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Sample records for therapy preserves bone

  1. Successful Function-Preserving Therapy for Chondroblastoma of the Temporal Bone Involving the Temporomandibular Joint

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    Junkichi Yokoyama

    2011-02-01

    Full Text Available We present a case involving a late diagnosis of chondroblastoma of the temporal skull base involving the temporomandibular joint (TMJ. Following an initial misdiagnosis and unsuccessful treatment over a period of 5 years, the patient was referred to our department for further evaluation and possible surgical intervention for occlusal abnormalities, trismus, clicking of the TMJ, and hearing impairment. Based on preoperative immunochemical studies showing positive reaction of multinucleated giant cells for S-100 protein, the final diagnosis was chondroblastoma. The surgical approach – postauricular incision and total parotidectomy, with complete removal of the temporal bone, including the TMJ via the extended middle fossa – was successful in preserving facial nerves and diminishing clinical manifestations. This study highlights a misdiagnosed case in an effort to underline the importance of medical examinations and accurate differential diagnosis in cases involving any tumor mass in the temporal bone.

  2. Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction.

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    Sharp, Thomas E; Schena, Giana J; Hobby, Alexander R; Starosta, Timothy; Berretta, Remus M; Wallner, Markus; Borghetti, Giulia; Gross, Polina; Yu, Daohai; Johnson, Jaslyn; Feldsott, Eric; Trappanese, Danielle M; Toib, Amir; Rabinowitz, Joseph E; George, Jon C; Kubo, Hajime; Mohsin, Sadia; Houser, Steven R

    2017-11-10

    Cortical bone stem cells (CBSCs) have been shown to reduce ventricular remodeling and improve cardiac function in a murine myocardial infarction (MI) model. These effects were superior to other stem cell types that have been used in recent early-stage clinical trials. However, CBSC efficacy has not been tested in a preclinical large animal model using approaches that could be applied to patients. To determine whether post-MI transendocardial injection of allogeneic CBSCs reduces pathological structural and functional remodeling and prevents the development of heart failure in a swine MI model. Female Göttingen swine underwent left anterior descending coronary artery occlusion, followed by reperfusion (ischemia-reperfusion MI). Animals received, in a randomized, blinded manner, 1:1 ratio, CBSCs (n=9; 2×10 7 cells total) or placebo (vehicle; n=9) through NOGA-guided transendocardial injections. 5-ethynyl-2'deoxyuridine (EdU)-a thymidine analog-containing minipumps were inserted at the time of MI induction. At 72 hours (n=8), initial injury and cell retention were assessed. At 3 months post-MI, cardiac structure and function were evaluated by serial echocardiography and terminal invasive hemodynamics. CBSCs were present in the MI border zone and proliferating at 72 hours post-MI but had no effect on initial cardiac injury or structure. At 3 months, CBSC-treated hearts had significantly reduced scar size, smaller myocytes, and increased myocyte nuclear density. Noninvasive echocardiographic measurements showed that left ventricular volumes and ejection fraction were significantly more preserved in CBSC-treated hearts, and invasive hemodynamic measurements documented improved cardiac structure and functional reserve. The number of EdU + cardiac myocytes was increased in CBSC- versus vehicle- treated animals. CBSC administration into the MI border zone reduces pathological cardiac structural and functional remodeling and improves left ventricular functional reserve

  3. Long-term hormone replacement therapy preserves bone mineral density in Turner syndrome

    DEFF Research Database (Denmark)

    Cleemann, Line; Hjerrild, Britta E; Lauridsen, Anna L

    2009-01-01

    CONTEXT: Reduced bone mineral density (BMD) and increased risk of fractures are present in many women with Turner syndrome (TS). OBJECTIVE: Examine longitudinal changes in BMD in TS and relate changes to biochemical parameters. DESIGN: Prospective, pragmatic, and observational study. Examinations...

  4. Male fertility preservation before gonadotoxic therapies

    OpenAIRE

    Wyns, C.

    2010-01-01

    Background: Recent advances in cancer therapy have resulted in an increased number of long-term cancer survivors. Unfortunately, aggressive chemotherapy, radiotherapy and preparative regimens for bone marrow transplantation can severely affect male germ cells, including spermatogonial stem cells (SSCs), and lead to permanent loss of fertility. Different options for fertility preservation are dependent on the pubertal state of the patient. Methods: Relevant studies were identified by an extens...

  5. Male fertility preservation before gonadotoxic therapies.

    Science.gov (United States)

    Wyns, C

    2010-01-01

    Recent advances in cancer therapy have resulted in an increased number of long-term cancer survivors. Unfortunately, aggressive chemotherapy, radiotherapy and preparative regimens for bone marrow transplantation can severely affect male germ cells, including spermatogonial stem cells (SSCs), and lead to permanent loss of fertility. Different options for fertility preservation are dependent on the pubertal state of the patient. Relevant studies were identified by an extensive Medline search of English and French language articles. Sperm cryopreservation prior to gonadotoxic treatment is a well established method after puberty. In case of ejaculation failure by masturbation, assisted ejaculation methods or testicular tissue sampling should be considered. Although no effective gonadoprotective drug is yet available for in vivo spermatogonial stem cell (SSC) protection in humans, current evidence supports the feasibility of immature testicular tissue (ITT) cryopreservation. The different cryopreservation protocols and available fertility restoration options from frozen tissue, i.e. cell suspension transplantation, tissue grafting and in vitro maturation, are presented. RESULTS obtained in humans are discussed in the light of lessons learned from animal studies. Advances in reproductive technology have made fertility preservation a real possibility in young patients whose gonadal function is threatened by gonadotoxic therapies. The putative indications for such techniques, as well as their limitations according to disease, are outlined.

  6. Targeted therapies for bone sarcomas

    International Nuclear Information System (INIS)

    Mudry, P.

    2011-01-01

    Therapy success in bone sarcoma is significantly better compared to history cohorts with 60 - 70 % overall survival to date. Unfortunately, there is yet no shift and movement in better survival of patients with relapsed and refractory bone sarcomas during last twenty years. This article reviews targeted therapeutics for bone sarcomas which are under investigation and which could give chance to patients suffering from relapsed and chemo resistant bone sarcomas. Majority of the targeted drugs are given as part of phase 1 or 2 studies. (author)

  7. Systemic therapy of bone metastases

    International Nuclear Information System (INIS)

    Skripekova, A.

    2012-01-01

    Complications of bone metastases can seriously influence quality of life of the patients including of their independence in activities of daily living. Bisfosfonates are reducing skeletal morbidity in solid tumors and in multiple myeloma by 30 - 50% (1). They are not only used in active antineoplastic therapy in the prevention of skeletal complications by bone metastases but they are also significantly useful in prevention of the decrease of osseous mass by hormonal manipulation. Preclinical and in part clinical data suppose that there is some role of bisfosfonates in prevention of formation of metastases by early cancer. Denosumab is fully humanized antibody against RANKL (receptor activator of nuclear factor κ-B ligand) which is very important in pathogenesis of bone resorption induced by osteoclasts. In this work we discuss about pathological mechanisms of bone resorption in multiple myeloma and solid tumors, we resume data from randomized clinical trials and we focus on the application of anti resorption therapy in clinical practice. (author)

  8. Comparing Ancient DNA Preservation in Petrous Bone and Tooth Cementum.

    Directory of Open Access Journals (Sweden)

    Henrik B Hansen

    Full Text Available Large-scale genomic analyses of ancient human populations have become feasible partly due to refined sampling methods. The inner part of petrous bones and the cementum layer in teeth roots are currently recognized as the best substrates for such research. We present a comparative analysis of DNA preservation in these two substrates obtained from the same human skulls, across a range of different ages and preservation environments. Both substrates display significantly higher endogenous DNA content (average of 16.4% and 40.0% for teeth and petrous bones, respectively than parietal skull bone (average of 2.2%. Despite sample-to-sample variation, petrous bone overall performs better than tooth cementum (p = 0.001. This difference, however, is driven largely by a cluster of viking skeletons from one particular locality, showing relatively poor molecular tooth preservation (<10% endogenous DNA. In the remaining skeletons there is no systematic difference between the two substrates. A crude preservation (good/bad applied to each sample prior to DNA-extraction predicted the above/below 10% endogenous DNA threshold in 80% of the cases. Interestingly, we observe signficantly higher levels of cytosine to thymine deamination damage and lower proportions of mitochondrial/nuclear DNA in petrous bone compared to tooth cementum. Lastly, we show that petrous bones from ancient cremated individuals contain no measurable levels of authentic human DNA. Based on these findings we discuss the pros and cons of sampling the different elements.

  9. DNA and bone structure preservation in medieval human skeletons.

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    Coulson-Thomas, Yvette M; Norton, Andrew L; Coulson-Thomas, Vivien J; Florencio-Silva, Rinaldo; Ali, Nadir; Elmrghni, Samir; Gil, Cristiane D; Sasso, Gisela R S; Dixon, Ronald A; Nader, Helena B

    2015-06-01

    Morphological and ultrastructural data from archaeological human bones are scarce, particularly data that have been correlated with information on the preservation of molecules such as DNA. Here we examine the bone structure of macroscopically well-preserved medieval human skeletons by transmission electron microscopy and immunohistochemistry, and the quantity and quality of DNA extracted from these skeletons. DNA technology has been increasingly used for analyzing physical evidence in archaeological forensics; however, the isolation of ancient DNA is difficult since it is highly degraded, extraction yields are low and the co-extraction of PCR inhibitors is a problem. We adapted and optimised a method that is frequently used for isolating DNA from modern samples, Chelex(®) 100 (Bio-Rad) extraction, for isolating DNA from archaeological human bones and teeth. The isolated DNA was analysed by real-time PCR using primers targeting the sex determining region on the Y chromosome (SRY) and STR typing using the AmpFlSTR(®) Identifiler PCR Amplification kit. Our results clearly show the preservation of bone matrix in medieval bones and the presence of intact osteocytes with well preserved encapsulated nuclei. In addition, we show how effective Chelex(®) 100 is for isolating ancient DNA from archaeological bones and teeth. This optimised method is suitable for STR typing using kits aimed specifically at degraded and difficult DNA templates since amplicons of up to 250bp were successfully amplified. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Minimally invasive esthetic ridge preservation with growth-factor enhanced bone matrix.

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    Nevins, Marc L; Said, Sherif

    2017-12-28

    Extraction socket preservation procedures are critical to successful esthetic implant therapy. Conventional surgical approaches are technique sensitive and often result in alteration of the soft tissue architecture, which then requires additional corrective surgical procedures. This case series report presents the ability of flapless surgical techniques combined with a growth factor-enhanced bone matrix to provide esthetic ridge preservation at the time of extraction for compromised sockets. When considering esthetic dental implant therapy, preservation, or further enhancement of the available tissue support at the time of tooth extraction may provide an improved esthetic outcome with reduced postoperative sequelae and decreased treatment duration. Advances in minimally invasive surgical techniques combined with recombinant growth factor technology offer an alternative for bone reconstruction while maintaining the gingival architecture for enhanced esthetic outcome. The combination of freeze-dried bone allograft (FDBA) and rhPDGF-BB (platelet-derived growth factor-BB) provides a growth-factor enhanced matrix to induce bone and soft tissue healing. The use of a growth-factor enhanced matrix is an option for minimally invasive ridge preservation procedures for sites with advanced bone loss. Further studies including randomized clinical trials are needed to better understand the extent and limits of these procedures. The use of minimally invasive techniques with growth factors for esthetic ridge preservation reduces patient morbidity associated with more invasive approaches and increases the predictability for enhanced patient outcomes. By reducing the need for autogenous bone grafts the use of this technology is favorable for patient acceptance and ease of treatment process for esthetic dental implant therapy. © 2017 Wiley Periodicals, Inc.

  11. Preservation of the bone protein osteocalcin in dinosaurs

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    Muyzer, Gerard; Sandberg, Philip; Knapen, Marjo H. J.; Vermeer, Cees; Collins, Matthew; Westbroek, Peter

    1992-10-01

    Two different immunological assays were used to identify the remains of a bone matrix protein, osteocalcin (OC), in the bones of dinosaurs and other fossil vertebrates. Antibodies raised against OC from modern vertebrates showed strong immunological cross-reactivity with modern and relatively young fossil samples and significant reactions with some of the dinosaur bone extracts. The presence of OC was confirmed by the detection of a peptide-bound, uniquely vertebrate amino acid, γcarboxyglutamic acid (Gla). Preservation of OC in fossil bones appears to be strongly dependent on the burial history and not simply on age. These results extend the range of protein preservation in the geologic record and provide a first step toward a molecular phylogeny of the dinosaurs.

  12. Bone changes from prostaglandin therapy

    International Nuclear Information System (INIS)

    Poznanski, A.K.; Fernbach, S.K.; Berry, T.E.; Northwestern Univ., Chicago, IL

    1985-01-01

    Prostaglandin E therapy in infants causes periosteal elevation. Although the changes usually take 30-40 days to become visible, we have seen them as early as nine days. In 15 infants who had prostaglandin E therapy for over six days, three developed periosteal elevation. Three other cases are described in greater detail, with long-term follow-up in two in which the bone remodeled to normal. Gallium scan in one showed increased uptake in areas involved. The periosteal cloaking may mimic Caffey disease but the pattern of involvement is different, since the mandible, which is commonly affected in Caffey disease, is rarely involved in prostaglandin E therapy. (orig.)

  13. Denosumab for bone diseases: translating bone biology into targeted therapy.

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    Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

    2011-12-01

    Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

  14. Artificial Gravity: Will it Preserve Bone Health on Long-Duration Missions?

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    Davis-Street, Janis; Paloski, William H.

    2005-01-01

    Prolonged microgravity exposure disrupts bone, muscle, and cardiovascular homeostasis, sensory-motor coordination, immune function, and behavioral performance. Bone loss, in particular, remains a serious impediment to the success of exploration-class missions by increasing the risks of bone fracture and renal stone formation for crew members. Current countermeasures, consisting primarily of resistive and aerobic exercise, have not yet proven fully successful for preventing bone loss during long-duration spaceflight. While other bone-specific countermeasures, such as pharmacological therapy and dietary modifications, are under consideration, countermeasure approaches that simultaneously address multiple physiologic systems may be more desirable for exploration-class missions, particularly if they can provide effective protection at reduced mission resource requirements (up-mass, power, crew time, etc). The most robust of the multi-system approaches under consideration, artificial gravity (AG), could prevent all of the microgravity-related physiological changes from occurring. The potential methods for realizing an artificial gravity countermeasure are reviewed, as well as selected animal and human studies evaluating the effects of artificial gravity on bone function. Future plans for the study of the multi-system effects of artificial gravity include a joint, cooperative international effort that will systematically seek an optimal prescription for intermittent AG to preserve bone, muscle, and cardiovascular function in human subjects deconditioned by 6 degree head-down-tilt-bed rest. It is concluded that AG has great promise as a multi-system countermeasure, but that further research is required to determine the appropriate parameters for implementation of such a countermeasure for exploration-class missions.

  15. Mechanical properties of human bone-tendon-bone grafts preserved by different methods and radiation sterilised

    International Nuclear Information System (INIS)

    Kaminski, A.; Gut, G.

    2008-01-01

    Full text: Patellar tendon auto and allografts are commonly used in orthopaedic surgery for reconstruction of the anterior crucial ligaments (ACL). Autografts are mainly used for primary reconstruction, while allografts are useful for revision surgery. To avoid the risk of infection diseases transmission allografts should be radiation-sterilised. As radiation-sterilisation is supposed to decrease the mechanical strength of tendon tissue, it is important to establish methods of allografts preservation and sterilisation resulting in their best quality and safety. Therefore, the purpose of the study was to compare the tensile strength of the central one third of human patellar tendon (as used for ACL reconstruction), preserved by different methods (deep fresh freezing, lyophilisation) and subsequently radiation-sterilised with doses of 0 (control), 25, 50 or 100 kGy. Bone-tendon-bone grafts were prepared from cadaveric human patella tendon with both patellar and tibial attachments. BTB grafts were preserved by deep freezing, glicerolisation or lyophilisation and radiation-sterilised with doses of 0 (control), 25, 50 or 100 kGy. To estimate mechanical properties all samples were subjected to tensile tests to failure using Instron system. Before these tests all lyophilised grafts were rehydrated. We found decrease of tensile strength of irradiated grafts compared to non-irradiated controls. Obtained results of the mechanical testing of studied grafts indicate their potential usefulness for clinical applications.(Author)

  16. Bone morphogenetic protein-2 and bone therapy: successes and pitfalls.

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    Poon, Bonnie; Kha, Tram; Tran, Sally; Dass, Crispin R

    2016-02-01

    Bone morphogenetic proteins (BMPs), more specifically BMP-2, are being increasingly used in orthopaedic surgery due to advanced research into osteoinductive factors that may enhance and improve bone therapy. There are many areas in therapy that BMP-2 is being applied to, including dental treatment, open tibial fractures, cancer and spinal surgery. Within these areas of treatment, there are many reports of successes and pitfalls. This review explores the use of BMP-2 and its successes, pitfalls and future prospects in bone therapy. The PubMed database was consulted to compile this review. With successes in therapy, there were descriptions of a more rapid healing time with no signs of rejection or infection attributed to BMP-2 treatment. Pitfalls included BMP-2 'off-label' use, which lead to various adverse effects. Our search highlighted that optimising treatment with BMP-2 is a direction that many researchers are exploring, with areas of current research interest including concentration and dose of BMP-2, carrier type and delivery. © 2015 Royal Pharmaceutical Society.

  17. Disparities in correlating microstructural to nanostructural preservation of dinosaur femoral bones

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    Kim, Jung-Kyun; Kwon, Yong-Eun; Lee, Sang-Gil; Lee, Ji-Hyun; Kim, Jin-Gyu; Huh, Min; Lee, Eunji; Kim, Youn-Joong

    2017-03-01

    Osteohistological researches on dinosaurs are well documented, but descriptions of direct correlations between the bone microstructure and corresponding nanostructure are currently lacking. By applying correlative microscopy, we aimed to verify that well-preserved osteohistological features correlate with pristine fossil bone nanostructures from the femoral bones of Koreanosaurus boseongensis. The quality of nanostructural preservation was evaluated based on the preferred orientation level of apatite crystals obtained from selected area electron diffraction (SAED) patterns and by measuring the “arcs” from the {100} and {002} diffraction rings. Unlike our expectations, our results revealed that well-preserved microstructures do not guarantee pristine nanostructures and vice versa. Structural preservation of bone from macro- to nanoscale primarily depends on original bioapatite density, and subsequent taphonomical factors such as effects from burial, pressure, influx of external elements and the rate of diagenetic alteration of apatite crystals. Our findings suggest that the efficient application of SAED analysis opens the opportunity for comprehensive nanostructural investigations of bone.

  18. Single dose of bisphosphonate preserves gains in bone mass following cessation of sclerostin antibody in Brtl/+ osteogenesis imperfecta model.

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    Perosky, Joseph E; Khoury, Basma M; Jenks, Terese N; Ward, Ferrous S; Cortright, Kai; Meyer, Bethany; Barton, David K; Sinder, Benjamin P; Marini, Joan C; Caird, Michelle S; Kozloff, Kenneth M

    2016-12-01

    Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3week old Brtl/+ and wild type mice for 5weeks with SclAb, and then withdrew treatment for an additional 6weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6weeks following cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Bone marrow dosimetry for monoclonal antibody therapy

    International Nuclear Information System (INIS)

    Bigler, R.E.; Zanzonico, P.B.; Leonard, R.

    1986-01-01

    Immunoglobulins must permeate through the basement membrane of capillaries in order to enter the extracellular space (ECS) of tissue. Since the process is quite slow, the blood plasma activity in various organs contributes considerably to the radiation dose of the dose-limiting tissues. In bone marrow the basement membrane is absent and the blood circulation is functionally open. Therefore, blood plasma and marrow ECS maintain equal concentrations of labeled immunoglobulins. A combination of factors including intravenous administration, slow absorption into most tissues, slow breakdown and elimination of labeled immunoglobulin, and rapid entry into bone marrow ECS as well as known radiosensitivity of marrow led the authors to expect this tissue would prove to be the primary tissue at risk for systemic monoclonal antibody therapy. They have developed and applied in a Phase I clinical study of 131 I labeled CEA antibody a procedure for estimation of radiation dose to red bone marrow. Serieal measurements of blood plasma and total body retention are carried out. Binding of labeled antibody to the cellular components of blood is verified to be very low. They have observed bone marrow depression at doses greater than 400 rad. If no special procedures are used to reconstitute marrow after radiation treatment, this level represents a much greater than generally recognized limitation to radiolabeled monoclonal antibody therapy. 25 references, 4 tables

  20. Radiation therapy of osteolytic bone metastases

    International Nuclear Information System (INIS)

    Weber, W.; Roesler, H.P.; Doll, G.; Dostert, M.; Kutzner, J.; Schild, H.

    1992-01-01

    Percutaneous radiotherapy is the most effective modality for treatment of metastatic bone cancer. Local irradiation improves overall quality of life by relieving pain in most patients. It also helps preventing complications as pathological fractures in lytic bone lesions by new bone formation. In a retrospective study on 100 patients, irradiated for lytic bone metastases, the radiotherapeutic effect on alleviation of pain and on recalcification rate was investigated. In our experience in 84% of the cases pain and disability associated with bone metastases could be decreased. 38% of the patients had complete relief of symptoms. A correlation between subjective therapy effect and histology of the primary tumor was not demonstrated. Remineralization was found in 67% of all irradiated skeletal areas (n=137) (recalcification rate in breast cancer 77%, in bronchial carcinoma 27%, and in renal cell carcinoma 25%). After a total dose of 30 Gy reduction of the metastases-associated pain was achieved in 81% of the cases and remineralization was observed in 70% of the cases. (orig.) [de

  1. Comparing ancient DNA preservation in petrous bone and tooth cementum

    DEFF Research Database (Denmark)

    Hansen, Henrik B.; Damgaard, Peter de Barros; Margaryan, Ashot

    2017-01-01

    Large-scale genomic analyses of ancient human populations have become feasible partly due to refined sampling methods. The inner part of petrous bones and the cementum layer in teeth roots are currently recognized as the best substrates for such research. We present a comparative analysis of DNA...... to thymine deamination damage and lower proportions of mitochondrial/nuclear DNA in petrous bone compared to tooth cementum. Lastly, we show that petrous bones from ancient cremated individuals contain no measurable levels of authentic human DNA. Based on these findings we discuss the pros and cons...

  2. [Organ-preserving interventions in combined therapy of children and adolescents with osteosarcoma].

    Science.gov (United States)

    Punanov, Iu A; Gafton, G I; Gudz', Iu V; Nabokov, V V; Ivanova, T V; Safonova, S A; Levchenko, E V; Kupatadze, D D; Novik, V I; Lazareva, Iu R; Krzhivitskiĭ, P I; Petrov, V G

    2012-01-01

    An analyzed cohort consists of 50 pediatric patients with osteosarcoma receiving combined therapy in N. N. Petrov Research Institute for Oncology (1999-2010). Thirty nine of them had localized disease, 11 patients had distant metastases. The treatment scheme included neoadjuvant therapy with cisplatin and doxorubicin, surgical treatment and adjuvant therapy depended on initial response and could include cisplatin, doxorubicin, high-dose methotrexate, ifosfamide, etoposide. Four-year overall and relapse-free survival in children with localized disease was 74.3% and 69.2% accordingly. In 62% of patients were performed organ-preserving surgical interventions, in 22 patients was performed endoprosthetics, in 4 patients the defect was replaced by a bone autograft on a vascular bundle. The effectiveness of initial treatment and secondary endoprosthetics were analyzed. Six patients with lung metastases received normotermic lung chemoperfusion, 4 of them are alive and disease-free for 8 to 24 months.

  3. Bacteriological examination and biological characteristics of deep frozen bone preserved by gamma sterilization

    International Nuclear Information System (INIS)

    Pham Quang Ngoc; Le The Trung; Vo Van Thuan; Ho Minh Duc

    1999-01-01

    To promote the surgical success in Vietnam, we should supply bone allografts of different sizes. For this reason we have developed a standard procedure in procurement, deep freezing, packaging and radiation sterilization of massive bone. The achievement in this attempt will be briefly reported. The dose of 10-15 kGy is proved to be suitable for radiation sterilization of massive bone allografts being treated in clean condition and preserved in deep frozen. Neither deep freezing nor radiation sterilization cause any significant loss of biochemical stability of massive bone allografts especially when deep freezing combines with radiation. There were neither cross infection nor change of biological characteristics found after 6 months of storage since radiation treatment. In addition to results of the previous research and development of tissue grafts for medical care, the deep freezing radiation sterilization has been established for preservation of massive bone that is of high demand for surgery in Vietnam

  4. Osteoporosis imaging: effects of bone preservation on MDCT-based trabecular bone microstructure parameters and finite element models

    International Nuclear Information System (INIS)

    Baum, Thomas; Grande Garcia, Eduardo; Burgkart, Rainer; Gordijenko, Olga; Liebl, Hans; Jungmann, Pia M.; Gruber, Michael; Zahel, Tina; Rummeny, Ernst J.; Waldt, Simone; Bauer, Jan S.

    2015-01-01

    Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength due to a reduction of bone mass and deterioration of bone microstructure predisposing an individual to an increased risk of fracture. Trabecular bone microstructure analysis and finite element models (FEM) have shown to improve the prediction of bone strength beyond bone mineral density (BMD) measurements. These computational methods have been developed and validated in specimens preserved in formalin solution or by freezing. However, little is known about the effects of preservation on trabecular bone microstructure and FEM. The purpose of this observational study was to investigate the effects of preservation on trabecular bone microstructure and FEM in human vertebrae. Four thoracic vertebrae were harvested from each of three fresh human cadavers (n = 12). Multi-detector computed tomography (MDCT) images were obtained at baseline, 3 and 6 month follow-up. In the intervals between MDCT imaging, two vertebrae from each donor were formalin-fixed and frozen, respectively. BMD, trabecular bone microstructure parameters (histomorphometry and fractal dimension), and FEM-based apparent compressive modulus (ACM) were determined in the MDCT images and validated by mechanical testing to failure of the vertebrae after 6 months. Changes of BMD, trabecular bone microstructure parameters, and FEM-based ACM in formalin-fixed and frozen vertebrae over 6 months ranged between 1.0–5.6 % and 1.3–6.1 %, respectively, and were not statistically significant (p > 0.05). BMD, trabecular bone microstructure parameters, and FEM-based ACM as assessed at baseline, 3 and 6 month follow-up correlated significantly with mechanically determined failure load (r = 0.89–0.99; p < 0.05). The correlation coefficients r were not significantly different for the two preservation methods (p > 0.05). Formalin fixation and freezing up to six months showed no significant effects on trabecular bone microstructure

  5. Quality of Life Following Amputation or Limb Preservation in Patients with Lower Extremity Bone Sarcoma

    Directory of Open Access Journals (Sweden)

    Gary E Mason

    2013-08-01

    Full Text Available PURPOSE: Although functional differences have been described between patients with lower extremity bone sarcoma with amputation and limb preservation surgery, differences have not clearly been shown between the two groups related to quality of life. The aim of the study was to determine if there is a difference in overall quality of life in lower extremity bone sarcoma survivors related to whether they had an amputation or a limb preservation procedure. PATIENTS AND METHODS: Eighty-two long-term survivors of lower extremity bone sarcoma were studied to make a comparison of the overall quality of life, pain assessment and psychological evaluations in limb preservation and amputation patients. Forty-eight patients with limb preservation and thirty-four patients with amputations were enrolled in the study. Validated psychometric measures including the Quality of Life Questionnaire, the Minnesota Multiphasic Personality Inventory and visual analog scales were utilized.RESULTS: The overall quality of life of patients with limb preservation was significantly higher than patients with amputation (p-value < 0.01. Significant differences were noted in the categories of material well being, job satisfiers and occupational relations. CONCLUSION: The overall quality of life of patients with limb preservation appears to be better than for those patients with amputation based on the quality of life questionnaire in patients surviving lower extremity bone sarcoma. Further analysis needs to verify the results and focus on the categories that significantly affect the overall quality of life.

  6. Reduced bone mass and preserved marrow adipose tissue in patients with inflammatory bowel diseases in long-term remission.

    Science.gov (United States)

    Bastos, C M; Araújo, I M; Nogueira-Barbosa, M H; Salmon, C E G; de Paula, F J A; Troncon, L E A

    2017-07-01

    Bone marrow adipose tissue has not been studied in patients with inactive inflammatory bowel disease. We found that these patients have preserved marrow adiposity even with low bone mass. Factors involved in bone loss in active disease may have long-lasting effects but do not seem to affect bone marrow adiposity. Reduced bone mass is known to occur at varying prevalence in patients with inflammatory bowel diseases (IBD) because of inflammation, malnutrition, and steroid therapy. Osteoporosis may develop in these patients as the result of an imbalanced relationship between osteoblasts and adipocytes in bone marrow. This study aimed to evaluate for the first time bone mass and bone marrow adipose tissue (BMAT) in a particular subgroup of IBD patients characterized by long-term, steroid-free remission. Patients with Crohn's disease (CD; N = 21) and ulcerative colitis (UC; N = 15) and controls (C; N = 65) underwent dual X-ray energy absorptiometry and nuclear magnetic resonance spectroscopy of the L3 lumbar vertebra for BMAT assessment. Both the CD and UC subgroups showed significantly higher proportions of patients than controls with Z-score ≤-2.0 at L1-L4 (C 1.54%; CD 19.05%; UC 20%; p = 0.02), but not at other sites. The proportions of CD patients with a T-score ˂-1.0 at the femoral neck (C 18.46%; CD 47.62%; p = 0.02) and total hip (C 16.92%; CD 42.86%; p = 0.03) were significantly higher than among controls. There were no statistically significant differences between IBD patients and controls regarding BMAT at L3 (C 28.62 ± 8.15%; CD 29.81 ± 6.90%; UC 27.35 ± 9.80%; p = 0.67). IBD patients in long-term, steroid-free remission may have a low bone mass in spite of preserved BMAT. These findings confirm the heterogeneity of bone disorders in IBD and may indicate that factors involved in bone loss in active disease may have long-lasting effects on these patients.

  7. Long term effects of formaldehyde preservation on subsequent bone ...

    African Journals Online (AJOL)

    This study was conducted to compare the effectiveness of cold and hot water maceration techniques for the development of bone specimens from cadavers. Three already dissected bodies of both sexes (two males and a female) obtained from the Department of Anatomy, Bowen University, Iwo, Osun State, Nigeria were ...

