP-4, and five cases showed weak staining for BMP-6. HO is a relatively infrequent finding and is more commonly seen in degenerative and reparative conditions than in neoplasms. PMID:17728073

  8. Intra-Articular Giant Heterotopic Ossification following Total Knee Arthroplasty for Charcot Arthropathy

    PubMed Central

    Tsuge, Shintaro; Aoki, Yasuchika; Sonobe, Masato; Shibata, Yoshifumi; Sasaki, Yu; Nakagawa, Koichi

    2013-01-01

    Although the Charcot arthropathy may be associated with serious complications, total knee arthroplasty (TKA) is the preferred choice of treatment by patients. This case report presents an 80-year-old man with intra-articular giant heterotopic ossification following loosening of femoral and tibial implants and femoral condylar fracture. He had undergone TKA because of Charcot neuropathy seven years ago and had been doing well since. Immediately after a left knee sprain, he became unable to walk. Because he had developed a skin ulcer on his left calf where methicillin-resistant Staphylococcus aureus was detected, we postponed revision surgery until the ulcer was completely healed. While waiting, intra-articular bony fragments grew larger and formed giant heterotopic ossified masses. Eventually, the patient underwent revision surgery, and two major ossified masses were carefully and successfully extirpated. It should be noted that intra-articular heterotopic giant ossification is a significant complication after TKA for neuropathic arthropathy. PMID:24151574

  9. Alk2 regulates early chondrogenic fate in fibrodysplasia ossificans progressiva heterotopic endochondral ossification.

    PubMed

    Culbert, Andria L; Chakkalakal, Salin A; Theosmy, Edwin G; Brennan, Tracy A; Kaplan, Frederick S; Shore, Eileen M

    2014-05-01

    Bone morphogenetic protein (BMP) signaling is a critical regulator of cartilage differentiation and endochondral ossification. Gain-of-function mutations in ALK2, a type I BMP receptor, cause the debilitating disorder fibrodysplasia ossificans progressiva (FOP) and result in progressive heterotopic (extraskeletal) endochondral ossification within soft connective tissues. Here, we used murine mesenchymal progenitor cells to investigate the contribution of Alk2 during chondrogenic differentiation and heterotopic endochondral ossification (HEO). Alk2(R206H/+) (gain-of-function), Alk2(CKO) (loss-of-function), and wild-type mouse embryonic fibroblasts were evaluated for chondrogenic potential. Chondrogenic differentiation was accelerated in Alk2(R206H/+) cells, due in part to enhanced sensitivity to BMP ligand. In vivo, Alk2(R206H/+) cells initiated robust HEO and recruited wild-type cell contribution. Despite expression of other type I BMP receptors (Alk3 and Alk6), chondrogenesis of Alk2(CKO) cells was severely impaired by absence of Alk2 during early differentiation. Alk2 is therefore a direct regulator of cartilage formation and mediates chondrogenic commitment of progenitor cells. These data establish that at least one effect of ALK2 gain-of-function mutations in FOP patients is enhanced chondrogenic differentiation which supports formation of heterotopic endochondral bone. This establishes ALK2 as a plausible therapeutic target during early chondrogenic stages of lesion formation for preventing heterotopic bone formation in FOP and other conditions.

  10. Post-traumatic heterotopic ossification of the crus. A case study.

    PubMed

    Onder, Kalenderer; Muhammed, Bozoglan; Saime, Unluoglu; Haluk, Agus

    2011-01-01

    The formation of mature lamellar bone at an ectopic site in the body is called heterotopic ossification. We report the case of a 28 year-old patient with heterotopic ossification (HO) in the left crus. He complained of difficulties with walking and limited ROM of the ankle joint. At surgery, an incision was made through the center of the HO focus, which was palpable. No change in ROM of the ankle joint was observed following HO removal. The decision was made to lengthen the Achilles tendon. After the lengthening of the Achilles tendon, the ROM of the ankle joint was increased. Lengthening of the Achilles tendon following the removal of posttraumatic HO in the crus is a safe and effective procedure; if the ROM of the ankle joint is restricted. PMID:21757788

  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. 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

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

    PubMed

    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

    2015-08-01

    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

  14. Real time early detection imaging system of failed wounds and heterotopic ossification using unique Raman signatures

    NASA Astrophysics Data System (ADS)

    Papour, Asael; Taylor, Zach; Stafsudd, Oscar; Grundfest, Warren

    2015-03-01

    Our team has established a method to enable imaging of heterotopic ossification and bone growth locations in tissue using Stokes Raman signals with fast acquisition times. This technique relies on the unique Raman signatures of bone to capture parallel, full-field, 1 cm2 field of view, without utilizing a spectrometer. This system was built in mind as a compact complementary tool for in vivo patient monitoring that can offer a high resolution optical characterization for early detection of failed wounds. Preliminary results of bone detection in flesh are presented here and pave the way for further development of this tool in clinical setting.

  15. Bilateral heterotopic ossification after bilateral hip arthroplasty in a geriatric patient.

    PubMed

    Tabert, I; Lekkos, K; Dettmer-Flügge, A; Schmidt, D; Gogol, M

    2011-12-01

    The case of a geriatric patient with total hip arthroplasty for coxarthrosis and an inpatient fall 12 days after the first operation is reported. Six weeks after the first operation, the patient reported new pain in the area of both hips and thighs. X-ray and scintigraphy confirmed the diagnosis of bilateral heterotopic ossification. NSAID therapy was started, and rapid improvement was observed. At discharge, the patient was able to walk with aids in- and outside. At the 12-month follow-up, x-ray control showed Brooker state 3 for the right and 4 for the left hip. Walking ability did not change during follow-up. PMID:22159834

  16. Heterotopic mesenteric ossification after a ruptured abdominal aortic aneurism: case report with a review of literatures.

    PubMed

    Honjo, Hiroaki; Kumagai, Youichi; Ishiguro, Toru; Imaizumi, Hideko; Ono, Tomojiro; Suzuki, Okihide; Ito, Tetsuya; Haga, Norihiro; Kuwabara, Kohki; Sobajima, Jun; Kumamoto, Kensuke; Ishibashi, Keiichiro; Baba, Hiroyuki; Sato, Osamu; Ishida, Hideyuki; Kuwano, Hiroyuki

    2014-01-01

    Heterotopic mesenteric ossification (HMO) is a rare disease that results in intra-abdominal ossification of unknown origin. An 88-year-old man developed an intestinal obstruction 2 weeks after undergoing an operation for a ruptured abdominal aortic aneurysm, resulting in intestinal obstructions those did not improved concervatively. During relaparotomy performed 30 days after the first operation, hard adhesions of the small intestine and mesentery were found; these adhesions were difficult to separate without damaging the serosa of the small intestine. We removed 240 cm of the small intestine and performed a jejuno-ileo anastomosis. Microscopically, trabecular bone tissue had increased irregularly in the fat tissue of the nodules with fibrosis, which were partially lined with osteoblasts. Accordingly, we histopathologically diagnosed the patient as having HMO. The patient was treated with NSAIDs and cimetidine to prevent the recurrence of HMO. No signs of recurrence have occurred as of one year after the second operation. PMID:25058788

  17. Heterotopic Mesenteric Ossification After a Ruptured Abdominal Aortic Aneurism: Case Report With a Review of Literatures

    PubMed Central

    Honjo, Hiroaki; Kumagai, Youichi; Ishiguro, Toru; Imaizumi, Hideko; Ono, Tomojiro; Suzuki, Okihide; Ito, Tetsuya; Haga, Norihiro; Kuwabara, Kohki; Sobajima, Jun; Kumamoto, Kensuke; Ishibashi, Keiichiro; Baba, Hiroyuki; Sato, Osamu; Ishida, Hideyuki; Kuwano, Hiroyuki

    2014-01-01

    Heterotopic mesenteric ossification (HMO) is a rare disease that results in intra-abdominal ossification of unknown origin. An 88-year-old man developed an intestinal obstruction 2 weeks after undergoing an operation for a ruptured abdominal aortic aneurysm, resulting in intestinal obstructions those did not improved concervatively. During relaparotomy performed 30 days after the first operation, hard adhesions of the small intestine and mesentery were found; these adhesions were difficult to separate without damaging the serosa of the small intestine. We removed 240cm of the small intestine and performed a jejuno-ileo anastomosis. Microscopically, trabecular bone tissue had increased irregularly in the fat tissue of the nodules with fibrosis, which were partially lined with osteoblasts. Accordingly, we histopathologically diagnosed the patient as having HMO. The patient was treated with NSAIDs and cimetidine to prevent the recurrence of HMO. No signs of recurrence have occurred as of one year after the second operation. PMID:25058788

  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. Risk Factors of Heterotopic Ossification Following Total Hip Arthroplasty in Patients With Ankylosing Spondylitis.

    PubMed

    Thilak, Jai; Panakkal, Jiss Joseph; Kim, Tae-Young; Goodman, Susan M; Lee, Sang-Soo; Salvati, Eduardo A

    2015-12-01

    This study was to identify the risk factors of heterotopic ossification (HO) after total hip arthroplasty (THA) in ankylosing spondylitis. We analyzed 47 hips (24 patients) with ankylosing spondylitis that underwent primary THA. The incidence of HO was 14.9%. The risk factors were divided into modifiable and nonmodifiable factors. Female gender (P=0.008), preoperative ankylosed hip (P<0.001), occurrence of HO in previous surgery (P=0.036) were nonmodifiable risk factors which increased the prevalence of HO. Of the various modifiable risk factors, elevated preoperative ESR (P=0.007), elevated preoperative CRP (P=0.004) and prolonged duration of surgery (P=0.014) were associated with increased occurrence of HO. Perioperative medical intervention to reduce inflammation (ESR and CRP) may help to decrease HO.

  20. Heterotopic ossification in victims of the London 7/7 bombings.

    PubMed

    Edwards, D S; Clasper, J C; Patel, H D L

    2015-12-01

    Heterotopic ossification (HO) is the formation of bone at extraskeletal sites. Over 60% of amputees injured by improvised explosive devices in the recent conflict in Afghanistan have developed HO, resulting in functional impairment. It is hypothesised that a key aetiological factor is the blast wave; however, other environmental and medical risk factors, which the casualties have been exposed to, have also been postulated. The suicide terrorist bombings in London in 2005 resulted in many blast-related casualties, many of whom were managed by the Royal London Hospital. This cohort of severely injured patients whose injuries also included trauma-related amputations shared some, but not all, of the risk factors identified in the military population. We reviewed these patients, in particular to assess the presence or absence of military-established risk factors for the formation of HO in these casualties. PMID:25645697

  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. 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. PMID:25712044

  3. Role of Gender in Burn-Induced Heterotopic Ossification and Mesenchymal Cell Osteogenic Differentiation

    PubMed Central

    Ranganathan, Kavitha; Peterson, Jonathan; Agarwal, Shailesh; Oluwatobi, Eboda; Loder, Shawn; Forsberg, Jonathan A.; Davis, Thomas A.; Wang, Stewart C.; Levi, Benjamin

    2015-01-01

    BACKGROUND Heterotopic ossification (HO) most commonly occurs after burn injury, joint arthroplasty, and trauma. Male gender has been identified as a risk factor for the development of HO. It remains unclear why adult males are more predisposed to this pathology than adult females. In this study, we explore differences in heterotopic ossification between male and female mice using an in vivo burn/tenotomy model. METHODS Our Achilles tenotomy and burn model was used to evaluate the osteogenic potential of tissue-derived mesenchymal stem cells (MSCs) of male and female mice in injured and non-injured mice. Groups consisted of injured male (n=3), injured female (n=3), non-injured male (n=3), and non-injured female (n=3). The osteogenic potential of cells harvested from each group was assessed through RNA and protein levels and quantified using micro-CT scan. Histomorphometry was used to verify micro-CT findings, and immunohistochemistry was used to assess osteogenic signaling at the site of HO. RESULTS MSCs of male mice demonstrated greater osteogenic gene and protein expression than female MSCs (p<.05). Male mice in the burn group formed 35% more bone as compared to female mice in the burn group. This bone formation correlated with increased pSmad and IGF-1 signaling at the HO site in male mice. Differences were also seen between the non-injured male and female groups. CONCLUSIONS We demonstrate that male mice form quantitatively more bone as compared to female mice using our burn/tenotomy model. These findings can be explained at least in part by differences in BMP and IGF-1 signaling. PMID:26017598

  4. 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.

  5. 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

  6. Heterotopic ossification after total hip replacement and the HLA system in the Sicilian population.

    PubMed

    Sessa, G; Costarella, L; Mollica, R; Pavone, V

    2002-06-01

    Heterotopic ossification (HO) is a frequent complication following total hip arthroplasty (THA). At present, the etiology HO is unknown, however, genetic predisposition may be a cause of HO in individuals in whom no risk factors can be detected. The goal of this study was to investigate the HLA system, searching for any correlation with the presence of HO after THA. Thirty-five patients of Sicilian origin were operated on between January 1997 and January 1999 for cementless THA under regional anesthesia. The entire series was divided into three groups and all underwent histocompatibility typing. Group I was made up of 10 patients who presented with HO Brooker grades 1 and 2 after THA; group 2 comprised 7 patients affected by grades 3 and 4 HO after THA; and group 3 was made up of 18 subjects who presented with one or more preoperative risk factors for developing peri-prosthetic HO before undergoing THA. No positivity for HLA-B27 antigen was observed, but there was as an increase in HLA-B18 (with respect to that in the Sicilian population) in patients with HO following THA. The main conclusion from the study is that there is a strong correlation between the presence of the antigens HLA-A2 and HLA-B18 in patients with HO grades 3 and 4. PMID:24604489

  7. 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

  8. Fibrodysplasia ossificans progressiva-related activated activin-like kinase signaling enhances osteoclast formation during heterotopic ossification in muscle tissues.

    PubMed

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

    2014-06-13

    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.

  9. 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. PMID:25820900

  10. 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

  11. Neuromuscular electrical stimulation and testosterone did not influence heterotopic ossification size after spinal cord injury: A case series.

    PubMed

    Moore, Pamela D; Gorgey, Ashraf S; Wade, Rodney C; Khalil, Refka E; Lavis, Timothy D; Khan, Rehan; Adler, Robert A

    2016-07-16

    Neuromuscular electrical stimulation (NMES) and testosterone replacement therapy (TRT) are effective rehabilitation strategies to attenuate muscle atrophy and evoke hypertrophy in persons with spinal cord injury (SCI). However both interventions might increase heterotopic ossification (HO) size in SCI patients. We present the results of two men with chronic traumatic motor complete SCI who also had pre-existing HO and participated in a study investigating the effects of TRT or TRT plus NMES resistance training (RT) on body composition. The 49-year-old male, Subject A, has unilateral HO in his right thigh. The 31-year-old male, Subject B, has bilateral HO in both thighs. Both participants wore transdermal testosterone patches (4-6 mg/d) daily for 16 wk. Subject A also underwent progressive NMES-RT twice weekly for 16 wk. Magnetic resonance imaging scans were acquired prior to and post intervention. Cross-sectional areas (CSA) of the whole thigh and knee extensor skeletal muscles, femoral bone, and HO were measured. In Subject A (NMES-RT + TRT), the whole thigh skeletal muscle CSA increased by 10%, the knee extensor CSA increased by 17%, and the HO + femoral bone CSA did not change. In Subject B (TRT), the whole thigh skeletal muscle CSA increased by 13% in the right thigh and 6% in the left thigh. The knee extensor CSA increased by 7% in the right thigh and did not change in the left thigh. The femoral bone and HO CSAs in both thighs did not change. Both the TRT and NMES-RT + TRT protocols evoked muscle hypertrophy without stimulating the growth of pre-existing HO. PMID:27458592

  12. Neuromuscular electrical stimulation and testosterone did not influence heterotopic ossification size after spinal cord injury: A case series

    PubMed Central

    Moore, Pamela D; Gorgey, Ashraf S; Wade, Rodney C; Khalil, Refka E; Lavis, Timothy D; Khan, Rehan; Adler, Robert A

    2016-01-01

    Neuromuscular electrical stimulation (NMES) and testosterone replacement therapy (TRT) are effective rehabilitation strategies to attenuate muscle atrophy and evoke hypertrophy in persons with spinal cord injury (SCI). However both interventions might increase heterotopic ossification (HO) size in SCI patients. We present the results of two men with chronic traumatic motor complete SCI who also had pre-existing HO and participated in a study investigating the effects of TRT or TRT plus NMES resistance training (RT) on body composition. The 49-year-old male, Subject A, has unilateral HO in his right thigh. The 31-year-old male, Subject B, has bilateral HO in both thighs. Both participants wore transdermal testosterone patches (4-6 mg/d) daily for 16 wk. Subject A also underwent progressive NMES-RT twice weekly for 16 wk. Magnetic resonance imaging scans were acquired prior to and post intervention. Cross-sectional areas (CSA) of the whole thigh and knee extensor skeletal muscles, femoral bone, and HO were measured. In Subject A (NMES-RT + TRT), the whole thigh skeletal muscle CSA increased by 10%, the knee extensor CSA increased by 17%, and the HO + femoral bone CSA did not change. In Subject B (TRT), the whole thigh skeletal muscle CSA increased by 13% in the right thigh and 6% in the left thigh. The knee extensor CSA increased by 7% in the right thigh and did not change in the left thigh. The femoral bone and HO CSAs in both thighs did not change. Both the TRT and NMES-RT + TRT protocols evoked muscle hypertrophy without stimulating the growth of pre-existing HO. PMID:27458592

  13. Role of osteoclasts in heterotopic ossification enhanced by fibrodysplasia ossificans progressiva-related activin-like kinase 2 mutation in mice.

    PubMed

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

    2016-09-01

    Fibrodysplasia ossificans progressiva (FOP) is a disorder of skeletal malformations and progressive heterotopic ossification. The constitutively activating mutation (R206H) of the bone morphogenetic protein type 1 receptor, activin-like kinase 2 (ALK2), is responsible for the pathogenesis of FOP. Although transfection of the causal mutation of FOP into myoblasts enhances osteoclast formation by transforming growth factor-β (TGF-β), the role of osteoclasts in heterotopic ossification is unknown. We therefore examined the effects of alendronate, SB431542 and SB203580 on heterotopic ossification induced by the causal mutation of FOP. Total bone mineral content as well as numbers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated and alkaline phosphatase (ALP)-positive cells in heterotopic bone were significantly higher in muscle tissues implanted with ALK2 (R206H)-transfected mouse myoblastic C2C12 cells than in the tissues implanted with empty vector-transfected cells in nude mice. Alendronate, an aminobisphosphonate, did not affect total mineral content or numbers of TRAP-positive multinucleated and ALP-positive cells in heterotopic bone, which were enhanced by the implantation of ALK2 (R206H)-transfected C2C12 cells, although it significantly decreased serum levels of cross-linked C-telopeptide of type I collagen, a bone resorption index. Moreover, neither SB431542, an inhibitor of TGF-β receptor type I kinase, nor SB203580, an inhibitor of p38 mitogen-activated protein kinase, affected the increase in heterotopic ossification due to the implantation of ALK2 (R206H)-transfected C2C12 cells. In conclusion, the present study indicates that osteoclast inhibition does not affect heterotopic ossification enhanced by FOP-related mutation.

  14. 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.

  15. Effects of Aging on Osteogenic Response and Heterotopic Ossification Following Burn Injury in Mice

    PubMed Central

    Peterson, Jonathan R.; Eboda, Oluwatobi N.; Brownley, R. Cameron; Cilwa, Katherine E.; Pratt, Lauren E.; De La Rosa, Sara; Agarwal, Shailesh; Buchman, Steven R.; Cederna, Paul S.; Morris, Michael D.; Wang, Stewart C.

    2015-01-01

    Heterotopic ossification (HO) is a common and debilitating complication of burns, traumatic brain injuries, and musculoskeletal trauma and surgery. Although the exact mechanism of ectopic bone formation is unknown, mesenchymal stem cells (MSCs) capable of osteogenic differentiation are known to play an essential role. Interestingly, the prevalence of HO in the elderly population is low despite the high overall occurrence of musculoskeletal injury and orthopedic procedures. We hypothesized that a lower osteogenicity of MSCs would be associated with blunted HO formation in old compared with young mice. In vitro osteogenic differentiation of adipose-derived MSCs from old (18–20 months) and young (6–8 weeks) C57/BL6 mice was assessed, with or without preceding burn injury. In vivo studies were then performed using an Achilles tenotomy with concurrent burn injury HO model. HO formation was quantified using μCT scans, Raman spectroscopy, and histology. MSCs from young mice had more in vitro bone formation, upregulation of bone formation pathways, and higher activation of Smad and nuclear factor kappa B (NF-κB) signaling following burn injury. This effect was absent or blunted in cells from old mice. In young mice, burn injury significantly increased HO formation, NF-κB activation, and osteoclast activity at the tenotomy site. This blunted, reactive osteogenic response in old mice follows trends seen clinically and may be related to differences in the ability to mount acute inflammatory responses. This unique characterization of HO and MSC osteogenic differentiation following inflammatory insult establishes differences between age populations and suggests potential pathways that could be targeted in the future with therapeutics. PMID:25122460

  16. Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification.

    PubMed

    Agarwal, Shailesh; Loder, Shawn; Brownley, Cameron; Cholok, David; Mangiavini, Laura; Li, John; Breuler, Christopher; Sung, Hsiao H; Li, Shuli; Ranganathan, Kavitha; Peterson, Joshua; Tompkins, Ronald; Herndon, David; Xiao, Wenzhong; Jumlongras, Dolrudee; Olsen, Bjorn R; Davis, Thomas A; Mishina, Yuji; Schipani, Ernestina; Levi, Benjamin

    2016-01-19

    Pathologic extraskeletal bone formation, or heterotopic ossification (HO), occurs following mechanical trauma, burns, orthopedic operations, and in patients with hyperactivating mutations of the type I bone morphogenetic protein receptor ACVR1 (Activin type 1 receptor). Extraskeletal bone forms through an endochondral process with a cartilage intermediary prompting the hypothesis that hypoxic signaling present during cartilage formation drives HO development and that HO precursor cells derive from a mesenchymal lineage as defined by Paired related homeobox 1 (Prx). Here we demonstrate that Hypoxia inducible factor-1α (Hif1α), a key mediator of cellular adaptation to hypoxia, is highly expressed and active in three separate mouse models: trauma-induced, genetic, and a hybrid model of genetic and trauma-induced HO. In each of these models, Hif1α expression coincides with the expression of master transcription factor of cartilage, Sox9 [(sex determining region Y)-box 9]. Pharmacologic inhibition of Hif1α using PX-478 or rapamycin significantly decreased or inhibited extraskeletal bone formation. Importantly, de novo soft-tissue HO was eliminated or significantly diminished in treated mice. Lineage-tracing mice demonstrate that cells forming HO belong to the Prx lineage. Burn/tenotomy performed in lineage-specific Hif1α knockout mice (Prx-Cre/Hif1α(fl:fl)) resulted in substantially decreased HO, and again lack of de novo soft-tissue HO. Genetic loss of Hif1α in mesenchymal cells marked by Prx-cre prevents the formation of the mesenchymal condensations as shown by routine histology and immunostaining for Sox9 and PDGFRα. Pharmacologic inhibition of Hif1α had a similar effect on mesenchymal condensation development. Our findings indicate that Hif1α represents a promising target to prevent and treat pathologic extraskeletal bone. PMID:26721400

  17. Heterotopic ossification after hemiarthroplasty of the hip – A comparison of three common approaches

    PubMed Central

    Corrigan, Chad M.; Greenberg, Sarah E.; Sathiyakumar, Vasanth; Mitchell, Phillip M.; Francis, Arie; Omar, Adan; Thakore, Rachel V.; Obremskey, William T.; Sethi, Manish K.

    2014-01-01

    Objective Heterotopic ossification (HO) about the hip after total hip arthroplasty and internal fixation of the hip, pelvis, and acetabulum has been linked to surgical approach. However, no study has investigated surgical approach and HO in patients undergoing hemiarthroplasty. We therefore aimed to explore the influence of operative approach in patients undergoing hemiarthroplasty. Methods Through a retrospective case series at an Urban level I trauma center, we found 80 patients over the age of 60 undergoing hemiarthroplasty for femoral neck fractures from 2000 to 2009. Patient charts, operative notes, and radiographs were reviewed for demographics, operative approach (anterior: A, anterior-lateral: AL, posterior: P), and any development of HO. Fisher's exact test compared rates of HO among the three approaches. Student's t-tests compared Brooker Classification levels of HO among the approaches. Results 82 hemiarthroplasties (26 A, 32 AL, 24 P) were included for analysis. 22 patients (27%) had HO. There was no significant difference in the development of HO based upon surgical approach: A: 19% (n = 5); AL: 34% (n = 11); P: 25% (n = 6). There was a significant difference in the grade of HO based on Brooker Classification (BC) with the posterior approach resulting in significantly lower grade of HO: A (BC: 2.60); AL (BC: 2.64); P (BC: 1.50) (p = 0.012). Conclusions Our data is the first to evaluate surgical approach and HO in patients with hemiarthroplasty. Patients have a significant risk of developing higher grade HO based on surgical approach (A or AL). Orthopedists should be mindful of these risks when considering A or AL approaches. PMID:26549944

  18. 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.

  19. 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.

  20. Indomethacin versus radiation therapy for prophylaxis against heterotopic ossification in acetabular fractures: a randomised, prospective study.

    PubMed

    Moore, K D; Goss, K; Anglen, J O

    1998-03-01

    We report a prospective, randomised, blinded clinical comparison of the use of indomethacin or radiation therapy for the prevention of heterotopic ossification (HO) in 75 adults who had open reduction and internal fixation of acetabular fractures through either a Kocher-Langenbeck, a combined ilioinguinal and Kocher-Langenbeck, or an extended iliofemoral approach. Indomethacin, 25 mg, was given three times daily for six weeks. Radiation with 800 cGy was delivered within three days of operation. Plain radiographs were reviewed and given Brooker classification scores by three independent observers who were unaware of the method of prophylaxis. One patient died from unrelated causes and two were lost to follow-up, leaving 72, 33 in the radiation group and 39 in the indomethacin group, available for evaluation at a mean of 12 months (6 to 48). There was no significant difference in the two groups in terms of age, gender, injury severity score, estimated blood loss, delay to surgery, head injury, presence of femoral head dislocation, or operating time, and no complications due to either method of treatment. The final extent of HO was already present by six weeks in all patients who were followed up. Three patients in the radiation group and five who received indomethacin developed HO of Brooker grade III. Two patients in the indomethacin group developed Brooker IV changes; both had failed to receive proper doses of the drug. Cochran-Armitage analysis showed no significant difference between the two treatment groups as regards the formation of HO. Indomethacin and single-dose radiation therapy are both safe and effective for the prevention of HO after operation for acetabular fractures. Radiation therapy is, however, approximately 200 times more expensive than indomethacin therapy at our institution and has other risks.

  1. 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

  2. Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification

    PubMed Central

    Agarwal, Shailesh; Loder, Shawn; Brownley, Cameron; Cholok, David; Mangiavini, Laura; Li, John; Breuler, Christopher; Sung, Hsiao H.; Li, Shuli; Ranganathan, Kavitha; Peterson, Joshua; Tompkins, Ronald; Herndon, David; Xiao, Wenzhong; Jumlongras, Dolrudee; Olsen, Bjorn R.; Davis, Thomas A.; Mishina, Yuji; Schipani, Ernestina; Levi, Benjamin

    2016-01-01

    Pathologic extraskeletal bone formation, or heterotopic ossification (HO), occurs following mechanical trauma, burns, orthopedic operations, and in patients with hyperactivating mutations of the type I bone morphogenetic protein receptor ACVR1 (Activin type 1 receptor). Extraskeletal bone forms through an endochondral process with a cartilage intermediary prompting the hypothesis that hypoxic signaling present during cartilage formation drives HO development and that HO precursor cells derive from a mesenchymal lineage as defined by Paired related homeobox 1 (Prx). Here we demonstrate that Hypoxia inducible factor-1α (Hif1α), a key mediator of cellular adaptation to hypoxia, is highly expressed and active in three separate mouse models: trauma-induced, genetic, and a hybrid model of genetic and trauma-induced HO. In each of these models, Hif1α expression coincides with the expression of master transcription factor of cartilage, Sox9 [(sex determining region Y)-box 9]. Pharmacologic inhibition of Hif1α using PX-478 or rapamycin significantly decreased or inhibited extraskeletal bone formation. Importantly, de novo soft-tissue HO was eliminated or significantly diminished in treated mice. Lineage-tracing mice demonstrate that cells forming HO belong to the Prx lineage. Burn/tenotomy performed in lineage-specific Hif1α knockout mice (Prx-Cre/Hif1αfl:fl) resulted in substantially decreased HO, and again lack of de novo soft-tissue HO. Genetic loss of Hif1α in mesenchymal cells marked by Prx-cre prevents the formation of the mesenchymal condensations as shown by routine histology and immunostaining for Sox9 and PDGFRα. Pharmacologic inhibition of Hif1α had a similar effect on mesenchymal condensation development. Our findings indicate that Hif1α represents a promising target to prevent and treat pathologic extraskeletal bone. PMID:26721400

  3. 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

  4. 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.

  5. Acute closed traumatic sciatic nerve injury: a complication of heterotopic ossification and prominence of the femoral nail: a case report.

    PubMed

    Niempoog, Sunyarn; Chumchuen, Sukanis

    2014-08-01

    The report of a 27-years-old man with presence of heterotopic ossification (HO) after femoral nailing 7years ago who developed foot drop afterfalling to the ground on his buttocks. Radiographs revealed a prominence ofthefemoral nail with HO in his right hip. EMG confirmedperoneal nerve injury ofthe hip region. Femoral nail and the HO were removed and external neurolysis was performed. At 9 months after surgery, he had not regain motor power thus posterior tibialis tendon transfer was performed to restore ankle dorsiflexion. Finally, at 2 years follow-up, he could ambulate well but did not regained sensation, extensor digitorum communis and peroneal muscle function. PMID:25518317

  6. Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification.

    PubMed

    Adegbite, N S; Xu, M; Kaplan, F S; Shore, E M; Pignolo, R J

    2008-07-15

    Progressive osseous heteroplasia (POH) is a rare, disabling disease of heterotopic ossification (HO) that progresses from skin and subcutaneous tissues into deep skeletal muscle. POH occurs in the absence of multiple developmental features of Albright hereditary osteodystrophy (AHO) or hormone resistance, clinical manifestations that are also associated with GNAS inactivation. However, occasional patients with AHO and pseudohypoparathyroidism 1a/c (PHP1a/c; AHO features plus hormone resistance) have also been described who have progressive HO. This study was undertaken to define the diagnostic and mutational spectrum of POH and progressive disorders of HO, and to distinguish them from related disorders in which HO remains confined to the skin and subcutaneous tissues. We reviewed the charts of 111 individuals who had cutaneous and subcutaneous ossification. All patients were assessed for eight characteristics: age of onset of HO, presence and location of HO, depth of HO, type of HO, progression of HO, features of AHO, PTH resistance, and GNAS mutation analysis. We found, based on clinical criteria, that POH and progressive HO syndromes are at the severe end of a phenotypic spectrum of GNAS-inactivating conditions associated with extra-skeletal ossification. While most individuals with superficial or progressive ossification had mutations in GNAS, there were no specific genotype-phenotype correlations that distinguished the more progressive forms of HO (e.g., POH) from the non-progressive forms (osteoma cutis, AHO, and PHP1a/c).

  7. 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

  8. Heterotopic ossification is less after THA in patients who receive aspirin compared to coumadin.

    PubMed

    Cohn, Randy M; Della Valle, Alejandro González; Cornell, Charles N

    2010-01-01

    The role of aspirin in the prevention of heterotopic ossification (HO) following total hip arthroplasty (THA) has been debated. This retrospective comparative study assesses the results of 167 total hip arthroplasties (THAs) performed between August 1998 and April 2005 on 150 consecutive patients (17 bilaterals) who were 70 years of age and under by a single orthopaedic surgeon. A comparison of the incidence and severity of HO between those patients who received aspirin (325 mg bid) with those who received Coumadin® (wafarin) for pharmacologic thromboprophylaxis. Surgery was performed through a posterolateral approach, with an enhanced soft tissue repair. There were 34 patients (35 hips) in the aspirin group and 68 patients (82 hips) in the Coumadin® group. All patients received prophylaxis for 6 weeks postoperatively. HO was classified according to Brooker and colleagues using anterior-posterior (AP) radiographs at last follow-up (range, 1 to 8 years). There were four hips (11.4%) with HO in the aspirin group and 28 (34.2%) in the Coumadin® group (p = 0.012). HO class III and IV was not detected in the aspirin group, but was in seven hips in the Coumadin® group (p = 0.13). Males had an incidence of HO of 40.4% (19 of 47 hips) and females had an incidence of 18.6% (13 of 70 hips) (p = 0.009). Males who received aspirin developed HO in 22.2% (4 of 18 hips), compared to 51.7% (15 of 29 hips) in the Coumadin® group (p = 0.045). No females (0 of 17 hips) who received aspirin developed HO, compared to 24.5% (13 of 53 hips) in females who received Coumadin® (p = 0.024). In this analysis, aspirin thromboprophylaxis decreased the prevalence of HO following elective THA in both females and males. This effect was not seen in patients who received Coumadin® after surgery. PMID:21162704

  9. Nonsteroidal Anti-inflammatory Drugs as Prophylaxis for Heterotopic Ossification after Total Hip Arthroplasty

    PubMed Central

    Kan, Shun-Li; Yang, Bo; Ning, Guang-Zhi; Chen, Ling-Xiao; Li, Yu-Lin; Gao, Shi-Jie; Chen, Xing-Yu; Sun, Jing-Cheng; Feng, Shi-Qing

    2015-01-01

    Abstract Heterotopic ossification (HO) is a frequent complication after total hip arthroplasty (THA). Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used as routine prophylaxis for HO after THA. However, the efficacy of NSAIDs on HO, particularly selective NSAIDs versus nonselective NSAIDs, is uncertain. We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov to identify randomized controlled trials with respect to HO after THA. Two reviewers extracted the data and estimated the risk of bias. For the ordered data, we followed the Bayesian framework to calculate the odds ratio (OR) with a 95% credible interval (CrI). For the dichotomous data, the OR and 95% confidence interval (CI) were calculated using Stata version 12.0. The subgroup analyses and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach were used. A total of 1856 articles were identified, and 21 studies (5995 patients) were included. In the NSAIDs versus placebo analysis, NSAIDs could decrease the incidence of HO, according to the Brooker scale (OR = 2.786, 95% CrI 1.879–3.993) and Delee scale (OR = 9.987, 95% CrI 5.592–16.17). In the selective NSAIDs versus nonselective NSAIDs analysis, there was no significant difference (OR = 0.7989, 95% CrI 0.5506–1.125) in the prevention of HO. NSAIDs could increase discontinuation caused by gastrointestinal side effects (DGSE) (OR = 1.28, 95% CI 1.00–1.63, P = 0.046) more than a placebo. Selective NSAIDs could decrease DGSE (OR = 0.48, 95% CI 0.24–0.97, P = 0.042) compared with the nonselective NSAIDs. There was no significant difference with respect to discontinuation caused by nongastrointestinal side effects (DNGSE) in NSAIDs versus a placebo (OR = 1.16, 95% CI 0.88–1.53, P = 0.297) and in selective NSAIDs versus nonselective NSAIDs (OR = 0.83, 95% CI 0.50–1.37, P = 0.462). NSAIDs might reduce the incidence of HO

  10. 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

  11. 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

  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. Posterior mini-incision total hip arthroplasty controls the extent of post-operative formation of heterotopic ossification.

    PubMed

    Edwards, D S; Barbur, S A R; Bull, A M J; Stranks, G J

    2015-08-01

    Heterotopic ossification (HO) is the formation of bone at extra-skeletal sites. Reported rates of HO after hip arthroplasty range from 8 to 90 %; however, it is only severe cases that cause problems clinically, such as joint stiffness. The effects of surgical-related controllable intra-operative risk factors for the formation of HO were investigated. Data examined included gender, age of patient, fat depth, length of operation, incision length, prosthetic fixation method, the use of pulsed lavage and canal brush, and component size and material. All cases were performed by the same surgeon using the posterior approach. A total of 510 cases of hip arthroplasty were included, with an overall rate of HO of 10.2 %. Longer-lasting operations resulted in higher grades of HO (p = 0.047). Incisions >10 cm resulted in more widespread HO formation (p = 0.021). No further correlations were seen between HO formation and fat depth, blood loss, instrumentation, fixation methods or prosthesis material. The mini-incision approach is comparable to the standard approach in the aetiology of HO formation, and whilst the rate of HO may not be controllable, a posterior mini-incision approach can limit its extent.

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

    PubMed

    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

    2016-07-12

    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. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. Rational design of YAP WW1 domain-binding peptides to target TGFβ/BMP/Smad-YAP interaction in heterotopic ossification.

    PubMed

    Chen, Dong; Liu, Shenghe; Zhang, Wen; Sun, Luyuan

    2015-11-01

    The transforming growth factor-β/bone morphogenic protein/Smad signaling pathway has been raised as a new and promising therapeutic target of heterotopic ossification, which is mediated by recruitment of transcription coactivator Yes-associated protein (YAP) to Smad. Here, we described a successful integration of computational modeling and experimental assay to rationally design novel peptide aptamers to disrupt YAP-Smad interaction by targeting YAP WW1 domain. In the protocol, a computational genetic evolution strategy was used to improve a population of potential YAP WW1-binding peptides generated from the YAP-recognition site in Smad protein, from which several promising peptides were selected and their affinities toward YAP WW1 domain were determined using binding assay. In addition, a high-activity peptide was further optimized based on its complex structure with YAP WW1 domain to derive a number of derivative peptides with higher binding potency to the domain. We also found that a strong YAP WW1 binder should have a negatively charged N-terminus, a positively charged C-terminus and a nonpolar core to match the electrostatic distribution pattern in peptide-binding pocket of YAP WW1 domain, which may also form additional nonbonded interactions such as hydrogen bond, salt bridge and π-π stacking to confer stability and specificity for the domain-peptide recognition.

  2. Rational design of YAP WW1 domain-binding peptides to target TGFβ/BMP/Smad-YAP interaction in heterotopic ossification.

    PubMed

    Chen, Dong; Liu, Shenghe; Zhang, Wen; Sun, Luyuan

    2015-11-01

    The transforming growth factor-β/bone morphogenic protein/Smad signaling pathway has been raised as a new and promising therapeutic target of heterotopic ossification, which is mediated by recruitment of transcription coactivator Yes-associated protein (YAP) to Smad. Here, we described a successful integration of computational modeling and experimental assay to rationally design novel peptide aptamers to disrupt YAP-Smad interaction by targeting YAP WW1 domain. In the protocol, a computational genetic evolution strategy was used to improve a population of potential YAP WW1-binding peptides generated from the YAP-recognition site in Smad protein, from which several promising peptides were selected and their affinities toward YAP WW1 domain were determined using binding assay. In addition, a high-activity peptide was further optimized based on its complex structure with YAP WW1 domain to derive a number of derivative peptides with higher binding potency to the domain. We also found that a strong YAP WW1 binder should have a negatively charged N-terminus, a positively charged C-terminus and a nonpolar core to match the electrostatic distribution pattern in peptide-binding pocket of YAP WW1 domain, which may also form additional nonbonded interactions such as hydrogen bond, salt bridge and π-π stacking to confer stability and specificity for the domain-peptide recognition. PMID:26435515

  3. 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

  4. Nonsteroidal Anti-inflammatory Drugs as Prophylaxis for Heterotopic Ossification after Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

    PubMed

    Kan, Shun-Li; Yang, Bo; Ning, Guang-Zhi; Chen, Ling-Xiao; Li, Yu-Lin; Gao, Shi-Jie; Chen, Xing-Yu; Sun, Jing-Cheng; Feng, Shi-Qing

    2015-05-01

    Heterotopic ossification (HO) is a frequent complication after total hip arthroplasty (THA). Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used as routine prophylaxis for HO after THA. However, the efficacy of NSAIDs on HO, particularly selective NSAIDs versus nonselective NSAIDs, is uncertain.We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov to identify randomized controlled trials with respect to HO after THA. Two reviewers extracted the data and estimated the risk of bias. For the ordered data, we followed the Bayesian framework to calculate the odds ratio (OR) with a 95% credible interval (CrI). For the dichotomous data, the OR and 95% confidence interval (CI) were calculated using Stata version 12.0. The subgroup analyses and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach were used.A total of 1856 articles were identified, and 21 studies (5995 patients) were included. In the NSAIDs versus placebo analysis, NSAIDs could decrease the incidence of HO, according to the Brooker scale (OR = 2.786, 95% CrI 1.879-3.993) and Delee scale (OR = 9.987, 95% CrI 5.592-16.17). In the selective NSAIDs versus nonselective NSAIDs analysis, there was no significant difference (OR = 0.7989, 95% CrI 0.5506-1.125) in the prevention of HO. NSAIDs could increase discontinuation caused by gastrointestinal side effects (DGSE) (OR = 1.28, 95% CI 1.00-1.63, P = 0.046) more than a placebo. Selective NSAIDs could decrease DGSE (OR = 0.48, 95% CI 0.24-0.97, P = 0.042) compared with the nonselective NSAIDs. There was no significant difference with respect to discontinuation caused by non-gastrointestinal side effects (DNGSE) in NSAIDs versus a placebo (OR = 1.16, 95% CI 0.88-1.53, P = 0.297) and in selective NSAIDs versus nonselective NSAIDs (OR = 0.83, 95% CI 0.50-1.37, P = 0.462).NSAIDs might reduce the incidence of HO and increase DGSE in the

  5. 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

  6. Extra-articular hip impingement due to heterotopic ossification formation at the anterior inferior iliac spine following previous pelvic external fixation.

    PubMed

    Sandilands, Scott M; Raudenbush, Brandon L; Carreira, Dominic S; Cross, Brian J

    2016-01-01

    Femoroacetabular impingements (FAIs), specifically cam type and pincer type, continue to be accepted as causes of intra-articular hip pathology and sources of hip pain. Reports of other causes of hip impingement including extra-articular causes have surfaced recently. One structure of importance is the anterior inferior iliac spine (AIIS) due to its inconsistent bony morphology and the pull of the rectus femoris muscle putting it at risk for an avulsion fracture. Under certain circumstances, open surgical excision of exostosis formation after an avulsion fracture of the AIIS has been used. The case below represents a clinical scenario in which a medically unstable and multiply injured trauma patient had an external pelvic fixator placed as part of the treatment plan for an unstable pelvic injury. Following this pelvic external fixation treatment, the patient went on to develop clinically significant heterotopic bone formation at the AIIS pin site with extra-articular hip impingement syndrome. PMID:27637275

  7. GNAS-associated disorders of cutaneous ossification: two different clinical presentations.

    PubMed

    Schimmel, R J; Pasmans, S G M A; Xu, M; Stadhouders-Keet, S A E; Shore, E M; Kaplan, F S; Wulffraat, N M

    2010-03-01

    Progressive osseous heteroplasia (POH) is a rare genetic disorder characterized by dermal ossification during infancy and progressive ossification into deep connective tissue during childhood. POH is at the severe end of a spectrum of GNAS-associated ossification disorders that include osteoma cutis and Albright Hereditary Osteodystrophy (AHO). Here we describe two girls who have different clinical presentations that reflect the variable expression of GNAS-associated disorders of cutaneous ossification. Each girl had a novel heterozygous inactivating mutation in the GNAS gene. One girl had POH limited to the left arm with severe contractures and growth retardation resulting from progressive heterotopic ossification in the deep connective tissues. The other girl had AHO with widespread, superficial heterotopic ossification but with little functional impairment. While there is presently no treatment or prevention for GNAS-associated ossification disorders, early diagnosis is important for genetic counselling and for prevention of iatrogenic harm.

  8. Genetic disorders with heterotopic ossificans

    PubMed Central

    Sankar, Ruthiramurthy; Gowrishankar, Kalpana; Viswanathan, Saraswati

    2015-01-01

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

  9. Hypoxic adipocytes pattern early heterotopic bone formation.

    PubMed

    Olmsted-Davis, Elizabeth; Gannon, Francis H; Ozen, Mustafa; Ittmann, Michael M; Gugala, Zbigniew; Hipp, John A; Moran, Kevin M; Fouletier-Dilling, Christine M; Schumara-Martin, Shannon; Lindsey, Ronald W; Heggeness, Michael H; Brenner, Malcolm K; Davis, Alan R

    2007-02-01

    The factors contributing to heterotopic ossification, the formation of bone in abnormal soft-tissue locations, are beginning to emerge, but little is known about microenvironmental conditions promoting this often devastating disease. Using a murine model in which endochondral bone formation is triggered in muscle by bone morphogenetic protein 2 (BMP2), we studied changes near the site of injection of BMP2-expressing cells. As early as 24 hours later, brown adipocytes began accumulating in the lesional area. These cells stained positively for pimonidazole and therefore generated hypoxic stress within the target tissue, a prerequisite for the differentiation of stem cells to chondrocytes and subsequent heterotopic bone formation. We propose that aberrant expression of BMPs in soft tissue stimulates production of brown adipocytes, which drive the early steps of heterotopic endochondral ossification by lowering oxygen tension in adjacent tissue, creating the correct environment for chondrogenesis. Results in misty gray lean mutant mice not producing brown fat suggest that white adipocytes convert into fat-oxidizing cells when brown adipocytes are unavailable, providing a compensatory mechanism for generation of a hypoxic microenvironment. Manipulation of the transcriptional control of adipocyte fate in local soft-tissue environments may offer a means to prevent or treat development of bone in extraskeletal sites. PMID:17255330

  10. 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

  11. Soft tissue ossification and condylar cartilage degeneration following TMJ disc perforation in a rabbit pilot study

    PubMed Central

    Embree, Mildred C.; Iwaoka, George M.; Kong, Danielle; Martin, Brittany N.; Patel, Ryan K.; Lee, Andrew; Nathan, John M.; Eisig, Sidney B.; Safarov, Aram; Koslovsky, David A; Koch, Alia; Romanov, Alex; Mao, Jeremy J

    2015-01-01

    Objective There are limited clinical treatments for temporomandibular joint pathologies, including degenerative disease, disc perforation and heterotopic ossification. One barrier hindering the development of new therapies is that animal models recapitulating TMJ diseases are poorly established. The objective of this study was to develop an animal model for TMJ cartilage degeneration and disc pathology, including disc perforation and soft tissue heterotopic ossification. Methods New Zealand white rabbits (n=9 rabbits) underwent unilateral TMJ disc perforation surgery and sham surgery on the contralateral side. A 2.5 mm defect was created using a punch biopsy in rabbit TMJ disc. The TMJ condyles and discs were evaluated macroscopically and histologically after 4, 8 and 12 weeks. Condyles were blindly scored by 4 independent observers using OARSI recommendations for macroscopic and histopathological scoring of osteoarthritis in rabbit tissues. Results Histological evidence of TMJ condylar cartilage degeneration was apparent in experimental condyles following disc perforation relative to sham controls after 4 and 8 weeks, including surface fissures and loss of Safranin O staining. At 12 weeks, OARSI scores indicated experimental condylar cartilage erosion into the subchondral bone. Most strikingly, heterotopic ossification occurred within the TMJ disc upon perforation injury in 6 rabbits after 8 and 12 weeks. Conclusion We report for the first time a rabbit TMJ injury model that demonstrates condylar cartilage degeneration and disc ossification, which is indispensible for testing the efficacy of potential TMJ therapies. PMID:25573797

  12. 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.