  8. Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

    Science.gov (United States)

    2015-11-01

    1 AD_________________ Award Number: W81XWH-11-1-0593 TITLE: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis PRINCIPAL...3. DATES COVERED (From - To) 09/15/2011 - 08/14/2015 4. TITLE AND SUBTITLE Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis 5a...4 Title of the Grant: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis Award number: W81XWH-11-1-0593 Principal Investigator

  9. Elastin overexpression by cell-based gene therapy preserves matrix and prevents cardiac dilation

    Science.gov (United States)

    Li, Shu-Hong; Sun, Zhuo; Guo, Lily; Han, Mihan; Wood, Michael F G; Ghosh, Nirmalya; Alex Vitkin, I; Weisel, Richard D; Li, Ren-Ke

    2012-01-01

    After a myocardial infarction, thinning and expansion of the fibrotic scar contribute to progressive heart failure. The loss of elastin is a major contributor to adverse extracellular matrix remodelling of the infarcted heart, and restoration of the elastic properties of the infarct region can prevent ventricular dysfunction. We implanted cells genetically modified to overexpress elastin to re-establish the elastic properties of the infarcted myocardium and prevent cardiac failure. A full-length human elastin cDNA was cloned, subcloned into an adenoviral vector and then transduced into rat bone marrow stromal cells (BMSCs). In vitro studies showed that BMSCs expressed the elastin protein, which was deposited into the extracellular matrix. Transduced BMSCs were injected into the infarcted myocardium of adult rats. Control groups received either BMSCs transduced with the green fluorescent protein gene or medium alone. Elastin deposition in the infarcted myocardium was associated with preservation of myocardial tissue structural integrity (by birefringence of polarized light; P elastin showed the greatest functional improvement (P elastin in the infarcted heart preserved the elastic structure of the extracellular matrix, which, in turn, preserved diastolic function, prevented ventricular dilation and preserved cardiac function. This cell-based gene therapy provides a new approach to cardiac regeneration. PMID:22435995

  10. Complications of bone tumors after multimodal therapy

    Energy Technology Data Exchange (ETDEWEB)

    Shapeero, L.G., E-mail: lshapeero@usuhs.edu [Department of Radiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Bone and Soft Tissue Program, United States Military Cancer Institute, 6900 Georgia Ave, NW, Washington, DC 20307 (United States); Poffyn, B. [Department of Orthopaedic Surgery, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); De Visschere, P.J.L. [Department of Radiology and Magnetic Resonance/MR-1K12 IB, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Sys, G. [Department of Orthopaedic Surgery, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Uyttendaele, D. [Department of Radiology and Magnetic Resonance/MR-1K12 IB, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Vanel, D. [Department of Radiology, Rizzoli Institute, 40136 Bologna (Italy); Forsyth, R. [Department of Pathology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Verstraete, K.L. [Department of Radiology and Magnetic Resonance/MR-1K12 IB, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium)

    2011-01-15

    Purpose: To define and compare the complications of bone tumors after resection, extracorporeal irradiation and re-implantation, with or without radiotherapy. Materials and methods: Eighty patients (40 males and 40 females, ages 4-77 years) with 61 malignant and 19 benign bone tumors were evaluated for local and distant complications after treatment. Two groups of patients were studied: (1) 53 patients had resection without (43 patients) or with external beam radiotherapy (RadRx) (10 patients) and (2) 27 patients underwent extracorporeal irradiation and re-implantation without (22 patients) or with RadRx (5 patients). Patient follow-up varied from 1 month to 13.63 years with mean follow-up of 4.7 years. Imaging studies included bone and chest radiography, spin echo T1- and T2-weighted (or STIR) magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed tomography (CT) for thoracic and abdominopelvic metastases and 3-phase technetium-99m-labeled-methylene-diphosphonate (Tc99m MDP) scintigraphy for bone metastases. Results: DCE-MRI differentiated the rapidly enhancing recurrences, residual tumors and metastases from the slowly enhancing inflammation, and the non-enhancing seromas and fibrosis. Recurrences, metastases (mainly to lung and bone), and seromas were greater than twice as frequent in patients after resection than after ECCRI. Although 11.3% of post-resection patients had residual tumor, no ECRRI-treated patient had residual tumor. In contrast, after ECRRI, infection was almost three times as frequent and aseptic loosening twice as frequent as compared with the post-resection patients. Bones treated with RadRx and/or ECRRI showed increased prevalence of fractures and osteoporosis. In addition, muscle inflammation was more common in the externally irradiated patient as compared with the patient who did not receive this therapy. However, another soft tissue complication, heterotopic ossification, was rare in the

  11. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2017-12-01

    Nanohydrox- yapatite- coated electrospun poly(L-lactide) nanofibers enhance osteogenic differentiation of stem cells and induce ectopic bone formation... Bone Regeneration in a Large Animal Critical Sized Defect Model, Second Annual Symposium on Cell Therapy and Regenerative Medicine, 2016 4...osteogenic cells and growth factors demonstrated success in facilitating bone regeneration in these cases. However, due to the lack of mechanical property

  12. Alveolar bone preservation subsequent to miniscrew implant placement in a canine model

    DEFF Research Database (Denmark)

    Melsen, Birte; Huja, Sarandeep; Chien, Hua-Hong

    2015-01-01

    Abstract OBJECTIVE: To assess the effects of transcortical screws on alveolar (bone) ridge preservation following extraction. DESIGN: Four adult beagle dogs had mandibular premolars extracted bilaterally. After 6 weeks, using a split-mouth design, two transcortical screws were inserted unilateral...

  13. The clinical significance of temporal bone CT with regard to hearing preservation in acoustic neurinoma removal

    International Nuclear Information System (INIS)

    Umezu, Hiromichi; Seki, Yojirou; Aiba, Tadashi

    1988-01-01

    Since Rand and Kurze discussed the possibility of the anatomic preservation of the cochlear nerve via the posterior fossa transmeatal approach for the acoustic neurinoma, there have been increasingly many reports on the preservation of cochlear nerve function. With recent advances in diagnostic tools, today's neurosurgeon is able to make an earlier and more precise diagnosis of acoustic neurinomas even when the patient has good hearing. If useful hearing is to be kept, the cochlear nerve and blood supply of the labyrinth have to be preserved. In addition, surgical entry into the labyrinth, upon the removal of the posterior wall of the internal auditory canal, must be avoided, since it is likely to result in permanent hearing loss. Because of its superior contrast and spatial resolution, thin-section and high-resolution computed tomography of the temporal bone has the great advantage of demonstrating the exact relationship of the internal auditory canal to the posterior semicircular canal, the vestibule, and the common crus. In this study, thin-section, high-resolution computed tomography of the temporal bone was performed in 11 cases of acoustic neurinoma pre- and postoperatively. At operation, the lateral limit of the bone removal of the posterior internal auditory canal was determined on the basis of preoperative computed tomography of the temporal bone. As a result, inadvertent entry into the labyrinth was avoided, and useful hearing was preserved in 8 cases. In order to preserve useful hearing following total tumor removal, it is essential to plan the operative strategy meticulously on the basis of the findings of the preoperative investigation, Including temporal bone CT. (author)

  14. Clinical significance of temporal bone CT with regard to hearing preservation in acoustic neurinoma removal

    Energy Technology Data Exchange (ETDEWEB)

    Umezu, Hiromichi; Seki, Yojirou; Aiba, Tadashi

    1988-02-01

    Since Rand and Kurze discussed the possibility of the anatomic preservation of the cochlear nerve via the posterior fossa transmeatal approach for the acoustic neurinoma, there have been increasingly many reports on the preservation of cochlear nerve function. With recent advances in diagnostic tools, today's neurosurgeon is able to make an earlier and more precise diagnosis of acoustic neurinomas even when the patient has good hearing. If useful hearing is to be kept, the cochlear nerve and blood supply of the labyrinth have to be preserved. In addition, surgical entry into the labyrinth, upon the removal of the posterior wall of the internal auditory canal, must be avoided, since it is likely to result in permanent hearing loss. Because of its superior contrast and spatial resolution, thin-section and high-resolution computed tomography of the temporal bone has the great advantage of demonstrating the exact relationship of the internal auditory canal to the posterior semicircular canal, the vestibule, and the common crus. In this study, thin-section, high-resolution computed tomography of the temporal bone was performed in 11 cases of acoustic neurinoma pre- and postoperatively. At operation, the lateral limit of the bone removal of the posterior internal auditory canal was determined on the basis of preoperative computed tomography of the temporal bone. As a result, inadvertent entry into the labyrinth was avoided, and useful hearing was preserved in 8 cases. In order to preserve useful hearing following total tumor removal, it is essential to plan the operative strategy meticulously on the basis of the findings of the preoperative investigation, Including temporal bone CT.

  15. Targeted Therapies for Myeloma and Metastatic Bone Cancers

    Science.gov (United States)

    2010-09-01

    Cancer J Clin 2003; 53:5. Kasugai S, Fujisawa R, Waki Y, Miyamoto K, Ohya K 2000 Selective drug delivery system to bone: small peptide (Asp)6...page. Bone targeted nanoparticles , bone cancer myeloma, mice studies, PLGA , Biodegradable materials. Targeted Therapies for Myeloma and Metastatic Bone...present results from this program at talk at the Particles 2006 –Medical/Biochemical Diagnostic , Pharmaceutical, and Drug Delivery . 3

  16. Bladder preservation using chemoradiation therapy for locally invasive bladder cancer

    International Nuclear Information System (INIS)

    Abe, Toyofumi; Yoshioka, Toshiaki; Sato, Mototaka; Mori, Naoki; Sekii, Ken-Ichiro; Itatani, Hiroaki

    2011-01-01

    We investigated the long-term results and molecular markers of outcome with selective organ preservation in invasive bladder cancer using chemoradiation therapy. We examined locally invasive bladder cancer in 32 patients (30 men, 2 women; mean age at treatment 68.1 years) who underwent bladder-sparing protocols in the Department of Urology at Sumitomo Hospital between 2000 and 2005. The clinical stage was T2, T3, and T4 in 13, 16, and 3 patients, respectively. Our protocol includes aggressive transurethral resection of the bladder tumor (TURBT) and 46 Gy radiotherapy (2 Gy/fraction, 5 fractions/week) to the pelvis with concurrent cisplatin chemotherapy (20 mg/body/day, 5 days/week, the first and fourth week, intravenously). The initial evaluation included magnetic resonance imaging (MRI), urine cytology, and cystoscopy with a biopsy. During follow-up, if the patients developed superficial recurrence, they was treated with TURBT and intravesical Bacillus Calmette-Guerin (BCG), while patients with invasive recurrence were advised to undergo a salvage cystectomy. We examined the association between the expression of the Bcl-2 family in pretreatment TUR specimens and patient outcome. The mean follow-up was 54.6 months. The first assessment after the induction chemoradiotherapy showed that bladder preservation was achieved in 27 patients (84.4%). The actuarial local control rate with an intact bladder was 56.3% (18 patients) at 3 years. The 1-, 3-, and 5-year cancer-specific survival rate was 90.6, 84.0, and 66.9%, respectively. The 5-year cancer-specific survival rate was 75.0, 67.2, and 33.3% in T2, T3, and T4, respectively. Bcl-x positivity was significantly associated with a poor cancer-specific survival rate (log-rank test, p=0.038). Chemoradiation therapy for invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation. Our results suggest that the expression of Bcl-x is a

  17. Laboratory methods used for testing the effect of radiation sterilization and preservation procedures on bone allografts

    International Nuclear Information System (INIS)

    Dziedzic-Goclawska, A.

    1999-01-01

    Sterilization of tissue allografts with ionizing radiation introduced in the mid of 1950s is more and more frequently used in tissue banking practice. The dose of 25 kGy is currently recommended and commonly used by many tissue banks in the world with the exception of the Central Tissue Bank in Warsaw where the dose of 33 kGy + 10 % has been routinely used since 1963, and from 1997 the dose of 35 kGy + 10 % has been introduced. To study the effect of radiation-sterilization on bone allografts the interdisciplinary investigations have been undertaken and several techniques have been implemented in our tissue bank. The electron paramagnetic resonance (EPR) spectroscopy has been applied to investigate the amount, origin and stability of free radicals and other paramagnetic entities induced in radiation-sterilized bone allografts. This technique has been also utilized for quantitative evaluation of remodeling process of radiation-sterilized bone allografts and for estimation of the absorbed dose of ionizing radiation using bone tissue as a dosimeter. A model of heterotopically induced osteogenesis after transplantation of devitalized bone matrix into the muscle (described by Urist in 1965) is very useful in tissue banking practice. It allows one to determine the contribution the graft itself makes to osteogenesis. This model is routinely used in our tissue bank to evaluate the effect of various sterilization and preservation procedures on osteoinductive properties of bone allografts. The solubility in vitro of collagen - a carrier for bone morphogenetic proteins (BMPS) and a major constituent of bone and the other connective tissue grafts, has been studied by measuring the amount of extracted neutral, acid and total soluble collagen from bone grafts preserved by different methods at irradiated at vanous experimental conditions. A positive correlation between collagen solubility in vitro and the rate of graft resorption in vivo has been observed. The high doses of

  18. Checking collagen preservation in archaeological bone by non-destructive studies (Micro-CT and IBA)

    Science.gov (United States)

    Beck, L.; Cuif, J.-P.; Pichon, L.; Vaubaillon, S.; Dambricourt Malassé, A.; Abel, R. L.

    2012-02-01

    The material to be studied is a piece of human skull discovered (1999) in Pleistocene sediments from the Orsang river (Gujarat state, India). From anatomical view point, this skull is highly composite: modern Homo sapiens characters are associated to undoubtedly more ancient features. Absolute dating by 14C is critical to understand this discovery. Prior to dating measurements, non-destructive studies have been carried out. Micro-CT reconstruction (X-ray microtomography) and Ion Beam Analysis (IBA) have been undertaken to check the structural preservation of the fossil and the collagen preservation. PIXE elemental map was used to select well-preserved bone area. RBS/EBS and NRA were used for light element quantification, in particular C, N and O contents. We also demonstrate that the PIXE-RBS/EBS combination is a effective tool for the whole characterization of archaeological and recent bones by analysing in one experiment both mineral and organic fractions. We have shown that the archaeological bone, a fragment of the potentially oldest modern Indian, is enough preserved for radiocarbon dating. We propose that Elastic Backscattering Spectrometry (EBS) using 3 MeV protons could be a good non destructive alternative to conventional CHN method using Carbon-Hydrogen-Nitrogen analyzer for measuring C and N before 14C dating.

  19. Checking collagen preservation in archaeological bone by non-destructive studies (Micro-CT and IBA)

    Energy Technology Data Exchange (ETDEWEB)

    Beck, L., E-mail: lucile.beck@cea.fr [C2RMF - UMR171 CNRS, Centre de Recherche et de Restauration des Musees de France, Palais du Louvre, Porte des Lions, 14 quai Francois Mitterrand, 75001 Paris (France); CEA, DEN, Service de Recherches de Metallurgie Physique, Laboratoire JANNUS, 91191 Gif-sur-Yvette (France); Cuif, J.-P. [UMR IDES 8148, Universite Paris XI-Orsay, 91405 Orsay cedex (France); Pichon, L. [C2RMF - UMR171 CNRS, Centre de Recherche et de Restauration des Musees de France, Palais du Louvre, Porte des Lions, 14 quai Francois Mitterrand, 75001 Paris (France); Vaubaillon, S. [CEA, INSTN, Laboratoire JANNUS, 91191 Gif-sur-Yvette (France); Dambricourt Malasse, A. [Departement de Prehistoire, Museum national d' Histoire naturelle, UMR 7194 - CNRS, Institut de Paleontologie Humaine, 1, rue Rene Panhard, 75013 Paris (France); Abel, R.L. [The Natural History Museum, London (United Kingdom)

    2012-02-15

    The material to be studied is a piece of human skull discovered (1999) in Pleistocene sediments from the Orsang river (Gujarat state, India). From anatomical view point, this skull is highly composite: modern Homo sapiens characters are associated to undoubtedly more ancient features. Absolute dating by {sup 14}C is critical to understand this discovery. Prior to dating measurements, non-destructive studies have been carried out. Micro-CT reconstruction (X-ray microtomography) and Ion Beam Analysis (IBA) have been undertaken to check the structural preservation of the fossil and the collagen preservation. PIXE elemental map was used to select well-preserved bone area. RBS/EBS and NRA were used for light element quantification, in particular C, N and O contents. We also demonstrate that the PIXE-RBS/EBS combination is a effective tool for the whole characterization of archaeological and recent bones by analysing in one experiment both mineral and organic fractions. We have shown that the archaeological bone, a fragment of the potentially oldest modern Indian, is enough preserved for radiocarbon dating. We propose that Elastic Backscattering Spectrometry (EBS) using 3 MeV protons could be a good non destructive alternative to conventional CHN method using Carbon-Hydrogen-Nitrogen analyzer for measuring C and N before {sup 14}C dating.

  20. Checking collagen preservation in archaeological bone by non-destructive studies (Micro-CT and IBA)

    International Nuclear Information System (INIS)

    Beck, L.; Cuif, J.-P.; Pichon, L.; Vaubaillon, S.; Dambricourt Malassé, A.; Abel, R.L.

    2012-01-01

    The material to be studied is a piece of human skull discovered (1999) in Pleistocene sediments from the Orsang river (Gujarat state, India). From anatomical view point, this skull is highly composite: modern Homo sapiens characters are associated to undoubtedly more ancient features. Absolute dating by 14 C is critical to understand this discovery. Prior to dating measurements, non-destructive studies have been carried out. Micro-CT reconstruction (X-ray microtomography) and Ion Beam Analysis (IBA) have been undertaken to check the structural preservation of the fossil and the collagen preservation. PIXE elemental map was used to select well-preserved bone area. RBS/EBS and NRA were used for light element quantification, in particular C, N and O contents. We also demonstrate that the PIXE-RBS/EBS combination is a effective tool for the whole characterization of archaeological and recent bones by analysing in one experiment both mineral and organic fractions. We have shown that the archaeological bone, a fragment of the potentially oldest modern Indian, is enough preserved for radiocarbon dating. We propose that Elastic Backscattering Spectrometry (EBS) using 3 MeV protons could be a good non destructive alternative to conventional CHN method using Carbon–Hydrogen–Nitrogen analyzer for measuring C and N before 14 C dating.

  1. What is the optimal bone-preserving strategy for patients with Addison's disease?

    Science.gov (United States)

    Lee, Paul; Greenfield, Jerry R

    2015-08-01

    Addison's disease is associated with low bone mineral density and increased risk of hip fractures. Causes are multifactorial, contributed by underlying adrenocortical hormonal deficiency, associated autoimmune endocrinopathies, electrolyte disturbances and, in some patients, supraphysiologic glucocorticoid replacement. Recent realization of physiologic cortisol production rate has revised downwards glucocorticoid replacement dosages. Meanwhile, new research has emerged suggesting complex interplay between sodium and calcium homoeostasis under the influence of mineralocorticoid and parathyroid hormone that may impact bone health. As the prevalence of Addison's disease is rising, and osteoporosis and fractures are associated with significant morbidity and increased mortality, attention to bone preservation in Addison's disease is of clinical relevance and importance. We suggest an approach to bone health in Addison's disease integrating physiologic adrenocortical hormonal replacement with electrolyte and mineral homoeostasis optimization. © 2015 John Wiley & Sons Ltd.

  2. Comparison of the effectiveness of two different bone substitute materials for socket preservation after tooth extraction: a controlled clinical study.

    Science.gov (United States)

    Shakibaie-M, Behnam

    2013-01-01

    The aim of this study was to compare the effectiveness of two bone substitute materials for socket preservation after tooth extraction. Extraction sockets in 10 patients were filled with either inorganic bovine bone material (Bio-Oss) or with synthetic material consisting of hydroxyapatite and silicon dioxide (NanoBone). Extraction sockets without filling served as the control. The results demonstrate the effectiveness of the presented protocol for socket preservation and that the choice of a suitable bone substitute material is crucial. The dimensions of the alveolar ridge were significantly better preserved with Bio-Oss than with NanoBone or without treatment. Bio-Oss treatment resulted in better bone quality and quantity for successful implant placement.

  3. Beneficial role of periosteum in distraction osteogenesis of mandible. Its preservation prevents the external bone resorption

    International Nuclear Information System (INIS)

    Takeuchi, Sawako; Matsuo, Akira; Chiba, Hiroshige

    2010-01-01

    Distraction osteogenesis (DO) is a surgical process of new bone generation through the gradual extension of two segments of existing bone. DO is applied for maxillofacial surgeries to manage defects in mandibular continuity. Vertical DO with an oral device is often employed to augment the alveolar bone height for better implant anchorage for esthetic purposes or functional prosthetic requirements. To determine how the periosteum affects the vertical DO in mandibular reconstruction, we extracted the teeth and resected the alveolar parts of the mandible on both sides of dogs, along with removal of the surrounding periosteum in the right, but not left side. Three months later, box-shaped bone segments (vectors) were prepared from the resected alveolar part, and the segments were vertically elongated using a distraction device on both sides at 0.9 mm/day for one week. The extent of bone formation after distraction was determined with micro-focused computed tomography and by measuring incorporation of tetracycline and calcein with confocal laser scanning microscopy. During the initial two months after distraction, new bone formation was observed more prominently in the left side than in the right side of mandible with the periosteum. However, this difference was less clear during the bone-remodeling period. One notable change was the reduced height of the alveolar part of the right-side mandible, a sign of external bone resorption, observed in two out of three dogs at 6-month post-consolidation. These findings suggest that preservation of periosteum prevents the external bone resorption during the vertical DO of mandible. (author)

  4. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben

    2015-01-01

    transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling....... Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...

  5. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2017-12-01

    can maintain bone length and allow successfully regeneration in segmental defects. r 2006 Elsevier Ltd. All rights reserved. Keywords: Bone...pre- formed endothelial networks, as the MSCs can act as pericytes to the newly formed blood vessels. Pirraco et al. [159] also cultured ECs and...AWARD NUMBER: W81XWH-13-1-0407 TITLE: Novel Therapy for Bone Regeneration in Large Segmental Defects PRINCIPAL INVESTIGATOR: Melissa Kacena

  6. Sphincter preservation with preoperative radiation therapy and coloanal anastomosis

    Energy Technology Data Exchange (ETDEWEB)

    Minsky, Bruce D; Cohen, Alfred M; Enker, Warren E; Paty, Philip

    1995-02-01

    Purpose: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer. Methods and Materials: Thirty patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (2: T2, 28: T3) involving the distal half of the rectum and required an abdominoperineal resection. The median tumor size was 4 cm (range: 1.5-6 cm) and the median distance from the anal verge was 4 cm (range: 3-7 cm). The whole pelvis received 46.8 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 43 months (range: 6-82 months). Results: Of the 29 patients who underwent resection, 3 (10%) had a complete pathologic response and 24 (83%) were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure was crude: 17% and 4-year actuarial: 23%. The 4-year actuarial survival was 75%. One patient developed a partial disruption of the anastomosis and two developed rectal stenosis. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in 22 of the 24 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 77%. The median number of bowel movements/day was two (range: 1-6). Conclusions: This technique may be an alternative to an abdominoperineal resection in selected patients. Continued follow-up is needed to determine if this approach ultimately has similar local control and survival rates as an abdominoperineal resection.

  7. Sphincter preservation with preoperative radiation therapy and coloanal anastomosis

    International Nuclear Information System (INIS)

    Minsky, Bruce D.; Cohen, Alfred M.; Enker, Warren E.; Paty, Philip

    1995-01-01

    Purpose: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer. Methods and Materials: Thirty patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (2: T2, 28: T3) involving the distal half of the rectum and required an abdominoperineal resection. The median tumor size was 4 cm (range: 1.5-6 cm) and the median distance from the anal verge was 4 cm (range: 3-7 cm). The whole pelvis received 46.8 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 43 months (range: 6-82 months). Results: Of the 29 patients who underwent resection, 3 (10%) had a complete pathologic response and 24 (83%) were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure was crude: 17% and 4-year actuarial: 23%. The 4-year actuarial survival was 75%. One patient developed a partial disruption of the anastomosis and two developed rectal stenosis. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in 22 of the 24 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 77%. The median number of bowel movements/day was two (range: 1-6). Conclusions: This technique may be an alternative to an abdominoperineal resection in selected patients. Continued follow-up is needed to determine if this approach ultimately has similar local control and survival rates as an abdominoperineal resection

  8. The effect of radiation therapy on bone scintigraphy

    International Nuclear Information System (INIS)

    Kado, Bunmei; Nakajima, Tetsuo; Sakura, Mizuyoshi; Ishihara, Akinori; Sasaki, Yasuhito; Nagai, Teruo.

    1982-01-01

    With the purpose to evaluate effect of radiation therapy on bone scintigraphy, ninety nine bone scans and Ga-67 citrate tumor scans were performed on 67 patients, including 42 with lung cancer, 5 with esophageal cancer, 4 malignant lymphoma and 15 with other malignancy. The spinal uptake of Tc-99m diphosphonate and Ga-67 citrate were evaluated during or after radiation therapy involving thoracic and lumbar spines. The correlation among the spinal uptake of radioactivity in the radiation field, the irradiation dose and the interval after radiotherapy was investigated. The results revealed that 34 of 99 bone scans (34%) showed ''decreased'' radioactivity in the irradiated spines. Twenty six of 41 bone scans (63%) performed more than three months after radiotherapy showed ''decreased'' spinal uptake. Among the same 41 bone scans, 16 of 21 bone scans (76%) taken in patients who received more than 5000 rads showed ''decreased'' spinal uptake. The decreased spinal uptake was irreversible. Eight cases changed to ''decreased'' from ''equilibrated'' during follow up study after radiotherapy. Twenty two of 31 cases (71%) with Ga tumor scans, which were performed in the earlier periods and with less dose of radiotherapy as compared with bone scans, showed ''decreased'' spinal uptake, which suggests impaired Ga-67 uptake by the bone marrow rather than the spinal bone. The factors causing decreased uptake of radioactivity in bone scan after irradiation were discussed in view of irradiation effect on bone tissue. The descrepancy of uptake of radioactivity between bone scan and Ga tumor scan was also discussed reviewing difference of radiation effect on bone and bone marrow cells. (author)

  9. Mandibular reconstruction using a titanium plate: the impact of radiation therapy on plate preservation

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Janice K; Stern, Robin L; Robinson, Marilyn G; Bowers, Michael K; Kubo, Hideo D; Donald, Paul J; Rosenthal, Seth A; Fu, Karen K

    1995-06-15

    Purpose: To evaluate the soft tissue and bone tolerance of radiation therapy (RT) in patients undergoing radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. Methods and Materials: From 1990 to 1994, 47 patients with primary or recurrent oral cavity or oropharyngeal carcinomas were treated with radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. Eleven patients received no RT (no RT), 10 patients received RT greater than 10 months from the time of surgery (remote RT), and 26 patients received RT within 12 weeks of surgery (perioperative RT). The radiation dose to the reconstructed mandible ranged from 45 to 75 Gy (median 63 Gy). The effect of the titanium plate on the radiation dose was measured using film dosimetry and soft tissue and bone-equivalent materials. The median follow-up was 17 months (range: 3-50 months). Results: Late complications included four patients with osteomyelitis or necrosis, two plate exposures requiring flap revision, one chronic infection, two cases of chronic pain, two fistulae, and one case of trismus and malocclusion. The crude incidence of late complications by treatment was: (a) no RT: 3 of 11 patients (27%); (b) remote RT: 2 of 10 patients (20%); and (c) perioperative RT: 9 of 26 patients (35%). One patient in the no-RT group lost the plate due to chronic pain. Five patients in the perioperative RT group also had plate loss, four due to osteomyelitis and/or necrosis, and one due to pain related to a recurrent tumor. No patients in the remote RT group had plate loss. The actuarial prosthesis preservation rate at 2 years was 88% for the no RT, 100% for the remote RT, and 57% for the perioperative RT groups (p = 0.05). Phantom dose measurements showed that for parallel opposed 6 MV photon beams, there was no significant increase in the dose proximal or distal to the plate in either a soft tissue- or

  10. Potency preservation following stereotactic body radiation therapy for prostate cancer

    International Nuclear Information System (INIS)

    Obayomi-Davies, Olusola; Pahira, John; McGeagh, Kevin G; Collins, Brian T; Kowalczyk, Keith; Bandi, Gaurav; Kumar, Deepak; Suy, Simeng; Dritschilo, Anatoly; Lynch, John H; Collins, Sean P; Chen, Leonard N; Bhagat, Aditi; Wright, Henry C; Uhm, Sunghae; Kim, Joy S; Yung, Thomas M; Lei, Siyuan; Batipps, Gerald P

    2013-01-01

    Erectile dysfunction after prostate radiation therapy remains an ongoing challenge and critical quality of life issue. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT impotency would be higher than conventional radiation therapy approaches. This study sought to evaluate potency preservation and sexual function following SBRT for prostate cancer. Between February 2008 and March 2011, 216 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. Potency was defined as the ability to have an erection firm enough for intercourse with or without sexual aids while sexual activity was defined as the ability to have an erection firm enough for masturbation and foreplay. Patients who received androgen deprivation therapy (ADT) were excluded from this study. Ninety-seven hormone-naïve men were identified as being potent at the initiation of therapy and were included in this review. All patients were treated to 35–36.25 Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Prostate specific antigen (PSA) and total testosterone levels were obtained pre-treatment, every 3 months for the first year and every 6 months for the subsequent year. Sexual function was assessed with the Sexual Health Inventory for Men (SHIM), the Expanded Prostate Index Composite (EPIC)-26 and Utilization of Sexual Medication/Device questionnaires at baseline and all follow-up visits. Ninety-seven men (43 low-, 50 intermediate- and 4 high-risk) at a median age of 68 years (range, 48–82 years) received SBRT. The median pre-treatment PSA was 5.9 ng/ml and the minimum follow-up was 24 months. The median pre-treatment total serum testosterone level was 11.4 nmol/L (range, 4.4-27.9 nmol/L). The median baseline SHIM was 22 and 36% of patients utilized sexual aids prior to treatment. Although potency rates declined following

  11. Avascular necrosis of bone complicating corticosteroid replacement therapy.

    OpenAIRE

    Williams, P L; Corbett, M

    1983-01-01

    Two patients who developed widespread severe avascular necrosis of bone while on steroid replacement therapy are described. One, a diabetic, underwent yttrium-90 pituitary ablation for retinopathy and developed avascular necrosis within 18 months of starting prednisolone. The other, who had Addison's disease, developed avascular necrosis within 14 months of starting cortisol replacement therapy. Both cases came to bilateral total hip replacement.

  12. Preservation of autophagy should not direct nutritional therapy

    NARCIS (Netherlands)

    McClave, S.A.; Weijs, P.J.M.

    2015-01-01

    PURPOSE OF REVIEW: Recent reports in the literature have proposed that forced mandatory feeding should be avoided in the first week of critical illness to preserve autophagy, in order to maximize responses to oxidative stress, preserve organ function, and improve outcomes. RECENT FINDINGS: Autophagy

  13. [Effects of growth hormone replacement therapy on bone metabolism].

    Science.gov (United States)

    Yamamoto, Masahiro; Sugimoto, Toshitsugu

    2014-06-01

    Growth hormone (GH) as well as insulin like growth factor-1 (IGF-1) are essential hormones to maintain homeostasis of bone turnover by activating osteoblastogenesis and osteoclastogenesis. Results from GH replacement therapy for primary osteoporosis and adult-onset GH deficiency (AGHD) suggest that one year or more treatment period by this agent is required to gain bone mineral density (BMD) over the basal level after compensating BMD loss caused by dominant increase in bone resorption which was observed at early phase of GH treatment. A recent meta-analysis demonstrates the efficacy of GH replacement therapy on increases in BMD in male patients with AGHD. Additional analyses are needed to draw firm conclusions in female patients with AGHD, because insufficient amounts of GH might be administrated to them without considerations of influence of estrogen replacement therapy on IGF-1 production. Further observational studies are needed to clarify whether GH replacement therapy prevent fracture risk in these patients.