  13. Trismus and multifocal soft tissue ossification. A presentation of fibrodysplasia ossificans progressiva?

    PubMed

    Kabala, J E; Watt, I; Hollingworth, P; Ross, J W

    1989-09-01

    A 21-year-old female patient presented with trismus, initially diagnosed as related to pericoronitis. Computed tomography demonstrated heterotopic soft tissue ossification involving both medial pterygoids which was later followed by similar features in the submandibular muscles and right quadriceps. A variant of fibrodysplasia ossificans progressiva was considered the likeliest diagnosis. The computed tomographic features of the condition and the importance of early diagnosis are stressed.

  14. Apoptosis during intramembranous ossification

    PubMed Central

    Palumbo, Carla; Ferretti, Marzia; De Pol, Anto

    2003-01-01

    This paper concerns the role of apoptosis during the onset of bone histogenesis. Previous investigations by us performed on intramembranous ossification revealed the existence of two types of osteogenesis: static (SBF) and dynamic bone formation (DBF). During SBF, the first to occur, stationary osteoblasts transform into osteocytes in the same location where they differentiated, forming the primary spongiosa. DBF takes place later, when movable osteoblastic laminae differentiate along the surface of the primary trabeculae. The main distinctive feature between SBF and DBF is that the latter involves the invasion of pre-existing adjacent tissue, whereas the former does not. To ascertain whether programmed cell death during the invasive DBF process determines the fate of surrounding pre-existing mesenchyme differently from that occurring during the non-invasive SBF process, we studied apoptosis in ossification centres of tibial diaphysis in chick embryos and newborn rabbits with TUNEL and TEM. It emerged that, in both SBF and DBF, apoptosis affects mesenchymal cells located between the forming trabeculae and capillaries. However, apoptotic cells were observed more frequently during DBF than during SBF. This suggests that, during bone histogenesis, apoptosis, which is mostly associated with the invasive process of DBF, is probably dedicated to making space for advancing bone growth. PMID:14686694

  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.

  16. CASE REPORT An Unusual Case of Abdominal Compartment Syndrome Following Resection of Extensive Posttraumatic Mesenteric Ossification

    PubMed Central

    Nabulyato, William M.; Alsahiem, Hebah; Hall, Nigel R.; Malata, Charles M.

    2013-01-01

    Introduction: Heterotopic mesenteric ossification is an extremely rare condition, which often follows trauma and is frequently symptomatic. To date, there are no reports in the literature of abdominal compartment syndrome occurring after surgical resection of mesenteric calcification. The present report documents an unusual case of compartment syndrome complicating resection of extensive mesenteric calcification despite abdominal closure with the components-separation technique. Method: A 48-year-old man undergoing components-separation technique for posttraumatic laparostomy hernia repair (ileostomy reversal and sigmoid stricture correction) was found to have extensive heterotopic mesenteric calcification, which needed resection. Results: Resection of the mesenteric calcification was complicated by intraoperative hemorrhage and unplanned small bowel resection. Later the patient developed secondary hemorrhage leading to an abdominal compartment syndrome, which was successfully treated by decompression, hemostasis, and Permacol-assisted laparotomy wound closure. The patient remains symptom-free more than 2 years after surgery. Discussion: The case herein reported gives an account of the rare occurrence of abdominal compartment syndrome following resection of posttraumatic ectopic mesenteric ossifications. It is highly unusual in that it occurred because of “secondary hemorrhage” and despite abdominal closure with the components-separation technique, which had been undertaken precisely to prevent compartment syndrome with direct closure. It therefore highlights the need for continued clinical vigilance in complex posttraumatic cases. PMID:23573333

  17. Heterotopic pregnancy. A case report.

    PubMed

    Skrajna, Adrianna; Cendrowski, Krzysztof; Alkhalayla, Habib; Sawicki, Włodzimierz

    2012-09-01

    Heterotopic pregnancy is the coexistence of living or dead intrauterine pregnancy, single or multiple, and extrauterine pregnancy located in the oviduct, ovary, uterine corner, cervix or peritoneal cavity. This condition is very rare (1:30 000 pregnancies). Nevertheless, in the latter years because of the development and accessibility of assisted reproductive techniques, the incidence of heterotopic pregnancies increased to 1:100 of pregnancies. The aim of this report is to present a case of early recognized intrauterine and extrauterine pregnancy. The case refers to 25-year-old patient, pregnant for the second time, in more or less 6th week of gestation, who had not been stated any heterotopic pregnancy incidence risk factors. After the observation lasting for several days in the Clinic, the presence of a living intrauterine and coexisting extrauterine pregnancy located in the right oviduct was stated. The patient had her right oviduct removed by means of laparoscopy. After the surgery the patient with the living intrauterine pregnancy was released from the Clinic. Normal further course of intrauterine pregnancy. The patient gave birth around her expected delivery date. The presented case indicates the significance of correctly and carefully performed ultrasound examination. Moreover, it is a warning for the doctors performing ultrasound examinations in the early weeks of pregnancy - the visualization of a normal pregnancy in the ultrasound examination does not release the examiner from a necessity of precise imaging of adnexa of the uterus. Early diagnosis of this pathology, thanks to a precise ultrasound examination, decreases the risk of complication incidence as well as women mortality.

  18. 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.

  19. Imaging symptomatic bone morphogenetic protein-2-induced heterotopic bone formation within the spinal canal: case report.

    PubMed

    Chryssikos, Timothy; Crandall, Kenneth M; Sansur, Charles A

    2016-05-01

    Heterotopic bone formation within the spinal canal is a known complication of bone morphogenetic protein-2 (BMP-2) and presents a clinical and surgical challenge. Imaging modalities are routinely used for operative planning in this setting. Here, the authors present the case of a 59-year-old woman with cauda equina syndrome following intraoperative BMP-2 administration. Plain film myelographic studies showed a region of severe stenosis that was underappreciated on CT myelography due to a heterotopic bony lesion mimicking the dorsal aspect of a circumferentially patent thecal sac. When evaluating spinal stenosis under these circumstances, it is important to carefully consider plain myelographic images in addition to postmyelography CT images as the latter may underestimate the true degree of stenosis due to the potentially similar radiographic appearances of evolving BMP-2-induced heterotopic bone and intrathecal contrast. Alternatively, comparison of sequentially acquired noncontrast CT scans with CT myelographic images may also assist in distinguishing BMP-2-induced heterotopic bony lesions from the thecal sac. Further studies are needed to elucidate the roles of the available imaging techniques in this setting and to characterize the connection between the radiographic and histological appearances of BMP-2-induced heterotopic bone. PMID:26824586

  20. Heterotopic pregnancy after a single embryo transfer

    PubMed Central

    Lee, Ji Sun; Cha, Hyun-Hwa; Han, Ae Ra; Lee, Seong Goo

    2016-01-01

    Heterotopic pregnancy is a rare and life-threatening condition which is defined as coexistent intrauterine and ectopic gestation. The risk of ectopic and heterotopic pregnancy is increasing due to the increased risk of multiple pregnancies with the aid of assisted reproductive technologies. However, it hardly happens in the setting of single embryo transfer, since single embryo transfer significantly reduces the incidence of multiple pregnancies. Surprisingly, we experienced a case of heterotopic pregnancy after a single embryo transfer caused by coincidental natural pregnancy during assisted reproductive technologies. An infertile woman who underwent, during her natural cycle, transfer of a single embryo that had been cryopreserved for 3 years was found to be heterotopically pregnant. After an early and successful management with laparoscopic right salpingectomy, she finally reached at full-term vaginal delivery. PMID:27462600

  1. [Multiple calcifications and ossifications of tendons].

    PubMed

    Gaucher, A; Péré, P; Gillet, P

    1991-06-21

    Multiple calcifications and ossifications of tendons are, as a rule, associated with similar lesions of other articular and/or periarticular structures. The nature and multiplicity of these lesions gives them an unquestionable diagnostic and nosological value. Multiple calcifications are part of the apatite arthritis or of diffuse articular chondrocalcinosis. Multiple ossifications of tendons often suggest Forestier's disease and ankylosing spondylitis.

  2. Evaluation of heterotopic bone formation induced by squalane and bone morphogenetic protein composite.

    PubMed

    Kawakami, T; Kawai, T; Takei, N; Kise, T; Eda, S; Urist, M R

    1997-04-01

    Bone morphogenetic protein is an important molecule whose bioactivity depends on the carrier. Squalane is used in the formulation of various kinds of cosmetics because it is easily emulsified and has the property of spreading well. Thus, squalane might be effective as a bone morphogenetic protein delivery system. As a test for this possibility, gelatin capsules containing squalane and bone morphogenetic protein (bovine derived partially purified) composite were implanted under the hind-quarter perimuscular membrane of ddY mice. Control capsules containing only bone morphogenetic protein were used for controls. The implants were radiographically and histologically examined at 1 to 4 weeks after the operation. According to the radiographic analysis, squalane and bone morphogenetic protein composite and bone morphogenetic protein only control specimens formed widespread heterotopic bone tissues. The amount of heterotopic bone formation in the composite experimental specimens was approximately 40% greater than that in the controls. Histologic examination of experimental and control specimens revealed varying amounts of perichondral ossification by 2 weeks. By 3 and 4 weeks, the bone deposits were colonized by hematopoietic bone marrow. Squalane was effective for the slow local release of bone morphogenetic protein. Furthermore, the squalane and bone morphogenetic protein composite was a reliable osteoinductive biomaterial.

  3. Spontaneous Heterotopic Triplet Pregnancy With Tubal Rupture

    PubMed Central

    Danso, Dennis

    2014-01-01

    The recent increase in heterotopic pregnancies has been largely attributed to the increased use of assisted reproduction technologies. We report the rare case of a multiparous woman with a spontaneous conception resulting in a triplet heterotopic pregnancy: a twin intrauterine pregnancy and a single right tubal ectopic pregnancy. Heterotopic pregnancy is a rare and potentially life-threatening condition in which simultaneous gestations occur at 2 or more implantation sites. It is infrequent in natural conception cycles, occurring in 1:30 000 pregnancies. However, the prevalence is rising with the increased use of assisted reproduction techniques to that of 1:100 to 1:500 in these patient subgroups, highlighting the need to incorporate it into a clinician’s diagnostic algorithm. PMID:26425603

  4. [Spontaneous heterotopic pregnancy and fetal survival].

    PubMed

    Luna Lugo, Gilberto; Rangel Ruiz, Irais; Gutiérrez Laiza, Nadia Saray; Martínez Guerrero, Misael Eleazar; Méndez Oceguera, José Raúl; Suárez López, Norma María Luisa

    2011-08-01

    The spontaneous heterotopic pregnancy is an unusual event. Generally the extrauterine product lost and the intrauterine present complications in different grade. The most common is the rupture and can be associated with hemodynamic unstable with risk for patient's life. The intrauterine pregnancy can be continuing to the end. We report the case of patient with spontaneous heterotopic pregnancy; the diagnosis was in the first trimester, with two products (intrauterine and in right fimbrius). The salpingectomy is doing with the extrauterine pregnancy and the patient has not complications trans or postoperative time and without complications for the intrauterine pregnancy, she continues with stricter control until to obtain a life product.

  5. Early Gastric Cancer Just above a Heterotopic Pancreas

    PubMed Central

    Murabayashi, Toji; Kawaguchi, Shinya; Okuda, Naoko; Oyamada, Jun; Yabana, Tadashi

    2016-01-01

    We report the first case of early gastric cancer just above a heterotopic pancreas for which the differential diagnosis was carcinoma arising from heterotopic pancreas. Routine upper gastrointestinal endoscopy in an 83-year-old man with sigmoid colon cancer revealed a gastric cancer in the lesser curvature of the antrum. Endoscopic ultrasonography (EUS) for evaluating the depth of tumor invasion revealed a hypoechoic mass in the submucosal layer. The depth of tumor invasion was diagnosed as muscularis propria. Distal gastrectomy and sigmoidectomy were performed. Histologically, the resected specimen of the stomach unexpectedly revealed a heterotopic pancreas just below the gastric cancer. They were not linked, and the heterotopic pancreas had no dysplasia. The gastric cancer had slightly invaded the submucosa. The hypoechoic mass on EUS was not the invasive tumor but the heterotopic pancreas. The preoperative staging of the gastric cancer on EUS was confounded by the presence of the heterotopic pancreas just below the gastric cancer. PMID:27482189

  6. [Posterior longitudinal ligament ossification: case report].

    PubMed

    Tella, Oswaldo Inácio de; Herculano, Marco Antonio; Paiva Neto, Manoel Antonio; Faedo Neto, Atílio; Crosera, João Francisco

    2006-03-01

    Posterior longitudinal ligament ossification of cervical spine is a rare condition among caucasians. A 42 years old japanese patient with progressive walking difficulty was diagnosed with this pathology by CT scan and MRI and treated surgically by an anterior approach with arthrodesis. Pathophysiology, racial prevalence, clinical picture, radiological characteristics and surgical approaches options are revised.

  7. Unusual ganglioglioma with extensive calcification and ossification.

    PubMed

    Kavishwar, Vikas Shashikant; Chadha, Kirti G; Barodawala, Shaikhali Moiz; Murthy, Anuradha Krishna

    2016-01-01

    Ganglioglioma is a slow-growing relatively low-grade mixed glioneuronal tumor with most cases corresponding to the WHO Grade I category. It frequently presents with seizures. The temporal lobe is the most common location followed by frontal, parietal, and occipital lobes. These generally behave in a benign fashion and have a favorable prognosis. We describe a case of a 24-year-old male presenting with convulsions and a calcified parieto-occipital mass. This mass removed from the parietal lobe showed neoplastic glial and dysplastic neuronal tissue amidst extensive areas of calcification and foci of ossification. On immunohistochemistry, the glial component expressed glial fibrillary acidic protein whereas the dysplastic neuronal component expressed synaptophysin and CD34. Epithelial membrane antigen was negative and Ki-67 showed a low proliferative index. After the surgery, the patient is free of neurological symptoms. Widespread calcification and ossification are very unusual in ganglioglioma, which prompted us to report this case. PMID:27510688

  8. Diffuse pulmonary ossification: A case report

    PubMed Central

    Roriz, Diogo; Abreu, Inês; Marques, Cristina; Teixeira, Luisa; Soares, Pedro Belo; Alves, Filipe Caseiro

    2016-01-01

    Diffuse pulmonary ossification (DPO) is a rarely diagnosed entity that may present with characteristic imaging features. It is listed in the differential diagnosis of lung parenchymal calcifications and should be considered by the radiologist if the appropriate findings are identified. We report a case of DPO secondary to mitral stenosis in a patient whose severe cardiac pathology lead to death few weeks after a chest CT was done. To date, there are no specific treatments with proved benefit in this pathology. PMID:27069979

  9. Heterotopic pregnancy: a growing diagnostic challenge.

    PubMed

    Ibrahim, Azza G; Badawi, Faiza; Tahlak, Muna

    2009-01-01

    This report describes a 26-year-old female who presented at 5 weeks of gestation with intrauterine pregnancy after gonadotrophin stimulation and intrauterine insemination. The patient complained of abdominal pain, abdominal distension and nausea diagnosed as moderate ovarian hyper-stimulation syndrome (OHSS) with early pregnancy and was treated accordingly. The patient was readmitted at 7 and 9 weeks of gestation with persistent left lower abdominal pain. At 9 weeks' gestation she also had a low grade fever and since the pelvic ultrasound showed a left tubo-ovarian mass she was treated for pelvic infection. The follow-up ultrasounds in the 5th, 9th and 12th weeks showed a normal intrauterine pregnancy in addition to a persistent left adnexal mass without any suspicion of a heterotopic pregnancy. The diagnosis of heterotopic pregnancy became possible only at 13 weeks of gestation during laparotomy when the right fallopian tube showed a leaking ectopic pregnancy. A right-sided salpingostomy was carried out. The intrauterine pregnancy is still ongoing without complications. PMID:21686636

  10. Orthotopic and heterotopic ovarian tissue transplantation

    PubMed Central

    Demeestere, I.; Simon, P.; Emiliani, S.; Delbaere, A.; Englert, Y.

    2009-01-01

    BACKGROUND Transplantation of ovarian tissue is, at present, the only clinical option available to restore fertility using cryopreserved ovarian tissue. More than 30 transplantations of cryopreserved tissue have been reported, and six babies have been born, worldwide, following this procedure. Despite these encouraging results, it is essential to optimize the procedure by improving the follicular survival, confirming safety and developing alternatives. Here, we review the different factors affecting follicular survival and growth after grafting. METHODS Relevant studies were identified by searching Pubmed up to January 2009 with English language limitation. The following key words were used: (ovarian tissue or whole ovary) AND (transplantation) AND (cryopreservation or pregnancy). Using the literature and personal experience, we examined relevant data on the different exogenous and clinical factors affecting follicular development after grafting. RESULTS Clinical factors such as the patient's age and the transplantation sites influenced the lifespan of the graft. A heterotopic transplantation site is not optimal but offers some advantages and it may also promote the hormonal environment after a combined heterotopic and orthotopic transplantation. Exogenous factors such as antioxidants, growth factors or hormones were tested to improve follicular survival; however, their efficiency regarding further follicular development and fertility potential remains to be established. CONCLUSION Additional evidence is required to define optimal conditions for ovarian tissue transplantation. Alternatives such as whole ovary or isolated follicles transplantations require further investigation but are likely to be successful in humans in the future. PMID:19474206

  11. [Symptomatic heterotopic splenic tissue in the adrenal gland area].

    PubMed

    Heider, J; Winter, P; Kreft, B

    1998-05-01

    We report on a 33-year-old man with symptomatic heterotopic suprarenal splenic tissue. Heterotopic splenic tissue can often be found after posttraumatic splenectomy. It is a result of autotransplantation induced by trauma (splenosis). Additionally it can grow during embryogenic development. Such an accessory spleen is found in 10-44% of all autopsies. In this case report the patient was treated by resection due to increasing flank pain and suspected neoplasm.

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

    PubMed Central

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

    2016-01-01

    Introduction. Heterotopic pregnancy is a rare complication usually seen in populations at risk for ectopic pregnancy or those undergoing fertility treatments. It is a potentially dangerous condition occurring in only 1 in 30,000 spontaneous pregnancies. With the advent of Assisted Reproduction Techniques (ART) and ovulation induction, the overall incidence of heterotopic pregnancy has risen to approximately 1 in 3,900 pregnancies. Other risk factors include a history of pelvic inflammatory disease (PID), tubal damage, pelvic surgery, uterine Mullerian abnormalities, and prior tubal surgery. Heterotopic pregnancy is a potentially fatal condition, rarely occurring in natural conception cycles. Most commonly, heterotopic pregnancy is diagnosed at the time of rupture when surgical management is required. Case. This paper represents two cases of heterotopic pregnancies as well as a literature review. Conclusion. Heterotopic pregnancy should be suspected in patients with an adnexal mass, even in the absence of risk factors. Clinicians must be alert to the fact that confirming an intrauterine pregnancy clinically or by ultrasound does not exclude the coexistence of an ectopic pregnancy. A high index of suspicion in women is needed for early and timely diagnosis, and management with laparotomy or laparoscopy can result in a favorable and successful obstetrical outcome. PMID:27413561

  13. Liposarcoma of the thigh with mixed calcification and ossification.

    PubMed

    Child, Jeremy R; Young, Colin R; Amini, Behrang

    2016-09-01

    Liposarcoma is one of the most common soft-tissue sarcomas. Calcification and ossification can occur in liposarcoma; however, the presence of both ossification and calcification is a very rare entity. We present a case of a partially calcified and ossified dedifferentiated liposarcoma of the thigh in a 76-year-old woman, which contained heterologous elements of chondrosarcoma and rhabdomyosarcoma. PMID:27594953

  14. 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

  15. 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

  16. Ossification of the bilateral Achilles tendon: a rare entity.

    PubMed

    Arora, Abhishek J; Arora, Richa

    2015-09-01

    Ossification of the Achilles tendon is a rare clinical entity comprising of one or more segments of variable sized ossified masses in the fibrocartilaginous substance of the tendon. The etiology of ossification of the Achilles tendon is multifactorial with recurrent trauma and surgery comprising major predisposing factors, with others being metabolic, systemic, and infectious diseases. The possibility of a genetic predisposition towards this entity has also been raised, but has not yet been proven. We present a rare case of ossification of the bilateral Achilles tendons without any history of trauma or surgery in a 48-year-old female patient. PMID:26413314

  17. Heterotopic tracheal transplants: techniques and applications.

    PubMed Central

    Klein-Szanto, A J; Pal, B C; Terzaghi, M; Marchok, A C

    1984-01-01

    Heterotopic tracheal transplants, placed subcutaneously in syngeneic rats have been extensively used in our laboratory. The objective of these experiments was to study the toxic and/or carcinogenic effect of several compounds on the respiratory tract mucosa. This was attained by exposing the transplants to an intraluminal pettet containing the toxicant or carcinogen mixed with an adequate matrix (gelatin, beeswax, stearyl alcohol, silastic, etc.). By varying the concentration of the test chemicals, it is possible to study dose-response relationships, and by changing the pellet matrix, the effects of release rate (dose rate) can be analyzed. Several end points can be studied, such as histological changes in the mucociliary epithelium, changes in mucus secretion, tumor induction and changes in the in vitro behavior of the epithelial cells after in vivo exposure. In addition, by de-epithelializing the tracheal transplants and reseeding them with another cell population, e.g., from previously treated cell cultures or from human specimens and transplanting them subcutaneously in nude mice, completely new vistas on the effect of chemicals can be opened. Images FIGURE 2. FIGURE 3. FIGURE 8. FIGURE 9. FIGURE 10. PMID:6383803

  18. Hypovolemic shock following induced abortion and spontaneous heterotopic pregnancy

    PubMed Central

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

    2015-01-01

    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. PMID:26813259

  19. 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.

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

    PubMed

    Cadieux, Catherine L; DesRosiers, Colleen; McMullen, Kevin

    2016-01-01

    Heterotopic ossification (HO) of the bone is defined as a benign condition in which abnormal bone formation occurs in soft tissue. One of the most common prophylactic treatments for HO is radiation therapy (RT). This study retrospectively reviewed 20 patients younger than the age of 40 who received radiation to prevent HO in a single fraction of 7 Gray. The purpose of this study is to assess the risk of a second malignancy in these patients by recreating their treatment fields and contouring organs at risk to estimate the radiation dose absorbed by normal tissues outside the radiation treatment field. Diagnostic computed tomography (CT) scans for each patient were used to recreate treatment fields and to calculate dose to structures of interest. The distance from the field edge to each structure and its depth was recorded. Dose measurements in a water phantom were performed for the range of depths, distances, and field sizes used in the actual treatment plans. Computer-generated doses were compared to estimates based on measurement. The structure dose recorded was the higher dose generated between the 2 methods. Scatter dose was recorded to the rectum, bladder, sigmoid colon, small bowel, ovaries and utero-cervix in female patients, and prostate and gonads in male patients. In some patients, there is considerable dose received by certain organs from scatter because of their proximity to the radiation field. The average dose to the ovarian region was 4.125Gy with a range of 1.085 to 6.228Gy. The risk estimate for these patients ranged from 0.16% to 0.93%. The average total lifetime risk estimate for the bladder in all patients is 0.22% and the average total lifetime risk estimate for the remainder organs in all patients is 1.25%. In conclusions, proper shielding created from multileaf collimators (MLCs), blocks, and shields should always be used when possible. PMID:27156238

  1. Yap/Taz transcriptional activity in endothelial cells promotes intramembranous ossification via the BMP pathway

    PubMed Central

    Uemura, Mami; Nagasawa, Ayumi; Terai, Kenta

    2016-01-01

    Osteogenesis is categorized into two groups based on developmental histology, intramembranous and endochondral ossification. The role of blood vessels during endochondral ossification is well known, while their role in intramembranous ossification, especially the intertissue pathway, is poorly understood. Here, we demonstrate endothelial Yap/Taz is a novel regulator of intramembranous ossification in zebrafish. Appropriate blood flow is required for Yap/Taz transcriptional activation in endothelial cells and intramembranous ossification. Additionally, Yap/Taz transcriptional activity in endothelial cells specifically promotes intramembranous ossification. BMP expression by Yap/Taz transactivation in endothelial cells is also identified as a bridging factor between blood vessels and intramembranous ossification. Furthermore, the expression of Runx2 in pre-osteoblast cells is a downstream target of Yap/Taz transcriptional activity in endothelial cells. Our results provide novel insight into the relationship between blood flow and ossification by demonstrating intertissue regulation. PMID:27273480

  2. Cholecystitis Associated with Heterotopic Pancreas, Pseudopyloric Metaplasia, and Adenomyomatous Hyperplasia: A Rare Combination.

    PubMed

    Kaur, Navjot; Chander, Bal; Kaur, Harjit; Kaul, Rashmi

    2016-01-01

    Heterotopic pancreatic tissue in the gall bladder is an uncommon incidental finding in most cases. We hereby describe the case of a 45-year-old woman who presented with symptoms of acalculous cholecystitis. Pathological examination detected heterotopic pancreatic tissue, pseudopyloric metaplasia, and adenomyomatous hyperplasia in the gall bladder. This is a rare combination of three entities which is being reported for the first time. This case emphasizes that heterotopic pancreas might be the causative factor for cholecystitis. PMID:27365925

  3. Progressive relapse of ligamentum flavum ossification following decompressive surgery.

    PubMed

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

    2014-12-01

    Thoracic ossification of the ligamentum flavum (T-OLF) is a relatively rare spinal disorder that generally requires surgical intervention, due to its progressive nature and the poor response to conservative therapy. The prevalence of OLF has been reported at 3.8%-26%, which is similar to that of cervical ossification of the posterior longitudinal ligament (OPLL). The progression of OPLL after cervical laminoplasty for the treatment of OPLL is often shown in long-term follow-up. However, there have been no reports on the progression of OLF following surgery. We report a case of thoracic myelopathy secondary to the progressive relapse of OLF following laminectomy. PMID:25558329

  4. A biochemical strategy for simulation of endochondral and intramembranous ossification.

    PubMed

    Garzón-Alvarado, Diego A

    2014-01-01

    Following the assumption that parathyroid hormone related protein and Indian hedgehog form a biochemical regulatory loop for the endochondral process and bone morphogenetic protein 2 and Noggin in the intramembranous process, this paper implements these regulatory mechanisms. For this purpose, we use a set of reaction-diffusion equations that are widely used in morphogenesis, in which biochemical factors are assumed to be secreted by precursor cells, mesenchymal cells and chondrocytes, in endochondral and intramembranous ossification, respectively. The solution leads to the so-called Turing patterns, which represent these processes of ossification in a very approximate way.

  5. 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.

  6. 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

  7. 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.

  8. Adhesion: a confounding bias in murine cervical heterotopic heart transplantation

    PubMed Central

    Yang, Jinghui; Chen, Qi; Liu, Fang; Fu, Zhiren; Wang, Quanxing

    2015-01-01

    Tissue adhesion is a common postsurgical phenomenon among the human population. This complication also occurs in murine transplant models. In this study, we investigated the impact of adhesion on murine cervical heterotopic heart transplantation by using sodium hyaluronate (SH) as an anti-adhesive agent. Our study revealed that SH administration produced no significant effect on histological change, TNF-α, IFN-γ, MCP-1, IL-2, IL-6 and IL-10 expression, CD4+ T, CD8+ T, or neutrophil and macrophage counts. Our findings suggest that SH was biocompatible and non-immunogenic. Later, we observed that adhesion not only affected the survival of the graft without mediating rejection, but was closely related to the severity of rejection as manifested by larger and more severe adhesion formation in total-allomismatched and MHC class II-allomismatched murine cardiac allografts. Therefore, we inferred that using the murine cervical heterotopic heart transplant model may lead to an exaggerated p-value in statistical significance testing which could mislead experimenters in considering that the results are more significant than the fact. To the best of our knowledge, this study is the first demonstration that proves that adhesion was a confounding bias in the murine cervical heterotopic heart transplant model and highlights the possibilities for improvement in future use. PMID:26550450

  9. 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).

  10. 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. PMID:23016907

  11. 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.

  12. Spinal dural ossification causing neurological signs in a cat

    PubMed Central

    2013-01-01

    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. PMID:23777582

  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. 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. PMID:21521190

  15. Jagged1 is essential for osteoblast development during maxillary ossification.

    PubMed

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

    2014-05-01

    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; Jagged1(f/f) (Jag1CKO) led to maxillary hypoplasia characterized by intrinsic differences in bone morphology and density using μCT evaluation. Jag1CKO maxillas revealed 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

  16. 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.

  17. Acquired lymphangiectasis.

    PubMed

    Celis, A V; Gaughf, C N; Sangueza, O P; Gourdin, F W

    1999-01-01

    Acquired lymphangiectasis is a dilatation of lymphatic vessels that can result as a complication of surgical intervention and radiation therapy for malignancy. Acquired lymphangiectasis shares clinical and histologic features with the congenital lesion, lymphangioma circumscriptum. Diagnosis and treatment of these vesiculo-bullous lesions is important because they may be associated with pain, chronic drainage, and cellulitis. We describe two patients who had these lesions after treatment for cancer and review the pertinent literature. Although a number of treatment options are available, we have found CO2 laser ablation particularly effective. PMID:9932832

  18. Tolosa-Hunt syndrome with heterotopic salivary gland tissue and absence of internal carotid artery.

    PubMed

    Akçam, Timur; Kocaoğlu, Murat; Gerek, Mustafa; Birkent, Hakan; Ozkaptan, Yalçin; Tayfun, Cem

    2003-08-01

    Tolosa-Hunt syndrome (THS), heterotopic salivary gland and hypoplasia of internal carotid artery (ICA) are all rare entities. We have reported a case of all these three conditions included in a patient. We have postulated that the heterotopic salivary gland tissue might have caused the hypoplasia of ICA and also triggered the THS. PMID:12927303

  19. What is the best treatment of heterotopic cervical pregnancies for a successful pregnancy outcome?

    PubMed Central

    Kim, Ji Won; Park, Han Moie; Lee, Woo Sik

    2012-01-01

    Heterotopic pregnancy is rare event and the risk is increased with assisted reproductive technology procedures. Heterotopic cervical pregnancy is even more unusual. We report a rare case of heterotopic cervical pregnancy that was managed successfully. A 36-year-old women who conceived by IVF-ICSI was diagnosed with heterotopic cervical pregnancy. She visited the emergency room with vaginal bleeding at 5 weeks of gestation and underwent careful intracervical gestational sac reduction with forceps under abdominal guidance the next day. The postoperative course was uneventful and with regular check-ups, the intrauterine pregnancy (IUP) progressed unremarkably through 41 weeks with delivery of a healthy newborn. We reviewed a total of 37 cases of heterotopic pregnancy that have been reported in the English language literature. There have been many attempts to eliminate the cervical embryo while preserving the IUP, and complete cervical evacuation is important in order to avoid infection, bleeding, and premature birth. PMID:23346531

  20. 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

    2012-06-01

    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.

  1. Acquired hyperpigmentations*

    PubMed Central

    Cestari, Tania Ferreira; Dantas, Lia Pinheiro; Boza, Juliana Catucci

    2014-01-01

    Cutaneous hyperpigmentations are frequent complaints, motivating around 8.5% of all dermatological consultations in our country. They can be congenital, with different patterns of inheritance, or acquired in consequence of skin problems, systemic diseases or secondary to environmental factors. The vast majority of them are linked to alterations on the pigment melanin, induced by different mechanisms. This review will focus on the major acquired hyperpigmentations associated with increased melanin, reviewing their mechanisms of action and possible preventive measures. Particularly prominent aspects of diagnosis and therapy will be emphasized, with focus on melasma, post-inflammatory hyperpigmentation, periorbital pigmentation, dermatosis papulosa nigra, phytophotodermatoses, flagellate dermatosis, erythema dyschromicum perstans, cervical poikiloderma (Poikiloderma of Civatte), acanthosis nigricans, cutaneous amyloidosis and reticulated confluent dermatitis PMID:24626644

  2. 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.

  3. Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification

    PubMed Central

    Ito, Tatsuo; Yadav, Neelu; Lee, Jaeho; Furumatsu, Takayuki; Yamashita, Satoshi; Yoshida, Kenji; Taniguchi, Noboru; Hashimoto, Megumi; Tsuchiya, Megumi; Ozaki, Toshifumi; Lotz, Martin; Bedford, Mark T; Asahara, Hiroshi

    2009-01-01

    Background Chondrogenesis and subsequent endochondral ossification are processes tightly regulated by the transcription factor Sox9 (SRY-related high mobility group-Box gene 9), but molecular mechanisms underlying this activity remain unclear. Here we report that coactivator-associated arginine methyltransferase 1 (CARM1) regulates chondrocyte proliferation via arginine methylation of Sox9. Results CARM1-null mice display delayed endochondral ossification and decreased chondrocyte proliferation. Conversely, cartilage development of CARM1 transgenic mice was accelerated. CARM1 specifically methylates Sox9 at its HMG domain in vivo and in vitro. Arg-methylation of Sox9 by CARM1 disrupts interaction of Sox9 with beta-catenin, regulating Cyclin D1 expression and cell cycle progression of chondrocytes. Conclusion These results establish a role for CARM1 as an important regulator of chondrocyte proliferation during embryogenesis. PMID:19725955

  4. Endobronchial Carcinoid Tumour with Extensive Ossification: An Unusual Case Presentation.

    PubMed

    Osmond, Allison; Filter, Emily; Joseph, Mariamma; Inculet, Richard; Kwan, Keith; McCormack, David

    2016-01-01

    Carcinoid tumour is a well-known primary endobronchial lung neoplasm. Although calcifications may be seen in up to 30% of pulmonary carcinoid tumours, near complete ossification of these tumours is an unusual finding. Such lesions can prove diagnostically challenging at the time of intraoperative frozen section as the latter technique requires thin sectioning of the lesion for microscopic assessment. We present an unusual case of endobronchial carcinoid tumour with extensive ossification in a 45-year-old male. Preliminary intraoperative diagnosis was achieved through the alternative use of cytology scrape smears. The final diagnosis was confirmed after decalcification of the tumour. The prognostic implications of heavily ossified carcinoid tumours remain elusive. Long-term clinical follow-up of these patients is recommended. PMID:27610135

  5. Endobronchial Carcinoid Tumour with Extensive Ossification: An Unusual Case Presentation

    PubMed Central

    Filter, Emily; Joseph, Mariamma; Inculet, Richard; Kwan, Keith; McCormack, David

    2016-01-01

    Carcinoid tumour is a well-known primary endobronchial lung neoplasm. Although calcifications may be seen in up to 30% of pulmonary carcinoid tumours, near complete ossification of these tumours is an unusual finding. Such lesions can prove diagnostically challenging at the time of intraoperative frozen section as the latter technique requires thin sectioning of the lesion for microscopic assessment. We present an unusual case of endobronchial carcinoid tumour with extensive ossification in a 45-year-old male. Preliminary intraoperative diagnosis was achieved through the alternative use of cytology scrape smears. The final diagnosis was confirmed after decalcification of the tumour. The prognostic implications of heavily ossified carcinoid tumours remain elusive. Long-term clinical follow-up of these patients is recommended.

  6. Endobronchial Carcinoid Tumour with Extensive Ossification: An Unusual Case Presentation

    PubMed Central

    Filter, Emily; Joseph, Mariamma; Inculet, Richard; Kwan, Keith; McCormack, David

    2016-01-01

    Carcinoid tumour is a well-known primary endobronchial lung neoplasm. Although calcifications may be seen in up to 30% of pulmonary carcinoid tumours, near complete ossification of these tumours is an unusual finding. Such lesions can prove diagnostically challenging at the time of intraoperative frozen section as the latter technique requires thin sectioning of the lesion for microscopic assessment. We present an unusual case of endobronchial carcinoid tumour with extensive ossification in a 45-year-old male. Preliminary intraoperative diagnosis was achieved through the alternative use of cytology scrape smears. The final diagnosis was confirmed after decalcification of the tumour. The prognostic implications of heavily ossified carcinoid tumours remain elusive. Long-term clinical follow-up of these patients is recommended. PMID:27610135

  7. Intracochlear Bleeding Enhances Cochlear Fibrosis and Ossification: An Animal Study

    PubMed Central

    Ryu, Kyeung A.; Lyu, Ah-Ra; Park, Heesung; Choi, Jin Woong; Hur, Gang Min; Park, Yong-Ho

    2015-01-01

    The aim of this study was to investigate the effects of intracochlear bleeding during cochleostomy on cochlear inflammatory response and residual hearing in a guinea pig animal model. Auditory brainstem response threshold shifts were greater in blood injected ears (p<0.05). Interleukin-1β, interleukin-10, tumor necrosis factor-α and nitric oxide synthase 2, cytokines that are related to early stage inflammation, were significantly increased in blood injected ears compared to normal and cochleostomy only ears at 1 day after surgery; with the increased IL-1β being sustained until 3 days after the surgery (p<0.05). Hair cells were more severely damaged in blood injected ears than in cochleostomy only ears. Histopathologic examination revealed more extensive fibrosis and ossification in blood injected ears than cochleostomy only ears. These results show that intracochlear bleeding enhanced cochlear inflammation resulting in increased fibrosis and ossification in an experimental animal model. PMID:26308864

  8. 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. PMID:7517071

  9. Laparoscopic Management of Heterotopic Interstitial Pregnancy with Subsequent Term Delivery.

    PubMed

    Kwon, Yong-Soon; Lee, Sang-Hun; Im, Kyong Shil; Ro, Jae Hun

    2015-01-01

    A 35 year-old woman at 7-week gestational age was referred to our hospital. The patient was diagnosed with the heterotopic interstitial pregnancy by transvaginal ultrasonogra- phy after receiving in vitro fertilization (IVF) and embryo transfer. Laparoscopic excision and curettage was successfully performed at 8.4-gestational age under general anesthesia and the patient was discharged 2 days after operation without any post-operative complications. The woman had normal antenatal follow-up and deliv- ered a healthy baby at term by cesarean section. PMID:26246887

  10. 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.

  11. 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.

  12. Relationship between the chondrocyte maturation cycle and the endochondral ossification in the diaphyseal and epiphyseal ossification centers.

    PubMed

    Pazzaglia, Ugo E; Congiu, Terenzio; Sibilia, Valeria; Pagani, Francesca; Benetti, Anna; Zarattini, Guido

    2016-09-01

    The chondrocyte maturation cycle and endochondral ossification were studied in human, fetal cartilage Anlagen and in postnatal meta-epiphyses. The relationship between the lacunar area, the inter-territorial fibril network variations, and calcium phosphorus nucleation in primary and secondary ossification centers were assessed using light microscopy and scanning electron microscopy (SEM) morphometry. The Anlage topographic, zonal classification was derived from the anatomical nomenclature of the completely developed long bone (diaphysis, metaphyses and epiphyses). A significant increase in the chondrocyte lacunar area was documented in the Anlage of epiphyseal zones 4 and 3 to zone 2 (metaphysis) and zone 1 (diaphysis), with the highest variation from zone 2 to zone 1. An inverse reduction in the intercellular matrix area and matrix interfibrillar empty space was also documented. These findings are consistent with the osmotic passage of free cartilage water from the interfibrillar space into the swelling chondrocytes, which increased the ion concentrations to a critical threshold for mineral precipitation in the matrix. The mineralized cartilage served as a scaffold for osteoblast apposition both in primary and secondary ossification centers and in the metaphyseal growth plate cartilage, though at different periods of bone Anlage development and with distinct patterns for each zone. All developmental processes shared a common initial pathway but progressed at different rates, modes and organization in diaphysis, metaphysis and epiphysis. In the ossification phase the developing vascular supply appeared to play a key role in determining the cortical or trabecular structure of the long bones. J. Morphol. 277:1187-1198, 2016. © 2016 Wiley Periodicals, Inc.

  13. Heterotopic gastrointestinal mucosa and pancreatic tissue in a retroperitoneal tumor.

    PubMed

    Hashimoto, Naoki; Hakamada, Kenichi; Narumi, Shunji; Totsuka, Eishi; Aoki, Kazunori; Kamata, Yoshimasa; Sasaki, Mutsuo

    2006-01-01

    We believe that this is the first report of a retroperitoneal tumor consisting of heterotopic gastrointestinal mucosa and pancreatic tissue. The patient was a 19-year-old woman with the chief complaint being occasional back pain. Abdominal computerized tomography demonstrated a 3.1 x 2.5 x 3.2-cm low-density solid and cystic lesion adjoining the left renal vein between the aorta and inferior vena cava. Angiography revealed that the inferior vena cava was displaced by the hypovascular tumor. The retroperitoneal lesion was diagnosed preoperatively as a benign tumor such as a neurogenic neoplasm or lymphangioma. At laparotomy, a cystic tumor was found, which existed behind the inferior vena cava and renal vessels, and contained reddish-brown fluid, suggesting hemorrhage in the past. The cut surface of the tumor showed a unilocular cyst with partially hypertrophic wall. Histopathological examination revealed a cystic tumor lined with heterotopic gastric and duodenal mucosa, with pancreatic tissue in the muscularis propria. In addition, evidence of bleeding from the gastric mucosa was observed in the cystic tumor. External secretion from these tissues could have triggered the hemorrhage and expanded the tumor, possibly resulting in the back pain.

  14. Undiagnosed heterotopic pregnancy, maternal hemorrhagic shock, and ischemic stroke in the intrauterine fetus.

    PubMed

    Ezzati, Mohammad; Shamshirsaz, Alireza A; Haeri, Sina

    2015-09-01

    Heterotopic pregnancy occurs rarely following natural conception; however, intrauterine embryo transfer following in vitro fertilization is a known risk factor for its occurrence. A 29-year-old woman presented with acute abdomen at 14w5d gestation following in vitro fertilization-embryo treatment. A ruptured heterotopic gestation in the left fallopian tube was identified at laparoscopy and treated by salpingectomy. Subsequently, at 21-week gestation, routine sonogram demonstrated bilateral ventriculomegaly in the intrauterine fetus. Fetal magnetic resonance imaging was highly suggestive of ischemic brain injury, most likely attributable to the maternal hypovolemic shock because of ruptured heterotopic gestation. The pregnancy was terminated by intracardiac injection and induction of labor. Timely diagnosis of heterotopic pregnancy requires a high index of suspicion as diagnostic delays can have catastrophic consequences for the mother and/or the intrauterine fetus. PMID:26095211

  15. [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.

  16. 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

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

    PubMed Central

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

    2016-01-01

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

  18. 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.

  19. 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

  20. Hdac-Mediated Control of Endochondral and Intramembranous Ossification

    PubMed Central

    Bradley, Elizabeth W.; McGee-Lawrence, Meghan E.; Westendorf, Jennifer J.

    2011-01-01

    Histone deacetylases (Hdacs) remove acetyl groups (CH3CO-) from ε-amino groups in lysine residues within histones and other proteins. This post-translational (de) modification alters protein stability, protein-protein interactions, and chromatin structure. Hdac activity plays important roles in the development of all organs and tissues, including the mineralized skeleton. Bone is a dynamic tissue that forms and regenerates by two processes: endochondral and intramembranous ossification. Chondrocytes and osteoblasts are responsible for producing the extracellular matrices of skeletal tissues. Several Hdacs contribute to the molecular pathways and chromatin changes that regulate tissue-specific gene expression during chondrocyte and osteoblast specification, maturation and terminal differentiation. In this review, we summarize the roles of class I and class II Hdacs in chondrocytes and osteoblasts. The effects of small molecule Hdac inhibitors on the skeleton are also discussed. PMID:22077150

  1. [A case of retroperitoneal serous cyst with ossification].

    PubMed

    Chihara, Yoshitomo; Horikawa, Naoki; Hayashi, Yoshiki; Fujimoto, Kiyohide; Hosokawa, Yukinari; Hirao, Yoshihiko

    2002-05-01

    A 36-year-old woman came to our hospital complaining of right flank pain. Computed tomographic (CT) scanning showed a cystic mass, 6 x 9 cm in size, including homogeneous low-density fluid contents, in the right retroperitoneal space. The cyst wall showed partly high-density epithelium, but there was no contrast enhancement. A 7.5 x 12 cm retroperitoneal cyst was easily removed with yellow serous fluid in it. Cytological examination showed no malignant cells in this fluid. The origin of the cyst was unknown. The histopathological diagnosis was retroperitoneal serous cyst with focal ossification in the lining epithelium. Here we report this rare case of retroperitoneal serous cyst and briefly discuss 57 cases reported in Japan.

  2. Management of Heterotopic Pregnancy: Experience From 1 Tertiary Medical Center.

    PubMed

    Li, Jin-Bo; Kong, Ling-Zhi; Yang, Jian-Bo; Niu, Gang; Fan, Li; Huang, Jing-Zhi; Chen, Shu-Qin

    2016-02-01

    The objective of this study is to summarize the experiences of our department in the management of heterotopic pregnancy (HP) and to analyze the influence of different treatment modality on the viable intrauterine pregnancy.There were 64 patients diagnosed as HP in the Department of Gynecology and Obstetrics in our hospital between January 2003 and June 2014, 52 HP patients with viable intrauterine pregnancy were included and analyzed in our study. Interventions included expectant management, surgical management and transabdominal sonographic guided transvaginal aspiration of ectopic gestational embryo (embryo aspiration) management.Main outcome measures are maternal outcome and pregnancy outcome.In expectant management group, 4 patients suffered rupture of ectopic pregnancy, 6 patients transferred to surgical management, 1 patient suffered a fever of 40.4°C, the abortion rate was 5% (1/20). In surgical management group, emergency surgery was performed in 9 patients with unstable hemodynamics and 3 patients with stable hemodynamics, 1 patient suffered uterine rupture 5 weeks later and dead fetus was demonstrated, 1 patient suffered urinary retention postoperative, the abortion rate was 14.8% (4/27). In embryo aspiration management group, 1 patient needed another embryo aspiration, all patients were eventful and no abortion was observed.In our retrospective study, transabdominal sonographic guided aspiration of ectopic gestational embryo has the best maternal outcome and the lowest abortion rate, surgical management group shows the highest abortion rate, and expectant management presents the worst maternal outcome. PMID:26844463

  3. Adenocarcinoma arising from heterotopic pancreas at the third portion of the duodenum.

    PubMed

    Fukino, Nobutada; Oida, Takatsugu; Mimatsu, Kenji; Kuboi, Youichi; Kida, Kazutoshi

    2015-04-01

    A 62-year-old Japanese man presented to our hospital with a history of weight loss of 6 kg in 4 mo. Imaging examinations revealed a tumor located on the third portion of the duodenum with stenosis. We suspected duodenal carcinoma and performed pancreas-preserving segmental duodenectomy. Adenocarcinoma arising from a heterotopic pancreas at the third portion of the duodenum was finally diagnosed by immunohistochemical staining. Malignant transformation in the duodenum arising from a heterotopic pancreas is extremely rare; to our knowledge, only 13 cases have been reported worldwide, including the present case. The most common location of malignancy is the proximal duodenum at the first and descending portion. Herein, we describe the first case of adenocarcinoma arising from a heterotopic pancreas, which was located in the third portion of the duodenum, with a review of the literature.

  4. Increased 18F-FDG uptake of heterotopic pancreatitis in the small intestine

    PubMed Central

    Ruan, Maomei; Liu, Min; Cheng, Lingxiao; Xie, Wenhui; Chen, Libo

    2016-01-01

    Abstract Backgroud: Heterotopic pancreas (HP), a relatively uncommon congenital anomaly, is rarely noted during 18F-FDG positron-emission tomography/computed tomography (PET/CT) scan. Methods: A 60-year-old woman was referred to our hospital due to a 10-day history of abdominal pain with elevated levels of serum amylase and lipase. Abdominal CT and ultrasound examinations were negative. In order to search for the cause, an 18F-FDG PET/CT whole body scan was suggested to an old woman revealing the presence of 18F-FDG accumulating nodule in small intestine. Results: Surgical findings and pathologic results confirmed the diagnosis of small intestinal heterotopic pancreas with active chronic inflammation. Conclusion: This uncommon case underscores the necessity of considering heterotopic pancreatitis in small intestine with focal 18F-FDG uptake as a possible differential diagnosis in intestinal tumor and tuberculosis. PMID:27603341

  5. Adenocarcinoma arising from heterotopic pancreas at the third portion of the duodenum

    PubMed Central

    Fukino, Nobutada; Oida, Takatsugu; Mimatsu, Kenji; Kuboi, Youichi; Kida, Kazutoshi

    2015-01-01

    A 62-year-old Japanese man presented to our hospital with a history of weight loss of 6 kg in 4 mo. Imaging examinations revealed a tumor located on the third portion of the duodenum with stenosis. We suspected duodenal carcinoma and performed pancreas-preserving segmental duodenectomy. Adenocarcinoma arising from a heterotopic pancreas at the third portion of the duodenum was finally diagnosed by immunohistochemical staining. Malignant transformation in the duodenum arising from a heterotopic pancreas is extremely rare; to our knowledge, only 13 cases have been reported worldwide, including the present case. The most common location of malignancy is the proximal duodenum at the first and descending portion. Herein, we describe the first case of adenocarcinoma arising from a heterotopic pancreas, which was located in the third portion of the duodenum, with a review of the literature. PMID:25852297

  6. 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.

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

    PubMed

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

    2015-01-01

    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.

  8. 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

  9. [Heterotopic pregnancy during the second trimester is a severe complication of pregnancy].

    PubMed

    Färkkilä, Anniina; Laitinen, Leena

    2016-01-01

    Heterotopic pregnancy is a rare form of ectopic pregnancy in which one gestational sac is found in the uterus and another one in an extrauterine location. The spontaneous heterotopic pregnancy of our patient continued until the second trimester. In the 19th week of pregnancy, undiagnosed ectopic pregnancy in the left fallopian tube ruptured into the abdominal cavity, leading to a massive intra-abdominal hemorrhage. Left-side uterine appendages were excised in open surgery, but intrauterine pregnancy continued in vital form. Histologic examination revealed the excised tumor to be an ectopic pregnancy. The hypotension experienced by the patient led, however, to severe brain damage of the intrauterine fetus and induced abortion.

  10. Heterotopic bone formation (myositis ossificans) and lower-extremity swelling mimicking deep-venous disease

    SciTech Connect

    Orzel, J.A.; Rudd, T.G.; Nelp, W.B.

    1984-10-01

    A quadriplegic patient with a swollen leg was suspected of having deep-venous thrombosis, and was studied with radionuclide venography (RNV) and contrast venography. Focal narrowing of the femoral vein, seen on RNV, was due to extrinsic compression. Although soft-tissue radiographs were normal, Tc-99m diphosphonate imaging established the diagnosis of early heterotopic bone formation (myositis ossificans), which was responsible for the venous compression. Clinically this inflammatory process can mimic deep-venous thrombosis, and should be considered in evaluating patients at risk for both heterotopic bone formation and deep-venous thrombosis.

  11. PIXE study of the kinetics of biomaterials ossification

    NASA Astrophysics Data System (ADS)

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

    1994-05-01

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

  12. Intramembranous ossification of scleral ossicles in Chelydra serpentina.

    PubMed

    Franz-Odendaal, Tamara A

    2006-01-01

    Scleral ossicles are present in many reptiles, including turtles and birds. In both groups the sclerotic ring situated in the eye is composed of a number of imbricating scleral ossicles or plates. Despite this gross morphological similarity, Andrews (1996. An endochondral rather than a dermal origin for scleral ossicles in Cryptodiran turtles. J. Herpetol. 30, 257-260) reported that the scleral ossicles of turtles develop endochondrally unlike those in birds, which develop intramembranously after a complex epithelial-mesenchymal inductive event. This study re-explores one of the species examined by Andrews in order to determine the mode of ossification of scleral ossicles in turtles. A growth series of Chelydra serpentina embryos, including the stages examined by Andrews, were examined by staining separately for cartilage and bone. Results clearly contradict Andrews (1996) and show that the scleral ossicles of Chelydra serpentina develop similarly to those in birds. That is, they develop intramembranously without a cartilage precursor and are likely induced by transient scleral papillae. The sequence of scleral papillae development is broadly similar, but the papillae themselves are not as distinct as those seen in chicken embryos. This study has important consequences for understanding the homology of scleral ossicles among tetrapods. PMID:16377163

  13. 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.

  14. Modified technique for heterotopic implantation of a right ventricular outflow tract conduit.

    PubMed

    Dave, Hitendu; Dodge-Khatami, Ali; Kadner, Alexander; Prêtre, René

    2006-06-01

    This article describes a modified technique of side-to-side proximal connection of a conduit during heterotopic implantation in the right ventricular outflow tract. It results in a better geometry of the right ventricular outflow and avoids distortion of the valve annulus, especially when the newer generation of straight xenografts are used. PMID:16731190

  15. Salivary gland choristoma (heterotopic salivary gland tissue) on the anterior chest wall of a newborn.

    PubMed

    Aby, Janelle L; Patel, Mayha; Sundram, Uma; Benjamin, Latanya T

    2014-01-01

    Salivary gland choristoma (heterotopic salivary gland tissue) is a rare condition typically seen in the newborn period. This developmental heterotopia is generally nonprogressive, with little risk of malignant transformation. We present the second known reported case of a salivary gland choristoma located on the anterior chest wall. Knowledge of this rare entity will allow for accurate diagnosis and management of this benign anatomic variant.

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

    ERIC Educational Resources Information Center

    Zembylas, Michalinos; Ferreira, Ana

    2009-01-01

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

  17. Heterotopic gastric mucosa mimicking a Meckel's diverticulum in a young girl.

    PubMed

    Davis, James S; Hirzel, Alicia C; Rodriguez, Maria M; Neville, Holly L; Sola, Juan E

    2015-05-01

    Heterotopic gastric mucosa (HGM) is a rare, but acknowledged source of gastrointestinal pathology in pediatric patients. Sometimes clinically confused with a Meckel's diverticulum, HGM diagnosis is often made postoperatively by pathology. We present a case of jejunal HGM with a positive technetium pertechnetate scan in the right lower quadrant that resembled a Meckel's diverticulum.

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

    PubMed

    Miller, M R; Beck, J

    1987-07-01

    The auditory hair cells of adults of eight species of lizards (three gekkonids: Coleonyx variegatus, Gekko gecko, and Cosymbotus platyurus; two teiids: Ameiva ameiva and Cnemidophorus tigris; one anguid: Celestus costatus; one lacertid: Podarcis (Lacerta) sicula; and one iguanid: Crotaphytus wislizeni) were studied by transmission electron microscopy. Heterotopic synaptic bodies were found in some of the auditory hair cells of all of the above species, occurring frequently in the gekkonids but infrequently in other species. The groups of heterotopic synaptic bodies occurred mainly in the infranuclear cytoplasm between the hair cell nucleus and the hair cell plasma membrane. The groups of synaptic bodies that were close to the hair cell nucleus were usually associated with specialized arrays of rough and smooth endoplasmic reticulum. The numbers of heterotopic synaptic bodies were greatest in the gekkonid species and were especially large in Coleonyx variegatus, where an average of 36.8 synaptic bodies occur in one group. The functional significance of the presence of heterotopic synaptic bodies in the auditory hair cells of adults animals is not known. PMID:2820267

  19. Unique presentation of heterotopic pancreatic tissue arising from small-bowel mesentery.

    PubMed

    Koshinaga, T; Okabe, I; Kurosu, Y

    1996-03-01

    Heterotopic pancreatic tissue in the small-bowel mesentery is an extremely rare anomaly: no such case has been reported in the English literature. We report a 5-year-old boy in whom the aberrant tissue formed a retroperitoneal cyst. The condition was further complicated by a ventral pancreatic duct defect. The unique clinical manifestations and difficulty in making the diagnosis are discussed.

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

    PubMed Central

    Jones, Watson; Roberts, R. E.

    1933-01-01

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

  1. 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.

  2. The Transcription Factor Hand1 Is Involved In Runx2-Ihh-Regulated Endochondral Ossification.

    PubMed

    Laurie, Lindsay E; Kokubo, Hiroki; Nakamura, Masataka; Saga, Yumiko; Funato, Noriko

    2016-01-01

    The developing long bone is a model of endochondral ossification that displays the morphological layers of chondrocytes toward the ossification center of the diaphysis. Indian hedgehog (Ihh), a member of the hedgehog family of secreted molecules, regulates chondrocyte proliferation and differentiation, as well as osteoblast differentiation, through the process of endochondral ossification. Here, we report that the basic helix-loop-helix transcription factor Hand1, which is expressed in the cartilage primordia, is involved in proper osteogenesis of the bone collar via its control of Ihh production. Genetic overexpression of Hand1 in the osteochondral progenitors resulted in prenatal hypoplastic or aplastic ossification in the diaphyses, mimicking an Ihh loss-of-function phenotype. Ihh expression was downregulated in femur epiphyses of Hand1-overexpressing mice. We also confirmed that Hand1 downregulated Ihh gene expression in vitro by inhibiting Runx2 transactivation of the Ihh proximal promoter. These results demonstrate that Hand1 in chondrocytes regulates endochondral ossification, at least in part through the Runx2-Ihh axis. PMID:26918743

  3. The Transcription Factor Hand1 Is Involved In Runx2-Ihh-Regulated Endochondral Ossification

    PubMed Central

    Laurie, Lindsay E.; Kokubo, Hiroki; Nakamura, Masataka; Saga, Yumiko; Funato, Noriko

    2016-01-01

    The developing long bone is a model of endochondral ossification that displays the morphological layers of chondrocytes toward the ossification center of the diaphysis. Indian hedgehog (Ihh), a member of the hedgehog family of secreted molecules, regulates chondrocyte proliferation and differentiation, as well as osteoblast differentiation, through the process of endochondral ossification. Here, we report that the basic helix-loop-helix transcription factor Hand1, which is expressed in the cartilage primordia, is involved in proper osteogenesis of the bone collar via its control of Ihh production. Genetic overexpression of Hand1 in the osteochondral progenitors resulted in prenatal hypoplastic or aplastic ossification in the diaphyses, mimicking an Ihh loss-of-function phenotype. Ihh expression was downregulated in femur epiphyses of Hand1-overexpressing mice. We also confirmed that Hand1 downregulated Ihh gene expression in vitro by inhibiting Runx2 transactivation of the Ihh proximal promoter. These results demonstrate that Hand1 in chondrocytes regulates endochondral ossification, at least in part through the Runx2-Ihh axis. PMID:26918743

  4. The Transcription Factor Hand1 Is Involved In Runx2-Ihh-Regulated Endochondral Ossification.

    PubMed

    Laurie, Lindsay E; Kokubo, Hiroki; Nakamura, Masataka; Saga, Yumiko; Funato, Noriko

    2016-01-01

    The developing long bone is a model of endochondral ossification that displays the morphological layers of chondrocytes toward the ossification center of the diaphysis. Indian hedgehog (Ihh), a member of the hedgehog family of secreted molecules, regulates chondrocyte proliferation and differentiation, as well as osteoblast differentiation, through the process of endochondral ossification. Here, we report that the basic helix-loop-helix transcription factor Hand1, which is expressed in the cartilage primordia, is involved in proper osteogenesis of the bone collar via its control of Ihh production. Genetic overexpression of Hand1 in the osteochondral progenitors resulted in prenatal hypoplastic or aplastic ossification in the diaphyses, mimicking an Ihh loss-of-function phenotype. Ihh expression was downregulated in femur epiphyses of Hand1-overexpressing mice. We also confirmed that Hand1 downregulated Ihh gene expression in vitro by inhibiting Runx2 transactivation of the Ihh proximal promoter. These results demonstrate that Hand1 in chondrocytes regulates endochondral ossification, at least in part through the Runx2-Ihh axis.

  5. Ossification sequence of the avian order anseriformes, with comparison to other precocial birds.

    PubMed

    Maxwell, Erin E

    2008-09-01

    Ossification sequences are poorly known for most amniotes, and yet they represent an important source of morphogenetic, phylogenetic, and life history information. Here, the author describes the ossification sequences of three ducks, the Common Eider Somateria mollissima dresseri, the Pekin Duck Anas platyrhynchos, and the Muscovy Duck Cairina moschata. Sequence differences exist both within and among these species, but are generally minor. The Common Eider has the most ossified skeleton prior to hatching, contrary to what is expected in a subarctic migrant species. This may be attributed to a tradeoff between growth rate and locomotory performance. Growth rate is higher in hatchlings with more cartilaginous skeletons, but this may compromise locomotion. No major ossification sequence differences were observed in the craniofacial skeleton when compared with Galliformes, which suggests that the influence of adult morphology on ossification sequence might be relatively minor in many taxa. Galliformes and Anseriformes, while both highly ossified at hatching, differ in the location of their late-stage ossification centers. In Anseriformes, these are most often located in the appendicular skeleton, whereas in Galliformes they are in the thoracic region and form the ventilatory apparatus.

  6. 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.

  7. Endochondral ossification of the condyle in rats on a strontium or low-calcium diet.

    PubMed

    Nagayama, M; Saburi, N; Oka, T; Matsumoto, A

    1985-09-01

    The mechanism of abnormal endochondral ossification induced by administration of strontium salts was studied in the mandibular condyles of rats by radiographic, histologic, and histochemical methods. It was shown by radiographic and histologic findings that ossification of the mandibular ramus was clearly inhibited in rats fed a low-calcium diet and rats fed a strontium diet. The change in appearance of the mandibular condyles of the rats fed strontium was more severe than that in those fed low amounts of calcium. From the histochemical findings, it was suggested that the metabolic dysfunction of chondroitin sulfate, periodic acid-Schiff positive materials, and collagen in the hypertrophic zone of the condylar cartilage (or in the part corresponding to trabecular bone of the mandibular ramus) was one factor inhibiting normal endochondral ossification.

  8. Surgical treatment for posterior ossifications of the glenoid in baseball players.

    PubMed

    Ozaki, J; Tomita, Y; Nakagawa, Y; Tamai, S

    1992-03-01

    Seven baseball pitchers with symptomatic posterior glenoid osteophytes were operated on between 1982 and 1988 and were followed for an average of 5.2 years. Five and two patients had ossifications on the posteroinferior glenoid rim and on the infraglenoid tubercle, respectively. Ossifications on the posteroinferior glenoid rim were associated with posterior glenohumeral impingement, posterior glenoid labrum tears, and axillary neuropathy. Ossifications on the infraglenoid tubercle were associated with axillary nerve entrapment by the osteophytes and the thickened long head of the triceps muscle. Histologic study showed the coexistence of reactive new bone formation and bone necrosis. Preoperative and postoperative pain, sensory loss, muscle strength, and throwing distance were assessed. After surgical resection of the osteophytes and release of the axillary nerve entrapment, improvement in all parameters was observed in all patients.

  9. Benign mixed tumour of the skin with extensive ossification and marrow formation: a case report.

    PubMed

    Awasthi, R; Harmse, D; Courtney, D; Lyons, C B A

    2004-12-01

    Benign mixed tumour of the skin (chondroid syringoma) is an uncommon skin adnexal tumour, usually presenting as a slow growing solitary painless nodule. The morphological appearances are similar to those of a pleomorphic adenoma of the salivary gland. Hair matrix and sebaceous differentiation can be seen in some lesions. Focal ossification is a rare finding. This report presents a case of a similar tumour arising in the cheek of a 43 year old white man, showing extensive ossification. Clinical, radiological, and pathological correlation and diagnosis proved to be difficult preoperatively. Only two cases of a benign mixed tumour with pronounced ossification have been reported so far, both in Japanese patients. This is the first reported case seen in a white man. Awareness of these lesions will avoid potential diagnostic pitfalls.

  10. Voriconazole-associated soft tissue ossification: an undescribed cause of glenohumeral joint capsulitis.

    PubMed

    Raghavan, Meera; Hayes, Alex

    2014-09-01

    Voriconazole-related periostitis has been increasingly described in the literature over the last several years as a recognizable disease entity, especially in lung transplant patients. This relationship should be considered when approaching immunosuppressed patients presenting with diffuse bone pain and imaging findings of periostitis. We present a case of voriconazole-associated periostitis, capsular and enthesial ossification and glenuhumeral capsulitis in a patient with a hematologic malignancy. To the authors' knowledge, soft tissue ossification associated with voriconazole has not been described in the radiology literature.

  11. 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.

  12. 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. PMID:20499761

  13. [Heterotopic pregnancy during the second trimester is a severe complication of pregnancy].

    PubMed

    Färkkilä, Anniina; Laitinen, Leena

    2016-01-01

    Heterotopic pregnancy is a rare form of ectopic pregnancy in which one gestational sac is found in the uterus and another one in an extrauterine location. The spontaneous heterotopic pregnancy of our patient continued until the second trimester. In the 19th week of pregnancy, undiagnosed ectopic pregnancy in the left fallopian tube ruptured into the abdominal cavity, leading to a massive intra-abdominal hemorrhage. Left-side uterine appendages were excised in open surgery, but intrauterine pregnancy continued in vital form. Histologic examination revealed the excised tumor to be an ectopic pregnancy. The hypotension experienced by the patient led, however, to severe brain damage of the intrauterine fetus and induced abortion. PMID:27244932

  14. 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.

  15. 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.

  16. 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

  17. Heterotopic Bone Formation Around Vessels: Pilot Study of a New Animal Model

    PubMed Central

    Cai, Wei-Xin; Zheng, Li-Wu; Weber, Franz E.; Li, Chun-Lei; Ma, Li; Ehrbar, Martin

    2013-01-01

    Abstract To achieve an easily established, safe, and reproducible animal model for the study of heterotopic bone formation around vessels, a small animal series using New Zealand White rabbits was performed. Three different dosages of recombinant human bone morphogenic protein (rhBMP-2) carried by fibrin matrix were tested. A guided tissue regeneration (GTR) membrane sheet was formed into a tube and allowed to harden; it served both to maintain the space around the vessel bundle and to separate the fibrin matrix with rhBMP-2 from skeletal muscle. Wrapped around the femoral vessel bundle and fixed in place, the tube was filled with the fibrin matrix containing rhBMP-2. The surgical site was closed in layers, and the postoperative healing was uneventful. All animals resumed their full preoperative daily activities 3–4 days after the operation. No adverse events such as wound dehiscence or infection occurred, and all animals could be sacrified at the scheduled date. Micro–computed tomography and histological investigations showed heterotopic bone formation around the vessel bundle in the medium- and high-dosage rhBMP-2 groups. An easy, safe, and reproducible animal model that allows the study of heterotopic bone formation around vessels was successfully established. PMID:23914333

  18. 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

  19. 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

  20. Giant cranionasal and cystic-solid craniopharyngioma associated with extensive bone erosion and ossification.

    PubMed

    Chen, Haifeng; Zhou, Liangxue; Luo, Linli; Jiang, Su; Guo, Gang; You, Chao

    2013-07-01

    Craniopharyngioma (CP), a rare benign and slow-growing epithelial tumor, is mainly located within the sellar/parasellar region. Primary CP involving the nasal cavity and the sellar region with extensive erosion of the skull base and ossification simultaneity has not been described previously. The authors report a 23-year-old man who presented to our institute with complaints of repeated nasal cavity bloodshed, liquid flow, and progressive visual loss. A neuroimaging examination showed a giant cranionasal and cystic-solid CP extending from the suprasellar region to the nasopharynx with inhomogeneous enhancement, which is associated with extensive erosion of the skull base and ossification. The patient underwent a transsphenoidal surgery to resect the nasopharyngeal component of CP and a subfrontal craniotomy with a total removal of intracranial component by grinding 3 months later. A histopathologic examination revealed characteristic features of adamantinomatous CP associated with ossification. The current study demonstrates that CP can exhibit cranionasal growth pattern and arise from residue of craniopharyngeal duct. Extensive erosion of the skull base, calcification, and ossification can present in tumor simultaneity. A 2-stage stratagem is important for its total removal because of the peculiar hardness. Postsurgical course is unevenly and should be dealt with carefully. PMID:23851734

  1. Posterior ossification of the shoulder: the Bennett lesion. Etiology, diagnosis, and treatment.

    PubMed

    Ferrari, J D; Ferrari, D A; Coumas, J; Pappas, A M

    1994-01-01

    We report a series of ossific lesions of the posterior inferior glenoid in a group of elite baseball players. We hope to clarify the etiology, diagnosis, and treatment of the Bennett lesion. From August 1985 to August 1991, we identified six professional baseball pitchers and one college pitcher with evidence of ossification of the shoulder on plain radiographs, computed tomography, or magnetic resonance imaging. Arthroscopic examination was performed in all cases. All seven players had identifiable posterior labral injury on arthroscopic examination; six of these seven also had varying degrees of undersurface posterior rotator cuff damage. No anterior tissue damage, anterior instability, or subacromial impingement was noted. No ossification was identified arthroscopically. Intraarticular labral and rotator cuff tears were debrided arthroscopically and patients underwent rehabilitation for 4 to 6 months after surgery. Six of the seven athletes returned to preinjury performance levels; however, one pitcher is no longer playing competitive baseball. The Bennett lesion is an extraarticular posterior ossification associated with posterior labral injury and posterior undersurface rotator cuff damage. It is not, however, a result of traction stresses in the region of the triceps insertion. Recognition is important for identification and treatment of the lesion and associated pathologic damage.

  2. Age estimation based on pelvic ossification using regression models from conventional radiography.

    PubMed

    Zhang, Kui; Dong, Xiao-Ai; Fan, Fei; Deng, Zhen-Hua

    2016-07-01

    To establish regression models for age estimation from the combination of the ossification of iliac crest and ischial tuberosity. One thousand three hundred and seventy-nine conventional pelvic radiographs at the West China Hospital of Sichuan University between January 2010 and June 2012 were evaluated retrospectively. The receiver operating characteristic analysis was performed to measure the value of estimation of 18 years of age with the classification scheme for the iliac crest and ischial tuberosity. Regression analysis was performed, and formulas for calculating approximate chronological age according to the combination developmental status of the ossification for the iliac crest and ischial tuberosity were developed. The areas under the receiver operating characteristic (ROC) curves were above 0.9 (p < 0.001), indicating a good prediction of the grading systems, and the cubic regression model was found to have the highest R-square value (R (2) = 0.744 for female and R (2) = 0.753 for male). The present classification scheme for apophyseal iliac crest ossification and the ischial tuberosity may be used for age estimation. And the present established cubic regression model according to the combination developmental status of the ossification for the iliac crest and ischial tuberosity can be used for age estimation. PMID:27169673

  3. Inhibition of cyclooxygenase-2 impacts chondrocyte hypertrophic differentiation during endochondral ossification.

    PubMed

    Welting, T J M; Caron, M M J; Emans, P J; Janssen, M P F; Sanen, K; Coolsen, M M E; Voss, L; Surtel, D A M; Cremers, A; Voncken, J W; van Rhijn, L W

    2011-01-01

    Skeletogenesis and bone fracture healing involve endochondral ossification, a process during which cartilaginous primordia are gradually replaced by bone tissue. In line with a role for cyclooxygenase-2 (COX-2) in the endochondral ossification process, non-steroidal anti-inflammatory drugs (NSAIDs) were reported to negatively affect bone fracture healing due to impaired osteogenesis. However, a role for COX-2 activity in the chondrogenic phase of endochondral ossification has not been addressed before. We show that COX-2 activity fulfils an important regulatory function in chondrocyte hypertrophic differentiation. Our data reveal essential cross-talk between COX-2 and bone morphogenic protein-2 (BMP-2) during chondrocyte hypertrophic differentiation. BMP-2 mediated chondrocyte hypertrophy is associated with increased COX-2 expression and pharmacological inhibition of COX-2 activity by NSAIDs (e.g., Celecoxib) decreases hypertrophic differentiation in various chondrogenic models in vitro and in vivo, while leaving early chondrogenic development unaltered. Our findings demonstrate that COX-2 activity is a novel factor partaking in chondrocyte hypertrophy in the context of endochondral ossification and these observations provide a novel etiological perspective on the adverse effects of NSAIDs on bone fracture healing and have important implications for the use of NSAIDs during endochondral skeletal development. PMID:22183916

  4. Chondrogenesis of the limbs and mesopodial ossification of Podocnemis expansa Schweigger, 1812 (Testudines: Podocnemidae).

    PubMed

    Vieira, Lucélia Gonçalves; Santos, André L Q; Lima, Fabiano Campos; Moura, Lea Resende

    2011-04-01

    We address the chondrogenic formation of the limbs and the mesopodial ossification pattern of the Pleurodira Podocnemis expansa, to resolve the homology of these elements as well as the pattern of connection of the autopodial elements and the origin of the digital arch. Embryos and juveniles of P. expansa were cleared and stained for cartilage and bone. The fore- and hind-limbs were also studied histologically. We describe the development of the stylopodium and zeugopodium originating from a Y-shaped cartilaginous condensation, and the differentiation of the primary axis and the digital arch in the initial stages of limb development. The most pronounced changes were observed in the chondrogenic pattern and ossification of the mesopodium, although development of the digits is similar and we found no ontogenetic reduction such as that described for other Testudines. In this study, as in previous research involving several groups of reptilian sauropsids, we found an inconsistent pattern between the chondrogenic formation and mesopodial ossification of the limbs, indicating that these developmental events are dissociated. In summary, the chondrogenic and ossification sequences of these elements do not follow the same pattern. In addition, the differences found between P. expansa and other species to which it was compared clearly indicate that these events follow more than one pattern in Testudines. PMID:21290416

  5. 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

  6. Effect of alendronate on endochondral ossification in mandibular condyles of growing rats

    PubMed Central

    Bradaschia-Correa, V.; Barrence, F.A.C.; Ferreira, L.B.; Massa, L.F.; Arana-Chavez, V.E.

    2012-01-01

    The replacement of the calcified cartilage by bone tissue during the endochondral ossification of the mandibular condyle is dependent of the resorbing activity of osteoclats. After partial resorption, calcified cartilage septa are covered by a primary bone matrix secreted by osteoblasts. Osteoadherin (OSAD) is a small proteoglycan present in bone matrix but absent in cartilage during the endochondral ossification. The aim of this study was to analyze the effect of alendronate, a drug known to inhibit bone resorption by osteoclasts, on the endochondral ossification of the mandibular condyle of young rats, by evaluating the distribution of osteoclasts and the presence of OSAD in the bone matrix deposited. Wistar newborn rats (n=45) received daily injections of alendronate (n=27) or sterile saline solution as control (n=18) from the day of birth until the ages of 4, 14 and 30 days. At the days mentioned, the mandibular condyles were collected and processed for transmission electron microscopy analysis. Specimens were also submitted to tartrate resistant acid phosphatase (TRAP) histochemistry and ultrastructural immunodetection of OSAD. Alendronate treatment did not impede the recruitment and fusion of osteoclasts at the ossification zone during condyle growth, but they presented inactivated phenotype. The trabeculae at the ossification area consisted of cartilage matrix covered by a layer of primary bone matrix that was immunopositive to OSAD at all time points studied. Apparently, alendronate impeded the removal of calcified cartilage and maturation of bone trabeculae in the mandibular ramus, while in controls they occurred normally. These findings highlight for giving attention to the potential side-effects of bisphosphonates administered to young patients once it may represent a risk of disturbing maxillofacial development. PMID:22688305

  7. 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

  8. 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. PMID:27410998

  9. Engineering Small-Scale and Scaffold-Based Bone Organs via Endochondral Ossification Using Adult Progenitor Cells.

    PubMed

    Scotti, Celeste; Tonnarelli, Beatrice; Papadimitropoulos, Adam; Piccinini, Elia; Todorov, Atanas; Centola, Matteo; Barbero, Andrea; Martin, Ivan

    2016-01-01

    Bone development, growth, and repair predominantly occur through the process of endochondral ossification, characterized by remodelling of cartilaginous templates. The same route efficiently supports engineering of bone marrow as a niche for hematopoietic stem cells (HSC). Here we describe a combined in vitro/in vivo system based on bone marrow-derived Mesenchymal Stem/Stromal Cells (MSC) that duplicates the hallmark cellular and molecular events of endochondral ossification during development. The model requires MSC culture with instructive molecules to generate hypertrophic cartilage tissues. The resulting constructs complete the endochondral route upon in vivo implantation, in the timeframe of up to 12 weeks. The described protocol is clearly distinct from the direct ossification approach typically used to drive MSC towards osteogenesis. Recapitulation of endochondral ossification allows modelling of stromal-HSC interactions in physiology and pathology and allows engineering processes underlying bone regeneration. PMID:27236686

  10. Acquired color vision deficiency.

    PubMed

    Simunovic, Matthew P

    2016-01-01

    Acquired color vision deficiency occurs as the result of ocular, neurologic, or systemic disease. A wide array of conditions may affect color vision, ranging from diseases of the ocular media through to pathology of the visual cortex. Traditionally, acquired color vision deficiency is considered a separate entity from congenital color vision deficiency, although emerging clinical and molecular genetic data would suggest a degree of overlap. We review the pathophysiology of acquired color vision deficiency, the data on its prevalence, theories for the preponderance of acquired S-mechanism (or tritan) deficiency, and discuss tests of color vision. We also briefly review the types of color vision deficiencies encountered in ocular disease, with an emphasis placed on larger or more detailed clinical investigations.

  11. Hospital-acquired pneumonia

    MedlinePlus

    ... tends to be more serious than other lung infections because: People in the hospital are often very sick and cannot fight off ... prevent pneumonia. Most hospitals have programs to prevent hospital-acquired infections.

  12. Acquired Cerebral Trauma: Epilogue.

    ERIC Educational Resources Information Center

    Bigler, Erin D., Ed.

    1988-01-01

    The article summarizes a series of articles concerning acquired cerebral trauma. Reviewed are technological advances, treatment, assessment, potential innovative therapies, long-term outcome, family impact of chronic brain injury, and prevention. (DB)

  13. [Acquired haemophilia (acquired factor VIII inhibitor)].

    PubMed

    Ceresetto, José M; Duboscq, Cristina; Fondevila, Carlos; Tezanos Pinto, Miguel

    2015-01-01

    Acquired haemophilia is a rare disorder. The clinical picture ranges from mild ecchymosis and anaemia to life threatening bleeding in up to 20% of patients. The disease is produced by an antibody against Factor VIII and it usually occurs in the elderly, with no previous history of a bleeding disorder. It can be associated to an underlying condition such as cancer, autoimmune disorders, drugs or pregnancy. It has a typical laboratory pattern with isolated prolonged activated partial thromboplastin time (aPTT) that fails to correct upon mixing tests with normal plasma and low levels of factor VIII. Treatment recommendations are based on controlling the acute bleeding episodes with either bypassing agent, recombinant activated factor VII or activated prothrombin complex concentrate, and eradication of the antibody with immunosuppressive therapy.

  14. 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

  15. Transient Paraparesis After Laminectomy in a Patient with Multi-Level Ossification of the Spinal Ligament

    PubMed Central

    Shim, Jae-Jun; Doh, Jae-Won; Yoon, Seok-Mann; Bae, Hack-Gun; Yun, Il-Gyu

    2004-01-01

    Acute neurologic deterioration is not a rare event in the surgical decompression for thoracic spinal stenosis. We report a case of transient paraparesis after decompressive laminectomy in a 50-yr-old male patient with multi-level thoracic ossification of the ligamentum flavum and cervical ossification of the posterior longitudinal ligament. Decompressive laminectomy from T9 to T11 was performed without gross neurological improvement. Two weeks after the first operation, laminoplasty from C4 to C6 and additional decompressive laminectomies of T3, T4, T6, and T8 were performed. Paraparesis developed 3 hr after the second operation, which recovered spontaneously 5 hr thereafter. CT and MRI were immediately performed, but there were no corresponding lesions. Vascular compromise of the borderlines of the arterial supply by microthrombi might be responsible for the paraparesis. PMID:15308861

  16. Matrix metalloproteinase expression and localization in turkey (Meleagris gallopavo) during the endochondral ossification process.

    PubMed

    Simsa, S; Genina, O; Ornan, E Monsonego

    2007-06-01

    Vertebrate long bones are formed by endochondral ossification, a process accompanied by changes in extracellular matrix synthesis and remodeling, performed mainly by the matrix metalloproteinases (MMP). The temporal/spatial expression patterns of 5 members of the MMP family known to be important for endochondral ossification were studied, for the first time, in the turkey growth plate during embryonic and juvenile stages. The expression of MMP-2 was detected in the proliferative zone, MMP-3, MMP-9, and MMP-13 in cells lining the blood vessels; MMP-13 was also detected in hypertrophic chondrocytes. The MMP-16 expression was detected in the reserve zone of the growth plate. These results present a detailed survey of turkey MMP, serving as a data source (atlas) for further studies in this subject.

  17. Deficiency of the alpha-subunit of the stimulatory G protein and severe extraskeletal ossification.

    PubMed

    Eddy, M C; Jan De Beur, S M; Yandow, S M; McAlister, W H; Shore, E M; Kaplan, F S; Whyte, M P; Levine, M A

    2000-11-01

    Progressive osseous heteroplasia (POH) is a rare disorder characterized by dermal ossification beginning in infancy followed by increasing and extensive bone formation in deep muscle and fascia. We describe two unrelated girls with typical clinical, radiographic, and histological features of POH who also have findings of another uncommon heritable disorder, Albright hereditary osteodystrophy (AHO). One patient has mild brachydactyly but no endocrinopathy, whereas the other manifests brachydactyly, obesity, and target tissue resistance to thyrotropin and parathyroid hormone (PTH). Levels of the alpha-subunit of the G protein (Gsalpha) were reduced in erythrocyte membranes from both girls and a nonsense mutation (Q12X) in exon 1 of the GNAS1 gene was identified in genomic DNA from the mildly affected patient. Features of POH and AHO in two individuals suggest that these conditions share a similar molecular basis and pathogenesis and that isolated severe extraskeletal ossification may be another manifestation of Gsalpha deficiency. PMID:11092390

  18. Embryogenesis and ossification of Emydura subglobosa (Testudines, Pleurodira, Chelidae) and patterns of turtle development.

    PubMed

    Werneburg, Ingmar; Hugi, Jasmina; Müller, Johannes; Sánchez-Villagra, Marcelo R

    2009-11-01

    Using the Standard Event System (SES) to study patterns of vertebrate development, we describe a series of 17 embryos of the pleurodire turtle Emydura subglobosa. Based on a sequence heterochrony analysis including 23 tetrapod taxa, we identified autapomorphic developmental shifts that characterise Testudines, Cryptodira, and Pleurodira. The main results are that Testudines are characterised by an autapomorphic late neck development, whereas pleurodires and cryptodires show a different developmental timing of the mandibular process. Additionally, we described the ossification pattern of E. subglobosa and compared the data to those of five other turtles. Pleurodires show the epiplastron to ossify before or simultaneously with maxilla and dentary. In contrast, cryptodires show a later ossification of this bone. Because evolutionary developmental studies on turtles have previously focused only on "model organisms" that all belong to Cryptodira, we underline the necessity to include a pleurodire taxon for a more comprehensive, phylogenetically more informative approach. PMID:19842173

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

    PubMed Central

    Miller, Amy; Burson, Hannah; Söling, Ariane

    2016-01-01

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

  20. Endoscopic Color Doppler Ultrasonography in Predicting the Safety of Endoscopic Submucosal Dissection for Antral Heterotopic Pancreas

    PubMed Central

    Xin, Ling; Jun, Li Qian; Hua, Xu Li; Hong, Zhu; Bao, Chen Tian; Hai, Tang Jin

    2016-01-01

    Background/Aims: Complications are important determining factors for safety of endoscopic submucosal dissection (ESD) for gastric heterotopic pancreas (HP). This study investigated whether endoscopic color Doppler ultrasonography (ECDUS) could be used to predict the feasibility, efficacy, and safety of ESD. Patients and Methods: The study included 52 patients with heterotopic pancreas of the gastric antrum who underwent ECDUS before ESD. ECDUS was used to evaluate the submucosal vascular structure and the location of HP in gastric wall. The patients who had a vessel at least 500 μm in diameter or at least 10 vascular structures per field of view were classified into the rich group (Group R), and others were classified into the non-rich group (Group N). Procedure time, decrease in hemoglobin, frequency of clip use, complications, recurrence rate, and others were retrospectively evaluated. Results: There were 18 patients in Group R and 34 patients in Group N. Mean procedure time was significantly longer in group R (55.4 min) than in group N (35.5 min) (P = 0.014). The incidence of muscle injury and clip use were significantly higher in group R (77.8/83.3%) than in group N (20.6/23.5%) (P < 0.05). Mean decrease in hemoglobin was 2.5 g/dL in group R and 2.4 g/dL in group N, with no significant difference. There were no recurrences in any cases during the follow-up period. Conclusion: Preoperative identification of submucosal vascular structure by ECDUS can predict procedure time and the incidence of muscle injury and clip use, which is particularly suitable for predicting ESD safety in heterotopic pancreas of stomach. PMID:27748325

  1. [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.

  2. Inactivation of Fam20B in Joint Cartilage Leads to Chondrosarcoma and Postnatal Ossification Defects.

    PubMed

    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;Fam20B(fl/fl) mice, indicating that FAM20B-catalyzed proteoglycans regulate postnatal endochondral ossification partially through the mediation of WNT signaling. PMID:27405802

  3. Variation in mammalian proximal femoral development: comparative analysis of two distinct ossification patterns

    PubMed Central

    Serrat, Maria A; Reno, Philip L; McCollum, Melanie A; Meindl, Richard S; Lovejoy, C Owen

    2007-01-01

    The developmental anatomy of the proximal femur is complex. In some mammals, including humans, the femoral head and greater trochanter emerge as separate ossification centres within a common chondroepiphysis and remain separate throughout ontogeny. In other species, these secondary centres coalesce within the chondroepiphysis to form a single osseous epiphysis much like the proximal humerus. These differences in femoral ontogeny have not been previously addressed, yet are critical to an understanding of femoral mineralization and architecture across a wide range of mammals and may have key implications for understanding and treating hip abnormalities in humans. We evaluated femora from 70 mammalian species and categorized each according to the presence of a ‘separate’ or ‘coalesced’ proximal epiphysis based on visual assessment. We found that ossification type varies widely among mammals: taxa in the ‘coalesced’ group include marsupials, artiodactyls, perissodactyls, bats, carnivores and several primates, while the ‘separate’ group includes hominoids, many rodents, tree shrews and several marine species. There was no clear relationship to body size, phylogeny or locomotion, but qualitative and quantitative differences between the groups suggest that ossification type may be primarily an artefact of femoral shape and neck length. As some osseous abnormalities of the human hip appear to mimic the normal morphology of species with coalesced epiphyses, these results may provide insight into the aetiology and treatment of human hip disorders such as femoroacetabular impingement and early-onset osteoarthritis. PMID:17331175

  4. 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

  5. Tranilast stimulates endochondral ossification by upregulating SOX9 and RUNX2 promoters.

    PubMed

    Hasegawa, Sachi; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Matsushita, Masaki; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2016-02-01

    Endochondral ossification is an essential process for reparative phase of fracture healing, which starts with the differentiation of mesenchymal cells into chondrocytes followed by substitution of bone tissue. It is strictly controlled by the expression of crucial transcriptional factors: SOX9 in the early phase and RUNX2 in the late phase. Screening of FDA-approved compounds revealed that an anti-allergic drug, tranilast, that has been used for more than 30 years in clinical practice, enhanced the SOX9 promoter in chondrogenic cells and the RUNX2 promoter in osteoblastic cells. We observed that tranilast increased mRNA expression of both Sox9 and Runx2 in differentiating ATDC5 chondrogenic progenitor cells. Tranilast upregulated mRNA expression of chondrogenic marker genes (Col2a1, Acan, Col10a1, and Mmp13) in differentiating ATDC5 cells. Moreover, tranilast upregulated mRNA expression of essential signaling molecules involved in endochondral ossification (Pthrp, Ihh, and Axin2). In the later phase of differentiation of ATDC5 cells, tranilast increased synthesis of matrix proteoglycans, induced the alkaline phosphatase activity, and tended to accelerate mineralization. Tranilast is a potential agent that accelerates fracture repair by promoting the regulatory steps of endochondral ossification. PMID:26777999

  6. Community-acquired pneumonia.

    PubMed

    Falguera, M; Ramírez, M F

    2015-11-01

    This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach. PMID:26186969

  7. Acquired hypofibrinogenemia: current perspectives

    PubMed Central

    Besser, Martin W; MacDonald, Stephen G

    2016-01-01

    Acquired hypofibrinogenemia is most frequently caused by hemodilution and consumption of clotting factors. The aggressive replacement of fibrinogen has become one of the core principles of modern management of massive hemorrhage. The best method for determining the patient’s fibrinogen level remains controversial, and particularly in acquired dysfibrinogenemia, could have major therapeutic implications depending on which quantification method is chosen. This review introduces the available laboratory and point-of-care methods and discusses the relative advantages and limitations. It also discusses current strategies for the correction of hypofibrinogenemia. PMID:27713652

  8. Community-acquired pneumonia.

    PubMed

    Falguera, M; Ramírez, M F

    2015-11-01

    This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach.

  9. Acquired Brain Injury Program.

    ERIC Educational Resources Information Center

    Schwartz, Stacey Hunter

    This paper reviews the Acquired Brain Injury (ABI) Program at Coastline Community College (California). The ABI Program is a two-year, for-credit educational curriculum designed to provide structured cognitive retraining for adults who have sustained an ABI due to traumatic (such as motor vehicle accident or fall) or non-traumatic(such as…

  10. Community-acquired pneumonia.

    PubMed

    Prina, Elena; Ranzani, Otavio T; Torres, Antoni

    2015-09-12

    Community-acquired pneumonia causes great mortality and morbidity and high costs worldwide. Empirical selection of antibiotic treatment is the cornerstone of management of patients with pneumonia. To reduce the misuse of antibiotics, antibiotic resistance, and side-effects, an empirical, effective, and individualised antibiotic treatment is needed. Follow-up after the start of antibiotic treatment is also important, and management should include early shifts to oral antibiotics, stewardship according to the microbiological results, and short-duration antibiotic treatment that accounts for the clinical stability criteria. New approaches for fast clinical (lung ultrasound) and microbiological (molecular biology) diagnoses are promising. Community-acquired pneumonia is associated with early and late mortality and increased rates of cardiovascular events. Studies are needed that focus on the long-term management of pneumonia.