  14. Preservation of Bone-Marrow Cells, Leucocytes and Platelets at Low Temperatures. A Review

    Energy Technology Data Exchange (ETDEWEB)

    Ashwood-Smith, M. J. [Medical Research Council, Radiobiological Research Unit, Harwell, Berks. (United Kingdom)

    1969-07-15

    The basic principles of cryobiology are discussed and applications of these principles by numerous workers in attempts to preserve marrow cells, leucocytes and platelets at low temperatures are reviewed. It is concluded that: (1) Lymphocytes from animals and man can be stored for long periods of time at low temperatures when cooled slowly in 10-15% DMSO or glycerol and thawed rapidly. Recovery figures are high and function is intact and unaltered. DMSO is probably a better preservative than glycerol, and storage life at -196 Degree-Sign C is probably indefinite for all practical purposes. Other leucocytes can be stored with similar techniques but recoveries after freezing and thawing are probably lower than with lymphocytes. (2) Bone-marrow cells of several animals including mouse, rabbit and dog can be preserved at -196 Degree-Sign C, probably indefinitely, and similar procedures to those used for lymphocytes give the best results. The comprehensive studies of Lewis and Trobaugh indicate that under carefully controlled conditions 95% of the stem cells in mouse marrow are viable after freezing and thawing. Opinions are divided over the efficacy of the two preservatives, DMSO and glycerol, but in view of the well documented accounts of the lack of toxicity of glycerol it would seem advisable for the moment to use this agent with all human marrow samples. The usefulness of PVP as a preservative for marrow is still to be resolved. Human marrow after freezing and thawing probably behaves in a similar manner to mouse marrow both in vitro and in vivo. However, it would be wise to consider that there might be differences which could cause wrong assessments of freezing procedures. (3) Platelet preservation, clinically perhaps the most useful procedure discussed in this review, is still to a large extent in the experimental stage. Much work has been done but even the best methods available permit relatively low recoveries of viable platelets. Preservation of human platelets

  15. Chronic intermittent hypoxia preserves bone density in a mouse model of sleep apnea.

    Science.gov (United States)

    Torres, Marta; Montserrat, Josep M; Pavía, Javier; Dalmases, Mireia; Ros, Domenec; Fernandez, Yolanda; Barbé, Ferran; Navajas, Daniel; Farré, Ramon

    2013-12-01

    Very recent clinical research has investigated whether obstructive sleep apnea (OSA) may modulate bone homeostasis but the few data available are conflicting. Here we report novel data obtained in a mouse study specifically designed to determine whether chronic intermittent hypoxia realistically mimicking OSA modifies bone mineral density (BMD). Normal male and female mice and orchidectomized mice (N=10 each group) were subjected to a pattern of high-frequency intermittent hypoxia (20s at 5% and 40s at 21%, 60 cycles/h) for 6h/day. Identical groups breathing room air (normoxia) were the controls. After 32 days of intermittent hypoxia/normoxia the trabecular bone mineral density (BMD) in the peripheral femora were measured by micro-CT scanning. When compared with normoxia (two-way ANOVA), intermittent hypoxia did not significantly modify BMD in the three animal groups tested. Data in this study suggest that the type of intermittent hypoxia characterizing OSA, applied as a single challenge, preserves bone homeostasis. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Preservation of rodent bones from El Harhoura 2 cave (Morocco, Neolithic - Middle Palaeolithic): Microstructure, mineralogy, crystallinity and composition

    Science.gov (United States)

    Farre, Bastien; Massard, Pierre; Nouet, Julius; Dauphin, Yannicke

    2014-04-01

    Thin sections, scanning electron microscopy (SEM), diffraction X (DRX) and infrared spectrometry (FTIR) have been used to study the structure, mineralogy, crystallinity and bulk composition of fossil rodent long bones extracted from a succession of sedimentary layers in a cave from Morocco (Neolithic - Middle Palaeolithic, El Harhoura 2). The microstructure of fossil bones is well-preserved at this scale of observation, and encrusted deposits are rare. All bones are preserved in apatite, but the crystallinity is modified, as well as the crystallite shape, the organic content and the organic-mineral ratio. No fluor enrichment has been observed. Alone or together, the studied parameters do not show a regular trend from the upper to the lower layers of the cave. The preservation of the fossil bones does not confirm the sequence of arid and humid periods inferred from taphonomic analyses.

  17. New aspects of radionuclide therapy of bone and joint diseases

    International Nuclear Information System (INIS)

    Fischer, M.

    2001-01-01

    Whereas in developing countries P-32 is widely used for radionuclide therapy of painful bone metastases, in Europe three radionuclides or radiopharmaceutical agents are available for pain palliation: Sr-89, Sm-153-EDTMP, and Re-186-HEDP. Radionuclide therapy for pain palliation is indicated for bone pain due to metastatic malignancy that has involved multiple skeletal sites and has evoked an osteoblastic response on bone scintigraphy. Response rates of about 70-80% in patients with breast or prostate cancer is reported in the literature, less in metastatic lesions of other primary malignancies. Sm-153-EDTMP may also be used for curative treatment of primary bone tumours or their metastases. Radiosynovectomy as therapeutic procedure or rheumatoid arthritis, other inflammatory joint diseases, persistent synovial perfusion, and other joint diseases is widely used. Using Y-90 for the knee joint, Re-186 for middle sized joints, and Er-169 for small joints an improvement of symptoms may be observed in about 70-80%. (author)

  18. Bone benefits of testosterone replacement therapy in male hypogonadism.

    Science.gov (United States)

    Tirabassi, G; Biagioli, A; Balercia, G

    2014-06-01

    Osteoporosis is an asymptomatic, systemic bone disease characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased bone fragility. Such condition is often underdiagnosed and undertreated, especially in men, therefore considerably increasing the fracture risk. Of note, fracture-related morbidity and mortality is generally higher in men, partly due to greater frailty. On the other hand, male hypogonadism is defined as the failure of the testes to produce androgens, sperm, or both and it is often due to the ageing process. This disorder, in turn, causes many systemic disorders, and it is the condition mainly associated with male osteoporosis. Testosterone replacement therapy (TRT) is usually prescribed to restore optimal hormone levels, but conflicting data are available about the efficacy of TRT treatment on bone mineral density. In this review we extensively examined literature data about the usefulness of TRT in improving hypogonadism-associated low bone mineral density. Furthermore, we considered the complex relationship between male osteoporosis and hypogonadism, by specifically addressing the role of androgens in male bone physiology and the diagnostic approach to male osteoporosis and hypogonadism and also by dealing with some new related aspects such as the new endocrine pathways between bone and testis and the role of androgen receptor CAG polymorphism on bone density.

  19. Pain palliation therapy of bone metastases: palliative or curative?

    International Nuclear Information System (INIS)

    Fischer, M.

    2007-01-01

    In Germany the incidence of breast cancer is about 85 and of prostate cancer about 50 new patients per 100.000 inhabitants/year. In about 80% of prostate cancer patients and 75% of breast cancer patients bone metastases are observed in autopsy. Most of these patients develop severe pain syndrome from bone metastases reducing quality of life during life time. Therapy of these patients should aim at adding life to the years not years to their life. The knowledge of metastatic cell biology, of cell-cell interaction and of tumor-cell, tumor cell-skeleton interaction may modify the therapeutic procedure. Already in 1940/41, Pecher treated a patient suffering from painful prostate cancer bone metastases administering 296 MBq 89 Strontium chloride. About 10 years later, Friedell introduced 32 Phosphorus for treatment of bone metastases from breast cancer. Today in Europe 3 radionuclides are approved for pain palliation therapy as shown in Table.1. Indication: - pain palliation therapy of bone metastases from prostate cancer ( 89 Sr and 186 Re); - pain palliation of all osteoblastic metastases independent from primary tumors ( 153 Sm). Contraindications: - pregnant and lactating females - myelosuppression ( 3 granulocytes; 3 platelets); - impaired renal function (urea >12 mmol/l; creatinine > 150 mmol/l) - incontinence; - acute or chronic spinal cord compression and/or brain metastases causing neurological symptoms; - disseminated intravascular coagulopathy. The recommended activities per treatment are: 89 Sr 150 MBq, 186 Re 1.295 MBq, and 153 Sm 37 MBq/kg BW. Shortly (6-8 weeks) prior to radionuclide therapy for pain palliation no high dose chemotherapy or large field radiation therapy should be performed. Stopping unlabelled bisphosphonate therapy prior to pain palliation therapy is not necessary. This radionuclide therapy may be repeated several time, the interval between tracer administration depends on blood cell count rate. The recommended intervals are for 89 Sr

  20. Non-viral gene therapy for bone tissue engineering.

    Science.gov (United States)

    Wegman, Fiona; Oner, F Cumhur; Dhert, Wouter J A; Alblas, Jacqueline

    2013-01-01

    The possibilities of using gene therapy for bone regeneration have been extensively investigated. Improvements in the design of new transfection agents, combining vectors and delivery/release systems to diminish cytotoxicity and increase transfection efficiencies have led to several successful in vitro, ex vivo and in vivo strategies. These include growth factor or short interfering ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have led to increased osteogenic differentiation and bone formation in vivo. These results provide optimism to consider use in humans with some of these gene-delivery strategies in the near future.

  1. Advances in Bone Marrow Stem Cell Therapy for Retinal Dysfunction

    Science.gov (United States)

    Park, Susanna S.; Moisseiev, Elad; Bauer, Gerhard; Anderson, Johnathon D.; Grant, Maria B.; Zam, Azhar; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan A.

    2016-01-01

    The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy. PMID:27784628

  2. Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy

    DEFF Research Database (Denmark)

    Hoy, Jennifer F; Grund, Birgit; Roediger, Mollie P

    2017-01-01

    Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect ...

  3. Variation in osteocytes morphology vs bone type in turtle shell and their exceptional preservation from the Jurassic to the present.

    Science.gov (United States)

    Cadena, Edwin A; Schweitzer, Mary H

    2012-09-01

    Here we describe variations in osteocytes derived from each of the three bone layers that comprise the turtle shell. We examine osteocytes in bone from four extant turtle species to form a morphological 'baseline', and then compare these with morphologies of osteocytes preserved in Cenozoic and Mesozoic fossils. Two different morphotypes of osteocytes are recognized: flattened-oblate osteocytes (FO osteocytes), which are particularly abundant in the internal cortex and lamellae of secondary osteons in cancellous bone, and stellate osteocytes (SO osteocytes), principally present in the interstitial lamellae between secondary osteons and external cortex. We show that the morphology of osteocytes in each of the three bone layers is conserved through ontogeny. We also demonstrate that these morphological variations are phylogenetically independent, as well as independent of the bone origin (intramembranous or endochondral). Preservation of microstructures consistent with osteocytes in the morphology in Cenozoic and Mesozoic fossil turtle bones appears to be common, and occurs in diverse diagenetic environments including marine, freshwater, and terrestrial deposits. These data have potential to illuminate aspects of turtle biology and evolution previously unapproachable, such as estimates of genome size of extinct species, differences in metabolic rates among different bones from a single individual, and potential function of osteocytes as capsules for preservation of ancient biomolecules. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Knee joint preservation surgery in osteosarcoma using tumour-bearing bone treated with liquid nitrogen.

    Science.gov (United States)

    Higuchi, Takashi; Yamamoto, Norio; Nishida, Hideji; Hayashi, Katsuhiro; Takeuchi, Akihiko; Kimura, Hiroaki; Miwa, Shinji; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Abe, Kensaku; Taniguchi, Yuta; Tsuchiya, Hiroyuki

    2017-10-01

    To preserve the joint structure in order to maintain good limb function in patients with osteosarcoma, we perform epiphyseal or metaphyseal osteotomy and reconstruction using frozen autografts that contain a tumour treated with liquid nitrogen. There are two methods of using liquid nitrogen-treated autografts: the free-freezing method and the pedicle-freezing method. The purpose of this study was to evaluate the results of intentional joint-preserving reconstruction using the free-freezing method and the pedicle-freezing method in patients with osteosarcoma. Between 2006 and 2014, we performed joint-preserving surgery (12 with the free-freezing method and six with the pedicle freezing method) to treat 18 cases of osteosarcoma (12 distal femurs and six proximal tibias) in patients who had achieved a good response to neoadjuvant chemotherapy. Among the 18 patients (nine boys and nine girls) who had a mean age of 11.6 years, 13 remained continuously disease-free, three showed no evidence of disease, one was alive with the disease, and one died from the disease. Functional outcomes were assessed as excellent in 15 patients and poor in three, with a mean follow-up period of 46.1 months. The mean Musculoskeletal Tumour Society (MSTS) score was 90.2%. Except for one patient who underwent amputation, all patients could bend their knee through >90° flexion, and nine achieved full ROM. All but two patients could walk without aid, and 11 were able to run normally throughout the follow-up period. No intraoperative complications were observed, such as surrounding soft-tissue damage, neurovascular injury, or recurrence from frozen bone. Joint-preserving reconstruction using frozen autografts yielded excellent function in patients with osteosarcoma.

  5. Bone scintigraphy during therapy with cytostatically acting drugs

    International Nuclear Information System (INIS)

    Schmidt, U.; Pries, H.H.; Joseph, K.; Mahlstedt, J.; Marburg Univ.

    1976-01-01

    Case reports show up, that bone scintigraphy during therapy of metastasing cancer of mamma or prostata with cytostatically acting drugs may reveal 'pseudonormal' results. False negative diagnosis can be excluded only by carefully regarding drug history. Gamma-camera with wholebody scan device for scintigraphy in two projections simplifies safe evaluation significantly. (orig.) [de

  6. Clodronate Therapy in Patients with Breast Cancer and Bone Metastases

    International Nuclear Information System (INIS)

    Saber, M.M.; Shouman, T.

    2003-01-01

    To assess whether clodronate can reduce frequency of skeletal morbidity in women with lytic bone metastases from breast cancer. Methods: Between 1997 and 2001,167 patients with stage IV breast cancer with bone metastases, were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for 12 months, in addition to the standard specific anti cancer therapy (87 patients) or standard anti cancer therapy only (80 patients). Skeletal complications, including pathological fractures, the need for radiation to bone or bone surgery, spinal cord compression and hypercalcaemia (a serum calcium concentration above 12 mg per deci liter (3.0 mmol per liter) or elevated to any degree and requiring treatment) were assessed monthly. Bone pam. use of analgesic drugs, performance status and quality of life were assessed throughout the trial. Results: There was no significant difference between the two groups at study entry regarding clinical characteristics. The median time for first skeletal complication was ,significantly less in the control group (6.1 vs 9.7 months, ρ=0.05). The proportion of patients who had any skeletal complication in the clodronate group than the control group, but the difference was insignificant (ρ 0.09). Clodronate was generally well tolerated and the main side effects were constipation (32%) flatulence/dyspepsia (17%) and anorexia (8%). The overall survival was not affected by clodronate therapy. The median survival was 14 months In the clodronate group and 13.8 months in the control group. Conclusions: Clodronate is an effective supplement to conventional anticancer treatment for breast cancer with bone metastasis. It reduces skeletal complications and relieves symptoms associated with lytic bone lesions. Further clinical trials that recruit a larger number of patients will be needed to clearly define the role of clodronate in metastatic breast cancer

  7. Gene therapy for cartilage and bone tissue engineering

    CERN Document Server

    Hu, Yu-Chen

    2014-01-01

    "Gene Therapy for Cartilage and Bone Tissue Engineering" outlines the tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery, specifically for cartilage and bone engineering. It is intended for tissue engineers, cell therapists, regenerative medicine scientists and engineers, gene therapist and virologists. Dr. Yu-Chen Hu is a Distinguished Professor at the Department of Chemical Engineering, National Tsing Hua University and has received the Outstanding Research Award (National Science Council), Asia Research Award (Society of Chemical Engineers, Japan) and Professor Tsai-Teh Lai Award (Taiwan Institute of Chemical Engineers). He is also a fellow of the American Institute for Medical and Biological Engineering (AIMBE) and a member of the Tissue Engineering International & Regenerative Medicine Society (TERMIS)-Asia Pacific Council.

  8. Preservation of bone mass and structure in hibernating black bears (Ursus americanus) through elevated expression of anabolic genes.

    Science.gov (United States)

    Fedorov, Vadim B; Goropashnaya, Anna V; Tøien, Øivind; Stewart, Nathan C; Chang, Celia; Wang, Haifang; Yan, Jun; Showe, Louise C; Showe, Michael K; Donahue, Seth W; Barnes, Brian M

    2012-06-01

    Physical inactivity reduces mechanical load on the skeleton, which leads to losses of bone mass and strength in non-hibernating mammalian species. Although bears are largely inactive during hibernation, they show no loss in bone mass and strength. To obtain insight into molecular mechanisms preventing disuse bone loss, we conducted a large-scale screen of transcriptional changes in trabecular bone comparing winter hibernating and summer non-hibernating black bears using a custom 12,800 probe cDNA microarray. A total of 241 genes were differentially expressed (P 1.4) in the ilium bone of bears between winter and summer. The Gene Ontology and Gene Set Enrichment Analysis showed an elevated proportion in hibernating bears of overexpressed genes in six functional sets of genes involved in anabolic processes of tissue morphogenesis and development including skeletal development, cartilage development, and bone biosynthesis. Apoptosis genes demonstrated a tendency for downregulation during hibernation. No coordinated directional changes were detected for genes involved in bone resorption, although some genes responsible for osteoclast formation and differentiation (Ostf1, Rab9a, and c-Fos) were significantly underexpressed in bone of hibernating bears. Elevated expression of multiple anabolic genes without induction of bone resorption genes, and the down regulation of apoptosis-related genes, likely contribute to the adaptive mechanism that preserves bone mass and structure through prolonged periods of immobility during hibernation.

  9. 3D printed hyperelastic "bone" scaffolds and regional gene therapy: A novel approach to bone healing.

    Science.gov (United States)

    Alluri, Ram; Jakus, Adam; Bougioukli, Sofia; Pannell, William; Sugiyama, Osamu; Tang, Amy; Shah, Ramille; Lieberman, Jay R

    2018-04-01

    The purpose of this study was to evaluate the viability of human adipose-derived stem cells (ADSCs) transduced with a lentiviral (LV) vector to overexpress bone morphogenetic protein-2 (BMP-2) loaded onto a novel 3D printed scaffold. Human ADSCs were transduced with a LV vector carrying the cDNA for BMP-2. The transduced cells were loaded onto a 3D printed Hyperelastic "Bone" (HB) scaffold. In vitro BMP-2 production was assessed using enzyme-linked immunosorbent assay analysis. The ability of ADSCs loaded on the HB scaffold to induce in vivo bone formation in a hind limb muscle pouch model was assessed in the following groups: ADSCs transduced with LV-BMP-2, LV-green fluorescent protein, ADSCs alone, and empty HB scaffolds. Bone formation was assessed using radiographs, histology and histomorphometry. Transduced ADSCs BMP-2 production on the HB scaffold at 24 hours was similar on 3D printed HB scaffolds versus control wells with transduced cells alone, and continued to increase after 1 and 2 weeks of culture. Bone formation was noted in LV-BMP-2 animals on plain radiographs at 2 and 4 weeks after implantation; no bone formation was noted in the other groups. Histology demonstrated that the LV-BMP-2 group was the only group that formed woven bone and the mean bone area/tissue area was significantly greater when compared with the other groups. 3D printed HB scaffolds are effective carriers for transduced ADSCs to promote bone repair. The combination of gene therapy and tissue engineered scaffolds is a promising multidisciplinary approach to bone repair with significant clinical potential. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1104-1110, 2018. © 2018 Wiley Periodicals, Inc.

  10. Current Molecular Targeted Therapies for Bone and Soft Tissue Sarcomas

    Directory of Open Access Journals (Sweden)

    Kenji Nakano

    2018-03-01

    Full Text Available Systemic treatment options for bone and soft tissue sarcomas remained unchanged until the 2000s. These cancers presented challenges in new drug development partly because of their rarity and heterogeneity. Many new molecular targeting drugs have been tried in the 2010s, and some were approved for bone and soft tissue sarcoma. As one of the first molecular targeted drugs approved for solid malignant tumors, imatinib’s approval as a treatment for gastrointestinal stromal tumors (GISTs has been a great achievement. Following imatinib, other tyrosine kinase inhibitors (TKIs have been approved for GISTs such as sunitinib and regorafenib, and pazopanib was approved for non-GIST soft tissue sarcomas. Olaratumab, the monoclonal antibody that targets platelet-derived growth factor receptor (PDGFR-α, was shown to extend the overall survival of soft tissue sarcoma patients and was approved in 2016 in the U.S. as a breakthrough therapy. For bone tumors, new drugs are limited to denosumab, a receptor activator of nuclear factor κB ligand (RANKL inhibitor, for treating giant cell tumors of bone. In this review, we explain and summarize the current molecular targeting therapies approved and in development for bone and soft tissue sarcomas.

  11. Microencapsulation of rifampicin: A technique to preserve the mechanical properties of bone cement.

    Science.gov (United States)

    Sanz-Ruiz, Pablo; Carbó-Laso, Esther; Del Real-Romero, Juan Carlos; Arán-Ais, Francisca; Ballesteros-Iglesias, Yolanda; Paz-Jiménez, Eva; Sánchez-Navarro, Magdalena; Pérez-Limiñana, María Ángeles; Vaquero-Martín, Javier

    2018-01-01

    Two-stage exchange with antibiotic-loaded bone cement spacers remains the gold standard for chronic periprosthetic joint infection (PJI). Rifampicin is highly efficient on stationary-phase staphylococci in biofilm; however, its addition to PMMA to manufacture spacers prevents polymerization and reduces mechanical properties. Isolation of rifampicin during polymerization by microencapsulation could allow manufacturing rifampicin-loaded bone cement maintaining elution and mechanical properties. Microcapsules of rifampicin with alginate, polyhydroxybutyratehydroxyvalerate (PHBV), ethylcellulose and stearic acid (SA) were synthesized. Alginate and PHBV microcapsules were added to bone cement and elution, compression, bending, hardness, setting time and microbiological tests were performed. Repeated measures ANOVA and Bonferroni post-hoc test were performed, considering a p cement specimens containing alginate microcapsules eluted more rifampicin than PHBV microcapsules or non-encapsulated rifampicin over time (p Cement with alginate microcapsules showed similar behavior in hardness tests to control cement over the study period (73 ± 1.68H D ). PMMA with alginate microcapsules exhibited the largest zones of inhibition in microbiological tests. Statistically significant differences in mean diameters of zones of inhibition between PMMA loaded with alginate-rifampicin (p = 0.0001) and alginate-PHBV microcapsules (p = 0.0001) were detected. Rifampicin microencapsulation with alginate is the best choice to introduce rifampicin in PMMA preserving mechanical properties, setting time, elution, and antimicrobial properties. The main applicability of this study is the opportunity for obtaining rifampicin-loaded PMMA by microencapsulation of rifampicin in alginate microparticles, achieving high doses of rifampicin in infected tissues, increasing the successful of PJI treatment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

  12. Bone Marrow Gene Therapy for HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Elena Herrera-Carrillo

    2015-07-01

    Full Text Available Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS caused by human immunodeficiency virus (HIV. This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described.

  13. Bone marrow and bone marrow derived mononuclear stem cells therapy for the chronically ischemic myocardium

    International Nuclear Information System (INIS)

    Waksman, Ron; Baffour, Richard

    2003-01-01

    Bone marrow stem cells have been shown to differentiate into various phenotypes including cardiomyocytes, vascular endothelial cells and smooth muscle. Bone marrow stem cells are mobilized and home in to areas of injured myocardium where they are involved in tissue repair. In addition, bone marrow secretes multiple growth factors, which are essential for angiogenesis and arteriogenesis. In some patients, these processes are not enough to avert clinical symptoms of ischemic disease. Therefore, in vivo administration of an adequate number of stem cells would be a significant therapeutic advance. Unfractionated bone marrow derived mononuclear stem cells, which contain both hematopoietic and nonhematopoietic cells may be more appropriate for cell therapy. Studies in animal models suggest that implantation of different types of stem cells improve angiogenesis and arteriogenesis, tissue perfusion as well as left ventricular function. Several unanswered questions remain. For example, the optimal delivery approach, dosage and timing of the administration of cell therapy as well as durability of improvements need to be studied. Early clinical studies have demonstrated safety and feasibility of various cell therapies in ischemic disease. Randomized, double blind and placebo-controlled clinical trials need to be completed to determine the effectiveness of stem cell

  14. Normal tissue tolerance to external beam radiation therapy: Adult bone

    International Nuclear Information System (INIS)

    Sargos, P.; Mamou, N.; Dejean, C.; Henriques de Figueiredo, B.; Kantor, G.; Huchet, A.; Italiano, A.

    2010-01-01

    Radiation tolerance for bone tissue has been mostly evaluated with regard to bone fracture. Main circumstances are mandibula osteoradionecrosis, hip and costal fracture, and patent or radiologic fractures in the treated volume. After radiation therapy of bone metastasis, the analysis of related radiation fracture is difficult to individualize from a pathologic fracture. Frequency of clinical fracture is less than 5% in the large series or cohorts and is probably under-evaluated for the asymptomatic lesions. Women older than 50 years and with osteoporosis are probably the main population at risk. Dose-effect relations are difficult to qualify in older series. Recent models evaluating radiations toxicity on diaphysa suggest an important risk after 60 Gy, for high dose-fraction and for a large volume. (authors)

  15. Growth hormone therapy and craniofacial bones: a comprehensive review.

    Science.gov (United States)

    Litsas, G

    2013-09-01

    Growth hormone (GH) has significant effects on linear bone growth, bone mass and bone metabolism. The primary role of GH supplementation in children with GH deficiency, those born small for gestational age or with other types of disorders in somatic development is to increase linear growth. However, GH therapy seems to elicit varying responses in the craniofacial region. Whereas the effects of GH administration on somatic development are well documented, comparatively little is known of its effects on the craniofacial region. The purpose of this review was to search the literature and compile results from both animal and human studies related to the impact of GH on craniofacial growth. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Neurotrophin gene therapy for sustained neural preservation after deafness.

    Science.gov (United States)

    Atkinson, Patrick J; Wise, Andrew K; Flynn, Brianna O; Nayagam, Bryony A; Hume, Clifford R; O'Leary, Stephen J; Shepherd, Robert K; Richardson, Rachael T

    2012-01-01

    The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the residual spiral ganglion neurons. These neurons, however, undergo progressive degeneration after hearing loss, marked initially by peripheral fibre retraction and ultimately culminating in cell death. This research aims to use gene therapy techniques to both hold and reverse this degeneration by providing a sustained and localised source of neurotrophins to the deafened cochlea. Adenoviral vectors containing green fluorescent protein, with or without neurotrophin-3 and brain derived neurotrophic factor, were injected into the lower basal turn of scala media of guinea pigs ototoxically deafened one week prior to intervention. This single injection resulted in localised and sustained gene expression, principally in the supporting cells within the organ of Corti. Guinea pigs treated with adenoviral neurotrophin-gene therapy had greater neuronal survival compared to contralateral non-treated cochleae when examined at 7 and 11 weeks post injection. Moreover; there was evidence of directed peripheral fibre regrowth towards cells expressing neurotrophin genes after both treatment periods. These data suggest that neurotrophin-gene therapy can provide sustained protection of spiral ganglion neurons and peripheral fibres after hearing loss.

  17. Effects of radiation therapy on growing long bones

    International Nuclear Information System (INIS)

    De Smet, A.A.; Kuhns, L.R.; Fayos, J.V.; Holt, J.F.

    1976-01-01

    Characteristic radiographic changes were seen in six of 14 children who received radiation therapy to the epiphyseal plate of a long bone. These changes, which include metaphyseal sclerosis, metaphyseal fraying, and epiphyseal plate widening, resemble rickets. In three patients, these changes were followed by development of a broad metaphyseal band of increased density. The absence of metaphyseal changes may indicate sterilization of cartilage cells and may be predictive of significant limb shortening

  18. Efficient decellularization for tissue engineering of the tendon-bone interface with preservation of biomechanics.

    Directory of Open Access Journals (Sweden)

    Kai Xu

    Full Text Available Interfaces between tendon/ligament and bone ("entheses" are highly specialized tissues that allow for stress transfer between mechanically dissimilar materials. Entheses show very low regenerative capacity resulting in high incidences of failure after surgical repair. Tissue engineering is a promising approach to recover functionality of entheses. Here, we established a protocol to decellularize porcine entheses as scaffolds for enthesis tissue engineering. Chemical detergents as well as physical treatments were investigated with regard to their efficiency to decellularize 2 mm thick porcine Achilles tendon entheses. A two-phase approach was employed: study 1 investigated the effect of various concentrations of sodium dodecyl sulfate (SDS and t-octylphenoxypolyethoxy-ethanol (Triton X-100 as decellularization agents. The most efficient combination of SDS and Triton was then carried forward into study 2, where different physical methods, including freeze-thaw cycles, ultrasound, perfusion, and hydrostatic washing were used to enhance the decellularization effect. Cell counts, DNA quantification, and histology showed that washing with 0.5% SDS + 1% Triton X-100 for 72 h at room temperature could remove ~ 98% cells from the interface. Further investigation of physical methods proved that washing under 200 mmHg hydrostatic pressure shortened the detergent exposing time from 72 h to 48 h. Biomechanical tensile testing showed that the biomechanical features of treated samples were preserved. Washing under 200 mmHg hydrostatic pressure with 0.5% SDS + 1% Triton X-100 for 48 h efficiently decellularized entheses with preservation of matrix structure and biomechanical features. This protocol can be used to efficiently decellularize entheses as scaffolds for tissue engineering.

  19. Increased FDG bone marrow uptake after intracoronary progenitor cell therapy

    Energy Technology Data Exchange (ETDEWEB)

    Doebert, N.; Menzel, C.; Diehl, M.; Hamscho, N.; Zaplatnikov, K.; Gruenwald, F. [Dept. of Nuclear Medicine, Univ. of Frankfurt (Germany)

    2005-02-01

    Patients with coronary artery disease who undergo FDG PET for therapy monitoring after intracoronary progenitor cell infusion (PCT) show an increased bone marrow uptake in some cases. Aim of the study was to evaluate the systemic bone marrow glucose metabolism in this patient group after PCT. Patients, methods: FDG bone marrow uptake (BMU), measured as standardized uptake value (SUVmax) in the thoracic spine, was retrospectively evaluated in 23 control patients who did not receive PCT and in 75 patients who received PCT 3{+-}2.2 days before PET scanning. Five out of them were pretreated with granulocyte colony-stimulating factor (G-CSF) 5 days prior to PCT and 10{+-}1.2 days before PET scanning. In 39 patients who received only PCT without G-CSF and underwent PET therapy monitoring 4 months later, baseline and follow up bone marrow uptake were measured. Leucocytes, C-reactive protein (CRP) levels and the influence of nicotine consumption were compared with the BMU. Results: In patients (n=70) who received PCT without G-CSF, BMU media (1.3) was slightly, but significantly higher than in the controls (1.0) (p=0.02) regardless nicotine consumption. BMU did not change significantly 4 months later (1.2) (p=0.41, n.s.). After G-CSF pretreatment, patients showed a significantly higher bone marrow uptake (3.7) compared to patients only treated with PCT (1.3) (p=0.023). Leucocyte blood levels were significantly higher in patients with a BMU {>=}2.5 compared to patients with a bone marrow SUVmax<2.5 (p<0.001). CRP values did not correlate with the BMU (rho -0.02, p=0.38). Conclusion: Monitoring PCT patients, a slightly increased FDG BMU may be observed which remains unchanged for several months. Unspecific bone marrow reactions after PCT may be associated with increased leucocyte blood levels and play a role in the changed systemic glucose BMU. In addition, pretreatment with G-CSF shows an intense amplitifcation of BMU. (orig.)

  20. A Novel HA/β-TCP-Collagen Composite Enhanced New Bone Formation for Dental Extraction Socket Preservation in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Ko-Ning Ho

    2016-03-01

    Full Text Available Past studies in humans have demonstrated horizontal and vertical bone loss after six months following tooth extraction. Many biomaterials have been developed to preserve bone volume after tooth extraction. Type I collagen serves as an excellent delivery system for growth factors and promotes angiogenesis. Calcium phosphate ceramics have also been investigated because their mineral chemistry resembles human bone. The aim of this study was to compare the performance of a novel bioresorbable purified fibrillar collagen and hydroxyapatite/β-tricalcium phosphate (HA/β-TCP ceramic composite versus collagen alone and a bovine xenograft-collagen composite in beagles. Collagen plugs, bovine graft-collagen composite and HA/β-TCP-collagen composite were implanted into the left and right first, second and third mandibular premolars, and the fourth molar was left empty for natural healing. In total, 20 male beagle dogs were used, and quantitative and histological analyses of the extraction ridge was done. The smallest width reduction was 19.09% ± 8.81% with the HA/β-TCP-collagen composite at Week 8, accompanied by new bone formation at Weeks 4 and 8. The HA/β-TCP-collagen composite performed well, as a new osteoconductive and biomimetic composite biomaterial, for socket bone preservation after tooth extraction.