  11. Systemic Acquired Resistance

    PubMed Central

    2006-01-01

    Upon infection with necrotizing pathogens many plants develop an enhanced resistance to further pathogen attack also in the uninoculated organs. This type of enhanced resistance is referred to as systemic acquired resistance (SAR). In the SAR state, plants are primed (sensitized) to more quickly and more effectively activate defense responses the second time they encounter pathogen attack. Since SAR depends on the ability to access past experience, acquired disease resistance is a paradigm for the existence of a form of “plant memory”. Although the phenomenon has been known since the beginning of the 20th century, major progress in the understanding of SAR was made over the past sixteen years. This review covers the current knowledge of molecular, biochemical and physiological mechanisms that are associated with SAR. PMID:19521483

  12. Trefoil factor family protein 3 (TFF3) is present in cartilage during endochondral ossification in the developing mouse fetus.

    PubMed

    Bijelić, Nikola; Belovari, Tatjana; Baus Lončar, Mirela

    2013-04-01

    Trefoil factor family protein 3 (TFF3) is found in cartilage affected by osteoarthritis and septic arthritis, whereas no TFF3 presence is observed in healthy cartilage. During endochondral ossification, bone tissue replaces degenerating cartilage. There is no data about the role of TFF3 in this process. Our aim was to study the localization of TFF3 in cartilage during endochondral ossification in the mouse fetus. CD1 mouse fetuses, days 14-17, were isolated, fixed, and paraffin embedded. Fetuses were cut into 6μm sections, and processed for immunohistochemical staining with affinity purified polyclonal rabbit anti-TFF3 antibody. TFF3 was present in cartilage chondrocytes undergoing endochondral ossification, particularly in zone of proliferation, hypertrophy and calcification as well as in zone of cartilage degeneration during the monitored fetal period. Resting cartilage showed no presence of TFF3, while during endochondral ossification TFF3 localization showed an analogous pattern to that reported in cartilage affected by osteoarthritis and septic arthritis. Our data indicate that the role of TFF3 in these pathological conditions is similar to its role in the physiological process of endochondral ossification.

  13. Skeletal dysplasia in perinatal lethal osteogenesis imperfecta. A complex disorder of endochondral and intramembranous ossification.

    PubMed

    Marion, M J; Gannon, F H; Fallon, M D; Mennuti, M T; Lodato, R F; Kaplan, F S

    1993-08-01

    Osteogenesis imperfecta (OI) Type II is a rare heritable disorder of bone matrix that results in catastrophic congenital skeletal dysplasia. Two cases of OI Type II had symmetric rhizomelic skeletal dysplasia apparent on ultrasound at 16 and 20 weeks' gestation. Histologic and histochemical studies performed on skeletal tissue from fetal autopsies showed the following: (1) abnormal growth plate tissue characterized by failure of formation of primary bony spongiosa; (2) persistence of calcified cartilage bars in the diaphysis; (3) metaphyseal microfractures; (4) abundant cartilaginous fracture callus; (5) absence of bony callus; (6) failure of formation of intramembranous cortical diaphyseal bone; (7) angulation of long bones in portions of the metadiaphyses bordered by fracture callus; and (8) mechanical failure of the perichondral ring of LaCroix with a normal fibrous ossification groove of Ranvier. These findings suggest that skeletal dysplasia in OI Type II results from the action of muscular forces on a skeleton weakened by a complex disorder of endochondral and intramembranous ossification. The paucity of primary metaphyseal trabeculae and subperiosteal cortical bone leads to pathologic fractures of the immature fiber bone and an imperfect attempt at fracture repair. Angulation and shortening of long bones occurs between numerous sites of focal endochondral fracture callus. Mechanical failure of the fibrous perichondral ring leads to further collapse and shortening without obvious functional impairment of the fibrous ossification groove. Perinatal lethal OI provides insight into how a molecular disorder predominantly of Type I collagen metabolism results in pathology of numerous tissues, leading to severe skeletal dysplasia without primarily affecting chondrogenesis. PMID:8339500

  14. Chondrocytic ephrin B2 promotes cartilage destruction by osteoclasts in endochondral ossification.

    PubMed

    Tonna, Stephen; Poulton, Ingrid J; Taykar, Farzin; Ho, Patricia W M; Tonkin, Brett; Crimeen-Irwin, Blessing; Tatarczuch, Liliana; McGregor, Narelle E; Mackie, Eleanor J; Martin, T John; Sims, Natalie A

    2016-02-15

    The majority of the skeleton arises by endochondral ossification, whereby cartilaginous templates expand and are resorbed by osteoclasts then replaced by osteoblastic bone formation. Ephrin B2 is a receptor tyrosine kinase expressed by osteoblasts and growth plate chondrocytes that promotes osteoblast differentiation and inhibits osteoclast formation. We investigated the role of ephrin B2 in endochondral ossification using Osx1Cre-targeted gene deletion. Neonatal Osx1Cre.Efnb2(Δ/Δ) mice exhibited a transient osteopetrosis demonstrated by increased trabecular bone volume with a high content of growth plate cartilage remnants and increased cortical thickness, but normal osteoclast numbers within the primary spongiosa. Osteoclasts at the growth plate had an abnormal morphology and expressed low levels of tartrate-resistant acid phosphatase; this was not observed in more mature bone. Electron microscopy revealed a lack of sealing zones and poor attachment of Osx1Cre.Efnb2(Δ/Δ) osteoclasts to growth plate cartilage. Osteoblasts at the growth plate were also poorly attached and impaired in their ability to deposit osteoid. By 6 months of age, trabecular bone mass, osteoclast morphology and osteoid deposition by Osx1Cre.Efnb2(Δ/Δ) osteoblasts were normal. Cultured chondrocytes from Osx1Cre.Efnb2(Δ/Δ) neonates showed impaired support of osteoclastogenesis but no significant change in Rankl (Tnfsf11) levels, whereas Adamts4 levels were significantly reduced. A population of ADAMTS4(+) early hypertrophic chondrocytes seen in controls was absent from Osx1Cre.Efnb2(Δ/Δ) neonates. This suggests that Osx1Cre-expressing cells, including hypertrophic chondrocytes, are dependent on ephrin B2 for their production of cartilage-degrading enzymes, including ADAMTS4, and this might be required for attachment of osteoclasts and osteoblasts to the cartilage surface during endochondral ossification.

  15. Epiphyseal chondrocyte secondary ossification centers require thyroid hormone activation of Indian hedgehog and osterix signaling

    PubMed Central

    Xing, Weirong; Cheng, Shaohong; Wergedal, Jon; Mohan, Subburaman

    2015-01-01

    Thyroid hormones (TH) are known to regulate endochondral ossification during skeletal development via acting directly in chondrocytes and osteoblasts. In this study, we focused on TH effects on the secondary ossification center (SOC), since the time of appearance of SOCs in several species coincides with the time when peak levels of TH are attained. Accordingly, μCT evaluation of femurs and tibias at day 21 in TH-deficient and control mice revealed that endochondral ossification of SOCs is severely compromised due to TH deficiency and that TH treatment for 10 days completely rescued this phenotype. Staining of cartilage and bone in the epiphysis revealed that while all of the cartilage is converted into bone in the prepubertal control mice, this conversion failed to occur in the TH-deficient mice. Immunohistochemistry studies revealed that TH treatment of Tshr−/− mice induced expression of Ihh and Osx in Col2 expressing chondrocytes in the SOC at day 7 which subsequently differentiate into Col10/osteocalcin expressing chondro-osteoblasts at day 10. Consistent with these data, treatment of tibia cultures from 3-day old mice with10 ng/ml TH increased expression of Osx, Col10, ALP and osteocalcin in the epiphysis by 6–60 fold. Furthermore, knockdown of the TH-induced increase in Osx expression using lentiviral shRNA significantly blocked TH-induced ALP and osteocalcin expression in chondrocytes. Treatment of chondrogenic cells with an Ihh inhibitor abolished chondro-osteoblast differentiation and SOC formation. Our findings indicate that TH regulates the SOC initiation and progression via differentiating chondrocytes into bone matrix producing osteoblasts by stimulating Ihh and Osx expression in chondrocytes. PMID:24753031

  16. Morphological influence of ascorbic acid deficiency on endochondral ossification in osteogenic disorder Shionogi rat.

    PubMed

    Sakamoto, Yujiro; Takano, Yoshiro

    2002-10-01

    The influences of chronic deficiency of L-ascorbic acid (AsA) on the differentiation of osteo-chondrogenic cells and the process of endochondral ossification were examined in the mandibular condyle and the tibial epiphysis and metaphysis by using Osteogenic Disorder Shionogi (ODS) rats that bear an inborn deficiency of L-gulonolactone oxidase. Weanling male rats were kept on an AsA-free diet for up to 4 weeks, until the symptoms of scurvy became evident. The tibiae and condylar processes of scorbutic rats displayed undersized and distorted profiles with thin cortical and scanty cancellous bones. In these scorbutic bones, the osteoblasts showed characteristic expanded round profiles of rough endoplasmic reticulum, and lay on the bone surface where the osteoid layer was missing. Trabeculae formation was deadlocked, although calcification of the cartilage matrix proceeded in both types of bone. Scorbutic condylar cartilage showed severe disorganization of cell zones, such as unusual thickening of the calcification zone, whereas the tibial cartilage showed no particular alterations (except for a moderately decreased population of chondrocytes). In condylar cartilage, hypertrophic chondrocytes were encased in a thickened calcification zone, and groups of nonhypertrophic chondrocytes occasionally formed cell nests surrounded by a metachromatic matrix in the hypertrophic cell zone. These results indicate that during endochondral ossification, chronic AsA deficiency depresses osteoblast function and disturbs the differentiation pathway of chondrocytes. The influence of scurvy on mandibular condyle cartilage is different from that on articular and epiphyseal cartilage of the tibia, suggesting that AsA plays different roles in endochondral ossification in the mandibular condyle and long bones.

  17. 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

  18. Genetics of Ossification of the Posterior Longitudinal Ligament of the Spine: A Mini Review

    PubMed Central

    2014-01-01

    Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common disease in aging populations and sometimes results in serious neurological problems due to compression of the spinal cord and nerve roots. OPLL is a multi-factorial (polygenic) disease controlled by genetic and environmental factors. Studies searching for the genetic component of OPLL, using linkage and association analyses, are in progress and several susceptibility genes have been reported. This paper reviews the recent progress in the genetic study of OPLL and comments on its future task. PMID:25006569

  19. Acquired methemoglobinemia revisited.

    PubMed

    Trapp, Larry; Will, John

    2010-10-01

    Dentistry has two medications in its pain management armamentarium that may cause the potentially life-threatening disorder methemoglobinemia. The first medications are the topical local anesthetics benzocaine and prilocaine. The second medication is the injectable local anesthetic prilocaine. Acquired methemoglobinemia remains a source of morbidity and mortality in dental and medical patients despite the fact that it is better understood now than it was even a decade ago. It is in the interest of all dental patients that their treating dentists review this disorder. The safety of dental patients mandates professional awareness.

  20. Heterotopic Gastric Mucosa in the Distal Part of Esophagus in a Teenager

    PubMed Central

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

    2015-01-01

    Abstract 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. PMID:26496283

  1. 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.

  2. [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. PMID:26580946

  3. Excess BMP Signaling in Heterotopic Cartilage Forming in Prg4-null TMJ Discs.

    PubMed

    Bechtold, T E; Saunders, C; Mundy, C; Um, H; Decker, R S; Salhab, I; Kurio, N; Billings, P C; Pacifici, M; Nah, H D; Koyama, E

    2016-03-01

    Heterotopic cartilage develops in certain pathologic conditions, including those affecting the human temporomandibular joint (TMJ), but the underlying molecular mechanisms remain obscure. This is in part due to the fact that a reliable animal model of such TMJ diseases is not available. Here, we show that aberrant chondrocyte differentiation and ectopic cartilage formation occur spontaneously in proteoglycan 4 (Prg4) mutant TMJ discs without further invasive procedure. By 2 mo of age, mutant disc cells displayed chondrocyte transdifferentiation, accompanied by strong expression of cartilage master gene Sox9 and matrix genes aggrecan and type II collagen. By 6 mo, heterotopic cartilage had formed in the discs and expressed cartilage hypertrophic markers Runx2 and ColX. The ectopic tissue grew in size over time and exhibited regional mineralization by 12 mo. Bone morphogenetic protein (BMP) signaling was activated with the ectopic chondrogenic cells and chondrocytes, as indicated by phosphorylated Smad 1/5/8 nuclear staining and by elevated expression of Bmp2, Bmpr1b, Bmpr2, and BMP signaling target genes. Likewise, we found that upon treatment with recombinant human BMP 2 in high-density micromass culture, mutant disc cells differentiated into chondrocytes and synthesized cartilage matrix more robustly than control cells. Importantly, a specific kinase inhibitor of BMP receptors drastically attenuated chondrogenesis in recombinant human BMP 2-treated mutant disc cultures. Unexpectedly, we found that Prg4 was expressed at joint-associated sites, including disc/muscle insertion and muscle/bone interface, and all these structures were abnormal in Prg4 mutants. Our data indicate that Prg4 is needed for TMJ disc integrity and function and that its absence leads to ectopic chondrogenesis and cartilage formation in conjunction with abnormal BMP signaling. Our findings imply that the BMP signaling pathway could be a potential therapeutic target for prevention or inhibition

  4. 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

  5. Complex Evolutionary and Genetic Patterns Characterize the Loss of Scleral Ossification in the Blind Cavefish Astyanax mexicanus.

    PubMed

    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 may

  6. 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

  7. 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.

  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

    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. PMID:27550480

  9. Bone morphogenetic protein 2 stimulates endochondral ossification by regulating periosteal cell fate during bone repair

    PubMed Central

    Yu, Yan Yiu; Lieu, Shirley; Lu, Chuanyong; Colnot, Céline

    2010-01-01

    Bone repair depends on the coordinated action of numerous growth factors and cytokines to stimulate new skeletal tissue formation. Among all the growth factors involved in bone repair, Bone Morphogenetic Proteins (BMPs) are the only molecules now used therapeutically to enhance healing. Although BMPs are known as strong bone inducers, their role in initiating skeletal repair is not entirely elucidated. The aim of this study was to define the role of BMP2 during the early stages of bone regeneration and more specifically in regulating the fate of skeletal progenitors. During healing of non-stabilized fractures via endochondral ossification, exogenous BMP2 increased the deposition and resorption of cartilage and bone, which was correlated with a stimulation of osteoclastogenesis but not angiogenesis in the early phase of repair. During healing of stabilized fractures, which normally occurs via intramembranous ossification, exogenous BMP2 induced cartilage formation suggesting a role in regulating cell fate decisions. Specifically, the periosteum was found to be a target of exogenous BMP2 as shown by activation of the BMP pathway in this tissue. Using cell lineage analyses, we further show that BMP2 can direct cell differentiation towards the chondrogenic lineage within the periosteum but not the endosteum, indicating that skeletal progenitors within periosteum and endosteum respond differently to BMP signals. In conclusion, BMP2 plays an important role in the early stages of repair by recruiting local sources of skeletal progenitors within periosteum and endosteum and by determining their differentiation towards the chondrogenic and osteogenic lineages. PMID:20348041

  10. Endochondral ossification process of the turkey (Meleagris gallopavo) during embryonic and juvenile development.

    PubMed

    Simsa, S; Ornan, E Monsonego

    2007-03-01

    The long bones of the developing skeleton arise from the process of endochondral ossification, which begins during the embryonic stages and resumes later in the growth plates located at the extremities of the long bones. This process includes commitment of cells to the chondrocytic lineage and further differentiation into hypertrophic chondrocytes, which subsequently undergo apoptosis and are replaced by osteoblasts laying down the trabecular bone. In this study we characterize, for the first time, the endochondral bone development of the turkey during embryonic and juvenile stages. Turkey tibias were collected on embryonic d 11, 14, and 18; and at 3 and 7 d posthatching, alcian blue and Von Kossa staining, alkaline phosphatase activity, and in situ expression of collagen types II and X were studied in these samples. We showed that the principles of bone development in the turkey follow the known vertebrate pattern, and that the initiation of ossification is related to the perichondrium and compact bone. These results increase the knowledge about this process in the turkey, which is an important animal in the agricultural industries.

  11. [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. PMID:27367352

  12. 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.

  13. Developmental and morphological variation in the teleost craniofacial skeleton reveals an unusual mode of ossification.

    PubMed

    Franz-Odendaal, Tamara A; Ryan, Kerrianne; Hall, Brian K

    2007-12-15

    We investigated the morphology and development of the scleral ossicles within the eyes of three species from three basal teleost orders, namely, the alewife (Alosa pseudoharengus; Clupeiformes), the surface morph of the Mexican tetra (Astyanax mexicanus; Characiformes) and zebrafish (Danio rerio; Cypriniformes). Two morphologies, circular and elongated, and one variation, fused elements, were identified. Zebrafish have small circular ossicles, whereas the alewife and the Mexican tetra have elongated ossicles. Surprisingly in the Mexican tetra these elements fuse at one end forming a continuous element with an antero-ventral opening; this may be typical for the Order Characiformes. Regardless of morphology, the ossicles develop via unilateral perichondral ossification of the scleral cartilage from two centers opposite one another in the eye. This unilateral type of ossification, in which only the perichondrium furthest from the retina contributes to the ossicles, has not previously been reported in any vertebrate. Because either the perichondrium and/or an extension of the perichondrium can transform into the scleral ossicle, we refer to the transitional tissue as periskeletal. Although the functional significance of the different shaped ossicles is unclear, skeletal muscle attaches directly to these bones, implying voluntary control. The morphological and developmental variation of teleost scleral ossicles makes them an ideal system for determining the genetic basis underlying phenotypic variation as well as for studying mechanisms underlying osteogenic and chondrogenic processes in teleosts. These data support our previous finding that scleral ossicles in teleosts may not be homologous to those in other vertebrates, such as reptiles. PMID:17577202

  14. Community-acquired pneumonia.

    PubMed

    Polverino, E; Torres Marti, A

    2011-02-01

    Despite the remarkable advances in antibiotic therapies, diagnostic tools, prevention campaigns and intensive care, community-acquired pneumonia (CAP) is still among the primary causes of death worldwide, and there have been no significant changes in mortality in the last decades. The clinical and economic burden of CAP makes it a major public health problem, particularly for children and the elderly. This issue provides a clinical overview of CAP, focusing on epidemiology, economic burden, diagnosis, risk stratification, treatment, clinical management, and prevention. Particular attention is given to some aspects related to the clinical management of CAP, such as the microbial etiology and the available tools to achieve it, the usefulness of new and old biomarkers, and antimicrobial and other non-antibiotic adjunctive therapies. Possible scenarios in which pneumonia does not respond to treatment are also analyzed to improve clinical outcomes of CAP. PMID:21242952

  15. Malignant lymphoma arising from heterotopic Warthin's tumor in the neck: case report and review of the literature.

    PubMed

    Gorai, Shigeki; Numata, Tsutomu; Kawada, Sawako; Nakano, Masayuki; Tamaru, Jun-ichi; Kobayashi, Toshimitsu

    2007-06-01

    Warthin's tumor (WT), so-called adenolymphoma, is a benign salivary gland tumor with both epithelial and lymphoid histological characteristics, so the histogenesis remains unclear. Treatment consists primarily of tumor removal or conservative follow up. Here we present a rare case of malignant lymphoma arising from heterotopic (ectopic) WT. A 102-year-old man presented with a mass in the left side of the neck which was painless but gradually enlarged over 1 month. The mass was 2-3 cm in diameter, and freely moveable below the angle of the mandible. The mass was totally removed. The histological diagnosis was malignant lymphoma, diffuse large B-cell type, arising from heterotopic WT. Postoperative staging examination including chest radiography, bone scan, and computed tomography of the abdomen and pelvis revealed no evidence of dissemination of malignant lymphoma. Malignant transformation within WT is rarer in the lymphoid component than in the epithelial component. Only 16 cases of malignant transformation arising from WT have been reported, including only three cases of non-Hodgkin lymphoma apparently arising from heterotopic WT. Tumor removal or careful follow up is recommended in patients with WT because of the potential risk posed by such malignant transformation.

  16. 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.

  17. NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone.

    PubMed

    Tomlinson, Ryan E; Li, Zhi; Zhang, Qian; Goh, Brian C; Li, Zhu; Thorek, Daniel L J; Rajbhandari, Labchan; Brushart, Thomas M; Minichiello, Liliana; Zhou, Fengquan; Venkatesan, Arun; Clemens, Thomas L

    2016-09-01

    Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA) directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkA(F592A) mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification. PMID:27568565

  18. Patterns of ossification in the manus of the harbor porpoise (Phocoena phocoena): hyperphalangy and delta-shaped bones.

    PubMed

    Dawson, Susan D

    2003-11-01

    With the transition from terrestrial to aquatic habitats, cetacean forelimbs have undergone significant modifications in bone morphology and soft tissue distribution. Some, but not all, of these modifications are also demonstrated in other lineages of extant and extinct secondarily aquatic tetrapods. This study examines the ontogenetic pattern of ossification of the manus of the harbor porpoise (Phocoena phocoena), using plain film radiography. Two modifications examined are hyperphalangy (number of phalanges per digit increased beyond the typical mammalian number) and the morphology of delta-shaped bones. Hyperphalangy in Phocoena phocoena is apparent in digits 2 and 3. Phalangeal counts in all digits are variable (sometimes between the right and left flippers of the same individual) and are not necessarily correlated with age. Phalangeal ossification and epiphyseal fusion proceeds along the proximo-distal axis within each digit. In addition, digits 2 and 3 are at a more advanced stage of ossification than more abaxial digits. Delta-shaped bones appear to be a normal stage in the ossification of phalanges in all digits except the third, and may persist in the adult in certain digits. In humans, this morphology is a developmental anomaly usually associated with other malformations, such as polydactyly or syndactyly. Delta-shaped bones in the cetacean manus display a consistent orientation and the process by which they are formed may be similar to that in extinct marine reptiles. PMID:14518013

  19. Acquired aplastic anemia.

    PubMed

    Keohane, Elaine M

    2004-01-01

    Acquired aplastic anemia (AA) is a disorder characterized by a profound deficit of hematopoietic stem and progenitor cells, bone marrow hypocellularity, and peripheral blood pancytopenia. It primarily affects children, young adults, and those over 60 years of age. The majority of cases are idiopathic; however, idiosyncratic reactions to some drugs, chemicals, and viruses have been implicated in its etiology. An autoimmune T-cell reaction likely causes the stem cell depletion, but the precise mechanism, as well as the eliciting and target antigens, is unknown. Symptoms vary from severe life-threatening cytopenias to moderate or non-severe disease that does not require transfusion support. The peripheral blood typically exhibits pancytopenia, reticulocytopenia, and normocytic or macrocytic erythrocytes. The bone marrow is hypocellular and may exhibit dysplasia of the erythrocyte precursors. First line treatment for severe AA consists of hematopoietic stem cell transplantation in young patients with HLA identical siblings, while immunosuppression therapy is used for older patients and for those of any age who lack a HLA matched donor. Patients with AA have an increased risk of developing paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), or acute leukemia. Further elucidation of the pathophysiology of this disease will result in a better understanding of the interrelationship among AA, PNH, and MDS, and may lead to novel targeted therapies.

  20. 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

  1. 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

  2. Heterotopic auxiliary rat liver transplantation with flow-regulated portal vein arterialization in acute hepatic failure.

    PubMed

    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

  3. 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.

  4. Late Occurrence of Cervicothoracic Ossification of Posterior Longitudinal Ligaments in a Surgically Treated Thoracic OPLL Patient

    PubMed Central

    Hyun, Seung-Jae; Hong, Seung-Chyul

    2010-01-01

    Ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine is rare, even in the Far East. A 45-year-old female presented with a 4-month history of progressive motor weakness in the lower extremities, numbness below the midthoracic area, and spastic gait disturbance. Neuroradiological examinations revealed massive OPLLs at the T4-T6 levels with severe anterior compression of the spinal cord. Anterior decompressive corpectomies with bone grafts were performed from T4 to T6 using a trans-thoracic approach. After surgery, the patient made an uneventful recovery. However, eleven years after surgery, the patient developed recurrent lower extremity weakness and spastic gait disturbance. De novo OPLLs at the C6-T2 levels were responsible for the severe spinal cord compression on this occasion. After second surgery, paralysis in both legs was resolved. We present a rare case of late cervicothoracic OPLL in a patient surgically treated for thoracic OPLL. PMID:20157380

  5. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.2 Acquiring... each holds half of V's shares. Therefore, A and B each control V (see § 801.1(b)), and V is included...” are acquiring persons. (b) Except as provided in paragraphs (a) and (b) of § 801.12, the...

  6. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.2 Acquiring... each holds half of V's shares. Therefore, A and B each control V (see § 801.1(b)), and V is included...” are acquiring persons. (b) Except as provided in paragraphs (a) and (b) of § 801.12, the...

  7. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...” are acquiring persons. (b) Except as provided in paragraphs (a) and (b) of § 801.12, the person(s.... Examples: 1. Corporation A (the ultimate parent entity included within person “A”) proposes to acquire Y, a... to be carried out by merging Y into X, a wholly-owned subsidiary of A, with X surviving, and...

  8. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...” are acquiring persons. (b) Except as provided in paragraphs (a) and (b) of § 801.12, the person(s.... Examples: 1. Corporation A (the ultimate parent entity included within person “A”) proposes to acquire Y, a... to be carried out by merging Y into X, a wholly-owned subsidiary of A, with X surviving, and...

  9. Effect of therapeutic ultrasound on folliculogenesis, angiogenesis and apoptosis after heterotopic mouse ovarian transplantation.

    PubMed

    Abtahi, N S; Eimani, H; Vosough, A; Shahverdi, Ab; Fathi, R; Hayati, N; Nasiri, N

    2014-07-01

    One of the challenges in ovarian transplantation is ischemia-reperfusion damage. When transitional tissue faces an acute and critical condition in terms of blood supply (immediately after organ transplantation), treatment with low-intensity pulsed ultrasound (LIPUS) seems to be very beneficial. The aim of this study was to evaluate the effects of ultrasound therapy on heterotopic transplanted mouse ovarian tissue. Adult female Naval Medical Research Institute mice were divided into three groups. In the experimental groups, the transplanted ovary was exposed 5 min daily to ultrasound with an intensity of 0.3 W/cm(2), frequency of 3 MHz and pulse mode of 1:4. The grafted ovaries were assessed with the usual histology and immunohistochemistry techniques. Results indicate that more CD31 angiogenic factor was expressed in irradiated animals than in control animals, and ultrasound therapy resulted in better follicular preservation, especially after 14 d. In conclusion, therapeutic ultrasound may accelerate and increase re-angiogenesis and can help to promote ovarian follicular growth.

  10. 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

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

    PubMed Central

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

    2015-01-01

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

  12. Lhermitte-Duclos disease with neurofibrillary tangles in heterotopic cerebral grey matter.

    PubMed

    Rusiecki, D; Lach, B

    2016-01-01

    Lhermitte-Duclos disease (LDD), a disorder first described by French physicians Lhermitte and Duclos in 1920 [25], is a benign, slow growing dysplastic gangliocytoma of the cerebellum, characterized by replacement of the granule cell layer by abnormal granule and Purkinje like cells. The most frequent presenting signs and symptoms are megalocephaly, increased intracranial pressure, nausea, hydrocephalus, ataxia, gait abnormalities, and intermittent headaches, all of which are attributed to the mass effect [6,11,25]. Many cases are associated with a mutation in the phosphatase and tensin homolog or PTEN gene which is also involved in numerous otherwise unrelated central nervous system abnormalities, namely Cowden syndrome [1,6,11], autism spectrum disorder [18], cerebral cortical dysplasia [11,30] and Bannayan-Riley-Ruvalcaba syndrome [30]. The presence of cortical heterotopia has been reported in a small number of LDD cases [3,5,17,32]. We describe a unique case of LDD with cerebral cortical heterotopic grey matter containing neurofibrillary tangles. PMID:27543776

  13. 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

  14. Intraductal papillary mucinous neoplasm of the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer: A case report.

    PubMed

    Lee, Sang Hwa; Kim, Wook Youn; Hwang, Dae-Yong; Han, Hye Seung

    2015-07-01

    We report a case of intraductal papillary mucinous neoplasm (IPMN) originating from the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer (HNPCC). A 49-year-old woman had a past history of total colectomy and total hysterectomy with bilateral salpingo-oophorectomy due to colonic adenocarcinoma and endometrial adenocarcinoma 11 years ago. Her parents died from colonic adenocarcinoma and her sister died from colonic adenocarcinoma and endometrial adenocarcinoma. The clinician found an ileal mass with necrotic change and the mass increased in size from 1.7 cm to 2.2 cm during the past 2 years on computed tomography. It was surgically resected. Microscopically, the ileal mass showed heterotopic pancreas with IPMN high grade dysplasia. Immunohistochemical staining revealed positive reactivity for MLH1/PMS2 and negative reactivity for MSH2/MSH6. This is the first report of IPMN originating from the ileal heterotopic pancreas in a patient with HNPCC in the English literature.

  15. Acquiring and Organizing Curriculum Materials.

    ERIC Educational Resources Information Center

    Lare, Gary A.

    This book addresses two areas of need in a curriculum materials center--where to find curriculum materials for acquisition and how to organize these materials for efficient and effective access once they are acquired. The book is arranged in two parts: "Acquiring and Organizing the Collection" and "Resources." The book brings together many…

  16. 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

  17. Congenital renal tubular dysplasia and skull ossification defects similar to teratogenic effects of angiotensin converting enzyme (ACE) inhibitors.

    PubMed Central

    Kumar, D; Moss, G; Primhak, R; Coombs, R

    1997-01-01

    An apparently autosomal recessive syndrome of congenital renal tubular dysplasia and skull ossification defects is described in five infants from two separate, consanguineous, Pakistani Muslim kindreds. The clinical, pathological, and radiological features are similar to the phenotype associated with fetal exposure to angiotensin converting enzyme (ACE) inhibitors: intrauterine growth retardation, skull ossification defects, and fetal/ neonatal anuric renal failure associated with renal tubular dysplasia. There was no fetal exposure to ACE inhibitors in the affected infants. Phenotypic similarities between these familial cases and those associated with ACE inhibition suggest an abnormality of the "renin-angiotensin-aldosterone" system (RAS). It is postulated that the molecular pathology in this uncommon autosomal recessive proximal renal tubular dysgenesis could be related to mutations of the gene systems governing the RAS. Images PMID:9222960

  18. BMP2 induces segment-specific skeletal regeneration from digit and limb amputations by establishing a new endochondral ossification center

    PubMed Central

    Yu, Ling; Han, Manjong; Yan, Mingquan; Lee, Jangwoo; Muneoka, Ken

    2012-01-01

    Bone morphogenetic proteins (BMPs) are required for bone development, the repair of damage skeletal tissue, and the regeneration of the mouse digit tip. Previously we showed that BMP treatment can induce a regeneration response in mouse digits amputated at a proximal level of the terminal phalangeal element (P3) (Yu et al., 2010). In this study, we show that the regeneration-inductive ability of BMP2 extends to amputations at the level of the second phalangeal element (P2) of neonatal digits, and the hindlimb of adult limbs. In these models the induced regenerative response is restricted in a segment-specific manner, thus amputated skeletal elements regenerate distally patterned skeletal structures but does not form joints or more distal skeletal elements. Studies on P2 amputations indicate that BMP2-induced regeneration is associated with a localized proliferative response and the transient expression of established digit blastema marker genes. This is followed by the formation of a new endochondral ossification center at the distal end of the bone stump. The endochondral ossification center contains proliferating chondrocytes that establish a distal proliferative zone and differentiate proximally into hypertrophic chondrocytes. Skeletal regeneration occurs from proximal to distal with the appearance of osteoblasts that differentiate in continuity with the amputated stump. Using the polarity of the endochondral ossification centers induced by BMP2 at two different amputation levels, we show that BMP2 activates a level-dependent regenerative response indicative of a positional information network. In summary, our studies provide evidence that BMP2 induces the regeneration of mammalian limb structures by stimulating a new endochondral ossification center that utilizes an existing network of positional information to regulate patterning during skeletal regeneration. PMID:23041115

  19. Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon

    PubMed Central

    Fukuda, Masayoshi; Mizutani, Tomohiro; Mochizuki, Wakana; Matsumoto, Taichi; Nozaki, Kengo; Sakamaki, Yuriko; Ichinose, Shizuko; Okada, Yukinori; Tanaka, Toshihiro; Watanabe, Mamoru

    2014-01-01

    To develop stem cell therapy for small intestinal (SI) diseases, it is essential to determine whether SI stem cells in culture retain their tissue regeneration capabilities. By using a heterotopic transplantation approach, we show that cultured murine SI epithelial organoids are able to reconstitute self-renewing epithelia in the colon. When stably integrated, the SI-derived grafts show many features unique only to the SI but distinct from the colonic epithelium. Our study provides evidence that cultured adult SI stem cells could be a source for cell therapy of intestinal diseases, maintaining their identity along the gastrointestinal tract through an epithelium-intrinsic mechanism. PMID:25128495

  20. Osteolytic bone metastasis is hampered by impinging on the interplay among autophagy, anoikis and ossification.

    PubMed

    Maroni, P; Bendinelli, P; Matteucci, E; Locatelli, A; Nakamura, T; Scita, G; Desiderio, M A

    2014-01-01

    Here we show that the fate of osteolytic bone metastasis depends on the balance among autophagy, anoikis resistance and ossification, and that the hepatocyte growth factor (HGF) signaling pathway seems to have an important role in orchestrating bone colonization. These findings are consistent with the pathophysiology of bone metastasis that is influenced by the cross-talk of supportive and neoplastic cells through molecular signaling networks. We adopted the strategy to target metastasis and stroma with the use of adenovirally expressed NK4 (AdNK4) and Dasatinib to block HGF/Met axis and Src activity. In human bone metastatic 1833 cells, HGF conferred anoikis resistance via Akt and Src activities and HIF-1α induction, leading to Bim isoforms degradation. When Src and Met activities were inhibited with Dasatinib, the Bim isoforms accumulated conferring anoikis sensitivity. The proviability effect of HGF, under low-nutrient stress condition, was related to a faster autophagy deactivation with respect to HGF plus Dasatinib. In the 1833 xenograft model, AdNK4 switched metastasis vasculature to blood lacunae, increasing HIF-1α in metastasis. The combination of AdNK4 plus Dasatinib gave the most relevant results for mice survival, and the following molecular and cellular changes were found to be responsible. In bone metastasis, we observed a hypoxic condition - marked by HIF-1α - and an autophagy failure - marked by p62 without Beclin-1. Then, osteolytic bone metastases were largely prevented, because of autophagy failure in metastasis and ossification in bone marrow, with osteocalcin deposition. The abnormal repair process was triggered by the dysfunctional autophagy/anoikis interplay. In conclusion, the concomitant blockade of HGF/Met axis and Src activity seemed to induce HIF-1α in metastasis, whereas the bone marrow hypoxic response was reduced. As a consequence, anoikis resistance might be hampered favoring, instead, autophagy failure and neoformation of woven

  1. 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. PMID:18624573

  2. 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

  3. 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. PMID:23769047

  4. 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

  5. The Risk Factors and Pregnancy Outcomes of 48 Cases of Heterotopic Pregnancy from a Single Center.

    PubMed

    Jeon, Ji Hyun; Hwang, Yu Im; Shin, Im Hee; Park, Chan Woo; Yang, Kwang Moon; Kim, Hye Ok

    2016-07-01

    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

  6. Analysis of Enteric Neural Crest Cell Migration Using Heterotopic Grafts of Embryonic Guts

    PubMed Central

    Soret, Rodolphe; Pilon, Nicolas

    2016-01-01

    Hirschsprung disease (HSCR), also named aganglionic megacolon, is a severe congenital malformation characterized by a lack of enteric nervous system (ENS) in the terminal regions of the bowel (Bergeron et al., 2013). As the ENS notably regulates motility in the whole gastrointestinal track, the segment without neurons remains tonically contracted, resulting in functional intestinal obstruction and accumulation of fecal material (megacolon). HSCR occurs when enteric neural progenitors of vagal neural crest origin fail to fully colonize the developing intestines. These “enteric” neural crest cells (ENCCs) have to migrate in a rostro-caudal direction during a fixed temporal window, which is between embryonic day (e) 9.5 and e14.5 in the mouse (Obermayr et al., 2013). Recently, our group generated a new HSCR mouse model called Holstein in which migration of ENCCs is impaired because of increased collagen VI levels in their microenvironment (Soret e al., 2015). Here, we describe the method that allowed us to demonstrate the cell-autonomous nature of this migration defect. In this system adapted from a previously described heterotopic grafting approach (Breau et al., 2006), the donor tissue is a fully colonized segment of e12.5 midgut while the host tissue is an aneural segment of e12.5 hindgut. Extent of ENCC migration in host tissue is assessed after 24 h of culture and is greatly facilitated when donor tissue has a transgenic background such as the Gata4-RFP (Pilon et al., 2008) that allows endogenous labeling of ENCCs with fluorescence. Depending of the genetic background of donor and host tissues, this approach can allow evaluating both cell-autonomous and non-cell-autonomous defects of ENCC migration.

  7. Attenuation of Obliterative Bronchiolitis by a CXCR4 antagonist in the murine heterotopic tracheal transplant model

    PubMed Central

    Xu, Jianguo; Torres, Edilson; Mora, Ana; Shim, Hyunsuk; Ramirez, Allan; Neujahr, David; Brigham, Kenneth L.; Rojas, Mauricio

    2008-01-01

    Long-term success in lung transplantation is limited by obliterative bronchiolits (OB), while the mechanism for this disease is not well-understood. Chemokine SDF-1 and its receptor CXCR4 have been reported to be involved in several fibrogenic processes by recruiting inflammatory and fibroblast progenitor cells into injured tissues. We hypothesized that SDF-1/CXCR4 axis also plays a role in the pathogenesis of OB. Using the mouse heterotopic allogeneic airway transplant model, we transplanted mouse tracheas from Balb/C donors into C57BL/6 recipients. At day 10 after transplant, we found high expression of SDF-1 in cells in sub-epithelial layers of the allograft. Approximately 26% of cells infiltrating the allograft were CD45+CXCR4+ as was determined by flow cytometry analysis. Treatment of the recipients with a CXCR4 antagonist, TN 14003, decreased cell infiltration into the grafts at day 10 post implantation. At day 42 a significant reduction of the luminal occlusion was found in the TN14003 treated animals compared to controls (57.40% versus 98.21%, p<0.01). To demonstrate the relevance of SDF-1/CXCR4 axis in OB, sections of lung tissue obtained from lung transplanted patients with OB, were examined for SDF-1 and CXCR4 expression. We found higher number of CXCR4 and SDF-1 positive cells in samples from patients with OB compared with normal lungs. These findings provide new insights into the mechanisms of lung chronic rejection and may lead to new intervention tools for the treatment of OB. PMID:19059110

  8. Analysis of Enteric Neural Crest Cell Migration Using Heterotopic Grafts of Embryonic Guts

    PubMed Central

    Soret, Rodolphe; Pilon, Nicolas

    2016-01-01

    Hirschsprung disease (HSCR), also named aganglionic megacolon, is a severe congenital malformation characterized by a lack of enteric nervous system (ENS) in the terminal regions of the bowel (Bergeron et al., 2013). As the ENS notably regulates motility in the whole gastrointestinal track, the segment without neurons remains tonically contracted, resulting in functional intestinal obstruction and accumulation of fecal material (megacolon). HSCR occurs when enteric neural progenitors of vagal neural crest origin fail to fully colonize the developing intestines. These “enteric” neural crest cells (ENCCs) have to migrate in a rostro-caudal direction during a fixed temporal window, which is between embryonic day (e) 9.5 and e14.5 in the mouse (Obermayr et al., 2013). Recently, our group generated a new HSCR mouse model called Holstein in which migration of ENCCs is impaired because of increased collagen VI levels in their microenvironment (Soret e al., 2015). Here, we describe the method that allowed us to demonstrate the cell-autonomous nature of this migration defect. In this system adapted from a previously described heterotopic grafting approach (Breau et al., 2006), the donor tissue is a fully colonized segment of e12.5 midgut while the host tissue is an aneural segment of e12.5 hindgut. Extent of ENCC migration in host tissue is assessed after 24 h of culture and is greatly facilitated when donor tissue has a transgenic background such as the Gata4-RFP (Pilon et al., 2008) that allows endogenous labeling of ENCCs with fluorescence. Depending of the genetic background of donor and host tissues, this approach can allow evaluating both cell-autonomous and non-cell-autonomous defects of ENCC migration. PMID:27642615

  9. 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.

  10. Effects of B-aminopropionitrile on mineralization during endochondral ossification in chick tibia.

    PubMed

    Sandhu, H S; Hing, A K

    1988-01-01

    Two-week-old white leghorn chicks were fed a diet containing BAPN (0.05%) for three weeks. Thirty-six hours before sacrifice, the controls and BAPN fed chicks were dosed with 35S. The zone of provisional calcification was isolated, and 35S incorporation was estimated by liquid scintillation counting. Alkaline phosphatase and Ca+2-ATPase were biochemically analyzed. Microdensitometry, to assess the level of mineralization, was done on epiphysis and the metaphysis. Morphometry was performed on the various zones of growth plate. 35S incorporation was significantly lower in the bones of BAPN treated chicks as compared to the controls. The enzymatic studies showed a significant inhibition of alkaline phosphatase and Ca+2-ATPase. The microdensitometric studies showed a smaller area of highly mineralized bone in the zones of provisional calcification of the BAPN treated chicks as compared to the controls. Morphometry showed a reduction in the width of the zone of calcification in BAPN treated chicks as compared to the controls. On the basis of the above data, it is suggested that BAPN induced inhibition of mineralization during endochondral ossification may be the result of a lower synthesis of sulfur containing GAG's, the inhibition of enzymes alkaline phosphatase and Ca+2-ATPase and the derangement of cellular zones of the growth plate. The implications of these results lie in the fact that mineralization is dependent on multifactorial control of the microenvironment of bone and cartilage.

  11. 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. PMID:25631789

  12. 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.

  13. 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

  14. 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.

  15. 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. PMID:27461718

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. The characteristic clinical symptoms of C-4 radiculopathy caused by ossification of the posterior longitudinal ligament.

    PubMed

    Katsumi, Keiichi; Yamazaki, Akiyoshi; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Endo, Naoto

    2014-05-01

    Cervical radiculopathy of the C2-4 spinal nerves is a rare condition and is poorly documented in terms of clinical symptoms, hindering its detection during initial patient screening based on imaging diagnostics. The authors describe in detail the clinical symptoms and successful surgical treatment of a patient diagnosed with isolated C-4 radiculopathy. This 41-year-old man suffered from sleep disturbance because of pain behind the right ear, along the right clavicle, and at the back of his neck on the right side. The Jackson and Spurling tests were positive, with pain radiating to the area behind the patient's ear. Unlike in cases of radiculopathy involving the C5-8 spinal nerves, no loss of upper-extremity motor function was seen. Magnetic resonance imaging showed foraminal stenosis at the C3-4 level on the right side, and multiplanar reconstruction CT revealed a beak-type ossification of the posterior longitudinal ligament in the foraminal region at the same level. In the absence of intracranial lesions or spinal cord compressive lesions, the positive Jackson and Spurling tests and the C3-4 foraminal stenosis were indicative of isolated C-4 radiculopathy. Microscopic foraminotomy was performed at the C3-4 vertebral level and the ossified lesion was resected. The patient's symptoms completely resolved immediately after surgery. To the authors' knowledge, this report is the first to describe the symptomatic features of isolated C-4 radiculopathy, in a case in which the diagnosis has been confirmed by both radiological findings and surgical outcome. Based on this case study, the authors conclude that the characteristic symptoms of C-4 radiculopathy are the presence of pain behind the ear and in the clavicular region in the absence of upper-limb involvement.

  1. Acquired Equivalence Changes Stimulus Representations

    ERIC Educational Resources Information Center

    Meeter, M.; Shohamy, D.; Myers, C. E.

    2009-01-01

    Acquired equivalence is a paradigm in which generalization is increased between two superficially dissimilar stimuli (or antecedents) that have previously been associated with similar outcomes (or consequents). Several possible mechanisms have been proposed, including changes in stimulus representations, either in the form of added associations or…

  2. 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

  3. Evaluation of age estimation in forensic medicine by examination of medial clavicular ossification from thin-slice computed tomography images.

    PubMed

    Gurses, Murat Serdar; Inanir, Nursel Turkmen; Gokalp, Gokhan; Fedakar, Recep; Tobcu, Eren; Ocakoglu, Gokhan

    2016-09-01

    Forensic age estimation, a recent topic of research in forensic medicine, is of primary importance to criminal and civil law. Previous studies indicate that the observation of medial clavicular ossification allows for age discrimination along the completed 18th and 21st years of life. Experts recommend that the Schmeling and Kellinghaus methods be used together. In this study, we used these staging methods to retrospectively analyze 725 case studies (385 males, 340 females) of thin-slice computed tomography (CT) images, ranging from 0.6 to 1 mm in thickness, from individuals aged 10 to 35 years. Stage 1 was found at 18 years of age maximum for males, whereas it was found at 17 years of age for females. Stage 2a was found at 18 years of age maximum for both genders. Stage 3c was initially observed at 18 years for both genders. Stage 4 was initially found at 21 years for males and 20 years for females. Stage 5 was initially observed at 25 years for both genders. Of note, stage 3c was found close to 19 years of age for both genders (18.92 years for male, 18.99 years for female), and it may be employed to differentiate along the age majority cutoff. The data obtained from our study were consistent with previous studies. We believe that such a comprehensive database will greatly contribute to future studies focusing on medial clavicular ossification based on thin-slice CT. Moreover, we also recommend that if medial clavicular ossification based on CT is to be examined for forensic age estimation, both methods should be employed together.

  4. 12 CFR 583.1 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly, ownership or control through an acquisition of shares, an acquisition of assets or assumption of...

  5. 12 CFR 583.1 - Acquire.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly, ownership or control through an acquisition of shares, an acquisition of assets or assumption of...

  6. 12 CFR 583.1 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly, ownership or control through an acquisition of shares, an acquisition of assets or assumption of...

  7. 12 CFR 583.1 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly, ownership or control through an acquisition of shares, an acquisition of assets or assumption of...

  8. 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

  9. 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. PMID:27207681

  10. 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.

  11. 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

  12. Acquired Aplastic Anemia in Children

    PubMed Central

    Hartung, Helge D.; Olson, Timothy S.; Bessler, Monica

    2013-01-01

    SYNOPSIS This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder. PMID:24237973

  13. Emotional attention in acquired prosopagnosia.

    PubMed

    Peelen, Marius V; Lucas, Nadia; Mayer, Eugene; Vuilleumier, Patrik

    2009-09-01

    The present study investigated whether emotionally expressive faces guide attention and modulate fMRI activity in fusiform gyrus in acquired prosopagnosia. Patient PS, a pure case of acquired prosopagnosia with intact right middle fusiform gyrus, performed two behavioral experiments and a functional imaging experiment to address these questions. In a visual search task involving face stimuli, PS was faster to select the target face when it was expressing fear or happiness as compared to when it was emotionally neutral. In a change detection task, PS detected significantly more changes when the changed face was fearful as compared to when it was neutral. Finally, an fMRI experiment showed enhanced activation to emotionally expressive faces and bodies in right fusiform gyrus. In addition, PS showed normal body-selective activation in right fusiform gyrus, partially overlapping the fusiform face area. Together these behavioral and neuroimaging results show that attention was preferentially allocated to emotional faces in patient PS, as observed in healthy subjects. We conclude that systems involved in the emotional guidance of attention by facial expression can function normally in acquired prosopagnosia, and can thus be dissociated from systems involved in face identification.

  14. Acquired causes of intestinal malabsorption.

    PubMed

    van der Heide, F

    2016-04-01

    This review focuses on the acquired causes, diagnosis, and treatment of intestinal malabsorption. Intestinal absorption is a complex process that depends on many variables, including the digestion of nutrients within the intestinal lumen, the absorptive surface of the small intestine, the membrane transport systems, and the epithelial absorptive enzymes. Acquired causes of malabsorption are classified by focussing on the three phases of digestion and absorption: 1) luminal/digestive phase, 2) mucosal/absorptive phase, and 3) transport phase. Most acquired diseases affect the luminal/digestive phase. These include short bowel syndrome, extensive small bowel inflammation, motility disorders, and deficiencies of digestive enzymes or bile salts. Diagnosis depends on symptoms, physical examination, and blood and stool tests. There is no gold standard for the diagnosis of malabsorption. Further testing should be based on the specific clinical context and the suspected underlying disease. Therapy is directed at nutritional support by enteral or parenteral feeding and screening for and supplementation of deficiencies in vitamins and minerals. Early enteral feeding is important for intestinal adaptation in short bowel syndrome. Medicinal treatment options for diarrhoea in malabsorption include loperamide, codeine, cholestyramine, or antibiotics. PMID:27086886

  15. Ossification of the Interosseous Membrane of the Leg in a Football Player: Case Report and Review of the Literature

    PubMed Central

    Postacchini, Roberto; Carbone, Stefano; Mastantuono, Marco; Della Rocca, Carlo; Postacchini, Franco

    2016-01-01

    Introduction. We report a case of ossification of the interosseous membrane (OIM) of the leg in a football player who had no history of severe local traumas. A review of the literature of the OIM of the leg in athletes was also carried out. Case Report. A 38-year-old Caucasian male patient complained of pain on lateral aspect of the leg when playing football. Pain progressively worsened until he had to stop the sporting activity. Radiographs, and then CT and MRI, showed OIM in the middle third of the left leg. MRI showed inflammation of tibia periosteum and bone adjacent to the ossification, which was then excised. Two months after surgery the patient returned to play football. Conclusion. A thorough analysis of the literature revealed three types of OIM of the leg in athletes. Type I usually occurs after a syndesmosis ankle sprain, Type II appears to result from a tibia fracture, and Type III, of which only one fully recorded case has been published, is probably caused, as in our patient, by repetitive minor traumas to the leg. Awareness of the existence of Type III OIM can avoid erroneous diagnoses leading to useless investigations and treatments. PMID:26881161

  16. Neural crest-specific loss of Prkar1a causes perinatal lethality resulting from defects in intramembranous ossification.

    PubMed

    Jones, Georgette N; Pringle, Daphne R; Yin, Zhirong; Carlton, Michelle M; Powell, Kimerly A; Weinstein, Michael B; Toribio, Ramiro E; La Perle, Krista M D; Kirschner, Lawrence S

    2010-08-01

    The cranial neural crest (CNC) undergoes complex molecular and morphological changes during embryogenesis in order to form the vertebrate skull, and nearly three quarters of all birth defects result from defects in craniofacial development. The molecular events leading to CNC differentiation have been extensively studied; however, the role of the cAMP-dependent protein kinase [protein kinase A (PKA)] during craniofacial development has only been described in palate formation. Here, we provide evidence that strict PKA regulation in postmigratory CNC cells is essential during craniofacial bone development. Selective inactivation of Prkar1a, a regulatory subunit of the PKA holoenzyme, in the CNC results in perinatal lethality caused by dysmorphic craniofacial development and subsequent asphyxiation. Additionally, aberrant differentiation of CNC mesenchymal cells results in anomalous intramembranous ossification characterized by formation of cartilaginous islands in some areas and osteolysis of bony trabeculae with fibrous connective tissue stabilization in others. Genetic interaction studies revealed that genetic reduction of the PKA catalytic subunit C(alpha) was able to rescue the phenotype, whereas reduction in Cbeta had no effect. Overall, these observations provide evidence of the essential role of proper regulation of PKA during the ossification of the bones of the skull. This knowledge may have implications for the understanding and treatment of craniofacial birth defects. PMID:20534695

  17. Dioscin stimulates differentiation of mesenchymal stem cells towards hypertrophic chondrocytes in vitro and endochondral ossification in vivo

    PubMed Central

    You, Murong; Jing, Juehua; Tian, Dasheng; Qian, Jun; Yu, Guangrong

    2016-01-01

    Dioscin has been shown to play important roles in suppression of osteoclast maturation. It is proposed as a potential natural product for the treatment of osteoclast-related diseases. We hypothesized in this study that treatment of dioscin on bone marrow mesenchymal stem cells (BMSCs) could increase the osteo-chondrogenic differentiation of BMSCs and promote endochondral ossification of BMSCs in bone fracture environment. BMSCs were extracted from femur and tibia of male C57b mice. Stemness of BMSCs was studied by performing proliferation assay and multilineage differentiation. Glycosaminoglycans (GAG) and collagen contents were assessed to examine the chondrogenesis of BMSCs. Real time quantitative PCR was carried out to examine the expression of hypertrophic marker collagen type X. Efficacy of Dioscin was then tested in mouse bone fracture model on the distal side of femur. Results showed treatment of dioscin on BMSCs increased chondrogenic differentiation of BMSCs as well as the expression of collagen type X. Local delivery of dioscin promoted endochondral ossification at bone fractured site, as shown by histological examination. Results of immunohistochemistry showed that dioscin increased collagen type X expression in bone facture model of mice. In conclusion, our results demonstrated that treatment of dioscin promote the hypertrophic differentiation of BMSCs derived chondrocytes. Dioscin could be a useful drug to promote bone regeneration after fracture. PMID:27725872

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

    PubMed Central

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

    2015-01-01

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

  19. Impaired neuronal migration and endochondral ossification in Pex7 knockout mice: a model for rhizomelic chondrodysplasia punctata.

    PubMed

    Brites, Pedro; Motley, Alison M; Gressens, Pierre; Mooyer, Petra A W; Ploegaert, Ingrid; Everts, Vincent; Evrard, Philippe; Carmeliet, Peter; Dewerchin, Mieke; Schoonjans, Luc; Duran, Marinus; Waterham, Hans R; Wanders, Ronald J A; Baes, Myriam

    2003-09-15

    Rhizomelic chondrodysplasia punctata is a human autosomal recessive disorder characterized by skeletal, eye and brain abnormalities. The disorder is caused by mutations in the PEX7 gene, which encodes the receptor for a class of peroxisomal matrix enzymes. We describe the generation and characterization of a Pex7 mouse knockout (Pex7(-/-)). Pex7(-/-) mice are born severely hypotonic and have a growth impairment. Mortality in Pex7(-/-) mice is highest in the perinatal period although some Pex7(-/-) mice survived beyond 18 months. Biochemically Pex7(-/-) mice display the abnormalities related to a Pex7 deficiency, i.e. a severe depletion of plasmalogens, impaired alpha-oxidation of phytanic acid and impaired beta-oxidation of very-long-chain fatty acids. In the intermediate zone of the developing cerebral cortex Pex7(-/-) mice have an increase in neuronal density. In vivo neuronal birthdating revealed that Pex7(-/-) mice have a delay in neuronal migration. Analysis of bone ossification in newborn Pex7(-/-) mice revealed a defect in ossification of distal bone elements of the limbs as well as parts of the skull and vertebrae. These findings demonstrate that Pex7 knockout mice provide an important model to study the role of peroxisomal functioning in the pathogenesis of the human disorder.

  20. [CHARACTERISTICS OF OSTEOCYTE CELL LINES FROM BONES FORMED AS A RESULT OF MEMBRANOUS (SKULL BONES) AND CHONDRAL (LONG BONES) OSSIFICATION].

    PubMed

    Avrunin, A S; Doktorov, A A

    2016-01-01

    The aim of this work was to analyze the literature data and the results of authors' own research, to answer the question--if the osteocytes of bone tissues resulting from membranous and chondral ossification, belong to one or to different cell lines. The differences between the cells of osteocyte lines derived from bones resulting from membranous and chondral ossification were established in: 1) the magnitude of the mechanical signal, initiating the development of the process of mechanotransduction; 2) the nature of the relationship between the magnitude of the mechanical signal that initiates the reorganization of the architecture of bone structures and the resource of their strength; in membranous bones significantly lower mechanical signal caused a substantially greater increment of bone strength resource; 3) the biological activity of bone structures, bone fragments formed from membranous tissue were more optimal for transplantation; 4) the characteristics of expression of functional markers of bone cells at different stages of their differentiation; 5) the nature of the reaction of bone cells to mechanical stress; 6) the sensitivity of bone cells to one of the factors controlling the process of mechanotransduction (PGI2); 7) the functioning of osteocytes during lactation. These differences reflect the functional requirements to the bones of the skeleton--the supporting function in the bones of the limbs and the shaping and protection in the bones of the cranial vault. These data suggest that the results of research conducted on the bones of the skull, should not be transferred to the entire skeleton as a whole.

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

    PubMed

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

    2015-11-16

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

  2. Iatrogenic Spinal Cord Injury during Removal of the Inferior Articular Process in the Presence of Ossification of the Ligamentum Flavum

    PubMed Central

    Burke, Shane M.; Hwang, Steven W.; Safain, Mina G.; Riesenburger, Ron I.

    2016-01-01

    Ossified ligamentum flavum (OLF) is a condition of heterotopic lamellar bone formation within the yellow ligament. Some patients with OLF can be asymptomatic. However, asymptomatic OLF may not be obvious on preoperative MRI and could increase the risk of iatrogenic injury during treatments for unrelated spinal conditions. This report describes a case of spinal cord injury caused by the indirect transmission of force from an osteotome to an asymptomatic OLF during the resection of a thoracic inferior articular process (IAP). To prevent this outcome, we urge careful review of CT imaging in the preoperative setting and advocate the use of a high-speed drill instead of an osteotome during bone removal in the setting of an adjacent area of OLF. PMID:26885431

  3. Acquired Hearing Loss in Children.

    PubMed

    Kenna, Margaret A

    2015-12-01

    Hearing loss is the most common congenital sensory impairment. According to National Health and Nutrition Examination Survey data from 2001 to 2008, 20.3% of subjects aged greater than or equal to 12 had unilateral or bilateral hearing loss. The World Health Organization notes that, worldwide, there are 360 million people with disabling hearing loss, with 50% preventable. Although many hearing losses are acquired, many others are manifestations of preexisting conditions. The purpose of a pediatric hearing evaluation is to identify the degree and type of hearing loss and etiology and to outline a comprehensive strategy that supports language and social development and communication.

  4. The inhibition of acquired fear.

    PubMed

    Izquierdo, Iván; Cammarota, Martín; Vianna, Mónica M R; Bevilaqua, Lía R M

    2004-01-01

    A conditioned stimulus (CS) associated with a fearsome unconditioned stimulus (US) generates learned fear. Acquired fear is at the root of a variety of mental disorders, among which phobias, generalized anxiety, the posttraumatic stress disorder (PTSD) and some forms of depression. The simplest way to inhibit learned fear is to extinguish it, which is usually done by repeatedly presenting the CS alone, so that a new association, CS-"no US", will eventually overcome the previously acquired CS-US association. Extinction was first described by Pavlov as a form of "internal inhibition" and was recommended by Freud and Ferenczi in the 1920s (who called it "habituation") as the treatment of choice for phobic disorders. It is used with success till this day, often in association with anxiolytic drugs. Extinction has since then been applied, also successfully and also often in association with anxiolytics, to the treatment of panic, generalized anxiety disorders and, more recently, PTSD. Extinction of learned fear involves gene expression, protein synthesis, N-methyl-D-aspartate (NMDA) receptors and signaling pathways in the hippocampus and the amygdala at the time of the first CS-no US association. It can be enhanced by increasing the exposure to the "no US" component at the time of behavioral testing, to the point of causing the complete uninstallment of the original fear response. Some theorists have recently proposed that reiteration of the CS alone may induce a reconsolidation of the learned behavior instead of its extinction. Reconsolidation would preserve the original memory from the labilization induced by its retrieval. If true, this would of course be disastrous for the psychotherapy of fear-motivated disorders. Here we show that neither the CS nor retrieval cause anything remotely like reconsolidation, but just extinction. In fact, our findings indicate that the reconsolidation hypothesis is essentially incorrect, at least for the form of contextual fear most

  5. Malaria acquired in Haiti - 2010.

    PubMed

    2010-03-01

    On January 12, 2010, a 7.0 magnitude earthquake struck Haiti, which borders the Dominican Republic on the island of Hispaniola. The earthquake's epicenter was 10 miles west of the Haiti capital city of Port-au-Prince (estimated population: 2 million). According to the Haitian government, approximately 200,000 persons were killed, and 500,000 were left homeless. Malaria caused by Plasmodium falciparum infection is endemic in Haiti, and the principal mosquito vector is Anopheles albimanus, which frequently bites outdoors. Thus, displaced persons living outdoors or in temporary shelters and thousands of emergency responders in Haiti are at substantial risk for malaria. During January 12-February 25, CDC received reports of 11 laboratory-confirmed cases of P. falciparum malaria acquired in Haiti. Patients included seven U.S. residents who were emergency responders, three Haitian residents, and one U.S. traveler. This report summarizes the 11 cases and provides chemoprophylactic and additional preventive recommendations to minimize the risk for acquiring malaria for persons traveling to Haiti.

  6. Intraductal papillary mucinous neoplasm of the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer: A case report

    PubMed Central

    Lee, Sang Hwa; Kim, Wook Youn; Hwang, Dae-Yong; Han, Hye Seung

    2015-01-01

    We report a case of intraductal papillary mucinous neoplasm (IPMN) originating from the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer (HNPCC). A 49-year-old woman had a past history of total colectomy and total hysterectomy with bilateral salpingo-oophorectomy due to colonic adenocarcinoma and endometrial adenocarcinoma 11 years ago. Her parents died from colonic adenocarcinoma and her sister died from colonic adenocarcinoma and endometrial adenocarcinoma. The clinician found an ileal mass with necrotic change and the mass increased in size from 1.7 cm to 2.2 cm during the past 2 years on computed tomography. It was surgically resected. Microscopically, the ileal mass showed heterotopic pancreas with IPMN high grade dysplasia. Immunohistochemical staining revealed positive reactivity for MLH1/PMS2 and negative reactivity for MSH2/MSH6. This is the first report of IPMN originating from the ileal heterotopic pancreas in a patient with HNPCC in the English literature. PMID:26167093

  7. 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.

  8. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Statements of Smaller Reporting Companies § 210.8-06 Real estate operations acquired or to be acquired. If, during the period for which income statements are required, the smaller reporting company has acquired... acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES...

  9. Heterochronic shifts in the ossification sequences of surface- and subsurface-dwelling skinks are correlated with the degree of limb reduction.

    PubMed

    Hugi, Jasmina; Hutchinson, Mark N; Koyabu, D; Sánchez-Villagra, Marcelo R

    2012-06-01

    Scincid lizards exhibit a variety of limb anatomies which reflect the functional requirements of different modes of life. Besides surface dwellers which show neither body elongation nor limb reduction, there are numerous examples that can be arranged as increasingly serpentiform taxa moving in sand, humus or leaf litter. We explored the question of whether limb reduction and body elongation in skinks are linked to heterochronic shifts in the ossification sequences. The study material comprises skinks showing four different morphotypes: Liopholis whitii, Lerista bougainvillii, Hemiergis peronii and Saiphos equalis. Results showed that (i) scincid lizards with limb reductions exhibit an earlier onset of ossification in the cervical vertebrae, and (ii) ossification starts earlier in the pectoral girdle (scapula and coracoid) and pelvic girdle (ilium, ischium and pubis) relative to the timing of the onset in elements of the forelimbs and hind limbs. Furthermore, they show (iii) an earlier strengthening of the premaxilla, which first completes the anterior part of the dorsal cranial roof, and (iv) an earlier onset of ossification in the forelimb elements than in the equivalent elements of the hind limbs. The species showing the least limb reduction (L. bougainvillii) had the greatest developmental similarity to the normally proportioned surface-dwelling species (L. whitii). S. equalis, as the morphotype with the greatest deviation from the normally proportioned, pentadactyle form, varies the most from L. whitii. The heterochronic shifts in the ossification sequences are linked to a shift in the emphasis from limbed locomotion to trunk locomotion in the species with body elongation and/or limb reduction. PMID:22502802

  10. Lymphoma in acquired generalized lipodystrophy.

    PubMed

    Brown, Rebecca J; Chan, Jean L; Jaffe, Elaine S; Cochran, Elaine; DePaoli, Alex M; Gautier, Jean-Francois; Goujard, Cecile; Vigouroux, Corinne; Gorden, Phillip

    2016-01-01

    Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression.

  11. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  12. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  13. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  14. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  15. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

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

    PubMed Central

    Epstein, Nancy E.

    2014-01-01

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

  17. [CHARACTERISTICS OF OSTEOCYTE CELL LINES FROM BONES FORMED AS A RESULT OF MEMBRANOUS (SKULL BONES) AND CHONDRAL (LONG BONES) OSSIFICATION].

    PubMed

    Avrunin, A S; Doktorov, A A

    2016-01-01

    The aim of this work was to analyze the literature data and the results of authors' own research, to answer the question--if the osteocytes of bone tissues resulting from membranous and chondral ossification, belong to one or to different cell lines. The differences between the cells of osteocyte lines derived from bones resulting from membranous and chondral ossification were established in: 1) the magnitude of the mechanical signal, initiating the development of the process of mechanotransduction; 2) the nature of the relationship between the magnitude of the mechanical signal that initiates the reorganization of the architecture of bone structures and the resource of their strength; in membranous bones significantly lower mechanical signal caused a substantially greater increment of bone strength resource; 3) the biological activity of bone structures, bone fragments formed from membranous tissue were more optimal for transplantation; 4) the characteristics of expression of functional markers of bone cells at different stages of their differentiation; 5) the nature of the reaction of bone cells to mechanical stress; 6) the sensitivity of bone cells to one of the factors controlling the process of mechanotransduction (PGI2); 7) the functioning of osteocytes during lactation. These differences reflect the functional requirements to the bones of the skeleton--the supporting function in the bones of the limbs and the shaping and protection in the bones of the cranial vault. These data suggest that the results of research conducted on the bones of the skull, should not be transferred to the entire skeleton as a whole. PMID:27487656

  18. 12 CFR 583.1 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly, ownership or control through an acquisition of shares, an acquisition of assets or assumption of liabilities, a merger or consolidation, or any similar transaction....

  19. Associative Learning Through Acquired Salience.

    PubMed

    Treviño, Mario

    2015-01-01

    Most associative learning studies describe the salience of stimuli as a fixed learning-rate parameter. Presumptive saliency signals, however, have also been linked to motivational and attentional processes. An interesting possibility, therefore, is that discriminative stimuli could also acquire salience as they become powerful predictors of outcomes. To explore this idea, we first characterized and extracted the learning curves from mice trained with discriminative images offering varying degrees of structural similarity. Next, we fitted a linear model of associative learning coupled to a series of mathematical representations for stimulus salience. We found that the best prediction, from the set of tested models, was one in which the visual salience depended on stimulus similarity and a non-linear function of the associative strength. Therefore, these analytic results support the idea that the net salience of a stimulus depends both on the items' effective salience and the motivational state of the subject that learns about it. Moreover, this dual salience model can explain why learning about a stimulus not only depends on the effective salience during acquisition but also on the specific learning trajectory that was used to reach this state. Our mathematical description could be instrumental for understanding aberrant salience acquisition under stressful situations and in neuropsychiatric disorders like schizophrenia, obsessive-compulsive disorder, and addiction.

  20. Infections Acquired in the Garden.

    PubMed

    Cunha, Cheston B; Cunha, Burke A

    2015-10-01

    Gardening is a wonderful pastime, and the garden is a very peaceful place to enjoy one's vacation. However, the garden may be a treacherous place for very young or compromised hosts when one takes into account the infectious potential residing in the soil, as well as the insect vectors on plants and animals. Even normal hosts may acquire a variety of infections from the soil, animals, or animal-related insect bites. The location of the garden, its natural animal and insect inhabitants, and the characteristics of the soil play a part in determining its infectious potential. The most important factor making the garden an infectious and dangerous place is the number and interaction of animals, whether they are pets or wild, that temporarily use the garden for part of their daily activities. The clinician should always ask about garden exposure, which will help in eliminating the diagnostic possibilities for the patient. The diagnostic approach is to use epidemiological principles in concert with clinical clues, which together should suggest a reasonable list of diagnostic possibilities. Organ involvement and specific laboratory tests help further narrow the differential diagnosis and determine the specific tests necessary to make a definitive diagnosis. PMID:26542044

  1. Inherited or acquired metabolic disorders.

    PubMed

    Eichler, Florian; Ratai, Eva; Carroll, Jason J; Masdeu, Joseph C

    2016-01-01

    This chapter starts with a description of imaging of inherited metabolic disorders, followed by a discussion on imaging of acquired toxic-metabolic disorders of the adult brain. Neuroimaging is crucial for the diagnosis and management of a number of inherited metabolic disorders. Among these, inherited white-matter disorders commonly affect both the nervous system and endocrine organs. Magnetic resonance imaging (MRI) has enabled new classifications of these disorders that have greatly enhanced both our diagnostic ability and our understanding of these complex disorders. Beyond the classic leukodystrophies, we are increasingly recognizing new hereditary leukoencephalopathies such as the hypomyelinating disorders. Conventional imaging can be unrevealing in some metabolic disorders, but proton magnetic resonance spectroscopy (MRS) may be able to directly visualize the metabolic abnormality in certain disorders. Hence, neuroimaging can enhance our understanding of pathogenesis, even in the absence of a pathologic specimen. This review aims to present pathognomonic brain MRI lesion patterns, the diagnostic capacity of proton MRS, and information from clinical and laboratory testing that can aid diagnosis. We demonstrate that applying an advanced neuroimaging approach enhances current diagnostics and management. Additional information on inherited and metabolic disorders of the brain can be found in Chapter 63 in the second volume of this series. PMID:27432685

  2. Infections Acquired in the Garden.

    PubMed

    Cunha, Cheston B; Cunha, Burke A

    2015-10-01

    Gardening is a wonderful pastime, and the garden is a very peaceful place to enjoy one's vacation. However, the garden may be a treacherous place for very young or compromised hosts when one takes into account the infectious potential residing in the soil, as well as the insect vectors on plants and animals. Even normal hosts may acquire a variety of infections from the soil, animals, or animal-related insect bites. The location of the garden, its natural animal and insect inhabitants, and the characteristics of the soil play a part in determining its infectious potential. The most important factor making the garden an infectious and dangerous place is the number and interaction of animals, whether they are pets or wild, that temporarily use the garden for part of their daily activities. The clinician should always ask about garden exposure, which will help in eliminating the diagnostic possibilities for the patient. The diagnostic approach is to use epidemiological principles in concert with clinical clues, which together should suggest a reasonable list of diagnostic possibilities. Organ involvement and specific laboratory tests help further narrow the differential diagnosis and determine the specific tests necessary to make a definitive diagnosis.

  3. Associative Learning Through Acquired Salience

    PubMed Central

    Treviño, Mario

    2016-01-01

    Most associative learning studies describe the salience of stimuli as a fixed learning-rate parameter. Presumptive saliency signals, however, have also been linked to motivational and attentional processes. An interesting possibility, therefore, is that discriminative stimuli could also acquire salience as they become powerful predictors of outcomes. To explore this idea, we first characterized and extracted the learning curves from mice trained with discriminative images offering varying degrees of structural similarity. Next, we fitted a linear model of associative learning coupled to a series of mathematical representations for stimulus salience. We found that the best prediction, from the set of tested models, was one in which the visual salience depended on stimulus similarity and a non-linear function of the associative strength. Therefore, these analytic results support the idea that the net salience of a stimulus depends both on the items' effective salience and the motivational state of the subject that learns about it. Moreover, this dual salience model can explain why learning about a stimulus not only depends on the effective salience during acquisition but also on the specific learning trajectory that was used to reach this state. Our mathematical description could be instrumental for understanding aberrant salience acquisition under stressful situations and in neuropsychiatric disorders like schizophrenia, obsessive-compulsive disorder, and addiction. PMID:26793078

  4. Associative Learning Through Acquired Salience.

    PubMed

    Treviño, Mario

    2015-01-01

    Most associative learning studies describe the salience of stimuli as a fixed learning-rate parameter. Presumptive saliency signals, however, have also been linked to motivational and attentional processes. An interesting possibility, therefore, is that discriminative stimuli could also acquire salience as they become powerful predictors of outcomes. To explore this idea, we first characterized and extracted the learning curves from mice trained with discriminative images offering varying degrees of structural similarity. Next, we fitted a linear model of associative learning coupled to a series of mathematical representations for stimulus salience. We found that the best prediction, from the set of tested models, was one in which the visual salience depended on stimulus similarity and a non-linear function of the associative strength. Therefore, these analytic results support the idea that the net salience of a stimulus depends both on the items' effective salience and the motivational state of the subject that learns about it. Moreover, this dual salience model can explain why learning about a stimulus not only depends on the effective salience during acquisition but also on the specific learning trajectory that was used to reach this state. Our mathematical description could be instrumental for understanding aberrant salience acquisition under stressful situations and in neuropsychiatric disorders like schizophrenia, obsessive-compulsive disorder, and addiction. PMID:26793078

  5. HETEROTOPICALLY TRANSPLANTED CVO NEURAL STEM CELLS GENERATE NEURONS AND MIGRATE WITH SVZ CELLS IN THE ADULT MOUSE BRAIN

    PubMed Central

    Bennett, Lori B.; Cai, Jingli; Enikolopov, Grigori; Iacovitti, Lorraine

    2010-01-01

    Production of new neurons throughout adulthood has been well characterized in two brain regions, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus. The neurons produced from these regions arise from neural stem cells (NSCs) found in highly regulated stem cell niches. We recently showed that midline structures called circumventricular organs (CVOs) also contain NSCs capable of neurogenesis and/or astrogliogenesis in vitro and in situ [3]. The present study demonstrates that NSCs derived from two astrogliogenic CVOs, the median eminence and organum vasculosum of the lamina terminalis of the Nestin-GFP mouse, possess the potential to integrate into the SVZ and differentiate into cells with a neuronal phenotype. These NSCs, following expansion and BrdU-labeling in culture and heterotopic transplantation into a region proximal to the SVZ in adult mice, migrate caudally to the SVZ and express early neuronal markers (TUC-4, PSA-NCAM) as they migrate along the rostral migratory stream. CVO-derived BrdU+ cells ultimately reach the olfactory bulb where they express early (PSA-NCAM) and mature (NeuN) neuronal markers. Collectively, these data suggest that although NSCs derived from the ME and OVLT CVOs are astrogliogenic in situ, they produce cells phenotypic of neurons in vivo when placed in a neurogenic environment. These findings may have implications for neural repair in the adult brain. PMID:20298755

  6. Non-viral human IL-10 gene expression reduces acute rejection in heterotopic auxiliary liver transplantation in rats.

    PubMed

    Hong, In Chul; Mullen, Patricia M; Precht, Andrew F; Khanna, Ajai; Li, Melissa; Behling, Cynthia; Lopez, Valerie F; Chiou, Henry C; Moss, Ronald B; Hart, Marquis E

    2003-01-01

    We studied nonviral delivery, expression, and the effect of the human interleukin-10 (Hu IL-10) gene on the rat model of heterotopic auxiliary liver transplantation (HALT). Two previous pilot studies showed remarkable expression of the Hu IL-10 gene in donor and recipient rats, and a decreasing effect of acute rejection in certain cases. In this study, we focused on the efficacy of Hu IL-10 gene expression to decrease acute rejection compared with cyclosporine A (CyA) in a HALT model. Three study groups and one control group were designed. Each group consisted of 6 DA donor and 6 Lewis recipient rats, which underwent HALT. In the control group, donors and recipients were not treated at all. In group II, recipients were treated with one dose of CyA. In group III, donors were treated with Hu IL-10 plasmid. In group IV, donors were treated with Hu IL-10 plasmid, and recipients were treated with one dose of CyA. Rejection was established by histopathology: it revealed 100% rejection in control and 33.3% rejection in study groups II, III, and IV. Human IL-10 gene expression prevented acute rejection with the same efficacy as CyA in the HALT model in rats.

  7. Two novel RFX6 variants in siblings with Mitchell-Riley syndrome with later diabetes onset and heterotopic gastric mucosa.

    PubMed

    Skopkova, Martina; Ciljakova, Miriam; Havlicekova, Zuzana; Vojtkova, Jarmila; Valentinova, Lucia; Danis, Daniel; Murgas, Dalibor; Szepeova, Renata; Stanik, Juraj; Banovcin, Peter; Klimes, Iwar; Gasperikova, Daniela

    2016-09-01

    Mitchell-Riley syndrome, an autosomal recessive disorder caused by mutations in the RFX6 gene, is defined as a combination of neonatal diabetes mellitus and serious congenital gastrointestinal defects. We describe Mitchell-Riley syndrome in two sisters with two novel compound heterozygous variants in the RFX6 gene: c.1154G > A, p.(Arg385Gln), and c.1316_1319delTCTA, p.(Ile439Thrfs*13). Both sisters present milder forms of the syndrome, likely due to possible residual activity of the p.Arg385Gln variant, which is localized in a dimerization domain of the RFX6 transcription factor. We propose that the prognosis is dependent on patient RFX6 genotype and possible residual activity of RFX6 transcription factor. Both sisters had atypical later onset of diabetes, at 2 years and 10 months and 2 years and 7 months, respectively. This supports the need of extending the definition of diabetes in Mitchell-Riley syndrome from neonatal to childhood onset and regular glyceamia check in patients with gastrointestinal tract malformations typical for Mitchell-Riley syndrome. The clinical course in both sisters improved significantly after surgical removal of parts of the small intestine with heterotopic gastric mucosa. We suggest that gastric mucosa heterotopy is an important actionable part of Mitchell-Riley syndrome and could have been responsible for the malabsorption, failure to thrive and severe anemia present in previously reported patients with Mitchell-Riley syndrome. PMID:27523286

  8. Heterotopic implantation of autologous bone marrow in rock pigeons (Columba livia): possible applications in avian bone grafting.

    PubMed

    Sanaei, M Reza; Abu, Jalila; Nazari, Mojgan; Faiz, Nik Mohd; Bakar, Mohd Zuki Abu; Allaudin, Zeenathul N

    2011-12-01

    Autologous bone marrow, alone or as a composite marrow graft, has received much attention in various species. To assess the potential osteogenicity of autologous, extramedullary bone marrow implants in an avian model, 24 adult pigeons (Columba livia) were given intramuscular implantations of autologous marrow aspirated from the medial tibiotarsus. Birds were euthanatized at 1, 4, 6, 8, 10, and 12 weeks after surgery to evaluate whether ectopic bone had formed at the implant sites. Primary evaluations by in situ radiography and postmortem histologic examinations showed no evidence of bone formation. Further evaluation with histologic scores and histomorphometry revealed a significantly increased rate of angiogenesis at the implant sites by the sixth and tenth week postimplantation (P < .05). No significant differences between the treatment and control sites were present at any other endpoints. Results of this study show that, although autologous bone marrow lacks heterotopic osteogenic potentials in this avian model, it could still function as a useful adjunct to routine bone grafting techniques because of its unique capabilities to promote early angiogenesis. PMID:22458179

  9. Clinicopathological associations of acquired erythroblastopenia

    PubMed Central

    Gunes, Gursel; Malkan, Umit Yavuz; Yasar, Hatime Arzu; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin; Demiroglu, Haluk; Sayinalp, Nilgun; Aksu, Salih; Etgul, Sezgin; Aslan, Tuncay; Goker, Hakan; Ozcebe, Osman Ilhami; Buyukasik, Yahya

    2015-01-01

    Introduction: Acquired erythroblastopenia (AE) is a rare clinical situation. It is characterized by the reduction of erythroid precursors in the bone marrow together with the low reticulocyte counts in the peripheral blood. Background: Main secondary causes of AE are drugs, Parvovirus B19 and other infectious reasons, lymphoid and myeloid neoplasia, autoimmune diseases, thymoma and pregnancy. The aim of this study is to assess the frequencies and clinical associations of AE via analyzing 12340 bone marrow samples in a retrospective manner. Material and method: Bone marrow aspirations which were obtained from patients who applied to Hacettepe University Hematology Clinic between 2002 and 2013, were analyzed retrospectively. Results: Thirty four erythroblastopenia cases were found. Patients ranged in age from 16 to 80 years with a median of 38 years. Fifteen patients were men (44%) and nineteen were women (56%). In these patients, detected causes of erythroblastopenia were MDS, idiopathic pure red cell aplasia (PRCA), parvovirus infection, post chemotherapy aplasia, plasma proliferative diseases, copper deficiency due to secondary amyloidosis, fever of unknown origin, hemophagocytic syndrome, enteric fever and legionella pneumonia. We found that between those reasons the most common causes of erythroblastopenia are MDS (17.7%) and idiopathic PRCA (17.7%). Discussion: As a result, erythroblastopenia in the bone marrow may be an early sign of MDS. In those AE cases possibility of being MDS must be kept in mind as it can be mistaken for PRCA. Conclusion: To conclude, in adults MDS without excess blast is one of the most common causes of erythroblastopenia in clinical practice and in case of erythroblastopenia the presence of MDS should be investigated. PMID:26885236

  10. Hand development and sequence of ossification in the forelimb of the European shrew Crocidura russula (Soricidae) and comparisons across therian mammals.

    PubMed

    Prochel, Jan; Vogel, Peter; Sánchez-Villagra, Marcelo R

    2004-08-01

    Hand development in the European shrew Crocidura russula is described, based on the examination of a cleared and double-stained ontogenetic series and histological sections of a c. 20-day-old embryo and a neonate. In the embryo all carpal elements are still mesenchymal condensations, and there are three more elements than in the adult stage: the 'lunatum', which fuses with the scaphoid around birth; a centrale, which either fuses with another carpal element or just disappears later in ontogeny; and the anlage of an element that later fuses with the radius. Carpal arrangement in the neonate and the adult is the same. In order to compare the relative timing of the onset of ossification in forelimb bones in C. russula with that of other therians, we built up two matrices of events based on two sets of data and used the event-pair method. In the first analysis, ossification of forelimb elements in general was examined, including that of the humerus, radius, ulna, the first carpal and metacarpal to ossify, and the phalanges of the third digit. The second analysis included each carpal, humerus, radius, ulna, the first metacarpal and the first phalanx to ossify. Some characters (= event-pairs) provide synapomorphies for some clades examined. There have been some shifts in the timing of ossification apparently not caused by ecological and/or environmental influences. In two species (Oryctolagus and Myotis), there is a tendency to start the ossification of the carpals relatively earlier than in all other species examined, the sauropsid outgroups included. PMID:15291793

  11. Ossification of the posterior longitudinal ligament in three geographically and genetically different populations of ankylosing spondylitis and other spondyloarthropathies

    PubMed Central

    Ramos-Remus, C.; Russell, A.; Gomez-Vargas, A.; Hernandez-Chavez, A.; Maksymowych, W.; Gamez-Nava, J.; Gonzalez-Lopez, L.; Garcia-Hernandez, A.; Meono-Morales, E.; Burgos-Vargas, R.; Suarez-Almazor, M.

    1998-01-01

    STUDY DESIGN—Cross sectional.
RESEARCH QUESTIONS—(a) Is any clinical variable of ankylosing spondylitis (AS) associated with the presence of ossification of the posterior longitudinal ligament (OPLL)? and (b) Is OPLL present in patients with AS from different geographical or genetic backgrounds?
METHODS—Three groups were assembled: (1) a prospective group of 103 consecutive AS patients from two community based rheumatology clinics from Guadalajara, who were evaluated using: a questionnaire with disease characteristic variables; clinical assessment by a neurologist; lateral radiographic views of the cervical spine and somatosensory evoked potentials (SSEP). (2) Fifty one spondyloarthropathies (SpA) patients from Mexico city whose cervical spine films were retrospectively reviewed. (3) Thirty nine AS patients from Edmonton, Canada whose cervical spine films were retrospectively reviewed and compared with 72 controls.
RESULTS—Group 1: 74% of the 103 patients were men and 86% were HLA-B27 positive. The mean age was 35 years, and mean (SD) disease duration 10 (8) years. OPLL was reported in 16 patients (15.5%; 95%C I 9, 22). OPLL was statistically associated with older age (p=0.001), longer disease duration (p=0.001), clinical myelopathy (p=0.03), worst functional index (p=0.042), restricted axial movement measurements (all p<0.001), radiological sacroiliitis (p<0.001 for linear association), osteitis pubis (p=0.009), hip involvement (p=0.006 for linear association), and abnormal SSEP (p=0.008). Group 2: 92% of 51 patients were men; the mean age was 30 years and the mean (SD) disease duration 11 (7) years. OPLL was reported in 15 (29%, 95%CI 17, 41) patients (nine AS, two psoriatic arthritis, three juvenile AS, and one Reiter's syndrome). Group 3: 95% of the 39 patients were men; the mean of age was 46 years and disease duration of 18 (10) years. OPLL was reported in nine (23%; 95%CI 10, 36) patients, including one with psoriatic arthritis

  12. Reliability of Schmeling's stages of ossification of medial clavicular epiphyses and its validity to assess 18 years of age in living subjects.

    PubMed

    Cameriere, R; De Luca, S; De Angelis, D; Merelli, V; Giuliodori, A; Cingolani, M; Cattaneo, C; Ferrante, L

    2012-11-01

    Nowadays, due to the global increase in migration movements, forensic age estimation of living young adults has become an important focus of interest. Minors often have no identification documents providing their correct birth dates. Establishing the age of majority is therefore fundamental in order to determine whether juvenile penal systems or penal systems in force for adults are to be applied. Radiological examination of the clavicles is one of the methods recommended by the Study Group on Forensic Age Diagnostics. In this retrospective study, a sample of chest radiographs of 274 subjects, aged between 12 and 25 years, was studied according to Schmeling's method in order to examine the ossification of both medial clavicular epiphyses. All stage classifications were evaluated by five examiners. Intra- and inter-examiner reliability was analysed by Cohen's K statistic. Intra-examiner agreement was insufficient for two of the experts. Inter-examiner agreement, among the other three operators, was moderate (K = 0.509). Study of reliability highlighted difficulties in interpretation, the need to select qualified personnel and choice of the best radiographic image in order to reduce any anatomic overlaps. Although ossification of the medial clavicular epiphyses is recommended to assess whether an individual has already reached the age of majority or not, these results suggested that it is very difficult to clearly identify the five stages of ossification by using conventional chest radiography.

  13. A new simplified volume-loaded heterotopic rabbit heart transplant model with improved techniques and a standard operating procedure

    PubMed Central

    Lu, Wei; Zheng, Jun; Pan, Xu-Dong; Li, Bing; Zhang, Jin-Wei; Wang, Long-Fei

    2015-01-01

    Background The classic non-working (NW) heterotopic heart transplant (HTX) model in rodents had been widely used for researches related to immunology, graft rejection, evaluation of immunosuppressive therapies and organ preservation. But unloaded models are considered not suitable for some researches. Accordingly, We have constructed a volume-loaded (VL) model by a new and simple technique. Methods Thirty male New Zealand White rabbits were randomly divided into two groups, group NW with 14 rabbits and group VL with 16 rabbits, which served as donors and recipients. We created a large and nonrestrictive shunt to provide left heart a sufficient preload. The donor superior vena cave and ascending aorta (AO) were anastomosed to the recipient abdominal aorta (AAO) and inferior vena cava (IVC), respectively. Results No animals suffered from paralysis, pneumonia and lethal bleeding. Recipients’ mortality and morbidity were 6.7% (1/15) and 13.3% (2/15), respectively. The cold ischemia time in group VL is slight longer than that in group NW. The maximal aortic velocity (MAV) of donor heart was approximately equivalent to half that of native heart in group VL. Moreover, the similar result was achieved in the parameter of late diastolic mitral inflow velocity between donor heart and native heart in group VL. The echocardiography (ECHO) showed a bidirectional flow in donor SVC of VL model, inflow during diastole and outflow during systole. PET-CT imaging showed the standard uptake value (SUV) of allograft was equal to that of native heart in both groups on the postoperative day 3. Conclusions We have developed a new VL model in rabbits, which imitates a native heart hemodynamically while only requiring a minor additional procedure. Surgical technique is simple compared with currently used HTX models. We also developed a standard operating procedure that significantly improved graft and recipient survival rate. This study may be useful for investigations in transplantation

  14. The effect of heterotopic noxious conditioning stimulation on Aδ-, C- and Aβ-fibre brain responses in humans.

    PubMed

    Torta, Diana M; Churyukanov, Maxim V; Plaghki, Leon; Mouraux, André

    2015-11-01

    Human studies have shown that heterotopic nociceptive conditioning stimulation (HNCS) applied to a given body location reduces the percept and brain responses elicited by noxious test stimuli delivered at a remote body location. It remains unclear to what extent this effect of HNCS relies on the spinal-bulbar-spinal loop mediating the effect of diffuse noxious inhibitory controls (DNICs) described in animals, and/or on top-down cortical mechanisms modulating nociception. Importantly, some studies have examined the effects of HNCS on the brain responses to nociceptive input conveyed by Aδ-fibres. In contrast, no studies have explored the effects of HNCS on the responses to selective nociceptive C-fibre input and non-nociceptive Aβ-fibre input. In this study, we measured the intensity of perception and event-related potentials (ERPs) to stimuli activating Aδ-, C- and Aβ-fibres, before, during and after HNCS, obtained by immersing one foot in painful cold water. We observed that (i) the perceived intensity of nociceptive Aδ- and C-stimuli was reduced during HNCS, and (ii) the ERPs elicited by Aδ- and Aβ- and C-stimuli were also reduced during HNCS. Importantly, because Aβ-ERPs are related to primary afferents that ascend directly through the dorsal columns without being relayed at spinal level, the modulation of these responses may not be explained by an influence of descending projections modulating the transmission of nociceptive input at spinal level. Therefore, our results indicate that, in humans, HNCS should be used with caution as a direct measure of DNIC-related mechanisms. PMID:26369522

  15. Fast-track surgery and exclusive enteral nutrition applied to a rat model of heterotopic intestinal transplantation

    PubMed Central

    XU, XINGWEI; FENG, TAO; GAO, XIN; ZHAO, XIN; LIAO, YANNIAN; JI, WU

    2016-01-01

    The present study applied fast-track surgery (FTS) concepts and exclusive enteral nutrition (EEN) to a rat model of heterotopic intestinal transplantation (HIT). A total of 96 pairs of Sprague-Dawley rats were randomly distributed into three groups, as follows: i) The conventional group (group 1); ii) the FTS group (group 2); and iii) the FTS with EEN group (EEN group). FTS alterations to the HIT protocol were as follows: i) The use of sevoflurane as an anesthetic; ii) alterations to the order of the procedure and iii) a modified suturing technique. In addition, the EEN group rats underwent an early EEN gavage. The operation time, success rate, recovery state and morphological characteristics of the grafts were compared among the groups. The average operative time was significantly decreased in the group 2 and EEN group rats (137.44±16.03 and 139.67±15.25 min, respectively), as compared with the group 1 rats (169.36±13.72 min; P<0.05). In addition, the percentage of rats surviving >14 days was significantly increased in the group 2 (87.5%) and EEN group (90.6%) rats, as compared with the group 1 rats (68.7%; P<0.05). Furthermore, the villi of graft in EEN group appeared longer, and exhibited narrower interspaces. The ischemia-reperfusion injury and mononuclear cell infiltration were attenuated at postoperative day 7. The results of the present study suggested that the application of FTS concepts and EEN gavage to HIT may accelerate recovery and ameliorate graft damage following surgery. PMID:26998015

  16. The Role of Lysophosphatidic Acid on Airway Epithelial Cell Denudation in a Murine Heterotopic Tracheal Transplant Model

    PubMed Central

    Tando, Yukiko; Ota, Chiharu; Yamada, Mitsuhiro; Kamata, Satoshi; Yamaya, Mutsuo; Kano, Kuniyuki; Okudaira, Shinichi; Aoki, Junken; Kubo, Hiroshi

    2015-01-01

    Background Chronic rejection is the major leading cause of morbidity and mortality after lung transplantation. Obliterative bronchiolitis (OB), a fibroproliferative disorder of the small airways, is the main manifestation of chronic lung allograft rejection. However, there is currently no treatment for the disease. We hypothesized that lysophosphatidic acid (LPA) participates in the progression of OB. The aim of this study was to reveal the involvement of LPA on the lesion of OB. Methods Ki16198, an antagonist specifically for LPA1 and LPA3, was daily administered into the heterotopic tracheal transplant model mice at the day of transplantation. At days 10 and 28, the allografts were isolated and evaluated histologically. The messenger RNA levels of LPAR in microdissected mouse airway regions were assessed to reveal localization of lysophosphatidic acid receptors. The human airway epithelial cell was used to evaluate the mechanism of LPA-induced suppression of cell adhesion to the extracellular matrix (ECM). Results The administration of Ki16198 attenuated airway epithelial cell loss in the allograft at day 10. Messenger RNAs of LPA1 and LPA3 were detected in the airway epithelial cells of the mice. Lysophosphatidic acid inhibited the attachment of human airway epithelial cells to the ECM and induced cell detachment from the ECM, which was mediated by LPA1 and Rho-kinase pathway. However, Ki16198 did not prevent obliteration of allograft at day 28. Conclusions The LPA signaling is involved in the status of epithelial cells by distinct contribution in 2 different phases of the OB lesion. This finding suggests a role of LPA in the pathogenesis of OB. PMID:27500235

  17. Inhibitory effects of heterotopic noxious counter-stimulation on perception and brain activity related to Aβ-fibre activation.