  1. Preservation and promotion of bone formation in the mandible as a response to a novel calcium-phosphate based biomaterial in mineral deficiency induced low bone mass male versus female rats

    Science.gov (United States)

    Srinivasan, Kritika; Naula, Diana P.; Mijares, Dindo Q.; Janal, Malvin N.; LeGeros, Raquel Z.; Zhang, Yu

    2016-01-01

    Calcium and other trace mineral supplements have previously demonstrated to safely improve bone quality. We hypothesize that our novel calcium-phosphate based biomaterial (SBM) preserves and promotes mandibular bone formation in male and female rats on mineral deficient diet (MD). Sixty Sprague-Dawley rats were randomly assigned to receive one of three diets (n = 10): basic diet (BD), MD or mineral deficient diet with 2% SBM. Rats were sacrificed after 6 months. Micro-Computed Tomography (μCT) was used to evaluate bone volume and 3D-microarchitecture while microradiography (Faxitron) was used to measure bone mineral density from different sections of the mandible. Results showed that bone quality varied with region, gender and diet. MD reduced bone mineral density (BMD) and volume and increased porosity. SBM preserved BMD and bone mineral content (BMC) in the alveolar bone and condyle in both genders. In the alveolar crest and mandibular body, while preserving more bone in males, SBM also significantly supplemented female bone. Results indicate that mineral deficiency leads to low bone mass in skeletally immature rats, comparatively more in males. Furthermore, SBM administered as a dietary supplement was effective in preventing mandibular bone loss in all subjects. This study suggests that the SBM preparation has potential use in minimizing low peak bone mass induced by mineral deficiency and related bone loss irrespective of gender. PMID:26914814

  2. Minimally Invasive Alveolar Ridge Preservation Utilizing an In Situ Hardening β-Tricalcium Phosphate Bone Substitute: A Multicenter Case Series

    Directory of Open Access Journals (Sweden)

    Minas D. Leventis

    2016-01-01

    Full Text Available Ridge preservation measures, which include the filling of extraction sockets with bone substitutes, have been shown to reduce ridge resorption, while methods that do not require primary soft tissue closure minimize patient morbidity and decrease surgical time and cost. In a case series of 10 patients requiring single extraction, in situ hardening beta-tricalcium phosphate (β-TCP granules coated with poly(lactic-co-glycolic acid (PLGA were utilized as a grafting material that does not necessitate primary wound closure. After 4 months, clinical observations revealed excellent soft tissue healing without loss of attached gingiva in all cases. At reentry for implant placement, bone core biopsies were obtained and primary implant stability was measured by final seating torque and resonance frequency analysis. Histological and histomorphometrical analysis revealed pronounced bone regeneration (24.4 ± 7.9% new bone in parallel to the resorption of the grafting material (12.9 ± 7.7% graft material while high levels of primary implant stability were recorded. Within the limits of this case series, the results suggest that β-TCP coated with polylactide can support new bone formation at postextraction sockets, while the properties of the material improve the handling and produce a stable and porous bone substitute scaffold in situ, facilitating the application of noninvasive surgical techniques.

  3. Socket preservation using freeze-dried bone allograft with and without plasma rich in growth factors in dogs

    Science.gov (United States)

    Samandari, Mohammad Hasan; Haghighat, Abbas; Torabinia, Nakisa; Taghian, Mehdi; Sadri, Leyli; Naemy, Vahid

    2016-01-01

    Background: Plasma rich in growth factors (PRGF) and freeze-dried bone allograft (FDBA) are shown to promote bone healing. This study was aimed to histologically and histomorphometrically investigate the effect of combined use of PRGF and FDBA on bone formation, and compare it to FDBA alone and control group. Materials and Methods: The distal roots of the lower premolars were extracted bilaterally in four female dogs. Sockets were randomly divided into FDBA + PRGF, FDBA, and control groups. Two dogs were sacrificed after 2 weeks and two dogs were sacrificed after 4 weeks. Sockets were assessed histologically and histomorphometrically. Data were analyzed by Kruskal–Wallis test followed by Mann–Whitney U-tests utilizing the SPSS software version 20. P PRGF groups was not significant in middle and apical portions. Conclusion: The superiority of PRGF+FDBA overFDBA in socket preservation cannot be concluded from this experiment. PMID:27857769

  4. Journey of bone graft materials in periodontal therapy: A chronological review

    Directory of Open Access Journals (Sweden)

    Jitendra Kumar

    2016-01-01

    Full Text Available Bone, the basic building block of the healthy periodontium, is affected in most of the periodontal diseases and can be managed either by mechanically recontouring it or by grafting techniques, which encourages regeneration where it has been lost. Bone replacement grafts are widely used to promote bone formation and periodontal regeneration. Bone grafting, placing bone or bone substitutes into defects created by the disease process, acts like a scaffold upon which the body generates its own, new bone. A wide range of bone grafting materials, including bone grafts and bone graft substitutes, have been applied and evaluated clinically, including autografts, allografts, xenografts, and alloplasts. This review provides an overview of the clinical application, biologic function, and advantages and disadvantages of various types of bone graft materials used in periodontal therapy till date with emphasis on recent advances in this field.

  5. Preservation of bone structure and function by Lithothamnion sp. – derived minerals

    Science.gov (United States)

    Aslam, Muhammad Nadeem; Bergin, Ingrid; Jepsen, Karl; Kreider, Jaclynn M.; Graf, Kristin H.; Naik, Madhav; Goldstein, Steven A.; Varani, James

    2013-01-01

    Progressive bone mineral loss and increasing bone fragility are hallmarks of osteoporosis. A combination of minerals isolated from the red marine algae, Lithothamnion sp. was examined for ability to inhibit bone mineral loss in female mice maintained on either a standard rodent chow (control) diet or a high-fat western diet (HFWD) for 5-, 12- and 18-months. At each time-point, femora were subjected to μ-CT analysis and biomechanical testing. A subset of caudal vertebrae was also analyzed. Following this, individual elements were assessed in bones. Serum levels of the 5b isoform of tartrate-resistant acid phosphatase (TRAP) and procollagen type I propeptide (P1NP) were also measured. Trabecular bone loss occurred in both diets (evident as early as 5-months). Cortical bone increased through month-5 and then declined. Cortical bone loss was primarily in mice on the HFWD. Inclusion of the minerals in the diet reduced bone mineral loss in both diets and improved bone strength. Bone mineral density (BMD) was also enhanced by these minerals. Of several cationic minerals known to be important to bone health, only strontium was significantly increased in bone tissue from animals fed the mineral diets, but the increase was large (5–10 fold). Serum levels of TRAP were consistently higher in mice receiving the minerals but levels of P1NP were not. These data suggest that trace minerals derived from marine red algae may be used to prevent progressive bone mineral loss in conjunction with calcium. Mineral supplementation could find use as part of an osteoporosis - prevention strategy. PMID:24096551

  6. Preservation of bone structure and function by Lithothamnion sp. derived minerals.

    Science.gov (United States)

    Aslam, Muhammad Nadeem; Bergin, Ingrid; Jepsen, Karl; Kreider, Jaclynn M; Graf, Kristin H; Naik, Madhav; Goldstein, Steven A; Varani, James

    2013-12-01

    Progressive bone mineral loss and increasing bone fragility are hallmarks of osteoporosis. A combination of minerals isolated from the red marine algae, Lithothamnion sp. was examined for ability to inhibit bone mineral loss in female mice maintained on either a standard rodent chow (control) diet or a high-fat western diet (HFWD) for 5, 12, and 18 months. At each time point, femora were subjected to μ-CT analysis and biomechanical testing. A subset of caudal vertebrae was also analyzed. Following this, individual elements were assessed in bones. Serum levels of the 5b isoform of tartrate-resistant acid phosphatase (TRAP) and procollagen type I propeptide (P1NP) were also measured. Trabecular bone loss occurred in both diets (evident as early as 5 months). Cortical bone increased through month 5 and then declined. Cortical bone loss was primarily in mice on the HFWD. Inclusion of the minerals in the diet reduced bone mineral loss in both diets and improved bone strength. Bone mineral density was also enhanced by these minerals. Of several cationic minerals known to be important to bone health, only strontium was significantly increased in bone tissue from animals fed the mineral diets, but the increase was large (5-10 fold). Serum levels of TRAP were consistently higher in mice receiving the minerals, but levels of P1NP were not. These data suggest that trace minerals derived from marine red algae may be used to prevent progressive bone mineral loss in conjunction with calcium. Mineral supplementation could find use as part of an osteoporosis-prevention strategy.

  7. Using laser-induced breakdown spectroscopy to assess preservation quality of archaeological bones by measurement of calcium-to-fluorine ratios.

    Science.gov (United States)

    Rusak, David Alexander; Marsico, Ryan Matthew; Taroli, Brett Louis

    2011-10-01

    We determined calcium-to-fluorine (Ca/F) signal ratios at the surface and in the depth dimension in approximately 6000-year-old sheep and cattle bones using Ca I 671.8 and F I 685.6 emission lines. Because the bones had been previously analyzed for collagen preservation quality by measurement of C/N ratios at the Oxford Radiocarbon Accelerator Unit, we were able to examine the correlation between our ratios and quality of preservation. In the bones analyzed in this experiment, the Ca I 671.8/F I 685.6 ratio was generally lower and decreased with successive laser pulses into poorly preserved bones while the ratio was generally higher and increased with successive laser pulses into well-preserved bones. After 210 successive pulses, a discriminator value for this ratio (5.70) could be used to distinguish well-preserved and poorly preserved bones regardless of species. © 2011 Society for Applied Spectroscopy

  8. Socket preservation using freeze-dried bone allograft with and without plasma rich in growth factors in dogs

    Directory of Open Access Journals (Sweden)

    Mohammad Hasan Samandari

    2016-01-01

    Full Text Available Background: Plasma rich in growth factors (PRGF and freeze-dried bone allograft (FDBA are shown to promote bone healing. This study was aimed to histologically and histomorphometrically investigate the effect of combined use of PRGF and FDBA on bone formation, and compare it to FDBA alone and control group. Materials and Methods: The distal roots of the lower premolars were extracted bilaterally in four female dogs. Sockets were randomly divided into FDBA + PRGF, FDBA, and control groups. Two dogs were sacrificed after 2 weeks and two dogs were sacrificed after 4 weeks. Sockets were assessed histologically and histomorphometrically. Data were analyzed by Kruskal-Wallis test followed by Mann-Whitney U-tests utilizing the SPSS software version 20. P < 0.05 was considered statistically significant. Results: While the difference in density of fibrous tissue in three groups was not statistically significant (P = 0.343, the bone density in grafted groups was significantly higher than the control group (P = 0.021. The least decrease in all socket dimensions was observed in the FDBA group. However, these differences were only significant in coronal portion at week 4. Regarding socket dimensions and bone density, the difference between FDBA and FDBA+PRGF groups was not significant in middle and apical portions. Conclusion: The superiority of PRGF+FDBA overFDBA in socket preservation cannot be concluded from this experiment.

  9. Effect of antiresorptive and anabolic bone therapy on development of osteoarthritis in a posttraumatic rat model of OA.

    Science.gov (United States)

    Bagi, Cedo M; Berryman, Edwin; Zakur, David E; Wilkie, Dean; Andresen, Catharine J

    2015-11-06

    Osteoarthritis (OA) is a leading cause of disability, but despite the high unmet clinical need and extensive research seeking dependable therapeutic interventions, no proven disease-modifying treatment for OA is currently available. Due to the close interaction and interplay between the articular cartilage and the subchondral bone plate, it has been hypothesized that antiresorptive drugs can also reduce cartilage degradation, inhibit excessive turnover of the subchondral bone plate, prevent osteophyte formation, and/or that bone anabolic drugs might also stimulate cartilage synthesis by chondrocytes and preserve cartilage integrity. The benefit of intensive zoledronate (Zol) and parathyroid hormone (PTH) therapy for bone and cartilage metabolism was evaluated in a rat model of OA. Medial meniscectomy (MM) was used to induce OA in male Lewis rats. Therapy with Zol and human PTH was initiated immediately after surgery. A dynamic weight-bearing (DWB) system was deployed to evaluate the weight-bearing capacity of the front and hind legs. At the end of the 10-week study, the rats were euthanized and the cartilage pathology was evaluated by contrast (Hexabrix)-enhanced μCT imaging and traditional histology. Bone tissue was evaluated at the tibial metaphysis and epiphysis, including the subchondral bone. Histological techniques and dynamic histomorphometry were used to evaluate cartilage morphology and bone mineralization. The results of this study highlight the complex changes in bone metabolism in different bone compartments influenced by local factors, including inflammation, pain and mechanical loads. Surgery caused severe and extensive deterioration of the articular cartilage at the medial tibial plateau, as evidenced by contrast-enhanced μCT and histology. The study results showed the negative impact of MM surgery on the weight-bearing capacity of the operated limb, which was not corrected by treatment. Although both Zol and PTH improved subchondral bone mass and

  10. Corticosteroid therapy and bone mass - comparisOfl of rheumatoid ...

    African Journals Online (AJOL)

    osis Int sis and et of ine in l energy. Tissue. Invasive. -72. cl Med f the ed. The ce ... needs to be re-evaluated, favouring earlier use of such ... There are also very few reports of bone ... compare bone mass at various sites in young, ambulant .... Bone mass ill patients with RA and SLE in relation to ..... on bone in young adults.

  11. Comparative investigation of viability, metabolism and osteogenic capability of tissue-engineered bone preserved in sealed osteogenic media at 37 0C and 4 0C

    International Nuclear Information System (INIS)

    Wang Hengjian; Liu Guangpeng; Zhou Guangdong; Cen Lian; Cui Lei; Cao Yilin

    2010-01-01

    Preservation of tissue-engineered (TE) bone is one of the key problems needed to be solved for its clinic application and industrialization. Traditional cryopreservation has been restricted because of the damages caused by ice formation and solution. Hypothermic preservation at 4 0 C has been widely used for the preservation of transplanted organ despite potential negative effects on viability of cells and tissue. 37 0 C is the best temperature for maintaining cellular bioactivities. However, 37 0 C also has a potential negative effect on preserved cells due to consumption of nutrients and accumulation of by-products. No studies have reported which temperature is more suitable for the preservation of TE bone constructs. The current study explored the feasibility of preservation of TE bone constructs in sealed osteogenic media at 37 0 C and 4 0 C. Human bone marrow stromal cells (hBMSCs) were seeded into partially demineralized bone matrix (pDBM) scaffolds and cultured for 7 days to form TE bone constructs. The constructs were preserved in sealed osteogenic media at either 37 0 C or 4 0 C for 5, 7, 9 and 11 days, respectively. Growth kinetics, viability, metabolism and osteogenic capability were evaluated to explore the feasibility of preservation at 37 0 C and 4 0 C. The constructs cultured in osteogenic media at humidified 37 0 C/5%CO 2 served as the positive control. The results demonstrated that all the constructs preserved at 4 0 C showed negative osteogenic capability at all time points with a much lower level of growth kinetics, viability and metabolism compared to the positive control. However, the constructs preserved at 37 0 C showed good osteogenic capability within 7 days with a certain level of growth kinetics, viability and metabolism, although an obvious decrease in osteogenic capability was observed in the constructs preserved at 37 0 C over 9 days. These results indicate that the preservation of TE bone constructs is feasible at 37 0 C within 7 days

  12. Improved outcome in solitary bone plasmacytomata with combined therapy.

    Science.gov (United States)

    Avilés, A; Huerta-Guzmán, J; Delgado, S; Fernández, A; Díaz-Maqueo, J C

    1996-09-01

    Solitary bone plasmacytoma (SBP) is a rare presentation of plasma cell dyscrasias. Radiotherapy has been considered the treatment of choice, however, most patients will develop multiple myeloma, 3 to 10 years after initial diagnosis and treatment. No innovations have been introduced in the treatment of SBP in the last 30 years. We began a prospective clinical trial to assess the efficacy and toxicity of adjuvant chemotherapy with low doses of melphalan and prednisone administered to patients with SBP after radiation therapy in an attempt to improve the disease-free survival and overall survival. Between 1982 and 1989, 53 patients with SBP were randomly assigned to be treated with either local radiotherapy with doses ranged from 4000 to 5000 cGy to achieve local control of disease (28 patients) or the same radiotherapy schedule followed by melphalan and prednisone given every 6 weeks for 3 years (25 patients). After a median follow-up of 8.9 years, disease-free survival and overall survival were improved in patients who were treated with combined therapy, 22 patients remain alive and free of disease in the combined treatment group compared to only 13 patients in the radiotherapy group (p radiotherapy in patients with SBP improved duration of remission and survival without severe side-effects. However, as with other studies in SBP, the group was too small to draw definitive conclusions and more controlled clinical trials are necessary to define the role of this therapeutic approach in patients with SBP.

  13. Analysis of intravesical recurrence after bladder-preserving therapy for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Onozawa, Mizuki; Miyanaga, Naoto; Hinotsu, Shiro

    2012-01-01

    The aim of the present study was to analyze the pattern of recurrences after bladder-preserving therapy for muscle-invasive bladder cancer. The subjects were 77 patients with T2-3N0M0 bladder cancer whose bladder was preserved by intra-arterial chemotherapy and radiation. The patterns of the first recurrences were retrospectively analyzed. With a median follow-up of 38.5 months, 17 patients (22.1%) experienced intravesical recurrence without metastasis, 14 (82.4%) of which were cases of non-muscle-invasive bladder cancer recurrence and 3 (17.6%) of which were muscle-invasive bladder cancer recurrences. Muscle-invasive bladder cancer recurred at the same site as the initial tumor site in all three cases, whereas non-muscle-invasive bladder cancer recurred at different sites in 64% of the patients in that group. The peak hazard of the non-muscle-invasive bladder cancer recurrence was observed at around a year after treatment. Recurrent non-muscle-invasive bladder cancer was of a significantly lower histological grade with lower Ki-67-labeling indices than the initial muscle-invasive bladder cancer. Twelve (85.7%) of 14 patients with non-muscle-invasive bladder cancer recurrence achieved disease-free status. The multivariate analysis revealed that multiplicity, grade and tumor size were significantly correlated with the recurrence (P=0.0001, 0.0442 and 0.0412, respectively). Most of the recurrences after bladder-preserving therapy were cases of non-muscle-invasive bladder cancer. The recurrence pattern and characteristics of the tumors did not differ from those of primary non-muscle-invasive bladder cancer. Patients with high-risk factors would be candidates for prophylactic intravesical therapy for non-muscle-invasive bladder cancer recurrence. (author)

  14. The effect of radiation-sterilization conditions and preservation procedures on physico-chemical and biological properties of bone allografts

    International Nuclear Information System (INIS)

    Goclawska, A.D.; Kaminski, A.; Wasilewska, M.

    1999-01-01

    Radiation-sterilization of connective tissue allografts (bone including) with a dose of 35 kGy is routinely used in the Central Tissue Bank in Warsaw since 1963. This method of sterilization offers many advantages: good penetration ability, relatively low temperature rise, and possibility of sterilization of grafts in closed beforehand vials, which protects against secondary contamination. It should be kept in mind, however that high doses of ionizing radiation (in the range of 20-35 kGy) used for sterilization evoke many chemical and physical changes which may influence biological properties of grafts. These changes have been studied using various methodological approaches. Using electron paramagnetic resonance (EPR) spectrometry it has been found that in radiation-sterilized bone two types of paramagnetic entities are generated: i/ coliagen radicals which are unstable and disappear completely in the presence of air oxygen, ii/ very stable at room temperature paramagnetic defects (centers) localized in the crystalline lattice of bone mineral. These stable paramagnetic defects have been treated as a new kind of markers and used for: a/ quantitative evaluation of remodeling process of radiation-sterilized bone allografts preserved by lyophilization or deep freezing; b/ estimation of the dose of ionizing radiation absorbed by living organism in the case of accidental exposure (skeleton serving as a dosimeter) and for control of radiation-sterilization process. The effect of radiation-sterilization and preservation procedures on bone allografts was studied using a model of heterotopically induced osteogenesis and measuring the solubility of bone collagen in vitro. It has been observed that lyophilized bone allografts irradiated at room temp. with doses of 35 and 50 kGy, respectively, were very quickly resorbed in vivo and did not induce osteogenesis, while lyophilized as well as deep-frozen matrices irradiated at -7OoC were slowly resorbed and induced de novo bone fon

  15. Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Coen, John J., E-mail: jcoen@harthosp.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Paly, Jonathan J.; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kaufman, Donald S. [Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Heney, Niall M. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2013-06-01

    Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.

  16. Importance of antiresorptive therapies for patients with bone metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Talreja DB

    2012-09-01

    Full Text Available Draupadi B TalrejaDepartment of Medicine, David Geffen School of Medicine at UCLA and Northridge Hospital Medical Center, Northridge, CA, USAAbstract: Patients with bone metastases are at risk of skeletal-related events such as pathologic fractures, spinal cord compression, the need for orthopedic surgery to bone, and palliative radiotherapy for severe bone pain. Antiresorptive therapies have demonstrated efficacy for reducing the risk of skeletal-related events and ameliorating bone pain. Despite the well documented clinical benefits of antiresorptive therapies, patient benefits can be limited or compromised by nonadherence with scheduled therapy. Potential reasons for poor compliance include lack of understanding of how antiresorptive therapies work, neglecting the importance of bone health in maintaining quality of life, and being unaware of the potentially debilitating effects of skeletal-related events caused by bone metastases. Indeed, patients may stop therapy after bone pain subsides or discontinue due to generally mild and usually manageable adverse events, leaving them at an increased risk of developing skeletal-related events. In addition, the cost of antiresorptive therapy can be a concern for many patients with cancer. Medical care for patients with cancer requires a coordinated effort between primary care physicians and oncologists. Patients' medical care teams can be leveraged to help educate them about the importance of adherence to antiresorptive therapy when cancer has metastasized to bone. Because primary care physicians generally have more contact with their patients than oncologists, they are in a unique position to understand patient perceptions and habits that may lead to noncompliance and to help educate patients about the benefits and risks of various antiresorptive therapies in the advanced cancer setting. Therefore, primary care physicians need to be aware of various mechanistic and clinical considerations regarding

  17. Repeated 89Sr therapy in breast cancer patient with multiple bone metastases

    International Nuclear Information System (INIS)

    Lee, Jae Soung; Yang, Weon Il; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo; Hong, Soung Woon

    2000-01-01

    The single 89 Sr therapy has been used for pain relief in patients with multiple bony metastases and it is known to be very effective without serious complications except mild bone marrow suppression. But usually repeated therapy is needed because it is not a completely curative therapy. This study was performed to evaluate the effects of repeated 89 Sr therapy on therapeutic outcome compared to first therapy. This study was performed retrospectively with fifteen breast cancer patients treated more than twice with 89 SrCl 2 against multiple bony metastases. There were total 42 cases-there were eight, four, two and one patients treated twice, three times, four times and six times respectively. The time interval between therapy was 179.1±107.5 (90-550) days. We scored zero to five about performance, analgesics, subjective pain, sleep pattern respectively and summed as the pain score (0-20). Before therapy and one month and three months after therapy the pain score was evaluated and blood leukocyte and platelet was estimated. Bone scan was performed before therapy and one, three and six months after therapy. The pain score was 6.5±2.4 (2-10) before first therapy. Among 42 cases the pain score was improved in 22 cases (52.4%), not changed in 8 cases (19.0%) and aggravated in 12 cases (28.6%). The pain score was not affected by therapy number. Bone scan showed various changes without statistical correlation with pain score. One month after therapy blood leukocyte and platelet was decreased more than 20% than before therapy in six cases (28.6%) and seven cases (16.7%) among 21 cases, respectively. The leukocyte and platelet was not more decreased as increased therapy number. The repeated 89 Sr therapy is not so different from the first therapy in effects and bone marrow suppression. Bone scan finding was independent to the pain score

  18. Simulated Space Radiation and Weightlessness: Vascular-Bone Coupling Mechanisms to Preserve Skeletal Health

    Science.gov (United States)

    Globus, R. K.; Alwood, J.; Tahimic, C.; Schreurs, A.-S.; Shirazi-Fard, Y.; Terada, M.; Zaragoza, J.; Truong, T.; Bruns, K.; Castillo, A.; hide

    2018-01-01

    We examined experimentally the effects of radiation and/or simulated weightlessness by hindlimb unloading on bone and blood vessel function either after a short period or at a later time after transient exposures in adult male, C57Bl6J mice. In sum, recent findings from our studies show that in the short term, ionizing radiation and simulate weightlessness cause greater deficits in blood vessels when combined compared to either challenge alone. In the long term, heavy ion radiation, but not unloading, can lead to persistent, adverse consequences for bone and vessel function, possibly due to oxidative stress-related pathways.

  19. A Danish randomized trial comparing breast-preserving therapy with mastectomy in mammary carcinoma

    International Nuclear Information System (INIS)

    Blichert-Toft, M.; Brincker, H.; Andersen, J.A.; Andersen, K.W.; Axelsson, C.K.; Mouridsen, H.T.; Dombernowsky, P.; Overgaard, M.; Gadeberg, C.; Knudsen, G.; Borgeskov, S.; Bertelsen, S.; Knudsen, J.B.; Hansen, J.B.; Poulsen, P.E.; Willumsen, H.; Schousen, P.; Froberg, D.; Oernsholt, J.; Andersen, M.; Olesen, S.; Skovgaard, S.; Oester, M.; Schumacher, H.; Lynderup, E.K.; Holm, C.N.

    1988-01-01

    The present study comprises 847 women operated upon for invasive breast carcinoma at 19 surgical departments and enrolled in protocol DBCG-82TM from January 1983 to November 1987. Among them 662 (78%) were allocated for breast-preserving therapy or mastectomy by randomization, while 185 patients (22%) did not accept randomization. Within the randomized group 6% could not be entered into adjuvant protocols, i.e. subsequent programmes of postoperative therapy and follow-up. This left 619 evaluable patients. In the non-randomized series 26% did not fulfil the demands for entrance into the adjuvant protocols, leaving 136 evaluable patients, 60 of whom had chosen a breast-preserving operation and 76 mastectomy. In the randomized series the patients in the two treatment arms were comparable in age, menopausal status, site of tumour, pathoanatomical diameter of the tumour, number of removed axillary lymph nodes, number of metastatic axillary lymph nodes, and distribution on adjuvant regimens. Ninety per cent of the patients in the randomized group accepted the method offered, whereas 10% declined and wanted the alternate form of operation. The median follow-up period was approximately 1.75 years. The cumulative recurrence rate in the randomized group was 13% and in the non-randomized group 7%. These results are preliminary. Life-table analyses have not so far demonstrated differences in recurrence-free survival either in the randomized or the non-randomized series. (orig.)

  20. Non-viral gene therapy for bone tissue engineering

    NARCIS (Netherlands)

    Wegman, F.

    2013-01-01

    In bone tissue engineering bone morphogentic protein-2 (BMP-2) is one of the most commonly used growth factors. It induces stem cells to differentiate into the osteogenic lineage to form new bone. Clinically however, high dosages of protein are administered due to fast degradation, which is

  1. The non-steroidal antiandrogen, bicalutamide ('Casodex'), may preserve bone mineral density as compared with castration

    DEFF Research Database (Denmark)

    Tyrrell, C J; Blake, G M; Iversen, P

    2003-01-01

    The impact of bicalutamide (Casodex) monotherapy on bone mineral density (BMD) was investigated in patients with locally advanced prostate cancer. BMD was assessed after treatment with bicalutamide 150 mg daily ( n=21) or by medical castration (goserelin acetate 3.6 mg every 28 days) ( n=8...

  2. The non-steroidal antiandrogen, bicalutamide ('Casodex'), may preserve bone mineral density as compared with castration

    DEFF Research Database (Denmark)

    Tyrrell, C J; Blake, G M; Iversen, P

    2003-01-01

    The impact of bicalutamide (Casodex) monotherapy on bone mineral density (BMD) was investigated in patients with locally advanced prostate cancer. BMD was assessed after treatment with bicalutamide 150 mg daily ( n=21) or by medical castration (goserelin acetate 3.6 mg every 28 days) ( n=8) for a...

  3. Exercise Preserves Physical Function in Prostate Cancer Patients with Bone Metastases.

    Science.gov (United States)

    Galvão, Daniel A; Taaffe, Dennis R; Spry, Nigel; Cormie, Prue; Joseph, David; Chambers, Suzanne K; Chee, Raphael; Peddle-McIntyre, Carolyn J; Hart, Nicolas H; Baumann, Freerk T; Denham, James; Baker, Michael; Newton, Robert U

    2018-03-01

    The presence of bone metastases has excluded participation of cancer patients in exercise interventions and is a relative contraindication to supervised exercise in the community setting because of concerns of fragility fracture. We examined the efficacy and safety of a modular multimodal exercise program in prostate cancer patients with bone metastases. Between 2012 and 2015, 57 prostate cancer patients (70.0 ± 8.4 yr; body mass index, 28.7 ± 4.0 kg·m) with bone metastases (pelvis, 75.4%; femur, 40.4%; rib/thoracic spine, 66.7%; lumbar spine, 43.9%; humerus, 24.6%; other sites, 70.2%) were randomized to multimodal supervised aerobic, resistance, and flexibility exercises undertaken thrice weekly (EX; n = 28) or usual care (CON; n = 29) for 3 months. Physical function subscale of the Medical Outcomes Study Short-Form 36 was the primary end point as an indicator of patient-rated physical functioning. Secondary end points included objective measures of physical function, lower body muscle strength, body composition, and fatigue. Safety was assessed by recording the incidence and severity of any adverse events, skeletal complications, and bone pain throughout the intervention. There was a significant difference between groups for self-reported physical functioning (3.2 points; 95% confidence interval, 0.4-6.0 points; P = 0.028) and lower body muscle strength (6.6 kg; 95% confidence interval, 0.6-12.7; P = 0.033) at 3 months favoring EX. However, there was no difference between groups for lean mass (P = 0.584), fat mass (P = 0.598), or fatigue (P = 0.964). There were no exercise-related adverse events or skeletal fractures and no differences in bone pain between EX and CON (P = 0.507). Multimodal modular exercise in prostate cancer patients with bone metastases led to self-reported improvements in physical function and objectively measured lower body muscle strength with no skeletal complications or increased bone pain. ACTRN12611001158954.

  4. Bone loss in long-term suppressive therapy with thyroid hormone

    International Nuclear Information System (INIS)

    Firooznia, H.; Blum, M.; Golimbu, C.; Rafii, M.

    1987-01-01

    The trabecular bone density of the spine was measured with CT in 31 women, aged 39-79 years, who had received an average of 13.5 years of thyroid suppressive therapy. The spinal trabecular bone density values in 24 (77%), 18 (58%), and 13 subjects (42%) were respectively below the mean for healthy age-matched controls, the fifth percentile for healthy premenopausal women, and the fifth percentile for age-matched controls. Cortical and trabecular bone loss occurs in hyperthyroidism. Although the intent is not to cause hyperthyroidism in subjects on suppressive therapy, supraphysical doses of thyroid hormone are usually necessary for suppression of thyroid-stimulating hormone. In this study, bone loss was noted in these subjects. Because most of these patients are middle-aged or postmenopausal women, who are at risk for osteoporosis, it is important to be aware of the risk of additional bone loss induced by thyroid suppressive therapy in them

  5. Effects of low-level laser therapy on orthodontic tooth movement and root resorption after artificial socket preservation

    Directory of Open Access Journals (Sweden)

    Massoud Seifi

    2014-01-01

    Full Text Available Background: Low- level laser therapy has been used to stimulate the orthodontic tooth movements (OTM previously. Furthermore, in the orthodontic treatments accompanying tooth extractions, the adjacent teeth move towards the extraction sites and close the space in some cases. Then, the adjacent tooth movements must be prevented in the treatments requiring space. Laser stimulates and at some doses decelerates tooth movement; it also improves healing process and enhances osteogenesis. Hence, it can prevent movement by osteogenesis adjacent to the tooth. The present study investigated the effects of low-level laser therapy on the OTM and root resorption following artificial socket preservation. Materials and Methods: In this experimental animal trial, 16 male albino rabbits were selected with similar characteristics and randomly divided in two groups. Under general anesthesia, an artificial socket, 8 mm in height, was created in the mesial aspect of the first premolars of the rabbits and filled with demineralized freeze dried bone allograft (DFDBA. The first premolars were connected to the incisors using nickel titanium coil springs. In experimental group, gallium-aluminum-arsenide (GaAlAs laser was irritated mesial to first premolar where artificial socket was created continuously (808 nm. The cycle was 10 days irritation, 14 days rest, 10 days irritation, 14 days rest (Biostimulation mode. Control group was not laser irradiated. All animals were sacrificed after 48 days and the distance between the distal aspect of the first premolars, and the mesial surface of the second premolars was measured with leaf gauge. The specimens underwent histological assessments. Integrity of root and its resorption was observed under microscope calibration. The size of resorption lacunae was calculated in mm 2 . Normality of data was proved according to Kolmogorov-Smirnov analysis, and Student′s t-test was done. P value less than 0.05 was considered as significant

  6. Long-term survival of bladder preservation therapy with radiation and chemotherapy for locally invasive bladder cancer

    International Nuclear Information System (INIS)

    Noguchi, Sumio; Takase, Kazunori; Kubota, Yoshinobu; Masuda, Mitsunobu; Yao, Masahiro; Hosaka, Masahiko

    1998-01-01

    The prognoses and prognostic factors of the 54 patients with locally invasive bladder cancer who underwent bladder preservation therapy at Yokohama City University Hospital between 1977 and 1995 were analyzed statistically. The therapeutic modalities of bladder preservation were mainly radiation or chemotherapy. The prognosis for the patients who underwent bladder preservation therapy was worse than that for the patients who underwent total cystectomy. The prognostic factors of these patients were size and grade of tumor, presence of hydronephrosis and performance status (PS) of the patients by univariate analysis. Tumor grade was the most predictable prognostic factor using multivariate analysis. Only 17 patients survived more than 5 years after treatment; 78% of the survivors had good PS (0 or 1). Five of them died of cancer and two patients were alive with cancer. All of them had G3 tumors. These results suggest that patients with locally invasive G2 tumor could be candiates for bladder preservation therapy and patients who underwent bladder preservation therapy should be evaluated at 10 years post-therapy. (author)

  7. Effect of hormone replacement therapy on bone quality in early postmenopausal women

    DEFF Research Database (Denmark)

    Paschalis, E P; Boskey, A L; Kassem, M

    2003-01-01

    HRT is an effective prophylaxis against postmenopausal bone loss. Infrared imaging of paired iliac crest biopsies obtained at baseline and after 2 years of HRT therapy demonstrate an effect on the mineral crystallinity and collagen cross-links that may affect bone quality. Several studies have de...

  8. Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links

    OpenAIRE

    Pardini,Dolores Perovano; Sabino,Anibal Tagliaferri; Meneses,Ana Maria; Kasamatsu,Teresa; Vieira,José Gilberto Henriques

    2000-01-01

    CONTEXT: The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. OBJECTIVE: To study the effect of hormone replacement therapy (HRT) on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN: Cohort correlational study. SETTING: Academic...

  9. Importance of antiresorptive therapies for patients with bone metastases from solid tumors

    International Nuclear Information System (INIS)

    Talreja, Draupadi B

    2012-01-01

    Patients with bone metastases are at risk of skeletal-related events such as pathologic fractures, spinal cord compression, the need for orthopedic surgery to bone, and palliative radiotherapy for severe bone pain. Antiresorptive therapies have demonstrated efficacy for reducing the risk of skeletal-related events and ameliorating bone pain. Despite the well documented clinical benefits of antiresorptive therapies, patient benefits can be limited or compromised by nonadherence with scheduled therapy. Potential reasons for poor compliance include lack of understanding of how antiresorptive therapies work, neglecting the importance of bone health in maintaining quality of life, and being unaware of the potentially debilitating effects of skeletal-related events caused by bone metastases. Indeed, patients may stop therapy after bone pain subsides or discontinue due to generally mild and usually manageable adverse events, leaving them at an increased risk of developing skeletal-related events. In addition, the cost of antiresorptive therapy can be a concern for many patients with cancer. Medical care for patients with cancer requires a coordinated effort between primary care physicians and oncologists. Patients’ medical care teams can be leveraged to help educate them about the importance of adherence to antiresorptive therapy when cancer has metastasized to bone. Because primary care physicians generally have more contact with their patients than oncologists, they are in a unique position to understand patient perceptions and habits that may lead to noncompliance and to help educate patients about the benefits and risks of various antiresorptive therapies in the advanced cancer setting. Therefore, primary care physicians need to be aware of various mechanistic and clinical considerations regarding antiresorptive treatment options

  10. k-space sampling optimization for ultrashort TE imaging of cortical bone: Applications in radiation therapy planning and MR-based PET attenuation correction

    International Nuclear Information System (INIS)

    Hu, Lingzhi; Traughber, Melanie; Su, Kuan-Hao; Pereira, Gisele C.; Grover, Anu; Traughber, Bryan; Muzic, Raymond F. Jr.

    2014-01-01

    Purpose: The ultrashort echo-time (UTE) sequence is a promising MR pulse sequence for imaging cortical bone which is otherwise difficult to image using conventional MR sequences and also poses strong attenuation for photons in radiation therapy and PET imaging. The authors report here a systematic characterization of cortical bone signal decay and a scanning time optimization strategy for the UTE sequence through k-space undersampling, which can result in up to a 75% reduction in acquisition time. Using the undersampled UTE imaging sequence, the authors also attempted to quantitatively investigate the MR properties of cortical bone in healthy volunteers, thus demonstrating the feasibility of using such a technique for generating bone-enhanced images which can be used for radiation therapy planning and attenuation correction with PET/MR. Methods: An angularly undersampled, radially encoded UTE sequence was used for scanning the brains of healthy volunteers. Quantitative MR characterization of tissue properties, including water fraction and R2 ∗ = 1/T2 ∗ , was performed by analyzing the UTE images acquired at multiple echo times. The impact of different sampling rates was evaluated through systematic comparison of the MR image quality, bone-enhanced image quality, image noise, water fraction, and R2 ∗ of cortical bone. Results: A reduced angular sampling rate of the UTE trajectory achieves acquisition durations in proportion to the sampling rate and in as short as 25% of the time required for full sampling using a standard Cartesian acquisition, while preserving unique MR contrast within the skull at the cost of a minimal increase in noise level. The R2 ∗ of human skull was measured as 0.2–0.3 ms −1 depending on the specific region, which is more than ten times greater than the R2 ∗ of soft tissue. The water fraction in human skull was measured to be 60%–80%, which is significantly less than the >90% water fraction in brain. High-quality, bone

  11. Socket preservation using demineralized freezed dried bone allograft with and without plasma rich in growth factor: A canine study

    Science.gov (United States)

    Mogharehabed, Ahmad; Birang, Reza; Torabinia, Nakisa; Nasiri, Saman; Behfarnia, Parichehr

    2014-01-01

    Background: The accelerating effect of plasma rich in growth factors (PRGFs) in the healing of extraction sockets has been demonstrated by some studies. The aim of the present study was to histologically and histomorphometrically evaluate whether bone formation would increase by the combined use of PRGF and demineralized freeze-dried bone allograft (DFDBA). Materials and Methods: In four female dogs, the distal root of the second, third and fourth lower premolars were extracted bilaterally and the mesial roots were preserved. The extraction sockets were randomly divided into DFDBA + PRGF, DFDBA + saline or control groups. Two dogs were sacrificed after 2 weeks and two dogs were sacrificed after 6 weeks. The extraction sockets were evaluated from both histological and histomorphometrical aspects. The data were analyzed by Mann-Whitney followed by Kruskal-Wallis tests using the Statistical Package for the Social Sciences version 20 (SPSS Inc., Chicago, IL, USA). Significant levels were set at 0.05. Results: The least decrease in socket height was observed in the DFDBA + PRGF group (0.73 ± 0.42 mm). The least decrease in the coronal portion was observed in the DFDBA + PRGF group (1.38 ± 1.35 mm²). The least decrease in the middle surface was observed in the DFDBA group (0.61 ± 0.80 mm²). The least decrease in the apical portion was observed in the DFDBA group (0.34 ± 0.39 mm²). Conclusion: The present study showed better socket preservation subsequent to the application of DFDBA and PRGF combination in comparison with the two other groups. However, the difference was not statistically significant. PMID:25225559

  12. Socket preservation using demineralized freezed dried bone allograft with and without plasma rich in growth factor: A canine study

    Directory of Open Access Journals (Sweden)

    Ahmad Mogharehabed

    2014-01-01

    Full Text Available Background: The accelerating effect of plasma rich in growth factors (PRGFs in the healing of extraction sockets has been demonstrated by some studies. The aim of the present study was to histologically and histomorphometrically evaluate whether bone formation would increase by the combined use of PRGF and demineralized freeze-dried bone allograft (DFDBA. Materials and Methods: In four female dogs, the distal root of the second, third and fourth lower premolars were extracted bilaterally and the mesial roots were preserved. The extraction sockets were randomly divided into DFDBA + PRGF, DFDBA + saline or control groups. Two dogs were sacrificed after 2 weeks and two dogs were sacrificed after 6 weeks. The extraction sockets were evaluated from both histological and histomorphometrical aspects. The data were analyzed by Mann-Whitney followed by Kruskal-Wallis tests using the Statistical Package for the Social Sciences version 20 (SPSS Inc., Chicago, IL, USA. Significant levels were set at 0.05. Results: The least decrease in socket height was observed in the DFDBA + PRGF group (0.73 ± 0.42 mm. The least decrease in the coronal portion was observed in the DFDBA + PRGF group (1.38 ± 1.35 mm². The least decrease in the middle surface was observed in the DFDBA group (0.61 ± 0.80 mm². The least decrease in the apical portion was observed in the DFDBA group (0.34 ± 0.39 mm². Conclusion: The present study showed better socket preservation subsequent to the application of DFDBA and PRGF combination in comparison with the two other groups. However, the difference was not statistically significant.

  13. Targeted Therapies for Myeloma and Metastatic Bone Cancers

    National Research Council Canada - National Science Library

    Vail, Neal

    2008-01-01

    ... done. Quantified functional groups available for ligand conjugation using S35-labeled ligands. Developed alternative assay to confirm affinity of bone-targeting nanoparticles to hydroxyapatite substrates...

  14. Cellular Therapy to Obtain Rapid Endochondral Bone Formation

    Science.gov (United States)

    2008-02-01

    length from the tibial fusion site, and then stop which would be consistent with the resorption being associated with the lack of weight bearing load. In...Defect in the Rat Femur with Use of a Vascularized Periosteal Flap, a Biodegradable Matric, and Bone Morphogenetic Protein. J Bone Joint Surg 87-A(6

  15. The effect of radiation therapy for bone metastasis in urinary organ cancer

    International Nuclear Information System (INIS)

    Chikazawa, Ippei; Inoue, Shinya; Nakazawa, Yusuke

    2016-01-01

    Bone metastasis symptoms are complications that greatly reduce the quality of life (QOL) of cancer patients. We report a retrospective study on the efficacy of radiation therapy for patients with bone metastasis in urinary organ cancer. (Subjects and methods) Subjects are comprised of 17 patients; total irradiated areas consist of 25 sites. There are 5 patients diagnosed with renal cell carcinoma, 1 patient with bladder cancer and 11 patients with prostatic cancer. All of them have undergone radiation therapy for bone metastasis in urinary organ cancer between April 2007 and March 2014 in the Department of Urology, Kanazawa Medical University. The mean age of the patients was 66.7 years old. We looked at irradiated areas, exposure dose and changes of symptom in all patients. Irradiated areas are thoracolumbar vertebrae (14 sites), cranial base (2 sites), pubic bone (1 site), ilium bone (2 sites), sacral bone (1 site), rib bone (1 site) and hip joint (1 site). The mean exposure dose of one area is 37.5 Gy (13.5-60). 19 irradiated sites which were previously reported to have sharp pain have gained improvement at 16 sites. These 16 sites have comparatively lesser pain or no pain. 8 cases in acknowledgment of walk difficulty, it was with 7 cases walking alone possibility again. This study showed that radiation therapy have significant improvement in terms of symptoms and QOL for the patients with bone metastasis in urinary organ cancer. (author)

  16. BONE MARKERS IN MONITORING OF ANTIRESORPTIVE THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS PATIENTS

    Directory of Open Access Journals (Sweden)

    Tanja Džopalić

    2015-09-01

    Full Text Available The aim of this work was to study the effect of two modalities of antiosteoporotic therapy in postmenopausal women at the level of biochemical markers of bone turnover such as bone specific alkaline phosphatase (BALP and deoxypiridinoline (Dpd as well as bone mineral density (BMD. The study included 87 patients with postmenopausal osteoporosis (OP. Group A consisted of 48 patients treated with alendronate (AL, whereas group B included 39 patients treated with hormone replacement therapy (HRT. BMD was measured by Lunar DPX 2000 device, on the lumbar spine and the femur, and bone markers (BM were measured by commercial ELISA assays. There was a statistically significant decrease in the levels of BALP and Dpd after 6 weeks and 8 months of both types of therapy compared to the level of these markers before therapy. There was a statistically significant increase of BMD on both locations after 8 months of both therapies. In addition, there was a statistically significantly higher degree of changes of Dpd values in the group treated with AL than in the group treated with HRT. On the other hand, the changes in the level of BALP were significantly higher in the group treated with HRT. We concluded that the early effect of the two studied antiosteoporotic medications can be monitored by changes in the levels of BM. Dpd as bone resorption marker proved to be a better indicator of the efficiency of applied medications compared to bone formation markers such as BALP.

  17. Reconversion of bone marrow in Gaucher disease treated with enzyme therapy documented by MR

    International Nuclear Information System (INIS)

    Allison, J.W.; James, C.A.; Arnold, G.L.; Stine, K.C.; Becton, D.L.; Bell, J.M.

    1998-01-01

    Background. Skeletal complications are responsible for significant morbidity in Gaucher patients. Plain radiographs have been unreliable in assessing bone marrow infiltration and activity. A way to assess bone marrow improvement is needed during enzyme therapy. Objective. The purpose of this paper is to assess the usefulness of MR in following improvement of abnormal bone marrow in Gaucher patients on enzyme therapy. Materials and methods. Three patients aged 2, 7, and 24 years underwent serial MR scans of the lower extremities before and during treatment with Alglucerase (two patients) and Imiglucerase (one patient). T1-weighted, T2-weighted, STIR and FSE T2-weighted images were utilized. Two patients were imaged after 16 months of therapy, and one patient was imaged after 6 months of therapy. Results. All patients had improvement in marrow signal consistent with partial reconversion to fatty marrow during treatment. The findings were more marked after prolonged therapy. T1-weighted images demonstrated findings most clearly. Conclusion. MR consistently showed improvement in marrow signal in Gaucher patients on enzyme therapy. As smaller doses of enzyme therapy are the trend, MR can be utilized to determine if therapy is effecting a change in the bone marrow. (orig.)

  18. [Extensive cranioplasty for sagittal synostosis in young children by preserving multiple cranial bone flaps adhered to the dura mater: experience with 63 cases].

    Science.gov (United States)

    Bao Nan; Chu Jun; Wang Xue; Yang, Bo; Song, Yunhai; Cai, Jinjing

    2016-01-01

    This study aimed to evaluate the effort of applying frontal and occipital bones in extensive cranioplasty and preserving multiple cranial bone flaps adhered to the dura mater in the treatment of sagittal synostosis. From April 2008 to June 2013, sixty-three children with sagittal synostosis, aged 5 months to 3 years, were included in the study. The frontal bone flap was removed using an air drill. The occipital and bilateral temporal bone flaps were cut open but not detached from the dura mater or fixed to produce floating bone flaps. The skull bone was cut into palisade-like structures. Brain compression from both sides and the base of the skull was released and the brain expanded bilaterally through the enlarged space. Only a long strip-shaped bone bridge remained in the central parietal bone. Subsequently, the frontal bone flaps and occipital bone flap were pushed towards the midline and fixed with the parietal bone bridge to shorten the anteroposterior diameter of the cranial cavity and allow the brain to expand bilaterally to correct scaphocephaly. The CT images showed that both sides of the parietal bone of artificial sagittal groove gradually merged postoperative 1 year, and skull almost completely normal healing after operation 2 or 3 years, without deformity recurrence within 5 years. Among them all, 61 children's intelligence is normal and 2 children's lagged behind normal level, no further improvement. Patients were followed up 1 - 5 years (an average of 43 months). Skull growth was excellent in all patients, the anteroposterior diameter was shortened by 14.6 mm averagely, the transverse diameter was increased by 12.3 mm averagely, the prominent forehead was corrected, and scaphocephaly improved significantly. There were no complications such as death and skull necrosis. The application of frontal and occipital bones in extensive cranioplasty and preserving multiple cranial bone flaps adhered to the dura mater can be used in the treatment of sagittal

  19. Preservação da proteína verde fluorescente no tecido ósseo descalcificado Preservation of the green fluorescent protein on decalcified bone tissue

    Directory of Open Access Journals (Sweden)

    Jankerle Neves Boeloni

    2010-10-01

    diseases. However, in the bone, the fluorescence generated by GFP can be lost during the decalcification process, hindering the tracking of stem cells used in the treatment of diseases or bone defects. The aim of this study was to compare different techniques of preservation of GFP in the decalcified bone tissue. Femurs of female Lewis GFP rats were distributed in four groups: 1 decalcified in formic acid and paraffin-embedded; 2 decalcified in formic acid submitted to cryomicrotomy; 3 decalcified in EDTA and paraffin-embedded and 4 decalcified in EDTA with cryomicrotomy. Sections of bone tissue of all the groups were analyzed for identification of the natural fluorescence and subsequently submitted to the immunofluorescence using anti-GFP and Alexa Flúor 555. The images were obtained by confocal microscopy. Osteocytes, osteoblasts and bone marrow cells of GFP rats only had natural fluorescence preserved in the bone tissue decalcified in EDTA and submitted to cryomicrotomy. In others groups there were loss of the natural fluorescence and the GFP cells could be only identified with the use of the immunofluorescence with anti-GFP. In conclusion, the decalcification in EDTA and the cryomicrotomy are the best techniques to preserve the natural fluorescence of the GFP cells in the bone tissue and the GFP cells in bone tissue decalcified in formic acid and paraffin-embedded can be visualized only with the use of the immunofluorescence with anti-GFP.

  20. Bone growth during rapamycin therapy in young rats

    Directory of Open Access Journals (Sweden)

    He Yu-Zhu

    2009-01-01

    Full Text Available Abstract Background Rapamycin is an effective immunosuppressant widely used to maintain the renal allograft in pediatric patients. Linear growth may be adversely affected in young children since rapamycin has potent anti-proliferative and anti-angiogenic properties. Methods Weanling three week old rats were given rapamycin at 2.5 mg/kg daily by gavage for 2 or 4 weeks and compared to a Control group given equivalent amount of saline. Morphometric measurements and biochemical determinations for serum calcium, phosphate, iPTH, urea nitrogen, creatinine and insulin-growth factor I (IGF-I were obtained. Histomorphometric analysis of the growth plate cartilage, in-situ hybridization experiments and immunohistochemical studies for various proteins were performed to evaluate for chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption. Results At the end of the 2 weeks, body and tibia length measurements were shorter after rapamycin therapy associated with an enlargement of the hypertrophic zone in the growth plate cartilage. There was a decrease in chondrocyte proliferation assessed by histone-4 and mammalian target of rapamycin (mTOR expression. A reduction in parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP and an increase in Indian hedgehog (Ihh expression may explain in part, the increase number of hypertrophic chondrocytes. The number of TRAP positive multinucleated chondro/osteoclasts declined in the chondro-osseous junction with a decrease in the receptor activator of nuclear factor kappa β ligand (RANKL and vascular endothelial growth factor (VEGF expression. Although body and tibial length remained short after 4 weeks of rapamycin, changes in the expression of chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption which were significant after 2 weeks of rapamycin improved at the end of 4 weeks. Conclusion When given to young rats, 2 weeks of rapamycin

  1. Bone mineral density trends in Indian patients with hyperthyroidism--effect of antithyroid therapy.

    Science.gov (United States)

    Dhanwal, Dinesh Kumar; Gupta, Nandita

    2011-09-01

    Hyperthyroidism is associated with bone loss, which is reversible after treatment. The extent of reversibility of loss of bone mass density (BMD) in hyperthyroid patients after treatment especially at forearm is not clear. Therefore, the present study was conducted to assess degree of reversibility in bone mineral density following one-year medical treatment in Indian patients with hyperthyroidism. A total of 30 consecutive patients with hyperthyroidism were included in this one year study at All India Institute of Medical Sciences, New Delhi, India. All the patients were assessed for parameters of bone mineral homeostasis such as calcium, phosphorous, alkaline phosphatase, 25-hydroxy vitamin D [25 (OH) D], parathyroid hormone (PTH) at the time of diagnosis and after one year medical treatment. Bone mineral density was measured using Hologic DXA scan at hip, spine and forearm. All the patients received medical therapy with carbimazole. The parameters of bone homeostasis and bone mineral density at base line and after one year medical treatment was compared. All patients attained euthyroid status after eight weeks of carbimazole therapy. Parameters of bone homeostasis such as calcium, phosphorous, 25 (OH) D and PTH did not show any significant change from base line. Bone mineral density expressed as bone mineral content in gm/cm2 at left hip neck, trochanteric and intertrochanteric region was significantly higher after carbimazole therapy (745.2 +/- 127.6 gm/cm2 vs. 688.2 +/- 123.5 gm/cm2; p = 0.02, 573.4 +/- 109.9 gm/cm2 vs. 641.0 +/- 138.0 gm/cm2, p = 0.005 and 1008.6 +/- 185.5 gm/cm2 vs. 938.0 +/- 145.3 gm/cm2 p = 0.0131 respectively). Bone mineral density at lumbar spine expressed as either T and Z score was significantly higher after treatment (10 months of euthyroid state) (-0.6 +/- 1.3 vs. -1.7 +/- 1.2, p = 0.013 and -0.4 +/- 1.2 vs. -1.4 +/- 1.2, p = 0.012 respectively). However Bone mineral measures as T and Z score at left forearm decreased significantly

  2. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2017-12-01

    variation . (B) After ComBat (Combing Batches) correction biological variables such as animal age and defect size accounted for largest variation in gene...growth plates), age accounted for more variation than defect size in PC1 (data not shown). This suggests, that age is a dominant factor in bone healing...correlates with histologic changes during fracture repair. J Bone Miner Res 1992; 7:1045-55. 103. Grimston SK, Goldberg DB, Watkins M, Brodt MD, Silva MJ

  3. Transdifferentiation of myoblasts into osteoblasts - possible use for bone therapy.

    Science.gov (United States)

    Lin, Daphne P L; Carnagarin, Revathy; Dharmarajan, Arun; Dass, Crispin R

    2017-12-01

    Transdifferentiation is defined as the conversion of one cell type to another and is an ever-expanding field with a growing number of cells found to be capable of such a process. To date, the fact remains that there are limited treatment options for fracture healing, osteoporosis and bone repair post-destruction by bone tumours. Hence, this review focuses on the transdifferentiation of myoblast to osteoblast as a means to further understand the transdifferentiation process and to investigate a potential therapeutic option if successful. The potent osteoinductive effects of the bone morphogenetic protein-2 are largely implicated in the transdifferentiation of myoblast to osteoblast. Bone morphogenetic protein-2-induced activation of the Smad1 protein ultimately results in JunB synthesis, the first transcriptional step in myoblast dedifferentiation. The upregulation of the activating protein-1 binding activity triggers the transcription of the runt-related transcription factor 2 gene, a transcription factor that plays a major role in osteoblast differentiation. This potential transdifferentiation treatment may be utilised for dental implants, fracture healing, osteoporosis and bone repair post-destruction by bone tumours. © 2017 Royal Pharmaceutical Society.

  4. Sequence preservation of osteocalcin protein and mitochondrial DNA in bison bones older than 55 ka

    Science.gov (United States)

    Nielsen-Marsh, Christina M.; Ostrom, Peggy H.; Gandhi, Hasand; Shapiro, Beth; Cooper, Alan; Hauschka, Peter V.; Collins, Matthew J.

    2002-12-01

    We report the first complete sequences of the protein osteocalcin from small amounts (20 mg) of two bison bone (Bison priscus) dated to older than 55.6 ka and older than 58.9 ka. Osteocalcin was purified using new gravity columns (never exposed to protein) followed by microbore reversed-phase high-performance liquid chromatography. Sequencing of osteocalcin employed two methods of matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS): peptide mass mapping (PMM) and post-source decay (PSD). The PMM shows that ancient and modern bison osteocalcin have the same mass to charge (m/z) distribution, indicating an identical protein sequence and absence of diagenetic products. This was confirmed by PSD of the m/z 2066 tryptic peptide (residues 1 19); the mass spectra from ancient and modern peptides were identical. The 129 mass unit difference in the molecular ion between cow (Bos taurus) and bison is caused by a single amino-acid substitution between the taxa (Trp in cow is replaced by Gly in bison at residue 5). Bison mitochondrial control region DNA sequences were obtained from the older than 55.6 ka fossil. These results suggest that DNA and protein sequences can be used to directly investigate molecular phylogenies over a considerable time period, the absolute limit of which is yet to be determined.

  5. Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

    OpenAIRE

    Olson, Erik J.; Lindgren, Bruce R.; Carlson, Cathy S.

    2007-01-01

    The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight...

  6. Contemporary guided bone regeneration therapy for unaesthetic anterior peri-implantitis case

    Directory of Open Access Journals (Sweden)

    Benso Sulijaya

    2016-12-01

    Full Text Available Background: Dental implant is one of an alternative solutions reconstruction therapy for missing teeth. Complication of dental implant could occurs and leading to implant failure. In order to restore the complication, surgical treatment with guided bone regeneration (GBR is indicated. The potential use of bone substitutes is widely known to be able to regenerate the bone surrounding the implant and maintain bone volume. Purpose: The study aimed to demonstrate the effectiveness of implant-bone fully coverage by using sandwich technique of biphasic calcium phosphate (BCP and demineralized freeze-dried bone allografts (DFDBA bone substitutes combined with collagen resorbable membrane. Case: A 24-year-old male came with diagnosis of peri-implantitis on implant #11. Clinical finding indicated that implant thread was exposed on the labial aspect. Case management: After initial therapy including oral hygiene improvement performed, an operator did a contemporary GBR to correct the defect. Bone graft materials used were 40% β-tri calcium phosphate (β-TCP-60% hydroxyapatite (HA on the outer layer and DFDBA on the inner layer of the defect. Resorbable collagen membrane was used to cover the graft. Conclusion: GBR with sandwich technique could serve as one of the treatment choices for correcting an exposed anterior implant that would enhance the successful aesthetic outcome.

  7. Effects of low-level laser therapy on orthodontic tooth movement and root resorption after artificial socket preservation.

    Science.gov (United States)

    Seifi, Massoud; Atri, Faezeh; Yazdani, Mohammad Masoud

    2014-01-01

    Low- level laser therapy has been used to stimulate the orthodontic tooth movements (OTM) previously. Furthermore, in the orthodontic treatments accompanying tooth extractions, the adjacent teeth move towards the extraction sites and close the space in some cases. Then, the adjacent tooth movements must be prevented in the treatments requiring space. Laser stimulates and at some doses decelerates tooth movement; it also improves healing process and enhances osteogenesis. Hence, it can prevent movement by osteogenesis adjacent to the tooth. The present study investigated the effects of low-level laser therapy on the OTM and root resorption following artificial socket preservation. In this experimental animal trial, 16 male albino rabbits were selected with similar characteristics and randomly divided in two groups. Under general anesthesia, an artificial socket, 8 mm in height, was created in the mesial aspect of the first premolars of the rabbits and filled with demineralized freeze dried bone allograft (DFDBA). The first premolars were connected to the incisors using nickel titanium coil springs. In experimental group, gallium-aluminum-arsenide (GaAlAs) laser was irritated mesial to first premolar where artificial socket was created continuously (808 nm). The cycle was 10 days irritation, 14 days rest, 10 days irritation, 14 days rest (Biostimulation mode). Control group was not laser irradiated. All animals were sacrificed after 48 days and the distance between the distal aspect of the first premolars, and the mesial surface of the second premolars was measured with leaf gauge. The specimens underwent histological assessments. Integrity of root and its resorption was observed under microscope calibration. The size of resorption lacunae was calculated in mm(2). Normality of data was proved according to Kolmogorov-Smirnov analysis, and Student's t-test was done. P value less than 0.05 was considered as significant. The mean OTM were 5.68 ± 1.21 mm in the control

  8. Utilization of bone densitometry for prediction and administration of bisphosphonates to prevent osteoporosis in patients with prostate cancer without bone metastases receiving antiandrogen therapy

    International Nuclear Information System (INIS)

    Holt, Abby; Khan, Muhammad A; Gujja, Swetha; Govindarajan, Rangaswmy

    2014-01-01

    Prostate cancer subjects with prostate-specific antigen (PSA) relapse who are treated with androgen deprivation therapy (ADT) are recommended to have baseline and serial bone densitometry and receive bisphosphonates. The purpose of this community population study was to assess the utilization of bone densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic prostate cancer. A cohort study of men aged 65 years or older with non-metastatic incident diagnoses of prostate cancer was obtained from the Surveillance Epidemiology End Results (SEER)-linked Medicare claims between 2004 and 2008. Claims were used to assess prescribed treatment of ADT, bone densitometry, and bisphosphonates. A total of 30,846 incident prostate cancer cases receiving ADT and aged 65 years or older had no bone metastases; 87.3% (n=26,935) on ADT did not receive either bone densitometry or bisphosphonate therapy. Three percent (n=931) of the cases on ADT received bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702) of the cases on ADT received bone densitometry without receiving intravenous bisphosphonates, while nearly 1% (0.90%, n=278) of the cases on ADT received both bone densitometry and bisphosphonates. Analysis showed treatment differed by patient characteristics. Contrary to the recommendations, bone densitometry and bisphosphonate therapy are underutilized in men receiving ADT for non-metastatic prostate cancer

  9. Nano-engineered titanium for enhanced bone therapy

    Science.gov (United States)

    Gulati, Karan; Atkins, Gerald J.; Findlay, David M.; Losic, Dusan

    2013-09-01

    Current treatment of a number of orthopaedic conditions, for example fractures, bone infection, joint replacement and bone cancers, could be improved if mechanical support could be combined with drug delivery. A very challenging example is that of infection following joint replacement, which is very difficult to treat, can require multiple surgeries and compromises both the implant and the patient's wellbeing. An implant capable of providing appropriate biomechanics and releasing drugs/proteins locally might ensure improved healing of the traumatized bone. We propose fabrication of nanoengineered titanium bone implants using bioinert titanium wires in order to achieve this goal. Titanium in the form of flat foils and wires were modified by fabrication of titania nanotubes (TNTs), which are hollow self-ordered cylindrical tubes capable of accommodating substantial drug amounts and releasing them locally. To further control the release of drug to over a period of months, a thin layer of biodegradable polymer PLGA poly(lactic-coglycolic acid) was coated onto the drug loaded TNTs. This delayed release of drug and additionally the polymer enhanced bone cell adhesion and proliferation.

  10. Labeling of MDP with 188Re for bone tumour therapy

    International Nuclear Information System (INIS)

    Barbezan, Angelica B.; Osso Junior, Joao A.

    2011-01-01

    188 Re is one of the most attractive radioisotopes for a variety of therapeutic applications in nuclear medicine, due to its physical decay properties, such as β - emission of 2.12 MeV, γ emission of 155 keV and half life of 16.9 hours. Biphosphonates are potent inhibitors of osteoclastic bone resorption and are effective in several diseases that cause bone fragility and bone metastases. Because of these characteristics, labeled biphosphonates have been studied for bone pathologies, also acting as palliation of bone pain in case of metastasis.The aim of this study was to optimize the labeling of a phosphonate-MDP (Sodium Methylene Diphosphonate) with 188 Re for use in bone pain palliation. 188 Re was obtained by eluting a 188 W- 188 Re generator from POLATOM. The labeling was performed at room temperature using MDP, SnCl 2 as reducing agent and ascorbic acid. The variables studied were: Mass of ligand (3, 6 and 10 mg), reducing agent mass (5, 7, 10 and 11 mg), ascorbic acid mass (1, 3, 5 and 6 mg), pH (1 and 2) and time of reaction (15, 60, 120, 360 and 4320 minutes), that also reflected the stability of the radiopharmaceutical. The radiochemical control, that also measures the labeling efficiency was evaluated by paper chromatography using Whatman 3MM paper and the solvents acetone and 0.9%NaCl. The best formulation was the following: Mass of ligand MDP: 10 mg, mass of SnCl 2 : 5 mg, ascorbic acid mass: 3 mg, time of reaction: 30 minutes, pH: 1. Under optimum conditions, 188 Re MDP radiolabeling yield was 98,07% and the radiopharmaceutical was stable up to 72 h. (author)

  11. Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment

    OpenAIRE

    Schwartz, Boris; Benadjaoud, Mohamed Amine; Clero, Enora; Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Teinturier, Cecile; Oberlin, Odile; Veres, Cristina; Pacquement, Helene; Munzer, Martine; Tan Dat N'Guyen; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne

    2014-01-01

    International audience; : Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated be...