    PubMed

    Rustamov, Nabi; Tessier, Jessica; Provencher, Benjamin; Lehmann, Alexandre; Piché, Mathieu

    2016-07-01

    Heterotopic noxious counter-stimulation (HNCS) inhibits pain and pain processes through cerebral and cerebrospinal mechanisms. However, it is unclear whether HNCS inhibits non-nociceptive processes, which needs to be clarified for a better understanding of HNCS analgesia. The aim of this study was to examine the effects of HNCS on perception and scalp somatosensory evoked potentials (SEPs). Seventeen healthy volunteers participated in two counter-balanced sessions, including non-nociceptive (selective Aβ-fibre activation) or nociceptive electrical stimulation, combined with HNCS. HNCS was produced by a 20-min cold pressor test (left hand) adjusted individually to produce moderate pain (mean ± SEM: 42.5 ± 5.3 on a 0-100 scale, where 0 is no pain and 100 the worst pain imaginable). Non-nociceptive electrical stimulation was adjusted individually at 80% of pain threshold and produced a tactile sensation in every subject. Nociceptive electrical stimulation was adjusted individually at 120% of RIII-reflex threshold and produced moderate pain (45.3 ± 4.5). Shock sensation was significantly decreased by HNCS compared with baseline for non-nociceptive (P < 0.001) and nociceptive (P < 0.001) stimulation. SEP peak-to-peak amplitude at Cz was significantly decreased by HNCS for non-nociceptive (P < 0.01) and nociceptive (P < 0.05) stimulation. These results indicate that perception and brain activity related to Aβ-fibre activation are inhibited by HNCS. The mechanisms of this effect remain to be investigated to clarify whether it involves inhibition of spinal wide-dynamic-range neurons by diffuse noxious inhibitory controls, supraspinal processes or both. PMID:27086672

  18. Acquired Surface Dyslexia: The Evidence from Hebrew.

    ERIC Educational Resources Information Center

    Birnboim, Smadar

    1995-01-01

    Investigates the symptoms of acquired surface dyslexia in Hebrew. Four acquired surface dyslexic adults were compared with eight normal second graders in terms of reading strategy. Homophones and homographs were a major source of difficulty for native Hebrew surface dyslexic readers; the normal second graders used a non-lexical strategy. (45…

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-02-01

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

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

    USGS Publications Warehouse

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

    1991-01-01

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

  2. Bone regeneration in a massive rat femur defect through endochondral ossification achieved with chondrogenically differentiated MSCs in a degradable scaffold.

    PubMed

    Harada, Noriko; Watanabe, Yoshinobu; Sato, Kenji; Abe, Satoshi; Yamanaka, Katsuyuki; Sakai, Yuhiro; Kaneko, Tadashi; Matsushita, Takashi

    2014-09-01

    Mesenchymal stem cells (MSCs) are multipotent cells capable of proliferating and differentiating into several lineages. In regenerative medicine, their potential as a resource for tissue-replacement therapy is receiving much attention. However, transplanting MSCs to repair larger bone defects in animal models has so far proved disappointing. Here we report on the healing of both critical-sized (5 mm) and massive (15 mm) full-thickness femur defects in rats by implanting a uniquely fabricated PLGA scaffold seeded with MSCs pre-differentiated in vitro into cartilage-forming chondrocytes (MSC-DCs). This strategy closely mimics endochondral ossification, the process by which long bones develop in nature. It is thought that because the transplanted MSC-DCs induced natural bone formation, the defect size was not critical to the outcome. Crucially, after 8 weeks the mean biomechanical strength of femora with the massive 15 mm implant reached 75% that of a normal rat femur, while in the case of 5 mm implants there was no significant difference. Successful healing was also highly reproducible, with bone union occurring in all treated animals examined radiologically 8 or 16 weeks after surgery.

  3. Probabilistic age classification with Bayesian networks: A study on the ossification status of the medial clavicular epiphysis.

    PubMed

    Sironi, Emanuele; Pinchi, Vilma; Taroni, Franco

    2016-01-01

    In the past few decades, the rise of criminal, civil and asylum cases involving young people lacking valid identification documents has generated an increase in the demand of age estimation. The chronological age or the probability that an individual is older or younger than a given age threshold are generally estimated by means of some statistical methods based on observations performed on specific physical attributes. Among these statistical methods, those developed in the Bayesian framework allow users to provide coherent and transparent assignments which fulfill forensic and medico-legal purposes. The application of the Bayesian approach is facilitated by using probabilistic graphical tools, such as Bayesian networks. The aim of this work is to test the performances of the Bayesian network for age estimation recently presented in scientific literature in classifying individuals as older or younger than 18 years of age. For these exploratory analyses, a sample related to the ossification status of the medial clavicular epiphysis available in scientific literature was used. Results obtained in the classification are promising: in the criminal context, the Bayesian network achieved, on the average, a rate of correct classifications of approximatively 97%, whilst in the civil context, the rate is, on the average, close to the 88%. These results encourage the continuation of the development and the testing of the method in order to support its practical application in casework.

  4. An intramembranous ossification model for the in silico analysis of bone tissue formation in tooth extraction sites.

    PubMed

    Corredor-Gómez, Jennifer Paola; Rueda-Ramírez, Andrés Mauricio; Gamboa-Márquez, Miguel Alejandro; Torres-Rodríguez, Carolina; Cortés-Rodríguez, Carlos Julio

    2016-07-21

    The accurate modeling of biological processes allows us to predict the spatiotemporal behavior of living tissues by computer-aided (in silico) testing, a useful tool for the development of medical strategies, avoiding the expenses and potential ethical implications of in vivo experimentation. A model for bone healing in mouth would be useful for selecting proper surgical techniques in dental procedures. In this paper, the formulation and implementation of a model for Intramembranous Ossification is presented aiming to describe the complex process of bone tissue formation in tooth extraction sites. The model consists in a mathematical description of the mechanisms in which different types of cells interact, synthesize and degrade extracellular matrices under the influence of biochemical factors. Special attention is given to angiogenesis, oxygen-dependent effects and growth factor-induced apoptosis of fibroblasts. Furthermore, considering the depth-dependent vascularization of mandibular bone and its influence on bone healing, a functional description of the cell distribution on the severed periodontal ligament (PDL) is proposed. The developed model was implemented using the finite element method (FEM) and successfully validated by simulating an animal in vivo experiment on dogs reported in the literature. A good fit between model outcome and experimental data was obtained with a mean absolute error of 3.04%. The mathematical framework presented here may represent an important tool for the design of future in vitro and in vivo tests, as well as a precedent for future in silico studies on osseointegration and mechanobiology. PMID:27113783

  5. Ossification of the posterior longitudinal ligament related genes identification using microarray gene expression profiling and bioinformatics analysis.

    PubMed

    He, Hailong; Mao, Lingzhou; Xu, Peng; Xi, Yanhai; Xu, Ning; Xue, Mingtao; Yu, Jiangming; Ye, Xiaojian

    2014-01-10

    Ossification of the posterior longitudinal ligament (OPLL) is a kind of disease with physical barriers and neurological disorders. The objective of this study was to explore the differentially expressed genes (DEGs) in OPLL patient ligament cells and identify the target sites for the prevention and treatment of OPLL in clinic. Gene expression data GSE5464 was downloaded from Gene Expression Omnibus; then DEGs were screened by limma package in R language, and changed functions and pathways of OPLL cells compared to normal cells were identified by DAVID (The Database for Annotation, Visualization and Integrated Discovery); finally, an interaction network of DEGs was constructed by string. A total of 1536 DEGs were screened, with 31 down-regulated and 1505 up-regulated genes. Response to wounding function and Toll-like receptor signaling pathway may involve in the development of OPLL. Genes, such as PDGFB, PRDX2 may involve in OPLL through response to wounding function. Toll-like receptor signaling pathway enriched genes such as TLR1, TLR5, and TLR7 may involve in spine cord injury in OPLL. PIK3R1 was the hub gene in the network of DEGs with the highest degree; INSR was one of the most closely related genes of it. OPLL related genes screened by microarray gene expression profiling and bioinformatics analysis may be helpful for elucidating the mechanism of OPLL.

  6. Probabilistic age classification with Bayesian networks: A study on the ossification status of the medial clavicular epiphysis.

    PubMed

    Sironi, Emanuele; Pinchi, Vilma; Taroni, Franco

    2016-01-01

    In the past few decades, the rise of criminal, civil and asylum cases involving young people lacking valid identification documents has generated an increase in the demand of age estimation. The chronological age or the probability that an individual is older or younger than a given age threshold are generally estimated by means of some statistical methods based on observations performed on specific physical attributes. Among these statistical methods, those developed in the Bayesian framework allow users to provide coherent and transparent assignments which fulfill forensic and medico-legal purposes. The application of the Bayesian approach is facilitated by using probabilistic graphical tools, such as Bayesian networks. The aim of this work is to test the performances of the Bayesian network for age estimation recently presented in scientific literature in classifying individuals as older or younger than 18 years of age. For these exploratory analyses, a sample related to the ossification status of the medial clavicular epiphysis available in scientific literature was used. Results obtained in the classification are promising: in the criminal context, the Bayesian network achieved, on the average, a rate of correct classifications of approximatively 97%, whilst in the civil context, the rate is, on the average, close to the 88%. These results encourage the continuation of the development and the testing of the method in order to support its practical application in casework. PMID:26699731

  7. Outcome of posterior decompression with instrumented fusion surgery for K-line (-) cervical ossification of the longitudinal ligament.

    PubMed

    Saito, Junya; Maki, Satoshi; Kamiya, Koshiro; Furuya, Takeo; Inada, Taigo; Ota, Mitsutoshi; Iijima, Yasushi; Takahashi, Kazuhisa; Yamazaki, Masashi; Aramomi, Masaaki; Mannoji, Chikato; Koda, Masao

    2016-10-01

    We investigated the outcome of posterior decompression and instrumented fusion (PDF) surgery for patients with K-line (-) ossification of the posterior longitudinal ligament (OPLL) of the cervical spine, who may have a poor surgical prognosis. We retrospectively analyzed the outcome of a series of 27 patients who underwent PDF without correction of cervical alignment for K-line (-) OPLL and were followed-up for at least 1 year after surgery. We had performed double-door laminoplasty followed by posterior instrumented fusion without excessive correction of cervical spine alignment. The preoperative Japanese Orthopedic Association (JOA) score for cervical myelopathy was 8.0 points and postoperative JOA score was 11.9 points on average. The mean JOA score recovery rate was 43.6%. The average C2-C7 angle was 2.2° preoperatively and 3.1° postoperatively. The average maximum occupation ratio of OPLL was 56.7%. In conclusion, PDF without correcting cervical alignment for patients with K-line (-) OPLL showed moderate neurological recovery, which was acceptable considering K-line (-) predicts poor surgical outcomes. Thus, PDF is a surgical option for such patients with OPLL. PMID:27591553

  8. Comparison of anterior decompression and fusion versus laminoplasty in the treatment of multilevel cervical ossification of the posterior longitudinal ligament: a systematic review and meta-analysis

    PubMed Central

    Liu, Weijun; Hu, Ling; Chou, Po-Hsin; Liu, Ming; Kan, Wusheng; Wang, Junwen

    2016-01-01

    Purpose A meta-analysis was conducted to evaluate the clinical outcomes, complications, reoperation rates, and late neurological deterioration between anterior decompression and fusion (ADF) and laminoplasty (LAMP) in the treatment of multilevel cervical ossification of the posterior longitudinal ligament (OPLL). Methods All related studies published up to August 2015 were acquired by searching PubMed and EMBASE. Exclusion criteria were case reports, revision surgeries, combined anterior and posterior surgeries, the other posterior approaches including laminectomy or laminectomy and instrumented fusion, non-English studies, and studies with quality assessment scores of <7. The main end points including Japanese Orthopedic Association (JOA) score, recovery rate of JOA, cervical lordosis, complication rate, reoperation rate, and late neurological deterioration were analyzed. All available data was analyzed using RevMan 5.2.0 and Stata 12.0. Results A total of seven studies were included in the meta-analysis. The mean surgical level of ADF was 3.1, and the mean preoperative occupation ratios of ADF and LAMP group were 55.9% and 51.9%, respectively. No statistical difference was observed with regard to preoperative occupation ratio and preoperative JOA score. Although LAMP group had a higher preoperative cervical lordosis than ADF group (P<0.05, weighted mean difference [WMD] =−5.73, 95% confidence interval [CI] =−9.67–−1.80), significantly decreased cervical lordosis was observed in LAMP group after operation. ADF group had higher postoperative JOA score (P<0.05, WMD =2.18, 95% CI =0.98–3.38) and neurological recovery rate (P<0.05, WMD =27.22, 95% CI =15.20–39.23). Furthermore, ADF group had a lower late neurological deterioration rate than the LAMP group (P<0.05, risk difference =0.16, 95% CI =0.04–0.73). The complication rates of both groups had no statistical difference. However, LAMP group had a significantly lower reoperation rate than ADF group

  9. Potential disadvantages of using socially acquired information.

    PubMed Central

    Giraldeau, Luc-Alain; Valone, Thomas J; Templeton, Jennifer J

    2002-01-01

    The acquisition and use of socially acquired information is commonly assumed to be profitable. We challenge this assumption by exploring hypothetical scenarios where the use of such information either provides no benefit or can actually be costly. First, we show that the level of incompatibility between the acquisition of personal and socially acquired information will directly affect the extent to which the use of socially acquired information can be profitable. When these two sources of information cannot be acquired simultaneously, there may be no benefit to socially acquired information. Second, we assume that a solitary individual's behavioural decisions will be based on cues revealed by its own interactions with the environment. However, in many cases, for social animals the only socially acquired information available to individuals is the behavioural actions of others that expose their decisions, rather than the cues on which these decisions were based. We argue that in such a situation the use of socially acquired information can lead to informational cascades that sometimes result in sub-optimal behaviour. From this theory of informational cascades, we predict that when erroneous cascades are costly, individuals should pay attention only to socially generated cues and not behavioural decisions. We suggest three scenarios that might be examples of informational cascades in nature. PMID:12495513

  10. Acquired Brown's syndrome: an unusual cause.

    PubMed

    Booth-Mason, S; Kyle, G M; Rossor, M; Bradbury, P

    1985-10-01

    A 62-year-old man with acquired Brown's syndrome is presented. This was due to an orbital metastatic deposit, a cause not previously reported. Other causes of this disorder and its treatment are discussed.

  11. Extracerebellar progenitors grafted to the neurogenic milieu of the postnatal rat cerebellum adapt to the host environment but fail to acquire cerebellar identities.

    PubMed

    Rolando, Chiara; Gribaudo, Simona; Yoshikawa, Kazuaki; Leto, Ketty; De Marchis, Silvia; Rossi, Ferdinando

    2010-04-01

    Stem or progenitor cells acquire specific regional identities during early ontogenesis. Nonetheless, there is evidence that cells heterotopically transplanted to neurogenic regions of the developing or mature central nervous system may switch their fate to adopt host-specific phenotypes. Here, we isolated progenitor cells from different germinative sites along the neuraxis where GABAergic interneurons are produced (telencephalic subventricular zone, medial ganglionic eminence, ventral mesencephalon and dorsal spinal cord), and grafted them to the prospective white matter of the postnatal rat cerebellum, at the time when local interneurons are generated. The phenotype acquired by transplanted cells was assessed by different criteria, including expression of region-specific transcription factors, acquisition of morphological and neurochemical traits, and integration in the cerebellar cytoarchitecture. Regardless of their origin, all the different types of donor cells engrafted in the cerebellar parenchyma and developed mature neurons that shared some morphological and neurochemical features with local inhibitory interneurons, particularly in the deep nuclei. Nevertheless, transplanted cells failed to activate cerebellar-specific regulatory genes. In addition, their major structural features, the expression profiles of type-specific markers and the laminar placement in the recipient cortex did not match those of endogenous interneurons generated during the same developmental period. Therefore, although exogenous cells are influenced by the cerebellar milieu and show remarkable capabilities for adapting to the foreign environment, they essentially fail to switch their fate, integrate in the host neurogenic mechanisms and adopt clear-cut cerebellar identities.

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

    PubMed

    Qian, Guofeng; Fan, Wei; Ahlemeyer, Barbara; Karnati, Srikanth; Baumgart-Vogt, Eveline

    2015-01-01

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

  13. Acquired bleeding disorders in the elderly.

    PubMed

    Kruse-Jarres, Rebecca

    2015-01-01

    The hemostatic balance changes with advancing age which may be due to factors such as platelet activation, increase of certain clotting factor proteins, slowing of the fibrinolytic system, and modification of the endothelium and blood flow. Generally, this predisposes the elderly to thrombosis rather than bleeding. It often necessitates antiplatelet or anticoagulation therapy, which can cause significant bleeding problems in an aging population. Additionally, changing renal function, modification in immune regulation, and a multitude of other disease processes, can give rise to acquired bleeding disorders. Bleeding can prove difficult to treat in a dynamic environment and in a population that may have underlying thrombotic risk factors.This article discusses some specific challenges of acquired bleeding arising in the elderly. The use of anticoagulation and nonsteroidal anti-inflammatory medications is prevalent in the treatment of the elderly and predisposes them to increased bleeding risk as their physiology changes. When prescribing and monitoring these therapies, it is exceedingly important to weigh thrombotic versus bleeding risks. There are additional rare acquired bleeding disorders that predominantly affect the elderly. One of them is acquired hemophilia, which is an autoimmune disorder arising from antibodies against factor VIII. The treatment challenge rests in the use of hemostatic agents in a population that is already at increased risk for thrombotic complications. Another rare disorder of intensifying interest, acquired von Willebrand syndrome, has a multitude of etiologic mechanisms. Understanding the underlying pathophysiology is essential in making a treatment decision for this disorder.

  14. Forensic age estimation via 3-T magnetic resonance imaging of ossification of the proximal tibial and distal femoral epiphyses: Use of a T2-weighted fast spin-echo technique.

    PubMed

    Ekizoglu, Oguzhan; Hocaoglu, Elif; Inci, Ercan; Can, Ismail Ozgur; Aksoy, Sema; Kazimoglu, Cemal

    2016-03-01

    Radiation exposure during forensic age estimation is associated with ethical implications. It is important to prevent repetitive radiation exposure when conducting advanced ultrasonography (USG) and magnetic resonance imaging (MRI). The purpose of this study was to investigate the utility of 3.0-T MRI in determining the degree of ossification of the distal femoral and proximal tibial epiphyses in a group of Turkish population. We retrospectively evaluated coronal T2-weighted and turbo spin-echo sequences taken upon MRI of 503 patients (305 males, 198 females; age 10-30 years) using a five-stage method. Intra- and interobserver variations were very low. (Intraobserver reliability was κ=0.919 for the distal femoral epiphysis and κ=0.961 for the proximal tibial epiphysis, and interobserver reliability was κ=0.836 for the distal femoral epiphysis and κ=0.885 for the proximal tibial epiphysis.) Spearman's rank correlation analysis indicated a significant positive relationship between age and the extent of ossification of the distal femoral and proximal tibial epiphyses (p<0.001). Comparison of male and female data revealed significant between-gender differences in the ages at first attainment of stages 2, 3, and 4 ossifications of the distal femoral epiphysis and stage 1 and 4 ossifications of the proximal tibial epiphysis (p<0.05). The earliest ages at which ossification of stages 3, 4, and 5 was evident in the distal femoral epiphysis were 14, 17, and 22 years in males and 13, 16, and 21 years in females, respectively. Proximal tibial epiphysis of stages 3, 4, and 5 ossification was first noted at ages 14, 17, and 18 years in males and 13, 15, and 16 years in females, respectively. MRI of the distal femoral and proximal tibial epiphyses is an alternative, noninvasive, and reliable technique to estimate age.

  15. Acquired cutis laxa associated with cutaneous mastocytosis.

    PubMed

    Hoang, Minh Van; Dang, Phuoc Van; Bui, Duc Van; Mejbel, Haider; Mani, Divya Thomas; Smoller, Bruce Robert; Phung, Thuy Linh

    2015-07-01

    Cutis laxa is characterized by dramatic wrinkling of skin that is lacking in elasticity due to inherent defects in dermal elastic fibers. Cutis laxa can be caused by genetic and metabolic disorders. It can also be acquired, possibly resulting from inflammatory processes with destruction of elastic fibers. This report describes a 26-year old woman who developed acquired cutis laxa and cutaneous mastocytosis leading to premature aging. She represents a unique co-occurrence of these two separate disease entities. To our knowledge, there has been only one published case report of acquired cutis laxa occurring in association with urticaria pigmentosa in a 4-year old girl. Our case would be a second case that exhibits the coexistence of these two disorders in an adult female. PMID:26436968

  16. Congenital and acquired bleeding disorders in infancy.

    PubMed

    Campbell, Sally Elizabeth; Bolton-Maggs, Paula H B

    2015-11-01

    The diagnosis of congenital and acquired bleeding disorders in infants requires an understanding of developmental haemostasis and the effect on laboratory testing. A systematic approach to bleeding in neonates will aid clinicians in the diagnosis and treatment, which may be caused by a wide variety of diseases. The clinical setting will help to direct the diagnostic pathway. This review will focus on the presentation and diagnosis of congenital and acquired bleeding disorders, including platelet disorders. Current research in this field is ongoing, including investigation into neonatal platelets and their different functionalities, platelet transfusion thresholds and how changes in coagulation factors may be linked to other homeostatic mechanisms.

  17. Ossification Pattern of Estuarine Dolphin (Sotalia guianensis) Forelimbs, from the Coast of the State of Espírito Santo, Brazil

    PubMed Central

    Botta, Silvina; de Queiroz, Fábio Ferreira; Campos, Adélia Sepúlveda

    2015-01-01

    The estuarine dolphin, Sotalia guianensis, is one of the most abundant cetacean species in Brazil. Determination of age and of aspects associated with the development of this species is significant new studies. Counts of growth layer groups in dentin are used to estimate age of these animals, though other ways to evaluate development are also adopted, like the measurement of total length (TL). This study presents a procedure to evaluate the development of the estuarine dolphin based on the ossification pattern of forelimbs. Thirty-seven estuarine dolphins found in the state of Espírito Santo, Brazil, were examined. Age was estimated, TL was measured and ossification of epiphyses was examined by radiography. We analyzed results using the Spearman correlation. Inspection of radiographs allowed evaluation of the significance of the correlation between age and development of the proximal (r = 0.9109) and distal (r = 0.9092) radial epiphyses, and of the distal ulnar epiphyses (r = 0.9055). Radiographic analysis of forelimbs proved to be an appropriate method to evaluate physical maturity, and may be a helpful tool to estimate age of these animals in ecological and population studies. PMID:26017269

  18. Ossification Pattern of Estuarine Dolphin (Sotalia guianensis) Forelimbs, from the Coast of the State of Espírito Santo, Brazil.

    PubMed

    de Carvalho, Anna Paula Martins; Lima, Juliana Ywasaki; Azevedo, Carolina Torres; Botta, Silvina; de Queiroz, Fábio Ferreira; Campos, Adélia Sepúlveda; Barbosa, Lupércio de Araújo; da Silveira, Leonardo Serafim

    2015-01-01

    The estuarine dolphin, Sotalia guianensis, is one of the most abundant cetacean species in Brazil. Determination of age and of aspects associated with the development of this species is significant new studies. Counts of growth layer groups in dentin are used to estimate age of these animals, though other ways to evaluate development are also adopted, like the measurement of total length (TL). This study presents a procedure to evaluate the development of the estuarine dolphin based on the ossification pattern of forelimbs. Thirty-seven estuarine dolphins found in the state of Espírito Santo, Brazil, were examined. Age was estimated, TL was measured and ossification of epiphyses was examined by radiography. We analyzed results using the Spearman correlation. Inspection of radiographs allowed evaluation of the significance of the correlation between age and development of the proximal (r = 0.9109) and distal (r = 0.9092) radial epiphyses, and of the distal ulnar epiphyses (r = 0.9055). Radiographic analysis of forelimbs proved to be an appropriate method to evaluate physical maturity, and may be a helpful tool to estimate age of these animals in ecological and population studies.

  19. A Case Of Bilateral Acquired Localized Lipoatrophy

    PubMed Central

    Tanrıkulu, Osman; Yesilova, Yavuz; Aksoy, Mustafa

    2016-01-01

    Lipoatrophy is characterized by inflammation and tissue loss in fatty tissue. This disease may be congenital or acquired, primary or secondary. Secondary lipoatrophy develops with infections, collagen tissue diseases, tumors and drug injections. In this report, we present the case of a 14-year-old female patient who developed lipoatrophy following intramuscular steroid injection to both buttocks. PMID:27504088

  20. Mitral valve repair in acquired dextrocardia.

    PubMed

    Elmistekawy, Elsayed; Chan, Vincent; Hynes, Mark; Mesana, Thierry

    2015-10-01

    Surgical correction of valvular heart disease in patients with dextrocardia is extremely rare. We report a surgical case of mitral valve repair in a patient with acquired dextrocardia. Successful mitral valve repair was performed through a right lateral thoracotomy. We describe our surgical strategy and summarize the literature.

  1. Acquired immunodeficiency syndrome with subacute sclerosing panencephalitis.

    PubMed

    Gowda, Vykuntaraju K N; Sukanya, V; Shivananda

    2012-11-01

    A 7-year-old boy with acquired immunodeficiency syndrome, receiving antiretroviral drugs for 2 years, presented with a recent onset of myoclonic jerks and cognitive deterioration. On examination, he manifested myoclonic jerks once every 10-15 seconds. His electroencephalogram indicated periodic complexes, and his cerebrospinal fluid tested positive for measles antibodies.

  2. How Did Light Acquire a Velocity?

    ERIC Educational Resources Information Center

    Lauginie, Pierre

    2013-01-01

    We discuss how light acquired a velocity through history, from the ancient Greeks to the early modern era. Combining abstract debates, models of light, practical needs, planned research and chance, this history illustrates several key points that should be brought out in science education.

  3. Group Treatment in Acquired Brain Injury Rehabilitation

    ERIC Educational Resources Information Center

    Bertisch, Hilary; Rath, Joseph F.; Langenbahn, Donna M.; Sherr, Rose Lynn; Diller, Leonard

    2011-01-01

    The current article describes critical issues in adapting traditional group-treatment methods for working with individuals with reduced cognitive capacity secondary to acquired brain injury. Using the classification system based on functional ability developed at the NYU Rusk Institute of Rehabilitation Medicine (RIRM), we delineate the cognitive…

  4. Support Network Responses to Acquired Brain Injury

    ERIC Educational Resources Information Center

    Chleboun, Steffany; Hux, Karen

    2011-01-01

    Acquired brain injury (ABI) affects social relationships; however, the ways social and support networks change and evolve as a result of brain injury is not well understood. This study explored ways in which survivors of ABI and members of their support networks perceive relationship changes as recovery extends into the long-term stage. Two…

  5. Interviewing Children with Acquired Brain Injury (ABI)

    ERIC Educational Resources Information Center

    Boylan, Anne-Marie; Linden, Mark; Alderdice, Fiona

    2009-01-01

    Research into the lives of children with acquired brain injury (ABI) often neglects to incorporate children as participants, preferring to obtain the opinions of the adult carer (e.g. McKinlay et al., 2002). There has been a concerted attempt to move away from this position by those working in children's research with current etiquette…

  6. Eye Movement Correlates of Acquired Central Dyslexia

    ERIC Educational Resources Information Center

    Schattka, Kerstin I.; Radach, Ralph; Huber, Walter

    2010-01-01

    Based on recent progress in theory and measurement techniques, the analysis of eye movements has become one of the major methodological tools in experimental reading research. Our work uses this approach to advance the understanding of impaired information processing in acquired central dyslexia of stroke patients with aphasia. Up to now there has…

  7. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  8. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  9. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  10. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  11. Neural Correlates of Acquired Color Category Effects

    ERIC Educational Resources Information Center

    Clifford, Alexandra; Franklin, Anna; Holmes, Amanda; Drivonikou, Vicky G.; Ozgen, Emre; Davies, Ian R. L.

    2012-01-01

    Category training can induce category effects, whereby color discrimination of stimuli spanning a newly learned category boundary is enhanced relative to equivalently spaced stimuli from within the newly learned category (e.g., categorical perception). However, the underlying mechanisms of these acquired category effects are not fully understood.…

  12. [Heterotopic fundus (author's transl)].

    PubMed

    Denden, A

    1976-07-01

    Fundus heterotopicus is the term used to describe a rare, non-hereditary curvature anomaly of the fundus in the non-myopic eye, which is characterized: 1. functionally, by a slowly increasing myopic-astigmatic refractive error, 2. by correctable bitemporal or binasal refractionscomata and 3. ophthalmoscopically by a posterior out-pouching of the nasal or temporal fundus portions, and including the optic disc and macula in the obliquely descending wall of the extasis.

  13. Acquired undescended testis: putting the pieces together.

    PubMed

    Hack, W W M; Goede, J; van der Voort-Doedens, L M; Meijer, R W

    2012-02-01

    Acquired undescended testis is now a well-recognized disorder. It is seen in 1.5% of pre-pubertal boys and accounts for the 1-2% orchidopexy rate in older boys. Its pathogenesis remains largely unclear, but it may be caused by a fibrous remnant of the processus vaginalis. There is much controversy over its management, and the proper management awaits a randomized-controlled trial. Until now, follow-up data are available only for cases of spontaneous descent or pubertal orchidopexy. It is speculated that acquired undescended testis is in fact congenital and because of a short funiculus at birth, allowing a low-scrotal position early in life. However, as the boy grows, the testis might evolve into an undescended state. When testosterone surges at puberty, spontaneous descent occurs in three of every four cases.

  14. Clinical laboratory data: acquire, analyze, communicate, liberate.

    PubMed

    Azzazy, Hassan M E; Elbehery, Ali H A

    2015-01-01

    The availability of portable healthcare devices, which can acquire and transmit medical data to remote experts would dramatically affect healthcare in areas with poor infrastructure. Smartphones, which feature touchscreen computer capabilities and sophisticated cameras, have become widely available with over billion units shipped in 2013. In the clinical laboratory, smartphones have recently brought the capabilities of key instruments such as spectrophotometers, fluorescence analyzers and microscopes into the palm of the hand. Several research groups have developed sensitive and low-cost smartphone-based diagnostic assay prototypes for testing cholesterol, albumin, vitamin D, tumor markers, and the detection of infectious agents. This review covers the use of smartphones to acquire, analyze, communicate, and liberate clinical laboratory data. Smartphones promise to dramatically improve the quality and quantity of healthcare offered in resource-limited areas.

  15. Acquired Cystic Fibrosis Transmembrane Conductance Regulator Deficiency.

    PubMed

    Cho, Do-Yeon; Woodworth, Bradford A

    2016-01-01

    In the genetic airway disease cystic fibrosis (CF), deficiency or dysfunction of the cystic fibrosis membrane conductance regulator (CFTR) alters anion transport in respiratory epithelium and consequently disrupts mucociliary clearance. An enriched understanding of the role of CFTR in the maintenance of normal epithelial function has revealed that mild and variable CFTR mutations play a causative role in a number of diseases not classically associated with CF. Furthermore, recent evidence indicates that acquired defects in wild-type CFTR protein processing, endocytic recycling and function can contribute to the pathogenesis of airway diseases, such as chronic obstructive pulmonary disease. In this chapter, we discuss emerging findings implicating acquired CFTR dysfunction in the pathogenesis of chronic rhinosinusitis and propose a new and leading edge approach to future CRS therapy using CFTR potentiators. PMID:27466849

  16. Acquired portosystemic collaterals: anatomy and imaging*

    PubMed Central

    Leite, Andréa Farias de Melo; Mota Jr., Américo; Chagas-Neto, Francisco Abaeté; Teixeira, Sara Reis; Elias Junior, Jorge; Muglia, Valdair Francisco

    2016-01-01

    Portosystemic shunts are enlarged vessels that form collateral pathological pathways between the splanchnic circulation and the systemic circulation. Although their causes are multifactorial, portosystemic shunts all have one mechanism in common-increased portal venous pressure, which diverts the blood flow from the gastrointestinal tract to the systemic circulation. Congenital and acquired collateral pathways have both been described in the literature. The aim of this pictorial essay was to discuss the distinct anatomic and imaging features of portosystemic shunts, as well as to provide a robust method of differentiating between acquired portosystemic shunts and similar pathologies, through the use of illustrations and schematic drawings. Imaging of portosystemic shunts provides subclinical markers of increased portal venous pressure. Therefore, radiologists play a crucial role in the identification of portosystemic shunts. Early detection of portosystemic shunts can allow ample time to perform endovascular shunt operations, which can relieve portal hypertension and prevent acute or chronic complications in at-risk patient populations. PMID:27777479

  17. [Acquired renal cysts in maintenance dialysis patients].

    PubMed

    Lie, B; Hust, W; Asgarzadeh, A; Mann, H

    1986-03-01

    Ultrasonographic examination of the kidneys of 111 patients on long term maintenance hemodialysis was performed. None of the patients had genuine polycystic kidney disease. In many patients acquired cysts were found. Frequency and volume of these cysts were the same on the right and left side. There was no correlation between the age of the patients and the number of cysts. There were no differences concerning sex and type of primary renal disease. There was a significant positive correlation between time on maintenance hemodialysis and number of cysts but no correlation between number of cysts and hemoglobin concentration. This is in contrast to data in the literature. Clinical relevance of acquired kidney cysts in dialysis patients concerns hematuria, retroperitoneal bleeding, kidney stone formation, septicemia and malignancy.

  18. System Acquires Data On Reactivities Of Foams

    NASA Technical Reports Server (NTRS)

    Walls, Joe T.

    1994-01-01

    Data-acquisition and -plotting system, called DAPS(TM), developed enabling accurate and objective determination of physical properties related to reactivities of polyurethane and polyisocyanurate foams. Automated, computer-controlled test apparatus that acquires data on rates of rise, rise profiles, exothermic temperatures, and internal pressures of foams prepared from both manual and machine-mixed batches. Data used to determine minute differences between reaction kinetics and exothermic profiles of foam formulations, properties of end products which are statistically undifferentiated.

  19. Management options of acquired punctal stenosis.

    PubMed

    Bukhari, Amal A

    2013-08-01

    Punctal stenosis is a frequent source of patients referral to the otoplasty clinic and the search for a procedure that can permanently eliminate epiphora without disturbing the normal lacrimal system anatomy and physiology started centuries ago and continues today. The following article summarizes the reported procedures in the English literature in the acquired punctal stenosis with a description of techniques, success rates, and potential complications with the goal of identifying the most effective treatment strategy based on the current knowledge available.

  20. Earth Knowledge Acquired by Middle School Students

    NASA Technical Reports Server (NTRS)

    Ride, Sally

    2008-01-01

    Earth Knowledge Acquired by Middle School Students (EarthKAM), an education activity, allows middle school students to program a digital camera on board the International Space Station to photograph a variety of geographical targets for study in the classroom. Photos are made available on the web for viewing and study by participating schools around the world. Educators use the images for projects involving Earth Science, geography, physics, and social science.

  1. Acquired protein energy malnutrition in glutaric acidemia.

    PubMed

    Ma, Liqiao; Savory, Stephanie; Agim, Nnenna G

    2013-01-01

    We report a case of acquired protein energy malnutrition with associated zinc deficiency in an 18-month-old boy with type 1 glutaric acidemia. Physical examination findings included generalized nonpitting edema, widespread desquamative plaques, and sparse hair with a reddish tinge. Laboratory abnormalities included low levels of zinc, albumin, alkaline phosphatase, and iron. A review of skin manifestations of nutritional deficiencies, specifically kwashiorkor, is presented, as well as the relatively new entity called acrodermatitis dysmetabolica.

  2. Acquired protein energy malnutrition in glutaric acidemia.

    PubMed

    Ma, Liqiao; Savory, Stephanie; Agim, Nnenna G

    2013-01-01

    We report a case of acquired protein energy malnutrition with associated zinc deficiency in an 18-month-old boy with type 1 glutaric acidemia. Physical examination findings included generalized nonpitting edema, widespread desquamative plaques, and sparse hair with a reddish tinge. Laboratory abnormalities included low levels of zinc, albumin, alkaline phosphatase, and iron. A review of skin manifestations of nutritional deficiencies, specifically kwashiorkor, is presented, as well as the relatively new entity called acrodermatitis dysmetabolica. PMID:23330977

  3. Acquired Antibiotic Resistance Genes: An Overview

    PubMed Central

    van Hoek, Angela H. A. M.; Mevius, Dik; Guerra, Beatriz; Mullany, Peter; Roberts, Adam Paul; Aarts, Henk J. M.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria. PMID:22046172

  4. The pathophysiology of acquired premature ejaculation.

    PubMed

    McMahon, Chris G; Jannini, Emmanuele A; Serefoglu, Ege C; Hellstrom, Wayne J G

    2016-08-01

    The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE. PMID:27652216

  5. The pathophysiology of acquired premature ejaculation

    PubMed Central

    Jannini, Emmanuele A.; Serefoglu, Ege C.; Hellstrom, Wayne J. G.

    2016-01-01

    The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE. PMID:27652216

  6. The pathophysiology of acquired premature ejaculation

    PubMed Central

    Jannini, Emmanuele A.; Serefoglu, Ege C.; Hellstrom, Wayne J. G.

    2016-01-01

    The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE.

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

    PubMed Central

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

    2015-01-01

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

  8. Acquired prosopagnosia without word recognition deficits.

    PubMed

    Susilo, Tirta; Wright, Victoria; Tree, Jeremy J; Duchaine, Bradley

    2015-01-01

    It has long been suggested that face recognition relies on specialized mechanisms that are not involved in visual recognition of other object categories, including those that require expert, fine-grained discrimination at the exemplar level such as written words. But according to the recently proposed many-to-many theory of object recognition (MTMT), visual recognition of faces and words are carried out by common mechanisms [Behrmann, M., & Plaut, D. C. ( 2013 ). Distributed circuits, not circumscribed centers, mediate visual recognition. Trends in Cognitive Sciences, 17, 210-219]. MTMT acknowledges that face and word recognition are lateralized, but posits that the mechanisms that predominantly carry out face recognition still contribute to word recognition and vice versa. MTMT makes a key prediction, namely that acquired prosopagnosics should exhibit some measure of word recognition deficits. We tested this prediction by assessing written word recognition in five acquired prosopagnosic patients. Four patients had lesions limited to the right hemisphere while one had bilateral lesions with more pronounced lesions in the right hemisphere. The patients completed a total of seven word recognition tasks: two lexical decision tasks and five reading aloud tasks totalling more than 1200 trials. The performances of the four older patients (3 female, age range 50-64 years) were compared to those of 12 older controls (8 female, age range 56-66 years), while the performances of the younger prosopagnosic (male, 31 years) were compared to those of 14 younger controls (9 female, age range 20-33 years). We analysed all results at the single-patient level using Crawford's t-test. Across seven tasks, four prosopagnosics performed as quickly and accurately as controls. Our results demonstrate that acquired prosopagnosia can exist without word recognition deficits. These findings are inconsistent with a key prediction of MTMT. They instead support the hypothesis that face

  9. Acquired prosopagnosia without word recognition deficits.

    PubMed

    Susilo, Tirta; Wright, Victoria; Tree, Jeremy J; Duchaine, Bradley

    2015-01-01

    It has long been suggested that face recognition relies on specialized mechanisms that are not involved in visual recognition of other object categories, including those that require expert, fine-grained discrimination at the exemplar level such as written words. But according to the recently proposed many-to-many theory of object recognition (MTMT), visual recognition of faces and words are carried out by common mechanisms [Behrmann, M., & Plaut, D. C. ( 2013 ). Distributed circuits, not circumscribed centers, mediate visual recognition. Trends in Cognitive Sciences, 17, 210-219]. MTMT acknowledges that face and word recognition are lateralized, but posits that the mechanisms that predominantly carry out face recognition still contribute to word recognition and vice versa. MTMT makes a key prediction, namely that acquired prosopagnosics should exhibit some measure of word recognition deficits. We tested this prediction by assessing written word recognition in five acquired prosopagnosic patients. Four patients had lesions limited to the right hemisphere while one had bilateral lesions with more pronounced lesions in the right hemisphere. The patients completed a total of seven word recognition tasks: two lexical decision tasks and five reading aloud tasks totalling more than 1200 trials. The performances of the four older patients (3 female, age range 50-64 years) were compared to those of 12 older controls (8 female, age range 56-66 years), while the performances of the younger prosopagnosic (male, 31 years) were compared to those of 14 younger controls (9 female, age range 20-33 years). We analysed all results at the single-patient level using Crawford's t-test. Across seven tasks, four prosopagnosics performed as quickly and accurately as controls. Our results demonstrate that acquired prosopagnosia can exist without word recognition deficits. These findings are inconsistent with a key prediction of MTMT. They instead support the hypothesis that face

  10. Fabrication and characterization of a recombinant fibronectin/cadherin bio-inspired ceramic surface and its influence on adhesion and ossification in vitro.

    PubMed

    Zhang, Yuan; Xiang, Qiang; Dong, Shiwu; Li, Changqing; Zhou, Yue

    2010-03-01

    This study has investigated the effects of a bio-inspired ceramic surface modified with a novel recombinant protein on surface parameters and cell behavior. The surface of a biphasic calcium phosphate ceramic was functionalized with a recombinant protein spanning the fragments of fibronectin module III7-10 and extracellular domains 1 and 2 of cadherin 11 (rFN/CDH) using a dimethyl-3,3'-dithiobispropionimidate cross-linking method. The surface was characterized by scanning electron microscopy, X-ray photoelectron spectroscopy and protein adsorption and surface density measurements. The material exhibited desirable properties for cell adhesion and proliferation. The effects of the surface on the adhesion and proliferation of human mesenchymal stem cells (hMSC) were investigated using a cell adhesion centrifugal assay and the 3-(4,5-dmethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The data demonstrated that the adhesive capacity and proliferation rate were significantly improved as compared with fibronectin and cadherin positive controls. Moreover, the rFN/CDH bio-inspired ceramic surface also induced osteoblastic differentiation, as evidenced by the higher alkaline phosphatase activity and osteocalcin mRNA expression level of hMSC cultured in osteogenic media for 7-10days. Furthermore, a functional blocking assay with a site-specific antibody against phosphotyrosine 397 (pY397) of focal adhesion kinase revealed that pY397 is involved in adhesion and ossification. These results suggest that the rFN/CDH bio-inspired BCP surface possesses enhanced functionality in adhesion, proliferation and ossification and may be a promising scaffold for tissue engineering.

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

    PubMed

    Pan, Zhengqi; Zhang, Xianrong; Shangguan, Yangfan; Hu, Hang; Chen, Liaobin; Wang, Hui

    2016-08-15

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

  12. Morphometric Study of Anterior Clinoid Process and Optic Strut and the Ossification of Carotico-Clinoid Ligament with their Clinical Importance

    PubMed Central

    Souza, Anne D; Ankolekar, Vrinda Hari; Nayak, Nivedita; Souza, Antony Sylvan D

    2016-01-01

    Introduction Knowledge about the ossification of the Carotico-Clinoid Foramen (CCF), as it forms a potential site for compression of the internal carotid artery may be beneficial for neurosurgeons and radiologists. Aim To obtain a detailed knowledge of morphometry of Anterior Clinoid Process (ACP) and Optic Strot (OS) and the type of ossification of CCF which would be necessary to increase the success of surgeries related to the cavernous sinus and internal carotid artery. Materials and Methods Parameters such as the length of ACP from its base to the tip, the width at its base and the distance between the tip of ACP to optic strut were measured in mm using digital calipers. SPSS version 17 was used for the statistical analysis. Paired t-test was applied to compare between right and left sides. Presence of carotico-clinoid foramen was observed and was classified as incomplete, contact form or complete. Results The average length of ACP ranged from 12 to 15mm on right side and 11 to 16mm on the left side. Paired t-test was applied to compare the means between the right and left sides. The width of ACP varied between right and left sides and this difference was statistically significant (p<0.05). Out of 12 CCF observed, the commonest type was incomplete (N=7) followed by complete (N=3) and contact form (N=2). Conclusion Considering the immense anatomical surgical and radiological importance of morphology of ACP, OS and CCF, this study highlighted the detailed morphometry of these structures. The study also has explained the sexual dimorphism in their morphology. PMID:27190784

  13. Prevalence and Distribution of Ossified Lesions in the Whole Spine of Patients with Cervical Ossification of the Posterior Longitudinal Ligament A Multicenter Study (JOSL CT study).