  12. Histologic Evaluation of Wound Healing After Ridge Preservation With Cortical, Cancellous, and Combined Cortico-Cancellous Freeze-Dried Bone Allograft: A Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Demetter, Randy S; Calahan, Blaine G; Mealey, Brian L

    2017-09-01

    Cortical and cancellous mineralized freeze-dried bone allografts (FDBA) are available for use in alveolar ridge preservation after tooth extraction. There are currently no data regarding use of a combination 50%/50% cortico-cancellous FDBA compared with a 100% cortical or 100% cancellous FDBA in ridge preservation. The primary objective of this study is to dimensionally and histologically evaluate healing after ridge preservation in non-molar sites using 50%/50% cortico-cancellous FDBA versus 100% cortical and 100% cancellous FDBA. Sixty-six patients requiring extraction of a non-molar tooth were enrolled and randomized into three groups to receive ridge preservation with the following: 1) 100% cortical FDBA; 2) 100% cancellous FDBA; or 3) 50%/50% cortico-cancellous FDBA. After 18 to 20 weeks of healing, a biopsy was harvested, and an implant was placed. The alveolar ridge was measured pre- and postoperatively to evaluate change in ridge height and width. Percentages of vital bone, residual graft, and connective tissue (CT)/other were determined via histomorphometric analysis. Histomorphometric analysis revealed no significant differences among groups regarding percentage of vital bone or CT/other. The 100% cortical FDBA group had significantly greater residual graft material (P = 0.04). Dimensional analysis revealed no significant between-group differences in any parameter measured. To the best knowledge of the authors, this study offers the first histologic evidence demonstrating no significant difference in vital bone formation or dimensional changes among 50%/50% cortico-cancellous FDBA, 100% cortical FDBA, and 100% cancellous FDBA when used in ridge preservation of non-molar tooth sites.

  13. Changes of articular cartilage and subchondral bone after extracorporeal shockwave therapy in osteoarthritis of the knee.

    Science.gov (United States)

    Wang, Ching-Jen; Cheng, Jai-Hong; Chou, Wen-Yi; Hsu, Shan-Ling; Chen, Jen-Hung; Huang, Chien-Yiu

    2017-01-01

    We assessed the pathological changes of articular cartilage and subchondral bone on different locations of the knee after extracorporeal shockwave therapy (ESWT) in early osteoarthritis (OA). Rat knees under OA model by anterior cruciate ligament transaction (ACLT) and medial meniscectomy (MM) to induce OA changes. Among ESWT groups, ESWT were applied to medial (M) femur (F) and tibia (T) condyles was better than medial tibia condyle, medial femur condyle as well as medial and lateral (L) tibia condyles in gross osteoarthritic areas (posteophyte formation and subchondral sclerotic bone (psubchondral bone repair in all ESWT groups compared to OA group (p T(M+L) > F(M) in OA rat knees.

  14. HIV-1 infection and antiretroviral therapies: risk factors for osteoporosis and bone fracture.

    Science.gov (United States)

    Ofotokun, Ighovwerha; Weitzmann, M Neale

    2010-12-01

    Patients with HIV-1 infection/AIDS are living longer due to the success of highly active antiretroviral therapy (HAART). However, serious metabolic complications including bone loss and fractures are becoming common. Understanding the root causes of bone loss and its potential implications for aging AIDS patients will be critical to the design of effective interventions to stem a tidal wave of fractures in a population chronically exposed to HAART. Paradoxically, bone loss may occur not only due to HIV/AIDS but also as a consequence of HAART. The cause and mechanisms driving these distinct forms of bone loss, however, are complex and controversial. This review examines our current understanding of the underlying causes of HIV-1 and HAART-associated bone loss, and recent findings pertaining to the relevance of the immuno-skeletal interface in this process. It is projected that by 2015 more than half of the HIV/AIDS population in the USA will be over the age of 50 and the synergy between HIV and/or HAART-related bone loss with age-associated bone loss could lead to a significant health threat. Aggressive antiresorptive therapy may be warranted in high-risk patients.

  15. [Evaluation and classification of drug therapy for breast cancer with bone-only metastasis].

    Science.gov (United States)

    Meng, X Y; Song, S T

    2017-03-23

    Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT. Effective treatment should be continued if the symptoms are relieved or osteogenesis is observed. Osteoblastic change in bone-window CT is a sign of improvement after treatment. Endocrine therapy is proper for ER-positive patients. The patients with initial osteoblastic metastasis should not be treated with salvage chemotherapy or anti-HER2 treatment, only if osteolytic metastasis or visceral metastasis is observed. Bishosphonates are just auxiliary drugs in bone metastasis, which should not be abused.

  16. Radiation Induced Rib Fractures on Bone Scan after Breast Cancer Surgery and Radiation Therapy

    International Nuclear Information System (INIS)

    Kim, Hae Won; Won, Kyoung Sook; Zeon, Seok Kil; Kim, Jin Hee

    2009-01-01

    This study is to evaluate rib fractures on bone scan in breast cancer patients treated with breast cancer surgery and radiation therapy and to evaluate its relation with radiation therapy and operation modality. Two hundred seventy cases that underwent serial bone scan after breast cancer surgery and radiation therapy were enrolled. Bone scan and chest CT findings of rib fracture were analyzed. The rib uptake was seen in 74 of 270 cases (27.4%) on bone scan and 50 cases (18.5%) were confirmed to have rib fracture by chest CT. The rate of modified radical mastectomy in patients with rib fracture was significantly higher than that in patients without rib fracture (66.0% vs. 27.0%, p=0.000). The rate of additional radiation therapy to axillar or supraclavicular regions in patients with rib fracture was significantly higher than that in patients without rib fracture (62.0% vs. 28.6%, p=0.000). Rib fracture was seen most frequently at 1-2 years after radiation therapy (51.9%) and single rib fracture was seen most frequently (55.2%). Of total 106 rib fractures, focal rib uptake was seen in 94 ribs (88.7%) and diffuse rib uptake was seen in 12 ribs (11.3%). On one year follow-up bone scan, complete resolution of rib uptake was seen in 15 ribs (14.2%). On chest CT, the rate of fracture line in ribs with intense uptake was significantly higher than that in ribs with mild or moderate uptake (p=0.000). The rate of presence of fracture line in ribs with focal uptake was significantly higher than that in ribs with diffuse uptake (p=0.001). Rib fracture in breast cancer patients after radiation therapy was related to radiation portal and operation modality. It should be interpreted carefully as a differential diagnosis of bone metastasis

  17. Radiation Induced Rib Fractures on Bone Scan after Breast Cancer Surgery and Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hae Won; Won, Kyoung Sook; Zeon, Seok Kil; Kim, Jin Hee [Keimyung University, School of Medicine, Daegu (Korea, Republic of)

    2009-08-15

    This study is to evaluate rib fractures on bone scan in breast cancer patients treated with breast cancer surgery and radiation therapy and to evaluate its relation with radiation therapy and operation modality. Two hundred seventy cases that underwent serial bone scan after breast cancer surgery and radiation therapy were enrolled. Bone scan and chest CT findings of rib fracture were analyzed. The rib uptake was seen in 74 of 270 cases (27.4%) on bone scan and 50 cases (18.5%) were confirmed to have rib fracture by chest CT. The rate of modified radical mastectomy in patients with rib fracture was significantly higher than that in patients without rib fracture (66.0% vs. 27.0%, p=0.000). The rate of additional radiation therapy to axillar or supraclavicular regions in patients with rib fracture was significantly higher than that in patients without rib fracture (62.0% vs. 28.6%, p=0.000). Rib fracture was seen most frequently at 1-2 years after radiation therapy (51.9%) and single rib fracture was seen most frequently (55.2%). Of total 106 rib fractures, focal rib uptake was seen in 94 ribs (88.7%) and diffuse rib uptake was seen in 12 ribs (11.3%). On one year follow-up bone scan, complete resolution of rib uptake was seen in 15 ribs (14.2%). On chest CT, the rate of fracture line in ribs with intense uptake was significantly higher than that in ribs with mild or moderate uptake (p=0.000). The rate of presence of fracture line in ribs with focal uptake was significantly higher than that in ribs with diffuse uptake (p=0.001). Rib fracture in breast cancer patients after radiation therapy was related to radiation portal and operation modality. It should be interpreted carefully as a differential diagnosis of bone metastasis.

  18. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2016-10-01

    final letter will be forth coming. Task 2. Perform surgeries on minipigs and evaluate bone healing with x-ray. Task 2a. Fabricate Scaffolds...2008;29(32):4300–5. 90. Raschke M, Kolbeck S, Bail H, Schmidmaier G, Flyvbjerg A, Lindner T, et al. Homologous growth hormone accelerates healing of

  19. Effects of massage therapy on pain and anxiety arising from intrathecal therapy or bone marrow aspiration in children with cancer.

    Science.gov (United States)

    Çelebioğlu, Ayda; Gürol, Ayşe; Yildirim, Zuhal Keskin; Büyükavci, Mustafa

    2015-12-01

    Cancer and its treatment are stressful and reduce the quality of life in children. The aim of this study was to investigate the effect of massage therapy on pain and anxiety arising from intrathecal therapy or bone marrow aspiration in children with cancer. We conducted a controlled pretest/posttest quasi-experimental study at a paediatric oncology unit in Turkey. Twenty-five children were enrolled in this study. Their pain and anxiety were determined using a visual analogue scale. When the pretest and posttest pain and anxiety levels of the groups were compared, no statistically significant difference was found (P > 0.05). It was determined that pain and anxiety levels in the experimental group decreased significantly. This study provides preliminary evidence for the effectiveness in children of massage in reducing pain and anxiety arising from intrathecal therapy or bone marrow aspiration. © 2014 Wiley Publishing Asia Pty Ltd.

  20. Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4+ T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

    Science.gov (United States)

    Estes, Jacob D.; Reilly, Cavan; Trubey, Charles M.; Fletcher, Courtney V.; Cory, Theodore J.; Piatak, Michael; Russ, Samuel; Anderson, Jodi; Reimann, Thomas G.; Star, Robert; Smith, Anthony; Tracy, Russell P.; Berglund, Anna; Schmidt, Thomas; Coalter, Vicky; Chertova, Elena; Smedley, Jeremy; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.

    2015-01-01

    Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4+ T cells/µL, and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. PMID:25246534

  1. Do Premenopausal Hypothyroid Women on Levothyroxine Therapy Need Bone Status Monitoring?

    Directory of Open Access Journals (Sweden)

    Ruby P. Babu

    2015-01-01

    Full Text Available Background Suppressive doses of levothyroxine therapy are reported to reduce bone mineral density (BMD in women. Data on bone changes in premenopausal hypothyroid women with replacement therapy are limited. Hence, this study was undertaken to evaluate bone changes in this group using bone markers and BMD. Materials and Methods A hospital-based case–control study including 75 premenopausal women aged 30–45 years was conducted. The subjects were categorized based on their thyroid function and history into three groups of 25 euthyroid, 25 newly diagnosed hypothyroid, and 25 hypothyroid women on 100–200 μg of levothyroxine for a minimum of 5 years. The bone changes were evaluated and compared among the groups biochemically by estimating their plasma osteocalcin and serum calcium and phosphorus and radiologically by measuring their BMD by quantitative ultrasonography. Statistical analysis was conducted by using analysis of variance, Tukey's test, and Pearson's correlation using IBM SPSS Statistics 20. Results Levels of plasma osteocalcin, serum calcium, and serum phosphorus in patients on long-term levothyroxine therapy were significantly higher than those in newly diagnosed hypothyroid women and in the euthyroid group. BMD showed definite features of osteopenia ( T -score: −2.26 ± 0.5 among the women in the treatment group, while it was well within the normal range in the newly diagnosed and euthyroid women. A significant correlation was found between the osteocalcin levels and T -score. Conclusion Hypothyroid women on long-term levothyroxine therapy showed signs of increased bone turnover and increased resorptive changes, though not frank osteoporosis. Hence, it may be important to evaluate the bone status of patients on levothyroxine for >5 years.

  2. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2014-10-01

    detailed bone analysis (and the majority of blood biochemistries will be completed together at the end of the study), the bulk of our findings will be...resume care for the first 48 hours as preferred by our large animal veterinarian. This brings us to 4p Friday afternoon at which time Dr. Cheng, our...postdoctoral fellow, and the combination of medical students split coverage from 4p Friday evening until 8a Monday morning for the post-operative

  3. μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy.

    Science.gov (United States)

    de Bakker, Chantal M J; Altman, Allison R; Tseng, Wei-Ju; Tribble, Mary Beth; Li, Connie; Chandra, Abhishek; Qin, Ling; Liu, X Sherry

    2015-04-01

    Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r=0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Health-related quality of life after bladder preservation therapy for muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Hashine, Katsuyoshi; Miura, Noriyoshi; Numata, Kousaku; Shirato, Akitomi; Sumiyoshi, Yoshiteru; Kataoka, Masaaki

    2008-01-01

    The objective of this study was to assess health-related quality of life (QOL) of bladder cancer patients following bladder preservation therapy (BPT). Eighty patients with muscle-invasive bladder cancer had been treated between January 1992 and July 2005 at our institutions with BPT consisting of transurethral resection, intra-arterial chemotherapy and radiotherapy. Among them, 48 were alive and free from recurrence at the time of survey and were asked to participate. A total of 168 patients who had been treated for superficial bladder cancer in the same period were used as a control group. Three questionnaires, namely the International Prostate Symptom Score (IPSS), the SF-36, and the Expanded Prostate Cancer Index Composite (EPIC) were used. Thirty-three patients in the BPT group (68.8%) and 128 patients in the control group (76.2%) answered the QOL survey. There was no significant difference in age, gender and other clinical factors among these two groups. No significant difference was found between the groups according to IPSS. The QOL score of BPT was lower than that of the control group in the SF-36, but there was no significant difference without body pain (P=0.047). There was a tendency toward a diminished physical functioning (P=0.053) and role-physical (P=0.064) in BPT. The EPIC scores for urinary function, especially storage and voiding symptoms, and bowel function were significantly lower in the BPT group. At multivariable analysis, body pain and bowel function were associated with the type of treatment. Although some of the QOL outcome parameters after BPT were found to be lower than the control group, these differences were not significant. Overall, patients retaining their bladder had an acceptable health related QOL. (author)

  5. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    OpenAIRE

    Xue, Peng; Wang, Yan; Yang, Jie; Li, Yukun

    2013-01-01

    Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochr...

  6. Nuclear Medicine in Diagnosis and Therapy of Bone and Joint Diseases

    International Nuclear Information System (INIS)

    Riccabona, G.

    1999-01-01

    Concerning bone and joint diseases therapy of rheumatic synovitis (radiosynoviorthesis) was introduced in 1952 before clinically relevant diagnostic procedures were developed. Radionuclides of Sr and later on 99mTc phosphonates then started the wide use of bone scintigraphy since > 30 years. The diagnostic methods have an excellent sensitivity for detection of local abnormalities of bone metabolism, the specificity of such studies, however, is low. Modifications of the technique (3-phase-bone-scintigraphy, pinhole collimators, ROI-technique), increasing knowledge of pathological scan patterns and introduction of other radionuclide studies (67Ga, 201Tl, inflammation scans with 99mTc-leukocytes or 99mTc-HIG) as well as 18FDG-PET have increased the specificity significantly in recent years and improvements of imaging systems (SPECT) also increased the accuracy of diagnostic methods in diseases of bone and joints. Therapy of such diseases has made considerable progress: inflamed, swollen joints can effectively be treated with 90Y-, 186Re, 169Er-colloids or with 165Dy-particles by radiosynoviorthesis. Severe pain due to disseminated bone metastases of cancer or polyarthritis can be controlled by radionuclide therapy with 89Sr, 153Sm-EDTMP, 186Re- or 188Re-HEDP and possibly 117mSn-DTPA with an acceptable risk of myelodepression. Possibilities, technical details and limitations of radionuclide applications for diagnostic and therapeutic purposes must be considered if optimal benefit for individual patients should be achieved. Overall Nuclear Medicine can become an essential element in management of bone and joint diseases. The relationship of Nuclear Medicine to bone and joint pathology is peculiar: In 1952 treatment of rheumatic synovitis by radiosynoviorthesis with 198Au Colloid was started by Fellinger and Schmid before diagnostic approaches to bone pathology existed. Bone scintigraphy was introduced only in 1961 using 85Sr but obviously the unfavourable radiation

  7. Bone-preserving total hip arthroplasty in avascular necrosis of the hip-a matched-pairs analysis.

    Science.gov (United States)

    Merschin, David; Häne, Richard; Tohidnezhad, Mersedeh; Pufe, Thomas; Drescher, Wolf

    2018-07-01

    Short-stem hip arthroplasty has the potential advantage of femoral bone stock preservation, especially in view of the expected revisions in the often relatively young patients. Despite short-stem hip prosthesis are increasingly used for total hip arthroplasty, there are no sufficient mid- and long-term results especially for patients with avascular femoral head osteonecrosis. The present study investigates mid-term functional results as well as the revision rate following implantation of a short-stem prosthesis. In the period 06/2005 until 12/2013, a total of 351 short-stem hip prostheses were implanted. The study included 331 complete data sets. A retrospective analysis was performed using the Oxford Hip Score. All revisions were registered. In a total of 331 prostheses, the Oxford Hip Score was "excellent" in 66.2%, "good" in 12.7%, "fair" in 13.0%, and "poor" in 8.2% with a mean follow-up of 57.4 months (SD ± 29.8; range 24-115). In 26 cases, aseptic osteonecrosis of the hip was the indication (7.9%). The Oxford Hip Score was "excellent" in 66.7%, "good" in 0.0%, "fair" in 20.8%, and "poor" in 12.5%. The cumulated five year survival rate was 96.7%. In mid-term observation, the Metha® short-stem prosthesis shows no disadvantage in functional outcome and in survival time compared to a standard hip stem. Providing a correct indication, the Metha® short stem is a valuable option in total hip arthroplasty for younger patients with avascular osteonecrosis of the femoral head. Evaluation has shown no significant differences between aseptic osteonecrosis and other indications.

  8. Role of three-phase bone scintigraphy in therapy of lower extremity infections

    International Nuclear Information System (INIS)

    Grund, F.M.; Larson, B.W.; Sinn, L.M.; Peterson, L.R.

    1990-01-01

    This paper evaluates the ability of three-phase bone scintigraphy to predict the need for prolonged antibiotic therapy and assess results of therapy of lower extremity infections in patients with diabetes mellitus and/or peripheral vascular disease. The authors retrospectively reviewed three-phase bone scans from 39 patients who completed either 3 weeks or 3 months of oral ciprofloxacin based on initial clinical and radiologic impression. bone scans were obtained at diagnosis and 1 year later. IN 31 patients, increased focal activity was shown on the delayed images. Nineteen of 25 were successfully treated with 3 months of antibiotics, but only one of six were successfully treated with 3 weeks of antibiotics. Eight patient showed no focal increased uptake on delayed images, and seven of these were successfully treated with 3 weeks of antibiotics

  9. No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone

    NARCIS (Netherlands)

    Peterse, E.F.P.; Cleven, A.H.G.; Jong, de Y.; Briaire-de, Bruijn I.; Fletcher, J.A.; Danen, E.H.J.; Cleton, A.M.; Bov'ee, J.V.M.G.

    2016-01-01

    Background Chondrosarcoma is a malignant cartilage forming bone tumour for which no effective systemic treatment is available. Previous studies illustrate the need for a better understanding of the role of the IGF pathway in chondrosarcoma to determine if it can be a target for therapy, which was

  10. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases

    NARCIS (Netherlands)

    Westhoff, Paulien G.; De Graeff, Alexander; Monninkhof, Evelyn M.; Pomp, Jacqueline; Van Vulpen, Marco; Leer, Jan Willem H; Marijnen, Corrie A M; Van Der Linden, Yvette M.

    2015-01-01

    Purpose: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. Patients and Methods: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within

  11. Established role of bisphosphonate therapy for prevention of skeletal complications from myeloma bone disease.

    Science.gov (United States)

    Terpos, Evangelos; Dimopoulos, Meletios A; Berenson, James

    2011-02-01

    Patients with advanced multiple myeloma (MM) often have increased osteolytic activity of osteoclasts and impaired osteogenesis by osteoblasts, resulting in osteolytic bone lesions that increase the risk of skeletal-related events (SREs) including pathologic fracture, the need for radiotherapy or surgery to bone, and spinal cord compression. Such SREs are potentially life-limiting, and can reduce patients' functional independence and quality of life. Bisphosphonates (e.g., oral clodronate and intravenous pamidronate and zoledronic acid) can inhibit osteoclast-mediated osteolysis, thereby reducing the risk of SREs, ameliorating bone pain, and potentially prolonging survival in patients with MM. Extensive clinical experience demonstrates that bisphosphonates are generally well tolerated, and common adverse events are typically mild and manageable. Studies are ongoing to optimize the timing and duration of bisphosphonate therapy in patients with bone lesions from MM. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. [Effects of the combined calcitonin and sodium etidronate therapy in Paget's disease of bone].

    Science.gov (United States)

    Nuti, R; Turchetti, V; Righi, G; Vattimo, A

    1982-03-03

    The therapy of Paget's bone disease is essentially based on the use of calcitonin and diphosphonates: both drugs, if used in large doses for long periods, have shown themselves able to provoke particular side-effects. It was, therefore, decided to study the therapeutic efficacy of combined low-dosage treatment using synthetic salmon calcitonin and sodium-etidronate on a group of patients with Paget's osteodystrophy. A clear evident diminution in plasma alkaline phosphatase, hydroxyprolinuria and whole body retention (WBR) of MDP-Tc99m was observed, demonstrating a reduction of metabolic turnover in the bone. No changes in the bone mass (BMC), evaluated by bone mineral detector, were observed at the end of treatment. With this treatment the plateau effect was shown to be appreciably less than normally occurs when either calcitonin or sodium etidronate are used alone.

  13. Selective bladder preservation by combined modality therapy for invasive bladder cancer

    International Nuclear Information System (INIS)

    Kachnic, L. A.; Kaufman, D. S.; Zietman, A. L.; Dallow, K. C.; Griffin, P. P.; Heney, N. M.; Althausen, A. F.; Shipley, W. U.

    1995-01-01

    Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

  14. Selective bladder preservation by combined modality therapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kachnic, L A; Kaufman, D S; Zietman, A L; Dallow, K C; Griffin, P P; Heney, N M; Althausen, A F; Shipley, W U

    1995-07-01

    Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

  15. Quantitative evaluation of bone metastases in patients with advanced prostate cancer during endocrine therapy

    International Nuclear Information System (INIS)

    Yahara, Jyunro

    2003-01-01

    A well-recognized difficulty in assessing the response to therapy for advanced prostate cancer is the infrequency of measurable metastatic disease. The most common metastatic site is bone, and it is manifested by diffuse ostoblastic lesions that cannot be measured reliably to allow for assessments of therapeutic benefits. We assessed the clinical usefulness of quantifying the extent of disease on bone scans in monitoring treatment response in patients with advance prostate cancer using computer-assisted image analysis. Percentage of the positive area on the bone scan (%PABS) was quantified automatically using a personal computer with the NIH Image program. Serial measurements of %PABS in 44 patients with bone metastasis from prostate cancer followed for a mean of 33 month (range 4 to 72) with hormonal therapy were compared with those of the extent of disease (EOD) grades in bone lesions and serum prostate specific antigen (PSA) levels according to treatment response. Serial measurements of EOD grades and %PABS in 13 patients with partial response (PR) disease and those in 12 patients with progressive disease (PD) who did not show bone metastasis progression demonstrated a downward trend during the treatment. On the other hand, changes of EOD grades and %PABS in the remaining 19 patients with PD who showed bone metastasis progression demonstrated an upward trend. Estimated survival curves showed that %PABS was a useful prognostic indicator, with the patients who showed a 25% decline in %PABS surviving longer than the patients who showed a less than 25% decline in %PABS after treatment (p=0.0207). The %PABS is a simple and reproducible estimate of the percentage of the skeleton involving tumors in patients with advanced prostate cancer, and serial measurements of %PABS can assist in monitoring the treatment response in patients with bone metastatic prostate cancer. (author)

  16. Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model.

    Directory of Open Access Journals (Sweden)

    Tzong-Tyng Hung

    Full Text Available BACKGROUND: The bisphosphonate, zoledronic acid (ZOL, can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM, to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. METHODS: The model involves intracardiac injection for arterial dissemination of the RM1(BM cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. FINDINGS: Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. CONCLUSIONS: ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a

  17. Comparative effects of enteric-coated pancreatin microsphere therapy after conventional and pylorus-preserving pancreatoduodenectomy

    NARCIS (Netherlands)

    Bruno, M. J.; Borm, J. J.; Hoek, F. J.; Delzenne, B.; Hofmann, A. F.; de Goeij, J. J.; van Royen, E. A.; van Gulik, T. M.; de Wit, L. T.; Gouma, D. J.; van Leeuwen, D. J.; Tytgat, G. N.

    1997-01-01

    BACKGROUND: A comparative study was performed between patients with exocrine pancreatic insufficiency after conventional pancreatoduodenectomy (Whipple's procedure) and pylorus-preserving pancreatoduodenectomy (PPPD). In these patients the pharmacodynamics of 2-mm enteric-coated pancreatin

  18. Pulsed electromagnetic fields preserve bone architecture and mechanical properties and stimulate porous implant osseointegration by promoting bone anabolism in type 1 diabetic rabbits.

    Science.gov (United States)

    Cai, J; Li, W; Sun, T; Li, X; Luo, E; Jing, D

    2018-05-01

    The effects of exogenous pulsed electromagnetic field (PEMF) stimulation on T1DM-associated osteopathy were investigated in alloxan-treated rabbits. We found that PEMF improved bone architecture, mechanical properties, and porous titanium (pTi) osseointegration by promoting bone anabolism through a canonical Wnt/β-catenin signaling-associated mechanism, and revealed the clinical potential of PEMF stimulation for the treatment of T1DM-associated bone complications. Type 1 diabetes mellitus (T1DM) is associated with deteriorated bone architecture and impaired osseous healing potential; nonetheless, effective methods for resisting T1DM-associated osteopenia/osteoporosis and promoting bone defect/fracture healing are still lacking. PEMF, as a safe and noninvasive method, have proven to be effective for promoting osteogenesis, whereas the potential effects of PEMF on T1DM osteopathy remain poorly understood. We herein investigated the effects of PEMF stimulation on bone architecture, mechanical properties, bone turnover, and its potential molecular mechanisms in alloxan-treated diabetic rabbits. We also developed novel nontoxic Ti2448 pTi implants with closer elastic modulus with natural bone and investigated the impacts of PEMF on pTi osseointegration for T1DM bone-defect repair. The deteriorations of cancellous and cortical bone architecture and tissue-level mechanical strength were attenuated by 8-week PEMF stimulation. PEMF also promoted osseointegration and stimulated more adequate bone ingrowths into the pore spaces of pTi in T1DM long-bone defects. Moreover, T1DM-associated reduction of bone formation was significantly attenuated by PEMF, whereas PEMF exerted no impacts on bone resorption. We also found PEMF-induced activation of osteoblastogenesis-related Wnt/β-catenin signaling in T1DM skeletons, but PEMF did not alter osteoclastogenesis-associated RANKL/RANK signaling gene expression. We reveal that PEMF improved bone architecture, mechanical properties, and

  19. Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

    Science.gov (United States)

    Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

    2016-04-07

    Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres. © 2016 by The American Society of Hematology.

  20. Hyperbaric Oxygen therapy effects on bone regeneration in Type 1 diabetes mellitus in rats.

    Science.gov (United States)

    Dias, Pâmella Coelho; Limirio, Pedro Henrique Justino Oliveira; Linhares, Camila Rodrigues Borges; Bergamini, Mariana Lobo; Rocha, Flaviana Soares; Morais, Richarlisson Borges de; Balbi, Ana Paula Coelho; Hiraki, Karen Renata Nakamura; Dechichi, Paula

    2018-01-29

    The aim of this study was evaluate the effect of HBO on diabetic rats. Twenty rats were distributed into four groups (n = 5): Control (C); Control + HBO (CH); Diabetes (D) and Diabetes + HBO (DH). Diabetes was induced by streptozotocin, and bone defects were created in both femurs in all animals. HBO therapy began immediately after surgery and was performed daily in the CH and DH groups. After 7 days, the animals were euthanized. The femurs were removed, demineralized, embedded in paraffin, and histologic images were analyzed. Qualitative histologic analyses showed more advanced stage bone regeneration in control groups (C and CH) compared with diabetic groups (D and DH). Histomorphometric analysis showed significantly increased bone neoformation in CH compared with the other groups (p  0.05). The mast cell population increased in CH compared with the other groups (C, D, and DH) (p < 0.05). The mast cell population did not differ between D and DH Groups. This study showed that HBO therapy improved early bone regeneration in diabetic rats and increased the mast cell population only in non-diabetic animals. HBO was shown to be important treatment for minimizing deleterious effects of diabetes on bone regeneration.

  1. Extensive cranioplasty for sagittal synostosis in young children by preserving cranial bone flaps adhered to the dura mater.

    Science.gov (United States)

    Nan, Bao; Bo, Yang; Yun-Hai, Song; Cheng, Chen; Xiong-Zheng, Mu

    2015-03-01

    This study aimed to evaluate extensive cranioplasty involving the frontal, parietal, occipital, and temporal bones without removing the floating bone flaps in the treatment of sagittal synostosis. Sixty-three children with sagittal synostosis, aged 5 months to 3 years, were included in the study. The frontal bone flap was removed using an air drill. The occipital and bilateral temporal bone flaps were cut open but not detached from the dura mater or fixed to produce floating bone flaps. The skull bone was cut into palisade-like structures. Brain compression from both sides and the base of the skull was released and the brain expanded bilaterally through the enlarged space. Only a long strip-shaped bone bridge remained in the central parietal bone. Subsequently, the frontal bone flaps and occipital bone flap were pushed towards the midline and fixed with the parietal bone bridge to shorten the anteroposterior diameter of the cranial cavity and allow the brain to expand bilaterally to correct scaphocephaly. Patients were followed up 1-5 years. Skull growth was excellent in all patients, the anteroposterior diameter was shortened, the transverse diameter was increased, the prominent forehead was corrected, and scaphocephaly improved significantly. There were no complications such as death and skull necrosis. Surgery without removing bone flaps is less traumatic and results in no massive bleeding. It can effectively relieve brain compression and promotes transversal expansion of the brain during surgery and subsequent normal brain development. The skull of young children is relatively thin and early surgery can easily achieve satisfactory bone reshaping. Our surgical technique is not only safe and effective but also can avoid subsequent psychological disorders caused by skull deformity.

  2. Cell therapy with bone marrow mononuclear cells in elastase-induced pulmonary emphysema.

    Science.gov (United States)

    Longhini-Dos-Santos, Nathalia; Barbosa-de-Oliveira, Valter Abraão; Kozma, Rodrigo Heras; Faria, Carolina Arruda de; Stessuk, Talita; Frei, Fernando; Ribeiro-Paes, João Tadeu

    2013-04-01

    Emphysema is characterized by destruction of alveolar walls with loss of gas exchange surface and consequent progressive dyspnea. This study aimed to evaluate the efficiency of cell therapy with bone marrow mononuclear cells (BMMC) in an animal model of elastase-induced pulmonary emphysema. Emphysema was induced in C57Bl/J6 female mice by intranasal instillation of elastase. After 21 days, the mice received bone marrow mononuclear cells from EGFP male mice with C57Bl/J6 background. The groups were assessed by comparison and statistically significant differences (p pulmonary emphysema.

  3. A methodology for incorporating functional bone marrow sparing in IMRT planning for pelvic radiation therapy

    International Nuclear Information System (INIS)

    McGuire, Sarah M.; Menda, Yusuf; Boles Ponto, Laura L.; Gross, Brandie; Juweid, Malik; Bayouth, John E.

    2011-01-01

    Background and purpose: The purpose of this study was to design a radiation therapy treatment planning approach that would spare hematopoietically active bone marrow using [ 18 F]FLT PET imaging. Materials and methods: We have developed an IMRT planning methodology to incorporate functional PET imaging using [ 18 F]FLT scans. Plans were generated for two simulated cervical cancer patients, where pelvic active bone marrow regions were incorporated as avoidance regions based on the ranges: SUV4 ≥ 4; 4 > SUV3 ≥ 3; and 3 > SUV2 ≥ 2. Dose objectives were set to reduce bone marrow volume that received 10 (V 10 ) and 20 (V 20 ) Gy. Results: Active bone marrow regions identified by [ 18 F]FLT with an SUV ≥ 2, SUV ≥ 3, and SUV ≥ 4 represented an average of 43.0%, 15.3%, and 5.8%, respectively of the total osseous pelvis for the two cases studied. Improved dose-volume histograms for all identified bone marrow SUV volumes and decreases in V 10 , and V 20 were achieved without clinically significant changes to PTV or OAR doses. Conclusions: Incorporation of [ 18 F]FLT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in pelvic malignancies.

  4. Extraction Socket Preservation Using Porcine-Derived Collagen Membrane Alone or Associated with Porcine-Derived Bone. Clinical Results of Randomized Controlled Study

    Directory of Open Access Journals (Sweden)

    Renzo Guarnieri

    2017-03-01

    Full Text Available Objectives: The aim of present randomized controlled clinical trial was to clinically evaluate hard tissue changes after extraction socket preservation procedures compared to natural spontaneous healing. Material and Methods: Thirty patients were enrolled in the present study and underwent single-tooth extraction in the premolar/molar areas. Ten sites were grafted with porcine-derived bone covered by collagen membrane, 10 covered by porcine-derived collagen membrane alone, and 10 underwent natural spontaneous healing. Vertical and horizontal bone changes after 3-month were evaluated at implant placement. Results: The vertical and horizontal bone changes at the extraction sockets treated with collagen membrane alone (vertical: -0.55 [SD 0.11] mm, and horizontal: -1.21 [SD 0.69] mm and collagen membrane plus porcine-derived bone (vertical: -0.37 [SD 0.7] mm, and horizontal: -0.91 [SD 0.53] mm were found significantly lower (P < 0.001, when compared to non-grafted sockets (vertical: -2.09 [SD 0.19] mm, and horizontal: -3.96 [SD 0.87] mm. In type 1 extraction sockets, in premolar sites, and in presence of vestibular bone thicknesses ≥ 1.5 mm, the use of collagen membrane alone revealed similar outcomes to those with additional graft material. Conclusions: At the re-entry surgery, extraction sockets grafted with porcine-derived bone and covered by collagen membrane, and extraction sockets covered by porcine-derived collagen membrane alone, showed significantly lower vertical and horizontal bone changes, compared to extraction sockets sites underwent natural spontaneous healing. However, a complete prevention of remodelling is not achievable, irrespective of the technique used.

  5. Radiation therapy for metastatic lesions from breast cancer. Breast cancer metastasis to bone

    International Nuclear Information System (INIS)

    Hayashi, Shinya; Hoshi, Hiroaki

    2000-01-01

    This paper summarizes radiation therapy in the treatment of bone metastases from breast cancer. Bone metastasis occurs in approximately 70% of breast cancer patients, and the goals of radiation therapy for bone metastasis are: palliation of pain, prevention and treatment of neuropathic symptoms, and prevention of pathologic fractures. The prognosis of bone metastasis from breast cancer is known to be better than that of bone metastasis from other solid tumors. Local-field radiation, hemibody (or wide-field) radiation, and systemic radionuclide treatment are the major methods of radiation therapy for pain palliation. Although many studies have shown that breast cancer is more responsive to radiation therapy for pain palliation than other solid tumors, some studies found no significant difference. Local-field radiation therapy, which includes multi-fraction irradiation and single-fraction irradiation, is currently the most generally used method of radiotherapy for pain palliation. Pain palliation has been reported to be achieved in approximately 80% to 90% of patients treated with local-field external beam irradiation. Three types of multi-fraction irradiation therapy are administered depending on the prognosis: high-dose fraction irradiation (36-50 Gy/12-25 Fr/2.4-5 wk), short-course irradiation (20-30 Gy/10-15 Fr/2-3 wk), and ultra-short-course irradiation (15-25 Gy/2-5 Fr/1 wk). The most common irradiation schedule is 30 Gy/10 Fr/2 wk. Although many reports indicate no significant difference in pain palliation according to the dose, the percentage of patients who show a complete cure is significantly higher in those treated with doses of 30 Gy or more, and thus the total irradiation dose should be at least 30 Gy. High-dose fraction irradiation is indicated for patients with an expected survival time of 6 months or more while short-course or single-fraction irradiation is indicated for those with an expected survival time of 3 months or more. Single

  6. Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring

    Science.gov (United States)

    Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo

    2016-01-01

    Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength. PMID:27115490

  7. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    International Nuclear Information System (INIS)

    Tsuno, Hiroaki; Yoshida, Toshiko; Nogami, Makiko; Koike, Chika; Okabe, Motonori; Noto, Zenko; Arai, Naoya; Noguchi, Makoto; Nikaido, Toshio

    2012-01-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAMα cells and induced to osteogenic status—their in vivo osteogenesis was subsequently investigated in rats. It was found that HAMα cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAMα cells. The expression of osteocalcin mRNA was increased in HAMα cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAMα cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: ► Human amniotic mesenchymal cells include cells (HAMα cells) that have the properties of MSCs. ► HAMα cells have excellent osteogenic differentiation potential. ► Osteogenic differentiation ability of HAMα was amplified by calcium phosphate scaffolds. ► HAMα cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  8. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tsuno, Hiroaki [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Yoshida, Toshiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nogami, Makiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Orthopedic Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Koike, Chika; Okabe, Motonori [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Noto, Zenko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Arai, Naoya; Noguchi, Makoto [Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nikaido, Toshio, E-mail: tnikaido@med.u-toyama.ac.jp [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan)

    2012-12-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAM{alpha} cells and induced to osteogenic status-their in vivo osteogenesis was subsequently investigated in rats. It was found that HAM{alpha} cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAM{alpha} cells. The expression of osteocalcin mRNA was increased in HAM{alpha} cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAM{alpha} cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: Black-Right-Pointing-Pointer Human amniotic mesenchymal cells include cells (HAM{alpha} cells) that have the properties of MSCs. Black-Right-Pointing-Pointer HAM{alpha} cells have excellent osteogenic differentiation potential. Black-Right-Pointing-Pointer Osteogenic differentiation ability of HAM{alpha} was amplified by calcium phosphate scaffolds. Black-Right-Pointing-Pointer HAM{alpha} cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  9. Experimental study of chemical embolus therapy combined with radiotherapy for VX2 bone tumors

    International Nuclear Information System (INIS)

    Yamaguchi, Hiroshi; Mochizuki, Kazuo; Ishii, Yoshiaki

    2000-01-01

    We conducted an experimental study, using a combination of coarse crystal cisplatin and radiotherapy for bone tumors, to evaluate the possibility of the clinical application of chemical embolus therapy in the field of orthopedic surgery. Experimental femoral bone tumors were produced, in rabbits, using VX2 carcinoma. The rabbits were allocated to five groups: untreated control, embolus, chemical embolus, irradiation alone, and chemical embolus and irradiation combination. These therapies were evaluated comparatively, in terms of local antitumor effects (including body weight, X-ray findings, angiography, and histopathology) and in terms of inhibition of pulmonary metastasis. Local antitumor effects, as evaluated by all parameters, except for body weight, were significantly greater for the chemical and irradiation combination group than for the chemical embolus, irradiation alone, untreated control, and embolus groups. There was no significant difference in the inhibition of pulmonary metastasis among the chemical embolus and irradiation combination, chemical embolus, and irradiation alone groups. These findings demonstrated the synergistic effect of the combination of chemical embolus therapy and radiotherapy. In this study, however, no significant difference was found between the chemical embolus therapy alone and the combination therapy groups in the inhibitory effect on pulmonary tumor metastasis, suggesting the need to conduct combination therapy repeatedly in the clinical setting. (author)

  10. Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment.

    Science.gov (United States)

    Schwartz, Boris; Benadjaoud, Mohamed Amine; Cléro, Enora; Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Teinturier, Cécile; Oberlin, Odile; Veres, Cristina; Pacquement, Hélène; Munzer, Martine; N'guyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Hawkins, Mike; Winter, David; Lefkopoulos, Dimitri; Chavaudra, Jean; Rubino, Carole; Diallo, Ibrahima; Bénichou, Jacques; de Vathaire, Florent

    2014-05-01

    Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated between 1942 and 1986 in France and Britain has been followed prospectively. We collected detailed information on treatments received during childhood cancer. Additionally, an innovative methodology has been developed to evaluate the dose-response relationship between bone sarcoma and radiation dose throughout this cohort. The median follow-up was 26 years, and 39 patients had developed bone sarcoma. It was found that the overall incidence was 45-fold higher [standardized incidence ratio 44.8, 95 % confidence interval (CI) 31.0-59.8] than expected from the general population, and the absolute excess risk was 35.1 per 100,000 person-years (95 % CI 24.0-47.1). The risk of bone sarcoma increased slowly up to a cumulative radiation organ absorbed dose of 15 Gy [hazard ratio (HR) = 8.2, 95 % CI 1.6-42.9] and then strongly increased for higher radiation doses (HR for 30 Gy or more 117.9, 95 % CI 36.5-380.6), compared with patients not treated with radiotherapy. A linear model with an excess relative risk per Gy of 1.77 (95 % CI 0.6213-5.935) provided a close fit to the data. These findings have important therapeutic implications: Lowering the radiation dose to the bones should reduce the incidence of secondary bone sarcomas. Other therapeutic solutions should be preferred to radiotherapy in bone sarcoma-sensitive areas.

  11. Random Start Ovarian Stimulation for Oocyte or Embryo Cryopreservation in Women Desiring Fertility Preservation Prior to Gonadotoxic Cancer Therapy.

    Science.gov (United States)

    Danis, Rachel B; Pereira, Nigel; Elias, Rony T

    2017-11-10

    Women of reproductive age diagnosed with cancer are often interested in preserving gametes or reproductive tissue that would allow for future genetic parenthood. Preservation of fertility is often accomplished in young cancer patients via ovarian stimulation followed by oocyte or embryo cryopreservation. Conventional stimulation protocols, however, require 2-4 weeks to complete ovarian stimulation, oocyte retrieval and possible fertilization. Such a strategy may not be feasible in patients requiring urgent cancer treatment. Recent studies have highlighted that random start ovarian stimulation can be initiated irrespective of the phase of the menstrual cycle and is an attractive alternative to conventional ovarian stimulation. The primary aim of the current review is to discuss the feasibility and success of random start ovarian stimulation for oocyte or embryo cryopreservation in women desiring fertility preservation prior to gonadotoxic cancer therapy. We performed a systematic review of medical literature published between January 2000 to June 2017 reporting the utility of random start ovarian stimulation for fertility preservation. Search terms included "fertility preservation," "cancer," "ovarian stimulation," "random-start ovarian stimulation," "embryo cryopreservation, and" "oocyte cryopreservation." Publications were included in this review only if patients underwent random start ovarian stimulation prior to cancer therapy. Nineteen publications were identified and perused by the authors. Most publications described the utility of random start ovarian stimulation in the setting of breast cancer. Radom-start stimulation was associated with a reduced time interval between ovarian stimulation initiation and oocyte or embryo cryopreservation. The yield of mature oocytes and their developmental potential into embryos was comparable between conventional and random-start protocols, albeit with higher gonadotropin doses in the latter. The current review suggests

  12. A vascular necrosis of bone. A complication of agressive therapy for acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Vaidya, S.; Saika, S.; Sirohi, B.; Pai, S.; Advani, S. [Tata Memorial Hospital, Bombay (India). Dept. of Medical Oncology

    1998-09-01

    The purpose of the present paper was to report cases of avascular necrosis of bone (AVNB) arising as a complication of chemotherapy for acute lymphoblastic leukemia (ALL). X-rays and {sup 99m}technicium-MDP bone scans were performed on patients with symptoms of bone pain, whereby five patients out of 850 patients were detected to have avascular necrosis of the femoral head. All had received aggressive chemotherapy with steroids. Two patients were still on therapy for the primary disease. In these patients further chemotherapy was continued without steroids. The medium period from diagnosis of ALL to development of AVNB was 29 months. Three patients underwent corrective surgical procedures. To conclude, the data suggest that patients receiving combination chemotherapy, especially those with high cumulative doses, run a risk of developing AVNB. Awarness of this complication is important in order to have an early diagnosis so as to limit disability. (orig.)

  13. A vascular necrosis of bone. A complication of agressive therapy for acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Vaidya, S.; Saika, S.; Sirohi, B.; Pai, S.; Advani, S.

    1998-01-01

    The purpose of the present paper was to report cases of avascular necrosis of bone (AVNB) arising as a complication of chemotherapy for acute lymphoblastic leukemia (ALL). X-rays and 99m technicium-MDP bone scans were performed on patients with symptoms of bone pain, whereby five patients out of 850 patients were detected to have avascular necrosis of the femoral he[. All h[ received aggressive chemotherapy with steroids. Two patients were still on therapy for the primary disease. In these patients further chemotherapy was continued without steroids. The medium period from diagnosis of ALL to development of AVNB was 29 months. Three patients underwent corrective surgical procedures. To conclude, the data suggest that patients receiving combination chemotherapy, especially those with high cumulative doses, run a risk of developing AVNB. Awarness of this complication is important in order to have an early diagnosis so as to limit disability. (orig.)

  14. Therapy for bone pain palliation in skeletal metastases with Samarium -153 EDTMP (Indonesian experience)

    International Nuclear Information System (INIS)

    Purnomo, E.

    2007-01-01

    Full text: Radiopharmaceutical therapy may be used for the treatment of cases with painful skeletal metastases. We evaluate and want to share an experience with application and efficacy of Sm-153 EDTMP in palliative painful bone metastases therapy. Our aim was to determine the efficacy and toxicity of single-dose Sm- 153 EDTMP as a palliative treatment for painful skeletal metastases. Material and methods: we selected 18 patients (9 male, 9 female). The average age 35-65 years weight 40- 60 kg; with metastatic bone confirmed with bone scan examination. 6 with breast cancer, 5 with nasopharyngeal cancer, 5 with prostatic cancer, 2 with lung cancer were treated with 30 mCi ( 1110 MBq) Sm-153 EDTMP. All showed extensive metastatic bone disease. The patients were given intravenous injections of 30 mCi Sm-153 EDTMP, after reconditioning, hydration . We established intensity of pain, haematological parameters, scintigraphic, Karnofsky scale. Clinical assessment was performed one month later. Responses were classified in completed (good response), partial and absent taking into account symptoms and drugs reduction. The discontinuation or the reduction of analgesic drugs like opiate dosage was also considered as successful palliative results of the treatment. Result: pain relief was obtained in 16/18 patients, Sm-153 was effective in patients with reduced drug assumption. The response to Sm-153 was good in 14/18(77,7%) of the patients and partial in 3/18(16,6%) and no response in 1/18(0,5%). The application of Sm-153 in patients with painful disseminated bone metastases has a satisfactory pain alleviating effects. Sides effects were noted, decrease hemoglobin counts and white blood cell and platelets, which gradually returned to near normal after 6 weeks. Easy application and low cost and produced in own country are important factors. Conclusion: radiopharmaceutical therapy can be recommended because of the favorable palliation effect and the low cost of Sm-153, especially

  15. Radiation therapy for metastatic lesions from breast cancer. Breast cancer metastasis to bone

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Shinya; Hoshi, Hiroaki [Gifu Univ. (Japan). School of Medicine

    2000-10-01

    This paper summarizes radiation therapy in the treatment of bone metastases from breast cancer. Bone metastasis occurs in approximately 70% of breast cancer patients, and the goals of radiation therapy for bone metastasis are: palliation of pain, prevention and treatment of neuropathic symptoms, and prevention of pathologic fractures. The prognosis of bone metastasis from breast cancer is known to be better than that of bone metastasis from other solid tumors. Local-field radiation, hemibody (or wide-field) radiation, and systemic radionuclide treatment are the major methods of radiation therapy for pain palliation. Although many studies have shown that breast cancer is more responsive to radiation therapy for pain palliation than other solid tumors, some studies found no significant difference. Local-field radiation therapy, which includes multi-fraction irradiation and single-fraction irradiation, is currently the most generally used method of radiotherapy for pain palliation. Pain palliation has been reported to be achieved in approximately 80% to 90% of patients treated with local-field external beam irradiation. Three types of multi-fraction irradiation therapy are administered depending on the prognosis: high-dose fraction irradiation (36-50 Gy/12-25 Fr/2.4-5 wk), short-course irradiation (20-30 Gy/10-15 Fr/2-3 wk), and ultra-short-course irradiation (15-25 Gy/2-5 Fr/1 wk). The most common irradiation schedule is 30 Gy/10 Fr/2 wk. Although many reports indicate no significant difference in pain palliation according to the dose, the percentage of patients who show a complete cure is significantly higher in those treated with doses of 30 Gy or more, and thus the total irradiation dose should be at least 30 Gy. High-dose fraction irradiation is indicated for patients with an expected survival time of 6 months or more while short-course or single-fraction irradiation is indicated for those with an expected survival time of 3 months or more. Single

  16. Systemic sarcoidosis with bone marrow involvement responding to therapy with adalimumab: a case report

    Directory of Open Access Journals (Sweden)

    Patel Supen R

    2009-07-01

    Full Text Available Abstract Introduction Sarcoidosis is an inflammatory disorder characterized by the presence of non-caseating granulomas in affected organs. The presence of CD4-positive T lymphocytes and macrophages in affected organs suggests an ongoing immune response. Systemic corticosteroids remain the mainstay of treatment, but therapy is often limited by adverse effects. This is the first report of the use of adalimumab (HUMIRA®, Abbott Laboratories, North Chicago, IL, USA, an anti-tumor necrosis factor monoclonal antibody, in a patient with systemic sarcoidosis with bone marrow involvement. Case presentation A 42-year-old African-American man with a medical history significant for hypertension and diabetes mellitus presented with anemia and thrombocytopenia of two months duration. The patient underwent physical examination, bone marrow aspiration and biopsy, chest X-ray, acid-fast bacilli stain, computed tomography with contrast, and additional laboratory tests. He was diagnosed with systemic sarcoidosis with splenomegaly and bone marrow involvement. Drug therapy included prednisone, which had to be discontinued owing to adverse effects, and adalimumab. Conclusion This is the first report describing the use of adalimumab in a patient with systemic sarcoidosis with bone marrow involvement. Tumor necrosis factor antagonism with adalimumab was efficacious and well-tolerated in this patient and may be considered as a treatment option for similar cases.

  17. Systemic sarcoidosis with bone marrow involvement responding to therapy with adalimumab: a case report.

    Science.gov (United States)

    Patel, Supen R

    2009-07-29

    Sarcoidosis is an inflammatory disorder characterized by the presence of non-caseating granulomas in affected organs. The presence of CD4-positive T lymphocytes and macrophages in affected organs suggests an ongoing immune response. Systemic corticosteroids remain the mainstay of treatment, but therapy is often limited by adverse effects. This is the first report of the use of adalimumab (HUMIRA((R)), Abbott Laboratories, North Chicago, IL, USA), an anti-tumor necrosis factor monoclonal antibody, in a patient with systemic sarcoidosis with bone marrow involvement. A 42-year-old African-American man with a medical history significant for hypertension and diabetes mellitus presented with anemia and thrombocytopenia of two months duration. The patient underwent physical examination, bone marrow aspiration and biopsy, chest X-ray, acid-fast bacilli stain, computed tomography with contrast, and additional laboratory tests. He was diagnosed with systemic sarcoidosis with splenomegaly and bone marrow involvement. Drug therapy included prednisone, which had to be discontinued owing to adverse effects, and adalimumab. This is the first report describing the use of adalimumab in a patient with systemic sarcoidosis with bone marrow involvement. Tumor necrosis factor antagonism with adalimumab was efficacious and well-tolerated in this patient and may be considered as a treatment option for similar cases.

  18. Fertility counseling and preservation practices in youth with lupus and vasculitis undergoing gonadotoxic therapy.

    Science.gov (United States)

    Nahata, Leena; Sivaraman, Vidya; Quinn, Gwendolyn P

    2016-11-01

    To assess fertility counseling and preservation practices among children, adolescents, and young adults with rheumatic diseases undergoing cyclophosphamide (CTX) treatment. Retrospective chart review (2006-2016). Academic pediatric center. Male and female patients with systemic lupus erythematosus, Wegener's granulomatosis/granulomatosis with polyangiitis, or other vaculitides, receiving CTX treatment. None. Documentation of fertility counseling and fertility preservation. A total of 58 subjects met the inclusion criteria; 5 were excluded due to incomplete records, thus N = 53. Of these 75% were female (N = 40). Median age was 14 years at diagnosis and 15 years at first CTX treatment. A total of 51% of subjects (69% of males and 45% of females) had no documentation about potential fertility loss before CTX treatment. Among females where fertility counseling was documented, the only fertility preservation option discussed was leuprolide acetate (LA), which was pursued in all of these cases. Of 13 males (77% postpubertal), 3 were offered sperm banking, of whom 2 declined and the other attempted after treatment began and was azoospermic. Of 53 patients, 1 was referred to a fertility specialist. Mean cumulative CTX dose was 9.2 g in males and 8 g in females. Based on these findings, increasing awareness about infertility risk, fertility preservation options, and referral to fertility specialists is needed among pediatric rheumatologists. Prospective studies are needed to assess fertility outcomes in this patient population (including effectiveness of LA with regard to pregnancy rates [PRs]), as well as barriers/facilitators to fertility counseling and fertility preservation. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Bone Fractures Following External Beam Radiotherapy and Limb-Preservation Surgery for Lower Extremity Soft Tissue Sarcoma: Relationship to Irradiated Bone Length, Volume, Tumor Location and Dose

    International Nuclear Information System (INIS)

    Dickie, Colleen I.; Parent, Amy L.; Griffin, Anthony M.; Fung, Sharon; Chung, Peter W.M.; Catton, Charles N.; Ferguson, Peter C.; Wunder, Jay S.; Bell, Robert S.; Sharpe, Michael B.; O'Sullivan, Brian

    2009-01-01

    Purpose: To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT). Methods and Materials: Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors. Mean dose to bone, RT field size (FS), maximum dose to a 2-cc volume of bone, and volume of bone irradiated to ≥40 Gy (V40) were compared. Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the dose distribution. Results: For fracture patients, mean dose to bone was 45 ± 8 Gy (mean dose at fracture site 59 ± 7 Gy), mean FS was 37 ± 8 cm, maximum dose was 64 ± 7 Gy, and V40 was 76 ± 17%, compared with 37 ± 11 Gy, 32 ± 9 cm, 59 ± 8 Gy, and 64 ± 22% for nonfracture patients. Differences in mean, maximum dose, and V40 were statistically significant (p = 0.01, p = 0.02, p = 0.01). Leg fractures were more common above the knee joint. Conclusions: The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy. There was a trend toward lower mean FS for nonfracture patients.

  20. Imaging response during therapy with radium-223 for castration-resistant prostate cancer with bone metastases

    DEFF Research Database (Denmark)

    Keizman, D; Fosboel, M O; Reichegger, H

    2017-01-01

    BACKGROUND: The imaging response to radium-223 therapy is at present poorly described. We aimed to describe the imaging response to radium-223 treatment. METHODS: We retrospectively evaluated the computed tomography (CT) and bone scintigraphy response of metastatic castration-resistant prostate c....../or radiological) may be noted during the first 3 months, and should not be confused with progression. Imaging by CT scan should be considered after three and six doses of radium-223 to rule out extraskeletal disease progression....

  1. Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications

    NARCIS (Netherlands)

    van Dussen, Laura; Biegstraaten, Marieke; Dijkgraaf, Marcel Gw; Hollak, Carla Em

    2014-01-01

    Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on

  2. Influence of antibacterial therapy on bone scan indices at foot inflammation in diabetes mellitus accompanied by diabetic foot syndrome

    International Nuclear Information System (INIS)

    Slavnov, V.M.; Bolgars'ka, S.V.; Taran, E.V.; Markov, V.V.

    2004-01-01

    The influence of antibacterial therapy on bone scan indices at foot inflammation in patients with diabetes mellitus (DM) accompanied by diabetic foot syndrome was studied. Bone scan was performed using scintillation tomographic gamma-camera hours after intravenous injection of 99m Tc-methylene diphosphonate

  3. Adherence to Voice Therapy Recommendations Is Associated With Preserved Employment Fitness Among Teachers With Work-Related Dysphonia.

    Science.gov (United States)

    Rinsky-Halivni, Lilah; Klebanov, Miriam; Lerman, Yehuda; Paltiel, Ora

    2017-05-01

    Referral to voice therapy and recommendations for voice rest and microphone use are common interventions in occupational medicine aimed at preserving the working capability of teachers with occupation-related voice problems. Research on the impact of such interventions in terms of employment is lacking. This study examined changes in fitness (ie, ability) to work of dysphonic teachers referred to an occupational clinic and evaluated employment outcomes following voice therapy, voice rest, and microphone use. A historical prospective study was carried out. Of 365 classroom teachers who were first referred to a regional occupational medicine clinic due to dysphonia between January 2007 and December 2012, 156 were sampled and 153 were followed-up for an average of 5 years (range 2-8). Data were collected from medical records and from interviews conducted in 2014 aimed at assessing employment status. Logistic regression models were used to assess associations between interventions and employment outcomes. Survival analyses were performed to evaluate the association between participating in voice therapy and length of retained employment fitness. Thirty-four (22.2%) teachers suffered declines in working capabilities due to dysphonia. Voice therapy was demonstrated as being a protective factor against such declines (odds ratio = 0.05 [0.01-0.27]). Adherence to recommendation of voice therapy was teachers occurred within 20 months after referral. Unlike voice therapy, voice rest and microphone use were not associated with retention of working capabilities. Voice therapy, especially when instituted early, is a strong predictor for retaining fitness for employment among dysphonic teachers. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  4. Bone fractures following external beam radiotherapy and limb-preservation surgery for lower extremity soft tissue sarcoma: relationship to irradiated bone length, volume, tumor location and dose.

    Science.gov (United States)

    Dickie, Colleen I; Parent, Amy L; Griffin, Anthony M; Fung, Sharon; Chung, Peter W M; Catton, Charles N; Ferguson, Peter C; Wunder, Jay S; Bell, Robert S; Sharpe, Michael B; O'Sullivan, Brian

    2009-11-15

    To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT). Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors. Mean dose to bone, RT field size (FS), maximum dose to a 2-cc volume of bone, and volume of bone irradiated to >or=40 Gy (V40) were compared. Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the dose distribution. For fracture patients, mean dose to bone was 45 +/- 8 Gy (mean dose at fracture site 59 +/- 7 Gy), mean FS was 37 +/- 8 cm, maximum dose was 64 +/- 7 Gy, and V40 was 76 +/- 17%, compared with 37 +/- 11 Gy, 32 +/- 9 cm, 59 +/- 8 Gy, and 64 +/- 22% for nonfracture patients. Differences in mean, maximum dose, and V40 were statistically significant (p = 0.01, p = 0.02, p = 0.01). Leg fractures were more common above the knee joint. The risk of radiation-induced fracture appears to be reduced if V40 Fracture incidence was lower when the mean dose to bone was lower mean FS for nonfracture patients.

  5. Sphincter preservation in rectal cancer with preoperative radiation therapy and coloanal anastomosis: long term follow-up

    International Nuclear Information System (INIS)

    Wagman, Raquel; Minsky, Bruce D.; Cohen, Alfred M.; Guillem, Jose G.; Paty, Philip P.

    1998-01-01

    Background: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer. Methods: Thirty six patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (5,T 2; 31,T 3 ) involving the distal half of the rectum and clinically required an abdominoperineal resection. The median tumor size was 3.8 cm [range: 1.5-7 cm] and the median distance from the anal verge was 4 cm [range: 3-7 cm]. The whole pelvis received 46.80 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 56 months [range: 4-121 months]. Results: Of the 35 patients who underwent resection, 5 (14%) had a complete pathologic response and 27 (77%) were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure was crude: 17% and 5-year actuarial: 21%. The 5-year actuarial survival was 64%. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in the 27 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 85%. The median number of bowel movements/day was 2 (range: 0-8). Conclusions: Our data suggest that preoperative radiation therapy allows sphincter preservation in 77% of selected patients who would otherwise require an abdominoperineal resection, and 85% have good to excellent sphincter function. Given the moderate local failure rate, we now routinely use preoperative combined modality therapy plus postoperative chemotherapy for patients with clinical T 3 disease

  6. Testing the Hypothesis of Biofilm as a Source for Soft Tissue and Cell-Like Structures Preserved in Dinosaur Bone.

    Directory of Open Access Journals (Sweden)

    Mary Higby Schweitzer

    Full Text Available Recovery of still-soft tissue structures, including blood vessels and osteocytes, from dinosaur bone after demineralization was reported in 2005 and in subsequent publications. Despite multiple lines of evidence supporting an endogenous source, it was proposed that these structures arose from contamination from biofilm-forming organisms. To test the hypothesis that soft tissue structures result from microbial invasion of the fossil bone, we used two different biofilm-forming microorganisms to inoculate modern bone fragments from which organic components had been removed. We show fundamental morphological, chemical and textural differences between the resultant biofilm structures and those derived from dinosaur bone. The data do not support the hypothesis that biofilm-forming microorganisms are the source of these structures.

  7. Testing the Hypothesis of Biofilm as a Source for Soft Tissue and Cell-Like Structures Preserved in Dinosaur Bone

    Science.gov (United States)

    2016-01-01

    Recovery of still-soft tissue structures, including blood vessels and osteocytes, from dinosaur bone after demineralization was reported in 2005 and in subsequent publications. Despite multiple lines of evidence supporting an endogenous source, it was proposed that these structures arose from contamination from biofilm-forming organisms. To test the hypothesis that soft tissue structures result from microbial invasion of the fossil bone, we used two different biofilm-forming microorganisms to inoculate modern bone fragments from which organic components had been removed. We show fundamental morphological, chemical and textural differences between the resultant biofilm structures and those derived from dinosaur bone. The data do not support the hypothesis that biofilm-forming microorganisms are the source of these structures. PMID:26926069

  8. Heart failure with preserved ejection fraction: mechanisms, clinical features, and therapies.

    Science.gov (United States)

    Sharma, Kavita; Kass, David A

    2014-06-20

    The clinical syndrome comprising heart failure (HF) symptoms but with a left ventricular ejection fraction (EF) that is not diminished, eg, HF with preserved EF, is increasingly the predominant form of HF in the developed world, and soon to reach epidemic proportions. It remains among the most challenging of clinical syndromes for the practicing clinician and scientist alike, with a multitude of proposed mechanisms involving the heart and other organs and complex interplay with common comorbidities. Importantly, its morbidity and mortality are on par with HF with reduced EF, and as the list of failed treatments continues to grow, HF with preserved EF clearly represents a major unmet medical need. The field is greatly in need of a more unified approach to its definition and view of the syndrome that engages integrative and reserve pathophysiology beyond that related to the heart alone. We need to reflect on prior treatment failures and the message this is providing, and redirect our approaches likely with a paradigm shift in how the disease is viewed. Success will require interactions between clinicians, translational researchers, and basic physiologists. Here, we review recent translational and clinical research into HF with preserved EF and give perspectives on its evolving demographics and epidemiology, the role of multiorgan deficiencies, potential mechanisms that involve the heart and other organs, clinical trials, and future directions. © 2014 American Heart Association, Inc.

  9. Body composition and bone density during and after childhood cancer therapy : The flip side of therapy

    NARCIS (Netherlands)

    den Hoed, M.A.H.