    PubMed

    Hirai, Takashi; Yoshii, Toshitaka; Iwanami, Akio; Takeuchi, Kazuhiro; Mori, Kanji; Yamada, Tsuyoshi; Wada, Kanichiro; Koda, Masao; Matsuyama, Yukihiro; Takeshita, Katsushi; Abematsu, Masahiko; Haro, Hirotaka; Watanabe, Masahiko; Watanabe, Kei; Ozawa, Hiroshi; Kanno, Haruo; Imagama, Shiro; Fujibayashi, Shunsuke; Yamazaki, Masashi; Matsumoto, Morio; Nakamura, Masaya; Okawa, Atsushi; Kawaguchi, Yoshiharu

    2016-01-01

    Ossification of the posterior longitudinal ligament (OPLL) can cause severe and irreversible paralysis in not only the cervical spine but also the thoracolumbar spine. To date, however, the prevalence and distribution of OPLL in the whole spine has not been precisely evaluated in patients with cervical OPLL. Therefore, we conducted a multi-center study to comprehensively evaluate the prevalence and distribution of OPLL using multi-detector computed tomography (CT) images in the whole spine and to analyze what factors predict the presence of ossified lesions in the thoracolumbar spine in patients who were diagnosed with cervical OPLL by plain X-ray. Three hundred and twenty-two patients with a diagnosis of cervical OPLL underwent CT imaging of the whole spine. The sum of the levels in which OPLL was present in the whole spine was defined as the OP-index and used to evaluate the extent of ossification. The distribution of OPLL in the whole spine was compared between male and female subjects. In addition, a multiple regression model was used to ascertain related factors that affected the OP-index. Among patients with cervical OPLL, women tended to have more ossified lesions in the thoracolumbar spine than did men. A multiple regression model revealed that the OP-index was significantly correlated with the cervical OP-index, sex (female), and body mass index. Furthermore, the prevalence of thoracolumbar OPLL in patients with a cervical OP-index ≥ 10 was 7.8 times greater than that in patients with a cervical OP-index ≤ 5. The results of this study reveal that the extent of OPLL in the whole spine is significantly associated with the extent of cervical OPLL, female sex, and obesity. PMID:27548354

  14. Ossified Posterior Longitudinal Ligament With Massive Ossification of the Anterior Longitudinal Ligament Causing Dysphagia in a Diffuse Idiopathic Skeletal Hyperostosis Patient.

    PubMed

    Murayama, Kazuhiro; Inoue, Shinichi; Tachibana, Toshiya; Maruo, Keishi; Arizumi, Fumihiro; Tsuji, Shotaro; Yoshiya, Shinichi

    2015-08-01

    Descriptive case report.To report a case of a diffuse idiopathic skeletal hyperostosis (DISH) patient with both massive ossification of the anterior longitudinal ligament (OALL) leading to severe dysphagia as well as ossification of the posterior longitudinal ligament (OPLL) causing mild cervical myelopathy, warranting not only an anterior approach but also a posterior one.Although DISH can cause massive OALL in the cervical spine, severe dysphagia resulting from DISH is a rare occurrence. OALLs are frequently associated with OPLL. Treatment for a DISH patient with OPLL in setting of OALL-caused dysphagia is largely unknown.A 70-year-old man presented with severe dysphagia with mild cervical myelopathy. Neurological examination showed mild spastic paralysis and hyper reflex in his lower extremities. Plane radiographs and computed tomography of the cervical spine revealed a discontinuous massive OALL at C4-5 and continuous type OPLL at C2-6. Magnetic resonance imaging revealed pronounced spinal cord compression due to OPLL at C4-5. Esophagram demonstrated extrinsic compression secondary to OALL at C4-5.We performed posterior decompressive laminectomy with posterior lateral mass screw fixation, as well as both resection of OALL and interbody fusion at C4-5 by the anterior approach. We performed posterior decompressive laminectomy with posterior lateral mass screw fixation, as well as both resection of OALL and interbody fusion at C4-5 by the anterior approach. Severe dysphagia markedly improved without any complications.We considered that this patient not only required osteophytectomy and fusion by the anterior approach but also required decompression and spinal fusion by the posterior approach to prevent both deterioration of cervical myelopathy and recurrence of OALL after surgery. PMID:26266365

  15. Cartilage-specific β-CATENIN signaling regulates chondrocyte maturation, generation of ossification centers, and perichondrial bone formation during skeletal development

    PubMed Central

    Dao, Debbie Y.; Jonason, Jennifer H.; Zhang, Yongchun; Hsu, Wei; Chen, Di; Hilton, Matthew J.; O’Keefe, Regis J.

    2012-01-01

    The WNT/β-CATENIN signaling pathway is a critical regulator of chondrocyte and osteoblast differentiation during multiple phases of cartilage and bone development. While the importance of β-CATENIN signaling during the process of endochondral bone development has been previously appreciated using a variety of genetic models that manipulate β-CATENIN in skeletal progenitors and osteoblasts, genetic evidence demonstrating a specific role for β-CATENIN in committed growth plate chondrocytes has been less robust. To identify the specific role of cartilage-derived β-CATENIN in regulating cartilage and bone development, we studied chondrocyte-specific gain- and loss-of-function genetic mouse models using the tamoxifen-inducible Col2CreERT2 transgene in combination with β-cateninfx(exon3)/wt or β-cateninfx/fx floxed alleles, respectively. From these genetic models and biochemical data, three significant and novel findings were uncovered. First, cartilage-specific β-CATENIN signaling promotes chondrocyte maturation, possibly involving a BMP2 mediated mechanism. Second, cartilage-specific β–CATENIN facilitates primary and secondary ossification center formation via the induction of chondrocyte hypertrophy, possibly through enhanced MMP expression at sites of cartilage degradation, and potentially by enhancing IHH signaling activity to recruit vascular tissues. Finally, cartilage-specific β-CATENIN signaling promotes perichondrial bone formation possibly via a mechanism in which BMP2 and IHH paracrine signals synergize to accelerate perichondrial osteoblastic differentiation. The work presented here supports the concept that the cartilage-derived β-CATENIN signal is a central mediator for major events during endochondral bone formation, including chondrocyte maturation, primary and secondary ossification center development, vascularization, and perichondrial bone formation. PMID:22508079

  16. Thyroid hormone receptor-β1 signaling is critically involved in regulating secondary ossification via promoting transcription of the Ihh gene in the epiphysis.

    PubMed

    Xing, Weirong; Aghajanian, Patrick; Goodluck, Helen; Kesavan, Chandrasekhar; Cheng, Shaohong; Pourteymoor, Sheila; Watt, Heather; Alarcon, Catrina; Mohan, Subburaman

    2016-05-15

    Thyroid hormone (TH) action is mediated through two nuclear TH receptors, THRα and THRβ. Although the role of THRα is well established in bone, less is known about the relevance of THRβ-mediated signaling in bone development. On ther basis of our recent finding that TH signaling is essential for initiation and formation of secondary ossification center, we evaluated the role of THRs in mediating TH effects on epiphysial bone formation. Two-day treatment of TH-deficient Tshr(-/-) mice with TH increased THRβ1 mRNA level 3.4-fold at day 7 but had no effect on THRα1 mRNA level at the proximal tibia epiphysis. Treatment of serum-free cultures of tibias from 3-day-old mice with T3 increased THRβ1 expression 2.1- and 13-fold, respectively, at 24 and 72 h. Ten-day treatment of Tshr(-/-) newborns (days 5-14) with THRβ1 agonist GC1 at 0.2 or 2.0 μg/day increased BV/TV at day 21 by 225 and 263%, respectively, compared with vehicle treatment. Two-day treatment with GC1 (0.2 μg/day) increased expression levels of Indian hedgehog (Ihh) 100-fold, osterix 15-fold, and osteocalcin 59-fold compared with vehicle at day 7 in the proximal tibia epiphysis. Gel mobility shift assay demonstrated that a putative TH response element in the distal promoter of mouse Ihh gene interacted with THRβ1. GC1 treatment (1 nM) increased Ihh distal promoter activity 20-fold after 48 h in chondroctyes. Our data suggest a novel role for THRβ1 in secondary ossification at the epiphysis that involves transcriptional upregulation of Ihh gene. PMID:27026086

  17. Prevalence and Distribution of Ossified Lesions in the Whole Spine of Patients with Cervical Ossification of the Posterior Longitudinal Ligament A Multicenter Study (JOSL CT study)

    PubMed Central

    Hirai, Takashi; Yoshii, Toshitaka; Iwanami, Akio; Takeuchi, Kazuhiro; Mori, Kanji; Yamada, Tsuyoshi; Wada, Kanichiro; Koda, Masao; Matsuyama, Yukihiro; Takeshita, Katsushi; Abematsu, Masahiko; Haro, Hirotaka; Watanabe, Masahiko; Watanabe, Kei; Ozawa, Hiroshi; Kanno, Haruo; Imagama, Shiro; Fujibayashi, Shunsuke; Yamazaki, Masashi; Matsumoto, Morio; Nakamura, Masaya; Okawa, Atsushi; Kawaguchi, Yoshiharu

    2016-01-01

    Ossification of the posterior longitudinal ligament (OPLL) can cause severe and irreversible paralysis in not only the cervical spine but also the thoracolumbar spine. To date, however, the prevalence and distribution of OPLL in the whole spine has not been precisely evaluated in patients with cervical OPLL. Therefore, we conducted a multi-center study to comprehensively evaluate the prevalence and distribution of OPLL using multi-detector computed tomography (CT) images in the whole spine and to analyze what factors predict the presence of ossified lesions in the thoracolumbar spine in patients who were diagnosed with cervical OPLL by plain X-ray. Three hundred and twenty-two patients with a diagnosis of cervical OPLL underwent CT imaging of the whole spine. The sum of the levels in which OPLL was present in the whole spine was defined as the OP-index and used to evaluate the extent of ossification. The distribution of OPLL in the whole spine was compared between male and female subjects. In addition, a multiple regression model was used to ascertain related factors that affected the OP-index. Among patients with cervical OPLL, women tended to have more ossified lesions in the thoracolumbar spine than did men. A multiple regression model revealed that the OP-index was significantly correlated with the cervical OP-index, sex (female), and body mass index. Furthermore, the prevalence of thoracolumbar OPLL in patients with a cervical OP-index ≥ 10 was 7.8 times greater than that in patients with a cervical OP-index ≤ 5. The results of this study reveal that the extent of OPLL in the whole spine is significantly associated with the extent of cervical OPLL, female sex, and obesity. PMID:27548354

  18. Women and the Acquired Immunodeficiency Syndrome

    PubMed Central

    Wofsy, Constance B.

    1988-01-01

    SPECIAL EDITOR'S NOTE: Constance B. Wofsy, MD, is Co-Director of AIDS Activities at San Francisco General Hospital and Medical Center, as well as Associate Clinical Professor of Medicine at the University of California, San Francisco; Assistant Chief, Infectious Diseases, San Francisco General Hospital; and Principal Investigator, Project AWARE (Association for Women's AIDS Research and Education). Although she was not able to contribute an article for WOMEN AND MEDICINE on this very important subject, she kindly agreed to an interview. Both physicians and nonphysicians were asked what questions they had about the acquired immunodeficiency syndrome (AIDS) and the human immunodeficiency virus (HIV) in women. Images PMID:3250110

  19. Acquired plate-like osteoma cutis.

    PubMed

    Vashi, Neelam; Chu, Julie; Patel, Rishi

    2011-10-15

    Plate-like osteoma cutis is a rare disorder that has been historically classified as a congenital syndrome. It has a possible relationship to a mutation in the gene (GNAS1) that encodes the α-subunit of the stimulatory G protein, which regulates adenyl cyclase activity. We report a case of extensive plaque-like masses on the scalp and face with no abnormalities in calcium or phosphate metabolism and no preceding inflammatory cutaneous conditions. With less than ten reported cases, to our knowledge, this is one the few cases of acquired plate-like osteoma cutis described in the literature.

  20. Psychological issues in acquired facial trauma

    PubMed Central

    De Sousa, Avinash

    2010-01-01

    The face is a vital component of one’s personality and body image. There are a vast number of variables that influence recovery and rehabilitation from acquired facial trauma many of which are psychological in nature. The present paper presents the various psychological issues one comes across in facial trauma patients. These may range from body image issues to post-traumatic stress disorder symptoms accompanied by anxiety and depression. Issues related to facial and body image affecting social life and general quality of life are vital and the plastic surgeon should be aware of such issues and competent to deal with them in patients and families. PMID:21217982

  1. Triple arthrodesis for adult acquired flatfoot.

    PubMed

    Catanzariti, Alan R; Dix, Brian T; Richardson, Phillip E; Mendicino, Robert W

    2014-07-01

    The primary goal of triple arthrodesis for stage III and IV adult acquired flatfoot is to obtain a well-aligned plantigrade foot that will support the ankle in optimal alignment. Ancillary procedures including posterior muscle group lengthening, medial displacement calcaneal osteotomy, medial column stabilization, peroneus brevis tenotomy, or transfer and harvest of regional bone graft are often necessary to achieve adequate realignment. Image intensification is helpful in confirming optimal realignment before fixation. Results of triple arthrodesis are enhanced with adequate preparation of joint surfaces, bone graft/orthobiologics, 2-point fixation of all 3 tritarsal joints, and a vertical heel position.

  2. Acquired progressive lymphangioma of the nipple

    PubMed Central

    Alkhalili, Eyas; Ayoubieh, Houriya; O'Brien, William; Billings, Steven D

    2014-01-01

    A 47-year-old woman presented with left nipple itch and discomfort. On physical examination she was found to have a 7 mm lesion. She underwent bilateral mammography and bilateral breast ultrasound which were normal. A punch biopsy of the lesion was performed in the office and the specimen submitted to pathology. Histopathological examination showed ectatic vascular spaces lined by flattened, cytologically bland endothelial cells dissecting the dermal collagen. Evident lymphatic valves were present within the vascular spaces confirming that the vessels were lymphatic in nature. The diagnosis of acquired progressive lymphangioma (benign lymphangioendothelioma) was rendered. PMID:25246470

  3. Acquired scalp alopecia. Part II: A review.

    PubMed

    Sullivan, J R; Kossard, S

    1999-05-01

    The neutrophil-associated and infiltrative scarring alopecias are reviewed including folliculitis decalvans, tufted folliculitis, dissecting cellulitis of the scalp, acne keloidalis and follicular degeneration syndrome. The management of acquired scalp alopecia is also reviewed including newer, promising therapies. More specific agents targeting components of the androgen system will make the treatment of androgenetic alopecia more rewarding. Similarly new immunomodulatory therapies show great promise for the lymphocyte-associated alopecias and include a new generation of macrolide immunosuppressives (tacrolimus, SDZ ASM 981, and SDZ 281-240), some of which appear to have good transcutaneous absorption. PMID:10333615

  4. Origins of species: acquired genomes and individuality

    NASA Technical Reports Server (NTRS)

    Margulis, L.

    1993-01-01

    Entire genomes with their accompanying protein synthetic systems are transferred throughout the biosphere primarily as bacteria and protists which become symbionts as they irreversibly integrate into pre-existing organisms to form more complex individuals. Individualization is stabilized by simultaneous transmission of once-separate heterologous genetic systems. The origin of new species is hypothesized to correlate with the acquisition, integration and subsequent inheritance of such acquired microbial genomes. These processes were recognized by Mereschkovsky ("Symbiogenesis" in Russian, 1909) and by Wallin ("Symbionticism", see p. 181, this issue).

  5. Origins of species: acquired genomes and individuality.

    PubMed

    Margulis, L

    1993-01-01

    Entire genomes with their accompanying protein synthetic systems are transferred throughout the biosphere primarily as bacteria and protists which become symbionts as they irreversibly integrate into pre-existing organisms to form more complex individuals. Individualization is stabilized by simultaneous transmission of once-separate heterologous genetic systems. The origin of new species is hypothesized to correlate with the acquisition, integration and subsequent inheritance of such acquired microbial genomes. These processes were recognized by Mereschkovsky ("Symbiogenesis" in Russian, 1909) and by Wallin ("Symbionticism", see p. 181, this issue).

  6. AGU acquires Springer-Verlag Series

    NASA Astrophysics Data System (ADS)

    AGU has acquired Springer-Verlag's (New York) Coastal and Estuarine Studies book series. This acquisition adds thirty-nine volumes to AGU's own Coastal and Estuarine Sciences book series.Coastal and estuarine science is a rapidly growing area of research driven in part by an increasing awareness of man's impact on the coastal zone, and the importance in understanding its delicate ecosystems. This area of study enhances AGU's initiatives in interdisciplinary research. Particular emphasis is being placed on understanding the complex interactions between the physical, geological, chemical, and biological aspects of marine science.

  7. Acquired Congenital Malalignment of the Great Toenails

    PubMed Central

    Decker, Ashley; Scher, Richard K.; Avarbock, Andrew

    2016-01-01

    Congenital malalignment is the lateral deviation of the nail plate along the longitudinal axis due to the lateral rotation of the nail matrix. The nail plate grows out in ridges caused by repeated microtrauma to the nail. Common complications include onychomycosis, Pseudomonas infection and acute or chronic paronychia. Treatment options range from conservative management to surgical options including realignment and nail matrixectomy. Congenital malalignment usually presents in infancy or childhood, but we present two cases of acquired malalignment occurring in the teenage years. PMID:27171597

  8. [Acquired cystic renal disease. Association with hypernephroma].

    PubMed

    Comesaña, E; Pesqueira, D; Tardáguila, F; De la Fuente, A; Antón, I; Vidal, L; Zungri, E

    1992-02-01

    Emergence of multiple bilateral renal cysts observed in patients undergoing periodic haemodialysis is 40%. The pathology, known as Acquired Cystic Renal Disease (A.C.R.D.) presents a high association to renal cancer. Two cases of A.C.R.D. and their association with hypernephroma, one resulting in secondary retroperitoneal haemorrhage and the other in intracystic haemorrhage, are presented. Forms and diagnosis are analyzed, insisting upon the need of monitoring the patients in haemodialysis from the point of view of tumour emergence.

  9. Asian elephants acquire inaccessible food by blowing.

    PubMed

    Mizuno, Kaori; Irie, Naoko; Hiraiwa-Hasegawa, Mariko; Kutsukake, Nobuyuki

    2016-01-01

    Many animals acquire otherwise inaccessible food with the aid of sticks and occasionally water. As an exception, some reports suggest that elephants manipulate breathing through their trunks to acquire inaccessible food. Here, we report on two female Asian elephants (Elephas maximus) in Kamine Zoo, Japan, who regularly blew to drive food within their reach. We experimentally investigated this behaviour by placing foods in inaccessible places. The elephants blew the food until it came within accessible range. Once the food was within range, the elephants were increasingly less likely to blow as the distance to the food became shorter. One subject manipulated her blowing duration based on food distance: longer when the food was distant. These results suggest that the elephants used their breath to achieve goals: that is, they used it not only to retrieve the food but also to fine-tune the food position for easy grasping. We also observed individual differences in the elephants' aptitude for this technique, which altered the efficiency of food acquisition. Thus, we added a new example of spontaneous behaviour for achieving a goal in animals. The use of breath to drive food is probably unique to elephants, with their dexterous trunks and familiarity with manipulating the act of blowing, which is commonly employed for self-comfort and acoustic communication.

  10. Asian elephants acquire inaccessible food by blowing.

    PubMed

    Mizuno, Kaori; Irie, Naoko; Hiraiwa-Hasegawa, Mariko; Kutsukake, Nobuyuki

    2016-01-01

    Many animals acquire otherwise inaccessible food with the aid of sticks and occasionally water. As an exception, some reports suggest that elephants manipulate breathing through their trunks to acquire inaccessible food. Here, we report on two female Asian elephants (Elephas maximus) in Kamine Zoo, Japan, who regularly blew to drive food within their reach. We experimentally investigated this behaviour by placing foods in inaccessible places. The elephants blew the food until it came within accessible range. Once the food was within range, the elephants were increasingly less likely to blow as the distance to the food became shorter. One subject manipulated her blowing duration based on food distance: longer when the food was distant. These results suggest that the elephants used their breath to achieve goals: that is, they used it not only to retrieve the food but also to fine-tune the food position for easy grasping. We also observed individual differences in the elephants' aptitude for this technique, which altered the efficiency of food acquisition. Thus, we added a new example of spontaneous behaviour for achieving a goal in animals. The use of breath to drive food is probably unique to elephants, with their dexterous trunks and familiarity with manipulating the act of blowing, which is commonly employed for self-comfort and acoustic communication. PMID:26541597

  11. Eye movement correlates of acquired central dyslexia.

    PubMed

    Schattka, Kerstin I; Radach, Ralph; Huber, Walter

    2010-08-01

    Based on recent progress in theory and measurement techniques, the analysis of eye movements has become one of the major methodological tools in experimental reading research. Our work uses this approach to advance the understanding of impaired information processing in acquired central dyslexia of stroke patients with aphasia. Up to now there has been no research attempting to analyze both word-based viewing time measures and local fixation patterns in dyslexic readers. The goal of the study was to find out whether specific eye movement parameters reflect pathologically preferred segmental reading in contrast to lexical reading. We compared oral reading of single words of normal controls (n=11) with six aphasic participants (two cases of deep, surface and residual dyslexia each). Participants were asked to read aloud lines of target words differing in length and frequency. Segmental reading was characterized by deviant spatial distribution of saccadic landing positions with initial fixations located mainly at the beginning of the word, while lexical readers showed the normative 'preferred landing positions' left to the center of the words. Contrary to expectation, word length did not distinguish between segmental and lexical readers, while word frequency showed the expected effect for lexical readers only. Their mean fixation duration was already prolonged during first pass reading reflecting their attempts of immediate access to lexical information. After first pass reading, re-reading time was significantly increased in all participants with acquired central dyslexia due to their exceedingly higher monitoring demands for oral reading.

  12. Acquiring functional object knowledge through motor imagery?

    PubMed

    Paulus, Markus; van Elk, Michiel; Bekkering, Harold

    2012-04-01

    A widely investigated question in the research on the acquisition of novel functional object representations is the role of the action system. Whereas most studies so far have investigated the role of active action training on the acquisition of object representation, we investigated whether people are able to acquire object representations by just imagining the use of novel objects, given that previous findings suggested that executed and imagined actions share a common representational format. To this end, participants trained the use of novel objects in a motor imagery condition. Training comprised the particular grip applied to the objects and the objects' typical end location. Subsequently, participants' object representations were assessed by means of an object detection task. The results show that participants responded slower when the novel objects were presented at functionally incorrect end locations, indicating that the participants had acquired functional knowledge about object use. Yet, there was no effect of correct versus incorrect grip. Altogether, the findings suggest that motor imagery can facilitate the acquisition of novel object representations, but point also to differences between first-hand action training and training by imagery.

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

    SciTech Connect

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

    1990-12-01

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

  14. Effects of acoustic and EHF impulses on multipotent stromal cells during formation of bone marrow containing heterotopic organs in tissue engineered constructions.

    PubMed

    Chaikhalyan, R K; Yusupov, V I; Gorskaya, Yu F; Kuralesova, A I; Gerasimov, Yu V; Sviridov, A P; Tambiev, A Kh; Vorob'eva, N N; Shishkova, A G Grosheva V V; Moskvina, I L; Bagratashvili, V N

    2015-03-01

    We studied the effects of physical factors (acoustic impulses of laser-induced hydrodynamics, AILIH, and EHF-radiation) on the formation of heterotopic bone marrow organs. Suspension of precipitated mouse bone marrow cells was exposed to AILIH and EHF or their combinations (AILIH+EHF, EHF+AILIH). The developed tissue engineering constructions (gelatin sponges containing 107 nucleated bone marrow cells exposed to physical factors) were transplanted under the renal capsule of syngeneic mice. Analysis of newly formed hemopoietic organs was performed after 3 and 5 months. The total amount of hemopoietic cells, number of multipotent stromal cells, efficiency of colony formation from these cells, and weight of bone capsule of the transplants were measured. Microscopic study showed that 5-month transplants were significantly larger than 3-month transplants and contained 3-fold more hemopoietic cells (20-fold in the AILIH+EHF group). The number of multipotent stromal cells was maximum in EHF+AILIH group (by 2.2 times higher than in the control) and minimum in AILIH+EHF group. Exposure to EHF+AILIH had most pronounced effect on the formation of the bone marrow transplants. The weight of bone capsules more rapidly increased in gelatin sponges of 3-month transplants of EHF+AILIH and AILIH groups. These data suggest that the studied physical factors can be used for acceleration of rehabilitation process.

  15. Electron spin resonance analysis of heme-nitrosyl and reduced iron-sulfur centered complexes in allogeneic, heterotopic cardiac transplants: effects of treatment with pyrrolidine dithiocarbamate.

    PubMed

    Nakanishi, A L; Roza, A M; Adams, M B; Seibel, R; Moore-Hilton, G; Kalyanaraman, B; Pieper, G M

    1998-07-15

    Inhibition of inducible nitric oxide synthase (iNOS) prolongs allograft survival suggesting a role for nitric oxide (.NO) in allograft rejection. Induction of iNOS is regulated by the oxidant-sensitive, nuclear factor kappa B (NF-kappaB) in many cell types. In the present study using electron spin resonance (ESR) spectroscopy, we evaluated whether pyrrolidine dithiocarbamate (PDTC), a metal chelator and antioxidant, might limit .NO production during the development of rejection in cardiac allografts. We performed either isogeneic (Lewis to Lewis) or allogeneic (Wistar-Furth to Lewis) heterotopic abdominal cardiac transplantation. Allograft recipients received daily injections of PDTC or aminoguanidine (a known inhibitor of iNOS). At postoperative days 4 or 6, grafted and native hearts of transplant recipients were flushed with cardioplegic solution to remove blood contamination. ESR data of allografts revealed a triplet nitrogen signal (aN=17.5 G) and centered at g=2.012 and an additional broad signal at g=2.08. This signal was not seen in either isografts or native hearts of either isograft or allograft recipients. Based upon these parameters, these signals are attributed to nitrosomyoglobin. This signal was inhibited by treatment with aminoguanidine or PDTC. Under these conditions, PDTC also prolonged graft survival from 6.6+/-0.2 to 11.7+/-0.3 days. Thus, it is conceivable that nitrosylmyoglobin formation precedes rejection in cardiac allografts and inhibition of nitrosomyoglobin with agents such as PDTC contribute to improved graft survival. PMID:9667497

  16. Acquiring case adaptation knowledge: A hybrid approach

    SciTech Connect

    Leake, D.B.; Kinley, A.; Wilson, D.

    1996-12-31

    The ability of case-based reasoning (CBR) systems to apply cases to novel situations depends on their case adaptation knowledge. However, endowing CBR systems with adequate adaptation knowledge has proven to be a very difficult task. This paper describes a hybrid method for performing case adaptation, using a combination of rule-based and case-based reasoning. It shows how this approach provides a framework for acquiring flexible adaptation knowledge from experiences with autonomous adaptation and suggests its potential as a basis for acquisition of adaptation knowledge from interactive user guidance. It also presents initial experimental results examining the benefits of the approach and comparing the relative contributions of case learning and adaptation learning to reasoning performance.

  17. Acquire CoOmmodities Easily Card

    1998-05-29

    Acquire Commodities Easily Card (AceCard) provides an automated end-user method to distribute company credit card charges to internal charge numbers. AceCard will allow cardholders to record card purchases in an on-line order log, enter multiple account distributions per order that can be posted to the General Ledger, track orders, and receipt information, and provide a variety of cardholder and administrative reports. Please note: Customers must contact Ed Soler (423)-576-6151, Lockheed Martin Energy Systems, for helpmore » with the installation of the package. The fee for this installation help will be coordinated by the customer and Lockheed Martin and is in addition to cost of the package from ESTSC. Customers should contact Sandy Presley (423)-576-4708 for user help.« less

  18. Acquired alexia: lessons from successful treatment.

    PubMed

    Beeson, P M; Insalaco, D

    1998-11-01

    Two individuals with anomic aphasia and acquired alexia were each provided treatment for their reading impairment. Although reading of single words in isolation was fairly accurate, their text reading was slow and effortful, including functor substitutions and semantic errors. Prior to treatment, reading reaction times for single words showed grammatical class and word-length effects. Both patients responded positively to a treatment protocol that included two phases: (1) multiple oral rereading of text, and (2) reading phrase-formatted text that had increased spacing between phrasal clauses. Their reading rates for text improved while maintaining good comprehension. Following treatment, reading reaction times for single words showed the elimination of grammatical class and word-length effects, suggesting improved access to word forms, particularly functors.

  19. Acquire CoOmmodities Easily Card

    SciTech Connect

    Soler, E. E.

    1998-05-29

    Acquire Commodities Easily Card (AceCard) provides an automated end-user method to distribute company credit card charges to internal charge numbers. AceCard will allow cardholders to record card purchases in an on-line order log, enter multiple account distributions per order that can be posted to the General Ledger, track orders, and receipt information, and provide a variety of cardholder and administrative reports. Please note: Customers must contact Ed Soler (423)-576-6151, Lockheed Martin Energy Systems, for help with the installation of the package. The fee for this installation help will be coordinated by the customer and Lockheed Martin and is in addition to cost of the package from ESTSC. Customers should contact Sandy Presley (423)-576-4708 for user help.

  20. Acquired loss of red cell Kell antigens.

    PubMed

    Vengelen-Tyler, V; Gonzalez, B; Garratty, G; Kruppe, C; Johnson, C L; Mueller, K A; Marsh, W L

    1987-02-01

    A 19-year-old patient with a long history of idiopathic thrombocytopenic purpura developed a potent antibody against a high-incidence antigen in the Kell blood group system. The direct antiglobulin test on his red cells was negative. His cells exhibited profound depression of Kell blood group antigens, but antigens of other blood groups were normal. Transfusion of incompatible blood was well tolerated and differential agglutination tests, using selected Rh antisera, showed in vivo survival of the transfused red cells for more than 8 weeks. However, the transfused red cells also showed acquired loss of Kell antigens. Five months after the initial findings, Kell-related antibody disappeared and Kell antigens reappeared on his red cells. The patient's serum stored from the initial investigation now reacted with his freshly collected red cells. These data suggest that an environmental agent in the patient's plasma was responsible for the temporary loss of Kell antigens from red cells in his circulation.

  1. Stereotypic movement disorder after acquired brain injury.

    PubMed

    McGrath, Cynthia M; Kennedy, Richard E; Hoye, Wayne; Yablon, Stuart A

    2002-05-01

    Stereotypic movement disorder (SMD) consists of repetitive, non-functional motor behaviour that interferes with daily living or causes injury to the person. It is most often described in patients with mental retardation. However, recent evidence indicates that this condition is common among otherwise normal individuals. This case study describes a patient with new-onset SMD occurring after subdural haematoma and brain injury. SMD has rarely been reported after acquired brain injury, and none have documented successful treatment. The current psychiatric literature regarding neurochemistry, neuroanatomy, and treatment of SMD are reviewed with particular application to one patient. Treatment options include serotonin re-uptake inhibitors, opioid antagonists and dopamine antagonists. SMD has been under-appreciated in intellectually normal individuals, and may also be unrecognized after brain injury. Further investigation is needed in this area, which may benefit other individuals with SMD as well.

  2. The acquired immunodeficiency syndrome in gay men.

    PubMed

    Jaffe, H W; Hardy, A M; Morgan, W M; Darrow, W W

    1985-11-01

    The acquired immunodeficiency syndrome (AIDS) is a major health problem for gay men in the United States. About three fourths of all reported cases have occurred in this population, and the number is projected to double in the next year. In Manhattan and San Francisco, AIDS is now the leading cause of premature mortality in men aged 25 to 44 years who have never married. In a sample of a cohort of gay men enrolled in a San Francisco clinic, 2.7% of the men had the syndrome and 26% had related conditions in 1984. Antibody to human T-lymphotropic virus, type III/lymphadenopathy-associated virus was found in sera from 67% of the men, including 58% of asymptomatic men. Behavioral factors associated with an increased risk of AIDS include large numbers of sexual partners, receptive anal intercourse, and "fisting." The adoption of safer lifestyles is currently the basis of attempts to control the syndrome in gay men.

  3. Signal regulators of systemic acquired resistance

    PubMed Central

    Gao, Qing-Ming; Zhu, Shifeng; Kachroo, Pradeep; Kachroo, Aardra

    2015-01-01

    Salicylic acid (SA) is an important phytohormone that plays a vital role in a number of physiological responses, including plant defense. The last two decades have witnessed a number of breakthroughs related to biosynthesis, transport, perception and signaling mediated by SA. These findings demonstrate that SA plays a crictical role in both local and systemic defense responses. Systemic acquired resistance (SAR) is one such SA-dependent response. SAR is a long distance signaling mechanism that provides broad spectrum and long-lasting resistance to secondary infections throughout the plant. This unique feature makes SAR a highly desirable trait in crop production. This review summarizes the recent advances in the role of SA in SAR and discusses its relationship to other SAR inducers. PMID:25918514

  4. Acquired immunodeficiency syndrome: Ga-67 citrate imaging

    SciTech Connect

    Woolfenden, J.M.; Carrasquillo, J.A.; Larson, S.M.; Simmons, J.T.; Masur, H.; Smith, P.D.; Shelhamer, J.H.; Ognibene, F.P.

    1987-02-01

    All gallium-67 citrate scans obtained in patients with acquired immunodeficiency syndrome (AIDS) at the Clinical Center, National Institutes of Health (Bethesda, Md.) were retrospectively analyzed and correlated with the results of bronchoscopy, chest radiography, and endoscopy. There were 164 scans of 95 patients. Twenty scans were from patients with Pneumocystis carinii pneumonia; 19 were abnormal, for a sensitivity of 95%. Ga-67 uptake tended to be less in patients receiving therapy for P. carinii pneumonia. Chest radiographs were normal at least initially in three patients with abnormal scans and P. carinii pneumonia. Unusually prominent colonic activity was associated with infection in some patients. No lesions of Kaposi sarcoma showed tracer uptake. Gallium scanning is useful for detecting P. carinii pneumonia and other opportunistic infections in patients with AIDS, but it is not useful for localizing Kaposi sarcoma.

  5. Antihelper T cell autoantibody in acquired agammaglobulinemia.

    PubMed Central

    Rubinstein, A; Sicklick, M; Mehra, V; Rosen, F S; Levey, R H

    1981-01-01

    A patient with acquired agammaglobulinemia had an antihelper T cell factor that was identified as an immunoglobulin of the IgG class. The factor specifically bound to the TH2- T cell subset and, in the presence of complement, abolished the helper effect of normal T cells. The antihelper T cell antibody preceded by several years the appearance of suppressor TH2+Ia+ T cells, at which time the clinical course rapidly deteriorated. Plasmapheresis resulted in lymphocytosis and reappearance of a functionally intact helper T cell population. It did not affect the suppressor cells. Conversely, total thymectomy resulted in a temporary disappearance of the TH2+Ia+ suppressor cells, but did not decrease the levels of the autoantibody to helper T cells. Neither of these treatments reversed the state of agammaglobulinemia. PMID:6450224

  6. Acquired methaemoglobinaemia related to phenazopyridine ingestion.

    PubMed

    Shahani, Lokesh; Sattovia, Stacy

    2012-09-17

    Methaemoglobin is an altered state of haemoglobin in which the ferrous ions of haeme are oxidised to the ferric state. This results in increased affinity to the bound oxygen and decreasing its availability to tissues. Most cases of methaemoglobinaemia are acquired, resulting from an increased methaemoglobin formation by various exogenous agents. The authors report an elderly patient presenting to the emergency department with a 1-month history of shortness of breath. Around the same time she had started using over-the-counter (OTC) phenazopyridine tablets for urinary symptoms. The patient was hypoxic and cyanotic; however, lacked evidence of hypoxaemia on the arterial blood gas. The presence of abnormal haemoglobin was suspected and confirmed by elevated levels of methaemoglobin. Phenazopyridine was proposed to be the likely aetiology of the methaemoglobinaemia, which the patient was not aware of. This case highlights the importance of always inquiring the OTC drug use especially in geriatric population.

  7. Acquired methaemoglobinaemia related to phenazopyridine ingestion

    PubMed Central

    Shahani, Lokesh; Sattovia, Stacy

    2012-01-01

    Methaemoglobin is an altered state of haemoglobin in which the ferrous ions of haeme are oxidised to the ferric state. This results in increased affinity to the bound oxygen and decreasing its availability to tissues. Most cases of methaemoglobinaemia are acquired, resulting from an increased methaemoglobin formation by various exogenous agents. The authors report an elderly patient presenting to the emergency department with a 1-month history of shortness of breath. Around the same time she had started using over-the-counter (OTC) phenazopyridine tablets for urinary symptoms. The patient was hypoxic and cyanotic; however, lacked evidence of hypoxaemia on the arterial blood gas. The presence of abnormal haemoglobin was suspected and confirmed by elevated levels of methaemoglobin. Phenazopyridine was proposed to be the likely aetiology of the methaemoglobinaemia, which the patient was not aware of. This case highlights the importance of always inquiring the OTC drug use especially in geriatric population. PMID:22987905

  8. Multiple myeloma associated with acquired cutis laxa.

    PubMed

    Cho, S Y; Maguire, R F

    1980-08-01

    Acquired cutis laxa is a rare disorder characterized by diffuse laxity of the skin and loss of connective tissue support with involvement of the lungs, gastrointestinal tract, pelvic organs, and aorta. The case report presented herein describes a forty-six year old woman with multiple myeloma and cutis laxa. Her history included several severe allergic reactions and the gradual development of lax skin, loss of connective tissue support throughout the body, and emphysema. At autopsy, multiple myeloma, diffuse laxity of the skin, and panacinar emphysema were found. The amount of elastic fiber in the skin, lungs, and aorta was decreased and showed abnormal fragmentation. Results of direct immunofluorescence study demonstrated IgG bound to dermal elastic fibers. Speculation regarding an immunologic etiology of the elastic tissue abnormality is presented herein.

  9. Guidelines for prevention of hospital acquired infections

    PubMed Central

    Mehta, Yatin; Gupta, Abhinav; Todi, Subhash; Myatra, SN; Samaddar, D. P.; Patil, Vijaya; Bhattacharya, Pradip Kumar; Ramasubban, Suresh

    2014-01-01

    These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. PMID:24701065

  10. Infantile and acquired nystagmus in childhood.

    PubMed

    Ehrt, Oliver

    2012-11-01

    Nystagmus is an involuntary, periodic eye movement caused by a slow drift of fixation which is followed by a fast refixation saccade (jerk nystagmus) or a slow movement back to fixation (pendular nystagmus). In childhood most cases are benign forms of nystagmus: idiopathic infantile, ocular or latent nystagmus. They arise at the age of 3 months, without oscillopsia and show the absence of the physiologic opto-kinetic nystagmus. A full ophthalmologic evaluation is all that is needed in most cases: albinism, macular or optic nerve hypoplasia and congenital retinal dystrophies are the most common forms of ocular nystagmus. Idiopathic infantile nystagmus can be hereditary, the most common and best analyzed form being a mutation of the FRMD7 gene on chromosome Xq26.2. The mutation shows a mild genotype-phenotype correlation. In all female carriers the opto-kinetic nystagmus is absent and half had mild nystagmus. Latent nystagmus is part of the infantile esotropia syndrome and shows the unique feature of change of direction when the fixing eye changes: it is always beating to the side of the fixing eye. There is no cure for infantile nystagmus but therapeutic options include magnifying visual aids or eye muscle surgery at the age of 6-8 y in patients with head turn. Less than 20% of childhood nystagmus are acquired and need further neurological and imaging work-up. Alarming signs and symptoms are: onset after the age of 4 months, oscillopsia, dissociated (asymmetric) nystagmus, preserved opto-kinetic nystagmus, afferent pupillary defect, papilloedema and neurological symptoms like vertigo and nausea. The most common cause is due to pathology of the anterior optic pathway (e.g. optic nerve gliomas). It shows the same clinical feature of dissociated nystagmus as spasmus nutans but has a higher frequency as in INO. Other forms of acquired nystagmus are due to brainstem, cerebellar or metabolic diseases. PMID:22459007

  11. 48 CFR 970.4102 - Acquiring utility services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Acquiring utility services... SUPPLEMENTARY REGULATIONS DOE MANAGEMENT AND OPERATING CONTRACTS Acquisition of Utility Services 970.4102 Acquiring utility services....

  12. 43 CFR 4110.1-1 - Acquired lands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Acquired lands. 4110.1-1 Section 4110.1-1... and Preference § 4110.1-1 Acquired lands. Where lands have been acquired by the Bureau of Land... of acquisition by the Bureau of Land Management, and are not subject to the requirements of § 4110.1....

  13. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  14. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  15. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  16. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  17. Preschoolers Acquire General Knowledge by Sharing in Pretense

    ERIC Educational Resources Information Center

    Sutherland, Shelbie L.; Friedman, Ori

    2012-01-01

    Children acquire general knowledge about many kinds of things, but there are few known means by which this knowledge is acquired. In this article, it is proposed that children acquire generic knowledge by sharing in pretend play. In Experiment 1, twenty-two 3- to 4-year-olds watched pretense in which a puppet represented a "nerp" (an unfamiliar…

  18. 7 CFR 1779.90 - Disposition of acquired property.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Disposition of acquired property. 1779.90 Section..., DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.90 Disposition of acquired property. (a) General. When the lender acquires title to the collateral and the...

  19. 7 CFR 770.8 - Use of acquired land.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Use of acquired land. 770.8 Section 770.8 Agriculture... SPECIAL PROGRAMS INDIAN TRIBAL LAND ACQUISITION LOANS § 770.8 Use of acquired land. (a) General. Subject to § 770.5(d) land acquired with loan funds, or other property serving as the security for a...

  20. 25 CFR 211.8 - Government employees cannot acquire leases.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... TRIBAL LANDS FOR MINERAL DEVELOPMENT General § 211.8 Government employees cannot acquire leases. U.S. Government employees are prevented from acquiring leases or interests in leases by the provisions of 25 CFR... 25 Indians 1 2011-04-01 2011-04-01 false Government employees cannot acquire leases. 211.8...

  1. 25 CFR 212.8 - Government employees cannot acquire leases.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ALLOTTED LANDS FOR MINERAL DEVELOPMENT General § 212.8 Government employees cannot acquire leases. U.S. Government employees are prevented from acquiring leases or interests in leases by the provisions of 25 CFR... 25 Indians 1 2011-04-01 2011-04-01 false Government employees cannot acquire leases. 212.8...

  2. 25 CFR 212.8 - Government employees cannot acquire leases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ALLOTTED LANDS FOR MINERAL DEVELOPMENT General § 212.8 Government employees cannot acquire leases. U.S. Government employees are prevented from acquiring leases or interests in leases by the provisions of 25 CFR... 25 Indians 1 2010-04-01 2010-04-01 false Government employees cannot acquire leases. 212.8...

  3. 25 CFR 211.8 - Government employees cannot acquire leases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TRIBAL LANDS FOR MINERAL DEVELOPMENT General § 211.8 Government employees cannot acquire leases. U.S. Government employees are prevented from acquiring leases or interests in leases by the provisions of 25 CFR... 25 Indians 1 2010-04-01 2010-04-01 false Government employees cannot acquire leases. 211.8...

  4. Acquired prosopagnosia: structural basis and processing impairments.

    PubMed

    Davies-Thompson, Jodie; Pancaroglu, Raika; Barton, Jason

    2014-01-01

    Cognitive models propose a hierarchy of parallel processing stages in face perception, and functional neuroimaging shows a network of regions involved in face processing. Reflecting this, acquired prosopagnosia is not a single entity but a family of disorders with different anatomic lesions and different functional deficits. One classic distinction is between an apperceptive variant, in which there is impaired perception of facial structure, and an associative/amnestic variant, in which perception is relatively intact, with subsequent problems matching perception to facial memories, because of either disconnection or loss of those memories. These disorders also have to be distinguished from people-specific amnesia, a multimodal impairment, and prosop-anomia, in which familiarity with faces is preserved but access to names is disrupted. These different disorders can be conceived as specific deficits at different processing stages in cognitive models, and suggests that these functional stages may have distinct neuroanatomic substrates. It remains to be seen whether a similar anatomic and functional variability is present in developmental prosopagnosia.

  5. Acquiring synaesthesia: insights from training studies

    PubMed Central

    Rothen, Nicolas; Meier, Beat

    2014-01-01

    Synaesthesia denotes a condition of remarkable individual differences in experience characterized by specific additional experiences in response to normal sensory input. Synaesthesia seems to (i) run in families which suggests a genetic component, (ii) is associated with marked structural and functional neural differences, and (iii) is usually reported to exist from early childhood. Hence, synaesthesia is generally regarded as a congenital phenomenon. However, most synaesthetic experiences are triggered by cultural artifacts (e.g., letters, musical sounds). Evidence exists to suggest that synaesthetic experiences are triggered by the conceptual representation of their inducer stimuli. Cases were identified for which the specific synaesthetic associations are related to prior experiences and large scale studies show that grapheme-color associations in synaesthesia are not completely random. Hence, a learning component is inherently involved in the development of specific synaesthetic associations. Researchers have hypothesized that associative learning is the critical mechanism. Recently, it has become of scientific and public interest if synaesthetic experiences may be acquired by means of associative training procedures and whether the gains of these trainings are associated with similar cognitive benefits as genuine synaesthetic experiences. In order to shed light on these issues and inform synaesthesia researchers and the general interested public alike, we provide a comprehensive literature review on developmental aspects of synaesthesia and specific training procedures in non-synaesthetes. Under the light of a clear working definition of synaesthesia, we come to the conclusion that synaesthesia can potentially be learned by the appropriate training. PMID:24624072

  6. Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome.

    PubMed Central

    Collins, F M

    1989-01-01

    The mycobacteria are an important group of acid-fast pathogens ranging from obligate intracellular parasites such as Mycobacterium leprae to environmental species such as M. gordonae and M. fortuitum. The latter may behave as opportunistic human pathogens if the host defenses have been depleted in some manner. The number and severity of such infections have increased markedly with the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic. These nontuberculous mycobacteria tend to be less virulent for humans than M. tuberculosis, usually giving rise to self-limiting infections involving the cervical and mesenteric lymph nodes of young children. However, the more virulent serovars of M. avium complex can colonize the bronchial and intestinal mucosal surfaces of healthy individuals, becoming virtual members of the commensal gut microflora and thus giving rise to low levels of skin hypersensitivity to tuberculins prepared from M. avium and M. intracellulare. Systemic disease develops when the normal T-cell-mediated defenses become depleted as a result of old age, cancer chemotherapy, or infection with human immunodeficiency virus. As many as 50% of human immunodeficiency virus antibody-positive individuals develop mycobacterial infections at some time during their disease. Most isolates of M. avium complex from AIDS patients fall into serotypes 4 and 8. The presence of these drug-resistant mycobacteria in the lungs of the AIDS patient makes their effective clinical treatment virtually impossible. More effective chemotherapeutic, prophylactic, and immunotherapeutic reagents are urgently needed to treat this rapidly increasing patient population. PMID:2680057

  7. [Acquired and congenital heart diseases during pregancy].

    PubMed

    De Feo, Stefania; Iacovoni, Attilio; Faggiano, Pompilio

    2012-05-01

    Heart diseases are the leading cause of maternal morbidity and mortality. The number of patients with congenital heart diseases reaching childbearing age, as well as the proportion of women with acquired conditions, such as ischemic heart disease, becoming pregnant is constantly increasing. All women with known heart disease should have pre-pregnancy counseling, to assess maternal and fetal risk. Women at moderate or high risk should be under the care of a specialist prenatal team with experience in managing women with heart disease during pregnancy. Conditions that are considered at particularly high risk (mortality >10%) include Marfan syndrome with dilated aortic root, severe left ventricular dysfunction, severe left heart obstructive lesions, and pulmonary hypertension. Peripartum cardiomyopathy is a rare and potentially fatal disease related to pregnancy and the postnatal period that presents with symptoms of congestion and/or hypoperfusion and may rapidly progress to acute and life-threatening heart failure. However, the majority of women with heart disease can tolerate pregnancy; therefore an adequate multidisciplinary approach with the gynecologist, anesthesiologist and cardiologist should be advocated in order to reduce maternal and fetal risks associated with pregnancy.

  8. Community-acquired pneumonia among smokers.

    PubMed

    Almirall, Jordi; Blanquer, José; Bello, Salvador

    2014-06-01

    Recent studies have left absolutely no doubt that tobacco increases susceptibility to bacterial lung infection, even in passive smokers. This relationship also shows a dose-response effect, since the risk reduces spectacularly 10 years after giving up smoking, returning to the level of non-smokers. Streptococcus pneumoniae is the causative microorganism responsible for community-acquired pneumonia (CAP) most frequently associated with smoking, particularly in invasive pneumococcal disease and septic shock. It is not clear how it acts on the progress of pneumonia, but there is evidence to suggest that the prognosis for pneumococcal pneumonia is worse. In CAP caused by Legionella pneumophila, it has also been observed that smoking is the most important risk factor, with the risk rising 121% for each pack of cigarettes smoked a day. Tobacco use may also favor diseases that are also known risk factors for CAP, such as periodontal disease and upper respiratory viral infections. By way of prevention, while giving up smoking should always be proposed, the use of the pneumococcal vaccine is also recommended, regardless of the presence of other comorbidities.

  9. Community-acquired pneumonia among smokers.

    PubMed

    Almirall, Jordi; Blanquer, José; Bello, Salvador

    2014-06-01

    Recent studies have left absolutely no doubt that tobacco increases susceptibility to bacterial lung infection, even in passive smokers. This relationship also shows a dose-response effect, since the risk reduces spectacularly 10 years after giving up smoking, returning to the level of non-smokers. Streptococcus pneumoniae is the causative microorganism responsible for community-acquired pneumonia (CAP) most frequently associated with smoking, particularly in invasive pneumococcal disease and septic shock. It is not clear how it acts on the progress of pneumonia, but there is evidence to suggest that the prognosis for pneumococcal pneumonia is worse. In CAP caused by Legionella pneumophila, it has also been observed that smoking is the most important risk factor, with the risk rising 121% for each pack of cigarettes smoked a day. Tobacco use may also favor diseases that are also known risk factors for CAP, such as periodontal disease and upper respiratory viral infections. By way of prevention, while giving up smoking should always be proposed, the use of the pneumococcal vaccine is also recommended, regardless of the presence of other comorbidities. PMID:24387877

  10. Community-acquired pneumonia: An overview.

    PubMed

    Mandell, Lionel A

    2015-08-01

    Community-acquired pneumonia is still a significant cause of morbidity and mortality and is often misdiagnosed and inappropriately treated. Although it can be caused by a wide variety of micro-organisms, the pneumococcus, atypicals, such as Mycoplasma pneumoniae and Chlamydophila pneumoniae, Staphylococcus aureus and certain Gram-negative rods are the usual pathogens encountered. The site-of-care decision is critical in determining the site and type of care as well as the extent of diagnostic workup. Antimicrobial therapy should be started as soon as possible particularly in those requiring admission to hospital, but typically the physician does not know with any degree of certainty the identity of the etiologic pathogen. A number of national guidelines have been published to help the physician with this choice. The initial drug(s) can be modified if necessary if the pathogen and its antimicrobial susceptibility pattern becomes known. Adjunctive therapy such as pressors and fluid replacement are of value and macrolides appear to help as well, likely secondary to their immunomodulatory effects. Recent data also suggest a role for steroids.

  11. [Severe community-acquired pneumonia in adults].

    PubMed

    Arancibia H, Francisco; Díaz P, Orlando

    2005-01-01

    Patients with severe community acquired pneumonia (CAP) need continuous surveillance and monitoring at intensive care units (ICU), where they can receive specialized support as mechanical ventilation and/or hemodynamic support. Patients that require ICU admittance represent 10 to 30% of all patients interned because a pneumonia. In this category, high complication rate, prolonged hospital stay and high mortality rate are the rule. The American Thoracic Society (ATS) criteria for severe pneumonia establishes the following main criteria: necessity of mechanical ventilation and presence of septic shock; minor criteria: systolic blood pressure < 90 mmHg, radiological multilobar involvement and PaO2/FiO2 < 250 mmHg. British Thoracic Society (BTS) criteria for severe CAP are: respiratory rate over 30 breaths/min, diastolic blood pressure under 60 mmHg, BUN > 20 mg/dl and mental confusion. In all patients with CAP it is recommended the evaluation of its severity at admission. This evaluation should be done in conjunction with an experienced physician, and if criteria for poor prognosis are met, an early admission to ICU is recommended. ATS and BTS modified criteria (CURB) are useful in this procedure. In severely ill patients with CAP it is recommended to perform the following microbiological analysis: sputum Gram stain and culture, blood culture, pleural fluid Gram stain and culture, if present and tapped, Legionella pneumophila urine antigen test, influenza A and B antigen detection tests (epidemic period: autumn and winter), and serology for atypical bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae).

  12. Acquired Hemophilia A Successfully Treated with Rituximab

    PubMed Central

    D’Arena, Giovanni; Grandone, Elvira; Di Minno, Matteo Nicola Dario; Musto, Pellegrino; Di Minno, Giovanni

    2015-01-01

    Acquired hemophilia A (AHA) is a rare bleeding disorder due to the development of specific autoantibodies against factor VIII. The anti-CD20 monoclonal antibody Rituximab has been proven to be effective in obtaining a long-term suppression of inhibitors of AHA, besides other immunosuppressive standard treatments. Here we describe a case of idiopathic AHA in a 60-year old man successfully treated with rituximab. He showed a complete clinical response with a normalization of clotting parameters after 5 weekly courses of rituximab given at a dose of 375 mg/sqm., but after stopping rituximab, an initial worsening of coagulation parameters induced the addition of 3 further courses. At present, the patient is in complete clinical and hematological remission after 200 days. This case confirms that Rituximab may be a safe and useful tool to treat AHA and, a prolonged administration can overcome the initial resistance. However, the precise position of this drug in the therapeutic strategy (first or second-line, alone or in combination with other drugs) remains to be established and warrants further investigation. PMID:25745551

  13. Acquired hemophilia a successfully treated with rituximab.

    PubMed

    D'Arena, Giovanni; Grandone, Elvira; Di Minno, Matteo Nicola Dario; Musto, Pellegrino; Di Minno, Giovanni

    2015-01-01

    Acquired hemophilia A (AHA) is a rare bleeding disorder due to the development of specific autoantibodies against factor VIII. The anti-CD20 monoclonal antibody Rituximab has been proven to be effective in obtaining a long-term suppression of inhibitors of AHA, besides other immunosuppressive standard treatments. Here we describe a case of idiopathic AHA in a 60-year old man successfully treated with rituximab. He showed a complete clinical response with a normalization of clotting parameters after 5 weekly courses of rituximab given at a dose of 375 mg/sqm., but after stopping rituximab, an initial worsening of coagulation parameters induced the addition of 3 further courses. At present, the patient is in complete clinical and hematological remission after 200 days. This case confirms that Rituximab may be a safe and useful tool to treat AHA and, a prolonged administration can overcome the initial resistance. However, the precise position of this drug in the therapeutic strategy (first or second-line, alone or in combination with other drugs) remains to be established and warrants further investigation. PMID:25745551

  14. Community-acquired Pneumonia and its Complications.

    PubMed

    Qin, Qiang; Shen, Kun-ling

    2015-08-01

    Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality worldwide in developing and developed countries, and its incidence is highest among children less than 5-y-old. Over the last five years, several international and local guidelines have been updated with new evidence concerning the epidemiology, etiology, pathogenesis, treatment and prevention of pediatric CAP, but there are still several major problems that need to be standardised. The aim of this review is to consider the available data concerning the termination, epidemiology, microbiology and pathogenesis, clinical features, diagnosis and differential diagnosis, treatment, and complications of pediatric CAP. There still are many unanswered questions concerning the management of CAP, including its definition, the difficulty to identify its etiological agents, the emergence of drug, and the lack of introduction of vaccines against respiratory pathogens in developing countries. More research is required in various areas (including therapy of atypical agents), and further efforts are needed to increase vaccination in order to reduce the incidence of the disease. PMID:25976616

  15. Salmonella acquires ferrous iron from haemophagocytic macrophages.

    PubMed

    Nagy, Toni A; Moreland, Sarah M; Detweiler, Corrella S

    2014-09-01

    Bacteria harbour both ferrous and ferric iron transporters. We now report that infection of macrophages and mice with a Salmonella enterica Typhimurium strain containing an inactivated feoB-encoded ferrous iron transporter results in increased bacterial replication, compared to infection with wild type. Inactivation of other cation transporters, SitABCD or MntH, did not increase bacterial replication. The feoB mutant strain does not have an intrinsically faster growth rate. Instead, increased replication correlated with increased expression in macrophages of the fepB-encoded bacterial ferric iron transporter and also required siderophores, which capture ferric iron. Co-infection of mice with wild type and a feoB mutant strain yielded a different outcome: FeoB is clearly required for tissue colonization. In co-infected primary mouse macrophages, FeoB is required for S. Typhimurium replication if the macrophages were IFNγ treated and contain phagocytosed erythrocytes, a model for haemophagocytosis. Haemophagocytes are macrophages that have engulfed erythrocytes and/or leucocytes and can harbour Salmonella in mice. These observations suggest that Salmonella acquires ferrous iron from haemophagocytic macrophages.

  16. [Acquired polycystic degeneration of the kidneys].

    PubMed

    Kreisel-Büstgens, C; Büstgens, L; Graben, N

    1990-12-15

    Kidneys of patients with advanced renal insufficiency undergo polycystic transformation, described as acquired cystic degeneration (ACD). In 118 chronic dialysis patients clinical data were compared with sonographic findings of their 221 cirrhotic kidneys: 74 (63%) patients showed distinctly discernible renal cysts: 19 patients hat one single cyst, nine patients had two to eight cysts, 46 patients had more than eight cysts. Accordingly 39% of patients had ACD. Cystic transformation was of the same degree on both sides and in a few cases so marked that a formal discrimination to congenital cystic disease seemed impossible. Cystic degeneration was not influenced by patient's age, sex or underlying renal disease, but was dependent on the duration of both, renal disease and dialysis treatment. After eight years 71% of dialysis patients had ACD. In coincidence with cystic transformation the size of the kidneys apparently normalized and Hb-concentration rose from 8 to 10 g/dl. Complications were seen in six patients: two severe retroperitoneal bleedings and four hypernephroma were observed. The etiology of cystic transformation and its possible role as precancerosis are discussed.

  17. Comparison of clinical outcomes in decompression and fusion versus decompression only in patients with ossification of the posterior longitudinal ligament: a meta-analysis.

    PubMed

    Mehdi, Syed K; Alentado, Vincent J; Lee, Bryan S; Mroz, Thomas E; Benzel, Edward C; Steinmetz, Michael P

    2016-06-01

    OBJECTIVE Ossification of the posterior longitudinal ligament (OPLL) is a pathological calcification or ossification of the PLL, predominantly occurring in the cervical spine. Although surgery is often necessary for patients with symptomatic neurological deterioration, there remains controversy with regard to the optimal surgical treatment. In this systematic review and meta-analysis, the authors identified differences in complications and outcomes after anterior or posterior decompression and fusion versus after decompression alone for the treatment of cervical myelopathy due to OPLL. METHODS A MEDLINE, SCOPUS, and Web of Science search was performed for studies reporting complications and outcomes after decompression and fusion or after decompression alone for patients with OPLL. A meta-analysis was performed to calculate effect summary mean values, 95% CIs, Q statistics, and I(2) values. Forest plots were constructed for each analysis group. RESULTS Of the 2630 retrieved articles, 32 met the inclusion criteria. There was no statistically significant difference in the incidence of excellent and good outcomes and of fair and poor outcomes between the decompression and fusion and the decompression-only cohorts. However, the decompression and fusion cohort had a statistically significantly higher recovery rate (63.2% vs 53.9%; p < 0.0001), a higher final Japanese Orthopaedic Association score (14.0 vs 13.5; p < 0.0001), and a lower incidence of OPLL progression (< 1% vs 6.3%; p < 0.0001) compared with the decompression-only cohort. There was no statistically significant difference in the incidence of complications between the 2 cohorts. CONCLUSIONS This study represents the only comprehensive review of outcomes and complications after decompression and fusion or after decompression alone for OPLL across a heterogeneous group of surgeons and patients. Based on these results, decompression and fusion is a superior surgical technique compared with posterior

  18. Comparison of clinical outcomes in decompression and fusion versus decompression only in patients with ossification of the posterior longitudinal ligament: a meta-analysis.

    PubMed

    Mehdi, Syed K; Alentado, Vincent J; Lee, Bryan S; Mroz, Thomas E; Benzel, Edward C; Steinmetz, Michael P

    2016-06-01

    OBJECTIVE Ossification of the posterior longitudinal ligament (OPLL) is a pathological calcification or ossification of the PLL, predominantly occurring in the cervical spine. Although surgery is often necessary for patients with symptomatic neurological deterioration, there remains controversy with regard to the optimal surgical treatment. In this systematic review and meta-analysis, the authors identified differences in complications and outcomes after anterior or posterior decompression and fusion versus after decompression alone for the treatment of cervical myelopathy due to OPLL. METHODS A MEDLINE, SCOPUS, and Web of Science search was performed for studies reporting complications and outcomes after decompression and fusion or after decompression alone for patients with OPLL. A meta-analysis was performed to calculate effect summary mean values, 95% CIs, Q statistics, and I(2) values. Forest plots were constructed for each analysis group. RESULTS Of the 2630 retrieved articles, 32 met the inclusion criteria. There was no statistically significant difference in the incidence of excellent and good outcomes and of fair and poor outcomes between the decompression and fusion and the decompression-only cohorts. However, the decompression and fusion cohort had a statistically significantly higher recovery rate (63.2% vs 53.9%; p < 0.0001), a higher final Japanese Orthopaedic Association score (14.0 vs 13.5; p < 0.0001), and a lower incidence of OPLL progression (< 1% vs 6.3%; p < 0.0001) compared with the decompression-only cohort. There was no statistically significant difference in the incidence of complications between the 2 cohorts. CONCLUSIONS This study represents the only comprehensive review of outcomes and complications after decompression and fusion or after decompression alone for OPLL across a heterogeneous group of surgeons and patients. Based on these results, decompression and fusion is a superior surgical technique compared with posterior

  19. Risk factors for early redislocation after primary treatment of developmental dysplasia of the hip: Is there a protective influence of the ossific nucleus?

    PubMed Central

    Bhaskar, Atul; Desai, Hardik; Jain, Gaurav

    2016-01-01

    Background: Re-dislocation after primary treatment of developmental dysplasia of the hip is a serious complication. We analyzed the various risk factors that contribute to re-dislocation, and whether the bony ossific nucleus (ON) confers increased stability against re-dislocation. Materials and Methods: Fifty-five children (60 hips) were classified into three treatment groups: Closed reduction (CR) in 15 children (17 hips), open reduction (OR) in 26 children (28 hips), and OR with bony surgery (ORB) in 14 children (15 hips). The mean age at initial treatment was 16 months (range 6–36 months). Fifty-one hips and 9 hips were Tonnis Grade 4 and 3, respectively. The mean preoperative acetabular index (AI) was 44.82° (range 32°–56°) for the study group. At initial treatment, bony ON was absent in 8 hips and present in 52 hips. Results: No hip developed stiffness and pain after primary treatment. Although the AI index, Tonnis grade, and absence of ossific nucleus were higher in the re-dislocated groups, this was not statistically significant. Excluding the re-dislocations, four children had a fair outcome, 11 had good outcome, and 36 had excellent outcome as per McKay's criteria. In the CR group (17 hips), two children (2 hips) with absent ON had re-dislocation. In the OR group (28 hips), three re-dislocations were seen (three children) at 3, 5, and 7 months, respectively. Two of these had an absent bony ON. In the ORB group (15 hips), one late sub-luxation occurred in a child with absent ON. The mean preoperative AI for the re-dislocated and located group was 44.66° (range 42°–48°) and 44.53° (range 39°–56°), respectively. The postoperative AI was 34.53. Conclusion: The experience of the treating surgeon and technical factors play an overwhelming role in preventing early dislocation. The absence of ON should perhaps alert the surgeon for enhanced spica care, postoperative splinting, and meticulous intra-operative management. PMID:27746489

  20. A New Animal Model for Investigation of Mechanical Unloading in Hypertrophic and Failing Hearts: Combination of Transverse Aortic Constriction and Heterotopic Heart Transplantation

    PubMed Central

    Stenzig, Justus; Biermann, Daniel; Jelinek, Marisa; Reichenspurner, Hermann; Eschenhagen, Thomas; Ehmke, Heimo; Schwoerer, Alexander P.

    2016-01-01

    Objectives Previous small animal models for simulation of mechanical unloading are solely performed in healthy or infarcted hearts, not representing the pathophysiology of hypertrophic and dilated hearts emerging in heart failure patients. In this article, we present a new and economic small animal model to investigate mechanical unloading in hypertrophic and failing hearts: the combination of transverse aortic constriction (TAC) and heterotopic heart transplantation (hHTx) in rats. Methods To induce cardiac hypertrophy and failure in rat hearts, three-week old rats underwent TAC procedure. Three and six weeks after TAC, hHTx with hypertrophic and failing hearts in Lewis rats was performed to induce mechanical unloading. After 14 days of mechanical unloading animals were euthanatized and grafts were explanted for further investigations. Results 50 TAC procedures were performed with a survival of 92% (46/50). When compared to healthy rats left ventricular surface decreased to 5.8±1.0 mm² (vs. 9.6± 2.4 mm²) (p = 0.001) after three weeks with a fractional shortening (FS) of 23.7± 4.3% vs. 28.2± 1.5% (p = 0.01). Six weeks later, systolic function decreased to 17.1± 3.2% vs. 28.2± 1.5% (p = 0.0001) and left ventricular inner surface increased to 19.9±1.1 mm² (p = 0.0001). Intraoperative graft survival during hHTx was 80% with 46 performed procedures (37/46). All transplanted organs survived two weeks of mechanical unloading. Discussion Combination of TAC and hHTx in rats offers an economic and reproducible small animal model enabling serial examination of mechanical unloading in a truly hypertrophic and failing heart, representing the typical pressure overloaded and dilated LV, occurring in patients with moderate to severe heart failure. PMID:26841021

  1. Acquired prosopagnosia abolishes the face inversion effect.

    PubMed

    Busigny, Thomas; Rossion, Bruno

    2010-09-01

    Individual faces are notoriously difficult to recognize when they are presented upside-down. Since acquired prosopagnosia (AP) has been associated with an impairment of expert face processes, a reduced or abolished face inversion effect (FIE) is expected in AP. However, previous studies have incongruently reported apparent normal effects of inversion, a decreased or abolished FIE, but also a surprisingly better performance for inverted faces for some patients. While these discrepant observations may be due to the variability of high-level processes impaired, a careful look at the literature rather suggests that the pattern of FIE in prosopagnosia has been obscured by a selection of patients with associated low-level defects and general visual recognition impairments, as well as trade-offs between accuracy and correct RT measures. Here we conducted an extensive investigation of upright and inverted face processing in a well-characterized case of face-selective AP, PS (Rossion et al., 2003). In 4 individual face discrimination experiments, PS did not present any inversion effect at all, taking into account all dependent measures of performance. However, she showed a small inversion cost for individualizing members of a category of non-face objects (cars), just like normal observers. A fifth experiment with personally familiar faces to recognize confirmed the lack of inversion effect for PS. Following the present report and a survey of the literature, we conclude that the FIE is generally absent, or at least clearly reduced following AP. We also suggest that the paradoxical superior performance for inverted faces observed in rare cases may be due to additional upper visual field defects rather than to high-level competing visual processes. These observations are entirely compatible with the view that AP is associated with a disruption of a process that is also abolished following inversion: the holistic representation of individual exemplars of the face class.

  2. Impact of lactobacilli on orally acquired listeriosis

    PubMed Central

    Archambaud, Cristel; Nahori, Marie-Anne; Soubigou, Guillaume; Bécavin, Christophe; Laval, Laure; Lechat, Pierre; Smokvina, Tamara; Langella, Philippe; Lecuit, Marc; Cossart, Pascale

    2012-01-01

    Listeria monocytogenes is a foodborne pathogen that crosses the intestinal barrier and disseminates within the host. Here, we report a unique comprehensive analysis of the impact of two Lactobacillus species, Lactobacillus paracasei CNCM I-3689 and Lactobacillus casei BL23, on L. monocytogenes and orally acquired listeriosis in a gnotobiotic humanized mouse model. We first assessed the effect of treatment with each Lactobacillus on L. monocytogenes counts in host tissues and showed that each decreases L. monocytogenes systemic dissemination in orally inoculated mice. A whole genome intestinal transcriptomic analysis revealed that each Lactobacillus changes expression of a specific subset of genes during infection, with IFN-stimulated genes (ISGs) being the most affected by both lactobacilli. We also examined microRNA (miR) expression and showed that three miRs (miR-192, miR-200b, and miR-215) are repressed during L. monocytogenes infection. Treatment with each Lactobacillus increased miR-192 expression, whereas only L. casei association increased miR-200b and miR-215 expression. Finally, we showed that treatment with each Lactobacillus significantly reshaped the L. monocytogenes transcriptome and up-regulated transcription of L. monocytogenes genes encoding enzymes allowing utilization of intestinal carbon and nitrogen sources in particular genes involved in propanediol and ethanolamine catabolism and cobalamin biosynthesis. Altogether, these data reveal that the modulation of L. monocytogenes infection by treatment with lactobacilli correlates with a decrease in host gene expression, in particular ISGs, miR regulation, and a dramatic reshaping of L. monocytogenes transcriptome. PMID:23012479

  3. [Clinical aspects of acquired antithrombin III deficiency].

    PubMed

    von Blohn, G; Hellstern, P; Köhler, M; Scheffler, P; Wenzel, E

    1986-02-01

    The significance of acquired antithrombin III (AT III) deficiency must be interpreted in close relation to the underlying disease process. In patients with acute or chronic liver impairment, the AT III activity is related to a decrease of procoagulatory factors, whereas, in protein loss syndromes such as nephrotic syndrome, the AT III indicates an increased risk of thromboembolic events. The effect of oral contraceptives (OC) on AT III levels in young healthy females (n = 30) was determined prospectively. AT III decreases during OC usage could not be related to the estrogen content of the examined oral contraceptives, and there was no parallel decrease of AT III activity and concentration in each type of OC. In a prospective study, the extent of AT III decrease was determined in patients undergoing cardiopulmonary bypass operations (CPB) receiving different anticoagulant schedules during extracorporeal circulation (n = 49). There was no significant influence on the effectiveness of anticoagulation by the observed AT III decreases. AT III deficiency during CPB was primarily the result of hemodilution. However, the AT III kinetics were significantly influenced by the different protamin dosages and were not affected by the different heparin dosages. Correction of diminished AT III levels by substitution of AT III concentrates is beneficial in cases, in which an interruption of an enhanced coagulatory process such as disseminated intravascular coagulation is necessary or in patients requiring high dosage heparinization as in deep vein thrombosis. In those cases the quality of AT III correction correlates to the course of the disease. However, the potency of concentrates as well as the individual AT III recovery and half-life must be considered for an appropriate treatment with AT III substitution. PMID:3718407

  4. Thymus involution in the acquired immunodeficiency syndrome.

    PubMed

    Grody, W W; Fligiel, S; Naeim, F

    1985-07-01

    Acquired immunodeficiency syndrome (AIDS) is a severe disorder of unknown etiology and pathogenesis, predominantly affecting homosexual males and other high-risk groups and characterized by profound alterations in T-lymphocyte function. The authors have examined thymus tissue from 14 patients who died of AIDS and compared the results with findings in five control groups: healthy age-matched controls, elderly individuals, patients with chronic or debilitating illnesses other than AIDS, infants with conditions causing "stress atrophy," and patients with myasthenia gravis. The AIDS group included 11 homosexual males, 1 Haitian, 1 homosexual who was also a drug abuser, and a 10-month-old infant believed to have contracted AIDS following blood transfusion. All the AIDS cases showed marked thymus involution with severe depletion of both lymphocytes and epithelial elements. The latter component consisted primarily of thin cords and nests of primitive-appearing epithelial cells that could be defined by positive immunohistochemical staining for keratin. Many cases showed a variable plasma cell infiltration, and the majority exhibited distinct vascular changes in the form of hyalinization and/or onion-skin patterns, primarily in the adventitia. Most striking of all was the marked paucity of Hassall's corpuscles; four patients had none at all, while in the other ten patients all the Hassall's corpuscles were calcified. These changes were far more extensive than those seen in any of the control groups, which retained most of their complement of Hassall's corpuscles even in the face of marked overall involution. The physiologic function of Hassall's corpuscles is not known, but recent immunohistochemical studies have implicated them in the synthesis of "facteur thymique serique" (FTS, thymulin) and other thymic hormones known to play a role in regulating T-helper and suppressor cell activity. It is conceivable that the extensive destruction of Hassall's corpuscles observed in

  5. MECHANISMS OF ACQUIRED RESISTANCE IN MOUSE TYPHOID

    PubMed Central

    Blanden, R. V.; Mackaness, G. B.; Collins, F. M.

    1966-01-01

    Experiments in vitro comparing normal mouse peritoneal macrophages with cells from Salmonella typhimurium-infected mice have shown that the "immune" macrophages have conspicuously enhanced microbicidal properties. Whereas normal macrophages could inactivate only 50 to 60% of intracellular S. typhimurium pretreated with immune serum, cells from infected animals killed virtually all ingested organisms and did so at an accelerated rate. Macrophages from Listeria monocytogenes-infected mice were shown to possess similarly enhanced microbicidal activity against S. typhimurium. Furthermore, the growth of S. typhimurium in the liver and spleen was more effectively restricted in Listeria-infected mice than in animals vaccinated with heat-killed S. typhimurium, even though the Listeria-infected animals possessed no demonstrable cross-reacting antibody to S. typhimurium. The lack of resistance in the mice vaccinated with heat-killed organisms could not be attributed to any deficiency of humoral factors, since the serum from these animals was as effective at promoting phagocytosis and killing by macrophages as serum from actively infected (and demonstrably resistant) mice. Conversely, Salmonella-infected mice were totally resistant to intravenous challenge with L. monocytogenes. The level of resistance in individual animals was related to the numbers of residual Salmonellae remaining in the tissues; mice with heavier residual infections being the more resistant. Specific antiserum from mice vaccinated with heat-killed S. typhimurium was found to be significantly protective only when the intraperitoneal route of challenge was employed. The foregoing studies have been interpreted to mean that enhancement of the microbicidal ability of macrophages is the mechanism of major importance in acquired resistance to S. typhimurium infection in mice. PMID:4958757

  6. Impact of lactobacilli on orally acquired listeriosis.

    PubMed

    Archambaud, Cristel; Nahori, Marie-Anne; Soubigou, Guillaume; Bécavin, Christophe; Laval, Laure; Lechat, Pierre; Smokvina, Tamara; Langella, Philippe; Lecuit, Marc; Cossart, Pascale

    2012-10-01

    Listeria monocytogenes is a foodborne pathogen that crosses the intestinal barrier and disseminates within the host. Here, we report a unique comprehensive analysis of the impact of two Lactobacillus species, Lactobacillus paracasei CNCM I-3689 and Lactobacillus casei BL23, on L. monocytogenes and orally acquired listeriosis in a gnotobiotic humanized mouse model. We first assessed the effect of treatment with each Lactobacillus on L. monocytogenes counts in host tissues and showed that each decreases L. monocytogenes systemic dissemination in orally inoculated mice. A whole genome intestinal transcriptomic analysis revealed that each Lactobacillus changes expression of a specific subset of genes during infection, with IFN-stimulated genes (ISGs) being the most affected by both lactobacilli. We also examined microRNA (miR) expression and showed that three miRs (miR-192, miR-200b, and miR-215) are repressed during L. monocytogenes infection. Treatment with each Lactobacillus increased miR-192 expression, whereas only L. casei association increased miR-200b and miR-215 expression. Finally, we showed that treatment with each Lactobacillus significantly reshaped the L. monocytogenes transcriptome and up-regulated transcription of L. monocytogenes genes encoding enzymes allowing utilization of intestinal carbon and nitrogen sources in particular genes involved in propanediol and ethanolamine catabolism and cobalamin biosynthesis. Altogether, these data reveal that the modulation of L. monocytogenes infection by treatment with lactobacilli correlates with a decrease in host gene expression, in particular ISGs, miR regulation, and a dramatic reshaping of L. monocytogenes transcriptome. PMID:23012479

  7. The Effects of Targeted Deliveries of Lovastatin and Tocotrienol on Ossification-Related Gene Expressions in Fracture Healing in an Osteoporosis Rat Model.

    PubMed

    Ibrahim, Nurul 'Izzah; Mohamed, Norazlina; Soelaiman, Ima Nirwana; Shuid, Ahmad Nazrun

    2015-10-01

    Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II-VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 µg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 µg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing. PMID:26501302

  8. Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma

    PubMed Central

    Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

    2016-01-01

    Summary Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT. PMID:27252748

  9. Involvement of MET/TWIST/APC Combination or the Potential Role of Ossification Factors in Pediatric High-Grade Osteosarcoma Oncogenesis1

    PubMed Central

    Entz-Werle, Natacha; Lavaux, Thomas; Metzger, Nadia; Stoetzel, Corinne; Lasthaus, Christelle; Marec, Perrine; Kalifa, Chantal; Brugieres, Laurence; Pacquement, Hélène; Schmitt, Claudine; Tabone, Marie-Dominique; Gentet, Jean-Claude; Lutz, Patrick; Babin, Annie; Oudet, Pierre; Gaub, Marie Pierre; Perrin-Schmitt, Fabienne

    2007-01-01

    Dysregulated cell growth or differentiation due to misexpression of developmental critical factors seems to be a decisive event in oncogenesis. As osteosarcomas are histologically defined by malignant osteoblasts producing an osteoid component, we prospected in pediatric osteosarcomas treated with OS94 protocol the genomic status of several genes implied in ossification processes. In 91 osteosarcoma cases, we focused on the analysis of the fibroblast growth factor receptors (FGFRs) TWIST, APC, and MET by allelotyping, real-time quantitative polymerase chain reaction, gene sequencing, and protein polymorphism study. Our study supports the frequent role of TWIST, APC, and MET as osteosarcoma markers (50%, 62%, and 50%, respectively). TWIST and MET were mainly found to be deleted, and no additional APC mutation was identified. Surprisingly, FGFRs are abnormal in only < 30%. Most of these factors and their abnormalities seem to be linked more or less to one clinical subgroup, but the most significant correlation is the link of MET, TWIST, and APC abnormalities to a worse outcome and their combination within abnormal tumors. A wider cohort is mandatory to define more robust molecular conclusions, but these results are to be considered as the beginning of a more accurate basis for diagnosis, in search of targeted therapies, and to further characterize prognostic markers. PMID:17786187

  10. Examination of ossification of the distal radial epiphysis using magnetic resonance imaging. New insights for age estimation in young footballers in FIFA tournaments.

    PubMed

    Schmidt, S; Vieth, V; Timme, M; Dvorak, J; Schmeling, A

    2015-03-01

    Alongside a variety of clinical and forensic issues, age determination in living persons also plays a decisive role in the field of professional sport. Only methods of determining skeletal age which do not expose individuals to ionizing radiation are suitable for this purpose. The present study examines whether MRI diagnosis of the distal radial epiphysis can be utilised to monitor internationally relevant age limits in professional football. The wrist area of 152 male footballers aged 18 to 22 years belonging to regional clubs was prospectively examined using MRI. The ossification stage of the distal radial epiphysis was subsequently determined on the basis of established criteria used in determining the maturity of the medial clavicular epiphysis. For the first time, we ascertained evidence of an increase in the prevalence of the phenomenon of threefold linear stratification (hypointense line, hyperintense line, and hypointense line) in the representation of the fused epiphyseal plate of the radius using magnetic resonance imaging with increasing chronological age. Within our study population, test persons with an ossified epiphyseal plate without any verifiable epiphyseal scar were not represented. The presumably high minimum age of entry into this final stage of development (>22 years) must be verified in the course of further studies. According to the results of the present study, the fused epiphyseal plate of the distal radius provides potential maturation criteria which appear suitable for reliable monitoring of all relevant age limits in international football with the aid of magnetic resonance imaging.

  11. A Case of Successful Foraminotomy for Severe Bilateral C5 Palsy following Posterior Decompression and Fusion Surgery for Cervical Ossification of Posterior Longitudinal Ligament

    PubMed Central

    Toyone, Tomoaki; Shirahata, Toshiyuki; Ozawa, Tomoyuki; Matsuoka, Akira; Jin, Yoichi; Inagaki, Katsunori

    2016-01-01

    We report a very rare (5~7%) case of bilateral C5 palsy after cervical surgery. A 71-year-old male patient with cervical ossification of posterior longitudinal ligament (OPLL) with foraminal stenosis at bilateral C4/5 underwent posterior decompression and fusion surgery. After surgery, muscle weakness in his both deltoid and biceps was detected and gradually deteriorated to complete paralysis. Postoperative MRI showed sufficient decompression of the spinal cord and posterior shifting. Subsequently, an additional bilateral foraminotomy at C4/5 was performed, with a suspicion that bilateral foraminal stenosis at C4/5 may have been the cause of the paresis. After foraminotomy, muscular contraction was seen in both deltoid and biceps. Finally, complete motor recovery was achieved in a year. Although the gold standard procedure for the prevention and treatment of postoperative C5 palsy has not yet been established, an additional foraminotomy may be recommended for severe C5 palsy in cases of foraminal stenosis even after the occurrence of palsy. PMID:27672463

  12. A Case of Successful Foraminotomy for Severe Bilateral C5 Palsy following Posterior Decompression and Fusion Surgery for Cervical Ossification of Posterior Longitudinal Ligament.

    PubMed

    Kudo, Yoshifumi; Toyone, Tomoaki; Shirahata, Toshiyuki; Ozawa, Tomoyuki; Matsuoka, Akira; Jin, Yoichi; Inagaki, Katsunori

    2016-01-01

    We report a very rare (5~7%) case of bilateral C5 palsy after cervical surgery. A 71-year-old male patient with cervical ossification of posterior longitudinal ligament (OPLL) with foraminal stenosis at bilateral C4/5 underwent posterior decompression and fusion surgery. After surgery, muscle weakness in his both deltoid and biceps was detected and gradually deteriorated to complete paralysis. Postoperative MRI showed sufficient decompression of the spinal cord and posterior shifting. Subsequently, an additional bilateral foraminotomy at C4/5 was performed, with a suspicion that bilateral foraminal stenosis at C4/5 may have been the cause of the paresis. After foraminotomy, muscular contraction was seen in both deltoid and biceps. Finally, complete motor recovery was achieved in a year. Although the gold standard procedure for the prevention and treatment of postoperative C5 palsy has not yet been established, an additional foraminotomy may be recommended for severe C5 palsy in cases of foraminal stenosis even after the occurrence of palsy. PMID:27672463

  13. Cameriere's approach modified for pelvic radiographs: a novel method to assess apophyseal iliac crest ossification for the purpose of forensic age diagnostics.

    PubMed

    Wittschieber, Daniel; Vieth, Volker; Wierer, Traugott; Pfeiffer, Heidi; Schmeling, Andreas

    2013-07-01

    According to a modified method originally developed by Cameriere et al. (Int J Legal Med 120:143-146, 2006; J Forensic Sci 52:1151-1155, 2007; Forensic Sci Int 174:59-62, 2008; Forensic Sci Int 174:178-181, 2008; Forensic Sci Int 193:128.e1-128.e6, 2009), the suitability of the iliac crest apophysis (ICA) for the purpose of forensic age estimation in living individuals was investigated by means of area measurements in 643 pelvic radiographs of patients aged between 10 and 30 years. The area of the ossification centre(s) of the iliac crest and the area of the iliac wing (IW) were determined by manual segmentation. In 116 cases, area measurements were possible. ICA/IW ratios were calculated and used for regression analyses, yielding different regression equations. Depending on sex, pelvic side and ratio considered, R (2) ranged between 0.20 and 0.38 and the standard error of the estimate, between 1.91 and 2.00 years. No statistical significant differences were found between the right and the left pelvic sides. In conclusion, this method is potentially applicable for forensic age estimation in living individuals. However, further studies under more standardised conditions and with higher case numbers are needed in order to decide whether the iliac crest apophysis might become suitable for routine age diagnostics.

  14. A Case of Successful Foraminotomy for Severe Bilateral C5 Palsy following Posterior Decompression and Fusion Surgery for Cervical Ossification of Posterior Longitudinal Ligament

    PubMed Central

    Toyone, Tomoaki; Shirahata, Toshiyuki; Ozawa, Tomoyuki; Matsuoka, Akira; Jin, Yoichi; Inagaki, Katsunori

    2016-01-01

    We report a very rare (5~7%) case of bilateral C5 palsy after cervical surgery. A 71-year-old male patient with cervical ossification of posterior longitudinal ligament (OPLL) with foraminal stenosis at bilateral C4/5 underwent posterior decompression and fusion surgery. After surgery, muscle weakness in his both deltoid and biceps was detected and gradually deteriorated to complete paralysis. Postoperative MRI showed sufficient decompression of the spinal cord and posterior shifting. Subsequently, an additional bilateral foraminotomy at C4/5 was performed, with a suspicion that bilateral foraminal stenosis at C4/5 may have been the cause of the paresis. After foraminotomy, muscular contraction was seen in both deltoid and biceps. Finally, complete motor recovery was achieved in a year. Although the gold standard procedure for the prevention and treatment of postoperative C5 palsy has not yet been established, an additional foraminotomy may be recommended for severe C5 palsy in cases of foraminal stenosis even after the occurrence of palsy.

  15. The Effects of Targeted Deliveries of Lovastatin and Tocotrienol on Ossification-Related Gene Expressions in Fracture Healing in an Osteoporosis Rat Model

    PubMed Central

    Ibrahim, Nurul ‘Izzah; Mohamed, Norazlina; Soelaiman, Ima Nirwana; Shuid, Ahmad Nazrun

    2015-01-01

    Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II–VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 µg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 µg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing. PMID:26501302

  16. Expansion of murine periosteal progenitor cells with fibroblast growth factor 2 reveals an intrinsic endochondral ossification program mediated by bone morphogenetic protein 2.

    PubMed

    van Gastel, Nick; Stegen, Steve; Stockmans, Ingrid; Moermans, Karen; Schrooten, Jan; Graf, Daniel; Luyten, Frank P; Carmeliet, Geert

    2014-09-01

    The preservation of the bone-forming potential of skeletal progenitor cells during their ex vivo expansion remains one of the major challenges for cell-based bone regeneration strategies. We report that expansion of murine periosteal cells in the presence of FGF2, a signal present during the early stages of fracture healing, is necessary and sufficient to maintain their ability to organize in vivo into a cartilage template which gives rise to mature bone. Implantation of FGF2-primed cells in a large bone defect in mice resulted in complete healing, demonstrating the feasibility of using this approach for bone tissue engineering purposes. Mechanistically, the enhanced endochondral ossification potential of FGF2-expanded periosteal cells is predominantly driven by an increased production of BMP2 and is additionally linked to an improved preservation of skeletal progenitor cells in the cultures. This characteristic is unique for periosteal cells, as FGF2-primed bone marrow stromal cells formed significantly less bone and progressed exclusively through the intramembranous pathway, revealing essential differences between both cell pools. Taken together, our findings provide insight in the molecular regulation of fracture repair by identifying a unique interaction between periosteal cells and FGF2. These insights may promote the development of cell-based therapeutic strategies for bone regeneration which are independent of the in vivo use of growth factors, thus limiting undesired side effects. PMID:24989687

  17. A newly developed robot suit hybrid assistive limb facilitated walking rehabilitation after spinal surgery for thoracic ossification of the posterior longitudinal ligament: a case report.

    PubMed

    Sakakima, Harutoshi; Ijiri, Kosei; Matsuda, Fumiyo; Tominaga, Hiroyuki; Biwa, Takanori; Yone, Kazunori; Sankai, Yoshiyuki

    2013-01-01

    Most patients with thoracic ossification of the posterior longitudinal ligament (OPLL) exhibit delayed recovery of gait dysfunction after spinal injury. The hybrid assistive limb (HAL) is a new robot suit controlling knee and hip joint motion by detecting very weak bioelectric signals on the surface of the skin. This study is to report the feasibility and benefits of patient-assistive HAL walking rehabilitation for facilitating locomotor function after spinal surgery. The patient was a 60-year-old woman with thoracic OPLL, and her motor and sensory paralyses did not improve after spinal surgery, indicating severe impairment in the paretic legs. The subject underwent 6 HAL sessions per week for 8 weeks, consisting of a standing and sitting exercise and walking on the ground with HAL. Clinical outcomes were evaluated before and after HAL training and 1 year after surgery. The subject improved considerably as a result of HAL training. Subsequently, her walking ability recovered rapidly, and she was able to walk unaided six months after surgery. This case study suggests that HAL training is a feasible and effective option to facilitating locomotor function and the early HAL training with physiotherapy may enhance motor recovery of patients with residual paralysis after surgery.

  18. Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma.

    PubMed

    Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

    2016-01-01

    Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT. PMID:27252748

  19. A Case of Successful Foraminotomy for Severe Bilateral C5 Palsy following Posterior Decompression and Fusion Surgery for Cervical Ossification of Posterior Longitudinal Ligament.

    PubMed

    Kudo, Yoshifumi; Toyone, Tomoaki; Shirahata, Toshiyuki; Ozawa, Tomoyuki; Matsuoka, Akira; Jin, Yoichi; Inagaki, Katsunori

    2016-01-01

    We report a very rare (5~7%) case of bilateral C5 palsy after cervical surgery. A 71-year-old male patient with cervical ossification of posterior longitudinal ligament (OPLL) with foraminal stenosis at bilateral C4/5 underwent posterior decompression and fusion surgery. After surgery, muscle weakness in his both deltoid and biceps was detected and gradually deteriorated to complete paralysis. Postoperative MRI showed sufficient decompression of the spinal cord and posterior shifting. Subsequently, an additional bilateral foraminotomy at C4/5 was performed, with a suspicion that bilateral foraminal stenosis at C4/5 may have been the cause of the paresis. After foraminotomy, muscular contraction was seen in both deltoid and biceps. Finally, complete motor recovery was achieved in a year. Although the gold standard procedure for the prevention and treatment of postoperative C5 palsy has not yet been established, an additional foraminotomy may be recommended for severe C5 palsy in cases of foraminal stenosis even after the occurrence of palsy.

  20. Origins of evolution: non-acquired characters dominates over acquired characters in changing environment.

    PubMed

    Gaucherel, Cédric; Jensen, Henrik Jeldtoft

    2012-07-01

    Natural Selection is so ubiquitous that we never wonder how it appeared as the evolution rule driving Life. We usually wonder how Life appeared, and seldom do we make an explicit distinction between Life and natural selection. Here, we apply the evolution concept commonly used for studying Life to evolution itself. More precisely, we developed two models aiming at selecting among different evolution rules competing for their supremacy. We explored competition between acquired (AQ) versus non-acquired (NAQ) character inheritance. The first model is parsimonious and non-spatial, in order to understand relationships between environmental forcings and rule selection. The second model is spatially explicit and studies the adaptation differences between AQ and NAQ populations. We established that NAQ evolution rule is dominating in case of changing environment. Furthermore, we observed that a more adapted population better fits its environmental constraints, but fails in rapidly changing environments. NAQ principle and less adapted populations indeed act as a reservoir of traits that helps populations to survive in rapidly changing environments, such as the ones that probably Life experienced at its origins. Although perfectible, our modeling approaches will certainly help us to improve our understanding of origins of Life and Evolution, on Earth or elsewhere.