    2017-01-01

    In the Netherlands, there are approximately 8000 childhood cancer survivors, and this population of survivors is expanding due to improved therapy. However, therapy has a consequent flip side, namely their inherent side effects. Approximately 75% of the CCS will develop one or more severe chronic

  10. Bone marrow stromal cell therapy for ischemic stroke: A meta-analysis of randomized control animal trials.

    Science.gov (United States)

    Wu, Qing; Wang, Yuexiang; Demaerschalk, Bart M; Ghimire, Saruna; Wellik, Kay E; Qu, Wenchun

    2017-04-01

    Background Results of animal studies assessing efficacy of bone marrow stromal cell therapy for ischemic stroke remain inconsistent. Aims The aims are to assess efficacy of bone marrow stromal cell therapy for ischemic stroke in animal studies. Methods Randomized controlled animal trials assessing efficacy of bone marrow stromal cell therapy were eligible. Stroke therapy academic industry round table was used to assess methodologic quality of included studies. Primary outcomes were total infarction volume and modified Neurological Severity Score. Multiple prespecified sensitivity analyses and subgroup analyses were conducted. Random effects models were used for meta-analysis. Results Thirty-three randomized animal trials were included with a total of 796 animals. The median quality score was 6 (interquartile range, 5-7). Bone marrow stromal cell therapy decreased total infarction volume (standardized mean difference, 0.897; 95% confidence interval, 0.553-1.241; P animals treated with bone marrow stromal cell and controls was 2.47 (95% confidence interval, 1.84-3.11; P animal studies. Conclusions Bone marrow stromal cell therapy significantly decreased total infarction volume and increased neural functional recovery in randomized controlled animal models of ischemic stroke.

  11. Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys.

    Science.gov (United States)

    Olson, Erik J; Lindgren, Bruce R; Carlson, Cathy S

    2008-05-01

    The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but

  12. Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

    Science.gov (United States)

    Olson, Erik J.; Lindgren, Bruce R.; Carlson, Cathy S.

    2008-01-01

    The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but

  13. The role of radiation therapy in the management of bone metastases

    International Nuclear Information System (INIS)

    Scarantino, Charles W.; Konski, Andre A.

    1997-01-01

    Purpose: The purpose of this course is to discuss the current radiotherapeutic strategies in the treatment of bone metastases. Radiation therapy continues to play a central role in the relief of symptoms associated with bone metastases. The introduction of large field or hemibody and systemic or isotopic radiation techniques has expanded the role of radiation therapy to include evaluation of the impact of radiation on occult and overt yet asymptomatic disease. This course will review some of the basic mechanisms involved in the genesis of bone pain. A comparative analysis of the clinical trials of local field irradiation on bone metastases including dose and fractionation schedules, response rates, duration and evaluation of response will be discussed. The role of large field hemibody and systemic irradiation (e.g. isotopestrontium) in the treatment of metastatic disease will be presented. The topics include the response rates and duration of response of symptomatic metastases, the effect of each technique on the delay in progression of overt symptomatic disease as well as a delay in the appearance of new disease and the morbidity associated with each treatment modality. The design of several current trials will be presented as well as concepts for an expanding role of large field and systemic radiation techniques will be presented. The current managed care climate has brought to the forefront some basic issues regarding the economic impact of palliative radiotherapy. Therefore, this course will present an analysis of radiotherapeutic and non-radiotherapeutic management of pain associated with bone metastases as well as discussion of the basic techniques of economic analyses. Techniques of cost-minimization, cost-utility, cost-benefit, and cost-effective analyses and the appropriateness of each type of analyses will be presented. A discussion of which costs and benefits to include in the analyses will also be presented

  14. [A Case of Locally Advanced Thoracic Esophageal Cancer with Larynx Preservation and Curative Resection via Combined Modality Therapy].

    Science.gov (United States)

    Iwama, Mitsuru; Kimura, Yutaka; Shiraishi, Osamu; Kato, Hiroaki; Hiraki, Yoko; Tanaka, Yumiko; Yasuda, Atsushi; Shinkai, Masayuki; Imano, Motohiro; Imamoto, Haruhiko; Yasuda, Takushi

    2017-11-01

    Prognosis of locally advanced esophageal cancer is poor. The greatest prognostic factor of locally advanced esophageal cancer is a local control. We experienced a case of T4 locally advanced thoracic esophageal cancer who was successfully resected without any combined resection after multimodality therapy. A male in 75-year-old. was diagnosed with type 3 locally advanced upper thoracic esophageal cancer whose metastatic right recurrent laryngeal lymph node invaded into the trachea. Definitive chemoradiation therapy(CRT)was performed, leading to a significant shrinkage of the main tumor, but T4 lesion remained. Next, adding DCF therapy(docetaxel, CDDP and 5-FU), a relief of T4 was finally obtained. Then, salvage surgery with subtotalesophagectomy and retrosternalesophagealreconstruction with gastric tube was performed, resulting in R0 resection without any combined resection. The postoperative course was uneventful, and the patient has been alive without recurrence for 1 year after surgery. In locally advanced cancer, focusing on T4 downstaging, it is significantly important in terms of safety, curativity and organ preservation to perform surgery after a sure sign of T4 relief by multimodality therapy.

  15. Therapeutic effects of strontium-89 combined with endocrine therapy for treatment of bone metastasis in patients with prostate cancer

    International Nuclear Information System (INIS)

    Guo Deming

    2009-01-01

    Objective: To evaluate the effects of strontium-89 ( 89 Sr) combined with endocrine therapy for the treatment of bone metastasis in patients with advanced prostate cancer. Methods: 45 cases of prostate cancer with bone metastasis were randomly divided into 2 groups: patients in study group (23 cases) were given 89 Sr combined with endocrine therapy while patients in control group (22 cases) were given endocrine therapy only. The effect on pain relief, the serum PSA level, hemogram and biochemical indicators of hepatic and renal function were observed. Results: The pain degree was not statistically significant between two groups before treatment (P>0.05) and was statistically significant after treatment (P 89 Sr radionuclide combined with endocrine therapy was more effective than endocrine therapy alone in relief of the pain from bone metastasis and reduction of metastasis size in patients with advaced prostatic cancer. (authors)

  16. Is it safe to preserve the deltoid when resecting the proximal humerus for a primary malignant bone tumour? A comparative study.

    Science.gov (United States)

    Cladière-Nassif, V; Bourdet, C; Audard, V; Babinet, A; Anract, P; Biau, D

    2017-09-01

    Resection of the proximal humerus for the primary malignant bone tumour sometimes requires en bloc resection of the deltoid. However, there is no information in the literature which helps a surgeon decide whether to preserve the deltoid or not. The aim of this study was to determine whether retaining the deltoid at the time of resection would increase the rate of local recurrence. We also sought to identify the variables that persuade expert surgeons to choose a deltoid sparing rather than deltoid resecting procedure. We reviewed 45 patients who had undergone resection of a primary malignant tumour of the proximal humerus. There were 29 in the deltoid sparing group and 16 in the deltoid resecting group. Imaging studies were reviewed to assess tumour extension and soft-tissue involvement. The presence of a fat rim separating the tumour from the deltoid on MRI was particularly noted. The cumulative probability of local recurrence was calculated in a competing risk scenario. There was no significant difference (adjusted p = 0.89) in the cumulative probability of local recurrence between the deltoid sparing (7%, 95% confidence interval (CI) 1 to 20) and the deltoid resecting group (26%, 95% CI 8 to 50). Patients were more likely to be selected for a deltoid sparing procedure if they presented with a small tumour (p = 0.0064) with less bone involvement (p = 0.032) and a continuous fat rim on MRI (p = 0.002) and if the axillary nerve could be identified (p = 0.037). A deltoid sparing procedure can provide good local control after resection of the proximal humerus for a primary malignant bone tumour. A smaller tumour, the presence of a continuous fat rim and the identification of the axillary nerve on pre-operative MRI will persuade surgeons to opt for a deltoid resecting procedure. Cite this article: Bone Joint J 2017;99-B:1244-9. ©2017 The British Editorial Society of Bone & Joint Surgery.

  17. Effect of music therapy on pain behaviors in rats with bone cancer pain.

    Science.gov (United States)

    Gao, Ji; Chen, Shaoqin; Lin, Suyong; Han, Hongjing

    2016-01-01

    To investigate the effects of music therapy on the pain behaviors and survival of rats with bone cancer pain and analyze the mediating mechanism of mitogen activated protein kinase (MAPK) signal transduction pathway. Male Wistar rats aged 5-8 weeks and weighing 160-200 g were collected. The rat models of colorectal cancer bone cancer pain was successfully established. Animals were divided into experimental and control group, each with 10 rats. The animals in the observation group were given Mozart K448 sonata, sound intensity of 60 db, played the sonata once every 1 hr in the daytime, stopped playing during the night, and this cycle was kept for 2 weeks. On the other hand, rats in the control group were kept under the same environment without music. Animals in the experimental group consumed more feed and gained significant weight in comparison to the control group. The tumor volume of the experimental group was significantly smaller than that of the control group (pMusic therapy may improve the pain behaviors in rats with bone cancer pain, which might be related with low expression of p38á and p38β in the MAPK signal transduction pathway.

  18. Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

    International Nuclear Information System (INIS)

    Forrer, Flavio; Krenning, Eric P.; Kooij, Peter P.; Bernard, Bert F.; Bakker, Willem H.; Teunissen, Jaap J.M.; Jong, Marion de; Kwekkeboom, Dik J.; Konijnenberg, Mark; Lom, Kirsten van; Herder, Wouter W. de

    2009-01-01

    Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called ''remainder of the body'' to the bone marrow. Bone marrow aspirates were drawn in 15 patients after treatment with [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate. Radioactivity in the bone marrow was compared with radioactivity in the blood drawn simultaneously. The nucleated cell fraction was isolated from the bone marrow aspirate and radioactivity was measured. The absorbed dose to the bone marrow was calculated. The results were correlated to the change in platelet counts 6 weeks after treatment. A strong linear correlation and high agreement between the measured radioactivities in the bone marrow aspirates and in the blood was found (r=0.914, p 177 Lu-DOTA 0 ,Tyr 3 ]octreotate, the radioactivity concentration in the bone marrow is identical to that in the blood; (2) There is no significant binding of the radiopharmaceutical to bone marrow precursor stem cells; (3) The contribution of the cross dose from source organs and tumours to the bone marrow dose is significant; and (4) There is considerable variation in bone marrow absorbed dose between patients. These findings imply that for individual dose optimization, individual calculation of the bone marrow absorbed dose is necessary. (orig.)

  19. Can Bone Tissue Engineering Contribute to Therapy Concepts after Resection of Musculoskeletal Sarcoma?

    Directory of Open Access Journals (Sweden)

    Boris Michael Holzapfel

    2013-01-01

    Full Text Available Resection of musculoskeletal sarcoma can result in large bone defects where regeneration is needed in a quantity far beyond the normal potential of self-healing. In many cases, these defects exhibit a limited intrinsic regenerative potential due to an adjuvant therapeutic regimen, seroma, or infection. Therefore, reconstruction of these defects is still one of the most demanding procedures in orthopaedic surgery. The constraints of common treatment strategies have triggered a need for new therapeutic concepts to design and engineer unparalleled structural and functioning bone grafts. To satisfy the need for long-term repair and good clinical outcome, a paradigm shift is needed from methods to replace tissues with inert medical devices to more biological approaches that focus on the repair and reconstruction of tissue structure and function. It is within this context that the field of bone tissue engineering can offer solutions to be implemented into surgical therapy concepts after resection of bone and soft tissue sarcoma. In this paper we will discuss the implementation of tissue engineering concepts into the clinical field of orthopaedic oncology.

  20. Utility of radius bone densitometry for the treatment of osteoporosis with once-weekly teriparatide therapy

    Directory of Open Access Journals (Sweden)

    Harumi Nakayama

    2018-03-01

    Full Text Available Objectives: As clinics that treat patients with osteoporosis do not usually have central dual-energy X-ray absorptiometry (DXA, bone density is often measured with radial DXA. However, no long-term evidence exists for radius bone density outcomes following treatment with once-weekly teriparatide in actual medical treatment. Methods: We evaluated changes in bone density at 6-, 12-, and 18-month intervals using radial DXA in patients treated with once-weekly teriparatide for more than 6 months. Results: A significant increase in bone mineral density (BMD was observed at the 1/3 and 1/10 radius sites 12 months after the initiation of once-weekly teriparatide. We also observed that the rate of change in BMD was greater at the distal 1/10 radius than at the 1/3 radius. Conclusions: Considering these points, the effect of once-weekly teriparatide therapy can be observed at the radius. In clinics that do not have central DXA, but instead have radial DXA, these findings can help to evaluate the effect of once-weekly teriparatide treatment on osteoporosis. Keywords: Once-weekly teriparatide, Osteoporosis, Radius, Dual-energy X-ray absorptiometry

  1. Update on fertility preservation in young women undergoing breast cancer and ovarian cancer therapy.

    Science.gov (United States)

    Lambertini, Matteo; Ginsburg, Elizabeth S; Partridge, Ann H

    2015-02-01

    The purpose of the article is to review the available options for fertility preservation in patients with breast and ovarian cancer, and the special issues faced by BRCA mutation carriers. Future fertility is an important consideration for many young patients with cancer. There are both experimental and standard available strategies for patients with breast and ovarian cancer to preserve fertility, and each has potential advantages and disadvantages. Embryo cryopreservation is widely available with a highly successful track record. Improvements in laboratory techniques have led to oocyte cryopreservation recently being recategorized as nonexperimental. Conservative gynecologic surgery is a standard consideration for patients with stage I ovarian cancer who desire future fertility. Ovarian tissue cryopreservation as well as ovarian suppression with luteinizing hormone-releasing hormone analogs during chemotherapy are considered experimental methods at this time, although recent data suggest both safety and efficacy for the use of luteinizing hormone-releasing hormone analogs in women receiving (neo)adjuvant chemotherapy for breast cancer. Special issues should be considered for women with BRCA mutations because of the need to undergo preventive surgery at young age. Multidisciplinary teams and well functioning relationships between the oncology and reproductive units are crucial to manage the fertility issues of young women with cancer.

  2. Effect of antitumour necrosis factor-alpha therapy on bone turnover in patients with active Crohn's disease: a prospective study.

    Science.gov (United States)

    Ryan, B M; Russel, M G V M; Schurgers, L; Wichers, M; Sijbrandij, J; Stockbrugger, R W; Schoon, E

    2004-10-15

    Patients with Crohn's disease are at increased risk of osteoporosis. Disease activity and circulating proinflammatory cytokines are thought to play a role in this process. Infliximab, a chimaeric antitumour necrosis factor-alpha antibody is effective in the treatment of Crohn's disease. The aim of this study was to investigate the impact of treatment with infliximab on bone turnover in Crohn's disease patients. This was a prospective trial. Twenty-four patients with active Crohn's disease were treated with infliximab (5 mg/kg). Bone markers were assayed pre- and post-treatment. Bone formation was measured using serum bone-specific alkaline phosphatase and total osteocalcin and bone resorption using serum N-telopeptide cross-linked type 1 collagen. Infliximab therapy caused a significant increase in both markers of bone formation in patients with active Crohn's disease. No significant change in the bone resorption marker serum N-telopeptide cross-linked type 1 was found. Infliximab therapy had a significant beneficial effect on bone metabolism in patients with active Crohn's disease. These findings further support the theory that active ongoing inflammation and high levels of circulating cytokines play a pivotal role in the pathogenesis of bone loss in patients with Crohn's disease.

  3. Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links.

    Science.gov (United States)

    Pardini, D P; Sabino, A T; Meneses, A M; Kasamatsu, T; Vieira, J G

    2000-01-06

    The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. To study the effect of hormone replacement therapy (HRT) on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. Cohort correlational study. Academic referral center. 53 post-menopausal women, aged 48-58 years. Urinary pyr and d-pyr were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion measured before treatment and after 1, 2, 4 and 12 months. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DEXA) before treatment and after 12 months of HRT. The BMD after HRT was about 4.7% (P < 0.0004); 2% (P < 0.002); and 3% (P < 0. 01) higher than the basal values in lumbar spine, neck and trochanter respectively. There were no significant correlations between pyridinium cross-links and age, weight, menopause duration and BMD. The decrease in pyr and d-pyr was progressive after HRT, reaching 28.9% (P < 0.0002), and 42% (P < 0.0002) respectively after 1 year. Urinary pyridinoline and deoxypyridinoline excretion decreases early in hormone replacement therapy, reflecting a decrease in the bone resorption rate, and no correlation was observed with the bone mass evaluated by densitometry.

  4. A comparative evaluation of extraction socket preservation with demineralized freeze-dried bone allograft alone and along with platelet-rich fibrin: A clinical and radiographic study

    Directory of Open Access Journals (Sweden)

    Dhaval J Thakkar

    2016-01-01

    Full Text Available Aims: To investigate clinically and radiographically, the bone fill in extraction sockets using demineralized freeze-dried bone allograft alone and along with platelet-rich fibrin (PRF. Materials and Methods: A randomized controlled clinical trial was carried out on 36 nonrestorable single-rooted teeth sites. Sites were randomized into demineralized freeze-dried bone allograft (DFDBA combined with PRF - test and DFDBA - control groups using a coin toss method. After the placement of graft material, collagen membrane was used to cover it. The clinical parameters recorded were ridge width and ridge height. All the parameters were recorded at baseline and at 90 and 180 days. Statistical Analysis Used: Independent t-test and paired t-test. Results: In both groups, there is significant reduction in loss of ridge width and ridge height from baseline to 90 days (P < 0.001, baseline to 180 days (P < 0.001, and 90-180 days (P < 0.001. However, when both the groups were compared the test group favored in the reduction of ridge width while there was no statistical difference in reduction of ridge height among at different intervals. Conclusions: Although DFDBA is considered as an ideal graft material, PRF can be used as an adjunctive with DFDBA for socket preservation.

  5. Effect of Thyrotropin Suppression Therapy on Bone in Thyroid Cancer Patients.

    Science.gov (United States)

    Papaleontiou, Maria; Hawley, Sarah T; Haymart, Megan R

    2016-02-01

    The thyroid cancer incidence is rising. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy. Also, its potential skeletal effects remain a concern to physicians caring for thyroid cancer patients. We conducted a review of published data to evaluate existing studies focusing on the skeletal effects of thyrotropin suppression therapy in thyroid cancer patients. A systematic search of the PubMed, Ovid/Medline, and Cochrane Central Register of Controlled Trials databases was conducted. The retained studies were evaluated for methodological quality, and the study populations were categorized into premenopausal women, postmenopausal women, and men. Twenty-five pertinent studies were included. Seven studies were longitudinal and 18 were cross-sectional. Of the 25 included studies, 13 were assigned an excellent methodological quality score. Three of 5 longitudinal studies and 3 of 13 cross-sectional studies reported decreased bone mineral density (BMD) in premenopausal women; 2 of 4 longitudinal studies and 5 of 13 cross-sectional studies reported decreased BMD in postmenopausal women. The remaining studies showed no effect on BMD. The only longitudinal study of men showed bone mass loss; however, cross-sectional studies of men did not demonstrate a similar effect. Studies to date have yielded conflicting results on the skeletal effects of thyrotropin suppression therapy and a knowledge gap remains, especially for older adults and men. Existing data should be cautiously interpreted because of the variable quality and heterogeneity. Identifying groups at risk of adverse effects from thyrotropin suppression therapy will be instrumental to providing focused and tailored thyroid cancer treatment. The standard treatment for thyroid cancer includes total thyroidectomy with or without radioactive iodine ablation, often followed by thyrotropin suppression therapy. Despite current guidelines, controversy exists

  6. Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

    DEFF Research Database (Denmark)

    Warming, Lise; Ravn, Pernille; Spielman, Danièle

    2004-01-01

    bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy...

  7. The rate of 99m Tc-MDP uptake in metastatic bone lesions before and after 89m Sr therapy

    International Nuclear Information System (INIS)

    Souza, Joseane Fonseca; Braga, Francisco J.H.N.

    1996-01-01

    The rate of 99m Tc-MDP uptake is studied in metastatic bone lesions, before and after 89m Sr therapy. Eight hopeless patients (age between 56 and 74) presenting disseminated carcinoma of the prostate are evaluated. No hormonal therapy and a limited radiotherapy were considered. It is concluded that therapeutical doses of 89m Sr reduces MDP uptake

  8. Preparation and characterization of an iron oxide-hydroxyapatite nanocomposite for potential bone cancer therapy.

    Science.gov (United States)

    Sneha, Murugesan; Sundaram, Nachiappan Meenakshi

    2015-01-01

    Recently, multifunctional magnetic nanostructures have been found to have potential applications in biomedical and tissue engineering. Iron oxide nanoparticles are biocompatible and have distinctive magnetic properties that allow their use in vivo for drug delivery and hyperthermia, and as T2 contrast agents for magnetic resonance imaging. Hydroxyapatite is used frequently due to its well-known biocompatibility, bioactivity, and lack of toxicity, so a combination of iron oxide and hydroxyapatite materials could be useful because hydroxyapatite has better bone-bonding ability. In this study, we prepared nanocomposites of iron oxide and hydroxyapatite and analyzed their physicochemical properties. The results suggest that these composites have superparamagnetic as well as biocompatible properties. This type of material architecture would be well suited for bone cancer therapy and other biomedical applications.

  9. Postoperative radiation therapy after hip replacement in high-risk patients for development of heterotopic bone formation

    International Nuclear Information System (INIS)

    Hashem, R.; Rene, N.; Souhami, L.; Tanzer, M.; Evans, M.

    2011-01-01

    Purpose. - To report the results of postoperative radiation therapy in preventing the development of heterotopic bone formation after hip replacement surgery in high-risk patients. Patients and methods. - Between 1991 and 2007, 44 patients were preventively treated with postoperative RT after total hip replacement. In total, 47 hips were treated. All patients were considered at high risk for developing heterotopic bone formation. Most patients (63.5%) were treated because of a history of severe osteoarthritis or ankylosing spondylitis. All patients were treated with shaped parallel-opposed fields with a single fraction of 7 Gy using 6 or 18 MV photons. Most patients (94%) received radiation therapy within 72 hours postoperative and in only three patients radiation therapy was delivered after 72 hours post-surgery (5-8 days). Results. - Minimum follow-up was 1 year. There were 18 females and 26 males. Median age was 63 years (range: 18-80). Treatments were well tolerated and no acute toxicity was seen post-radiation therapy. Only one of the 47 hips (2%) developed heterotopic bone formation. This patient received postoperative radiation therapy to both hips but only developed heterotopic bone formation in one of them. None of the three patients treated beyond 72 hours failed. To date no late toxicity has been observed. Conclusion. - The use of postoperative radiation therapy was an effective and safe treatment in the prevention of heterotopic bone formation in a high-risk group of patients undergoing total hip replacement. (authors)

  10. Prediction of Splint Therapy Efficacy Using Bone Scan in Patients with Unilateral Temporomandibular Disorder

    International Nuclear Information System (INIS)

    Lee, Sang Mi; Lee, Won Woo; Yun, Pil Young; Kim, Young Kyun; Kim, Sang Eun

    2009-01-01

    It is not known whether bone scan is useful for the prediction of the prognosis of patients with temporomandibular disorders (TMD). The aim of the present study was to identify useful prognostic markers on bone scan for the pre-therapeutic assessment of patients with unilateral TMD. Between January 2005 and July 2007, 55 patients (M:F=9:46; mean age, 34.7±14.1 y) with unilateral TMD that underwent a pre-therapeutic bone scan were enrolled. Uptake of Tc-99m HDP in each temporomandibular joint (TMJ) was quantitated using a 13X13 pixel-square region-of-interest over TMJ and parietal skull area as background. TMJ uptake ratios and asymmetric indices were calculated. TMD patients were classified as improved or not improved and the bone scan findings associated with each group were investigated. Forty-six patients were improved, whereas 9 patients were not improved. There was no significant difference between the two groups of patients regarding the TMJ uptake ratio of the involved joint, the TMJ uptake ratio of the non-involved joint, and the asymmetric index (p>0.05). However, in a subgroup analysis, the patients with an increased uptake of Tc-99m HDP at the disease-involved TMJ, by visual assessment, could be easily identified by the asymmetric index; the patients that improved had a higher asymmetric index than the patients that did not improve (1.32±0.35 vs. 1.08±0.04, p=0.023), The Tc-99m HDP bone scan may help predict the prognosis of patients with unilateral TMD after splint therapy when the TMD-involved joint reveals increased uptake by visual assessment

  11. Prediction of Splint Therapy Efficacy Using Bone Scan in Patients with Unilateral Temporomandibular Disorder

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Mi; Lee, Won Woo; Yun, Pil Young; Kim, Young Kyun; Kim, Sang Eun [Seoul National University Bundang Hospital, Seoul (Korea, Republic of)

    2009-04-15

    It is not known whether bone scan is useful for the prediction of the prognosis of patients with temporomandibular disorders (TMD). The aim of the present study was to identify useful prognostic markers on bone scan for the pre-therapeutic assessment of patients with unilateral TMD. Between January 2005 and July 2007, 55 patients (M:F=9:46; mean age, 34.7{+-}14.1 y) with unilateral TMD that underwent a pre-therapeutic bone scan were enrolled. Uptake of Tc-99m HDP in each temporomandibular joint (TMJ) was quantitated using a 13X13 pixel-square region-of-interest over TMJ and parietal skull area as background. TMJ uptake ratios and asymmetric indices were calculated. TMD patients were classified as improved or not improved and the bone scan findings associated with each group were investigated. Forty-six patients were improved, whereas 9 patients were not improved. There was no significant difference between the two groups of patients regarding the TMJ uptake ratio of the involved joint, the TMJ uptake ratio of the non-involved joint, and the asymmetric index (p>0.05). However, in a subgroup analysis, the patients with an increased uptake of Tc-99m HDP at the disease-involved TMJ, by visual assessment, could be easily identified by the asymmetric index; the patients that improved had a higher asymmetric index than the patients that did not improve (1.32{+-}0.35 vs. 1.08{+-}0.04, p=0.023), The Tc-99m HDP bone scan may help predict the prognosis of patients with unilateral TMD after splint therapy when the TMD-involved joint reveals increased uptake by visual assessment.

  12. Patterns of Care Among Patients Receiving Radiation Therapy for Bone Metastases at a Large Academic Institution

    Energy Technology Data Exchange (ETDEWEB)

    Ellsworth, Susannah G. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Alcorn, Sara R., E-mail: salcorn2@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hales, Russell K.; McNutt, Todd R.; DeWeese, Theodore L. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Smith, Thomas J. [Department of Medical Oncology and Harry J. Duffey Family Program in Palliative Care, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2014-08-01

    Purpose: This study evaluates outcomes and patterns of care among patients receiving radiation therapy (RT) for bone metastases at a high-volume academic institution. Methods and Materials: Records of all patients whose final RT course was for bone metastases from April 2007 to July 2012 were identified from electronic medical records. Chart review yielded demographic and clinical data. Rates of complicated versus uncomplicated bone metastases were not analyzed. Results: We identified 339 patients whose final RT course was for bone metastases. Of these, 52.2% were male; median age was 65 years old. The most common primary was non-small-cell lung cancer (29%). Most patients (83%) were prescribed ≤10 fractions; 8% received single-fraction RT. Most patients (52%) had a documented goals of care (GOC) discussion with their radiation oncologist; hospice referral rates were higher when patients had such discussions (66% with vs 50% without GOC discussion, P=.004). Median life expectancy after RT was 96 days. Median survival after RT was shorter based on inpatient as opposed to outpatient status at the time of consultation (35 vs 136 days, respectively, P<.001). Hospice referrals occurred for 56% of patients, with a median interval between completion of RT and hospice referral of 29 days and a median hospice stay of 22 days. Conclusions: These data document excellent adherence to American Society for Radiation Oncolology Choosing Wisely recommendation to avoid routinely using >10 fractions of palliative RT for bone metastasis. Nonetheless, single-fraction RT remains relatively uncommon. Participating in GOC discussions with a radiation oncologist is associated with higher rates of hospice referral. Inpatient status at consultation is associated with short survival.

  13. Three-phase Bone Scintigraphy Can Predict the Analgesic Efficacy of Ketamine Therapy in CRPS.

    Science.gov (United States)

    Sorel, Marc; Beatrix, Jacques-Christian; Locko, Blanche; Armessen, Catherine; Domec, Anne-Marie; Lecompte, Otilia; Boucheneb, Sofiane; Harache, Benoit; Robert, Jacques; Lefaucheur, Jean-Pascal

    2018-03-13

    The efficacy of ketamine in relieving complex regional pain syndrome (CRPS) lacks predictive factors. The value of three-phase bone scintigraphy (TPBS) was assessed or this purpose. TPBS was performed in 105 patients with unilateral, focal CRPS of type 1 before 5 days of ketamine infusions. Tracer uptake was measured in the region of interest concerned by CRPS and the contralateral homologous region. For the three scintigraphic phases (vascular, tissular, and bone phases), an asymmetry ratio of fixation was calculated between the affected and the unaffected sides (VPr, TPr, and BPr). Ketamine efficacy was assessed on pain intensity scores. Ketamine-induced pain relief did not correlate with VPr, TPr, and BPr, but with the ratios of these ratios: BPr/TPr (r=0.32, P=0.009), BPr/VPr (r=0.34, P=0.005), and TPr/VPr (r=0.23, P=0.02). The optimum cut-off value for predicting the response to ketamine therapy was >1.125 for BPr/TPr, >1.075 for BPr/VPr, and >0.935 for TPr/VPr. The combination of increased values of BPr/TPr, BPr/VPr, and TPr/VPr was extremely significantly associated with ketamine therapy outcome. The relative hyperfixation of the radioactive tracer in the limb region concerned by CRPS in phases 2 and 3 versus phase 1 of TPBS correlated positively to the analgesic efficacy of ketamine. This study shows for the first time the potential predictive value of TPBS regarding ketamine therapy outcome. In addition, these results suggest that the analgesic action of ketamine is not restricted to "central" mechanisms, but may also involve "peripheral" mechanisms related to tissue inflammation and bone remodeling.

  14. Initial Results of Retrospective Study: Preoperative Transurethral Excision Plus Chemotherapy and Radiation Therapy and Trial of Bladder Preservation

    International Nuclear Information System (INIS)

    Gammal El-Deen, H.S.

    2007-01-01

    For patients with invasive bladder cancer the usual recommended treatment is radical cystectomy, although transurethral resection of the tumor, systemic chemotherapy, and radiotherapy are each effective in some patients. This retrospective study evaluated the experience of the Clinical Oncology Department, Tanta University Hospital with combined modality treatment and selective bladder preservation in patients with muscle-invading bladder cancer with assessment of its safety, tolerance, and efficacy to determine whether these treatments in combination might be as effective as radical cystectomy and thus might allow the bladder to be preserved and the cancer cured and to identify factors that may predict treatment response, risk of relapse and survival. Patients and Methods: Between January 2000 and January 2006, 55 consecutive patients with muscle invading bladder cancer (stages T2 through T4, NX M0) were treated with as complete transurethral surgery as possible, followed by induction combination chemotherapy, and irradiation with 4500 cGy with concurrent cisplatin administration. Urologic evaluation by cystoscopy, cytology, and re biopsy 2-3 weeks later of the tumor response directed further therapy: either radical cystectomy in the patients who had incomplete responses, or additional chemotherapy with the same drugs and doses and radiotherapy up to 6480 cGy in the patients who had complete responses. The median follow-up was 48 months. Results: In 37 patients (67.3%) the bladder was free of invasive tumor and functioning well, even though in 13(23.6%) a superficial tumor recurred and required further transurethral surgery and intravesical drug therapy. Of the 18 (32.7%) patients who still had detectable tumor after initial treatment, all of them underwent radical cystectomy. None of the patients had required a cystectomy for radiation toxicity. Of the 37 (67.3%) patients who had complete responses with no tumor detectable on urine cytology or re biopsy after

  15. [The influence of drug liberation from drug forms on local therapy of infected bone cavities].

    Science.gov (United States)

    Süss, W; Wehr, M

    1984-09-01

    With regard to an optimum local pharmaco-therapy in infected bone cavities, in vitro examinations by means of a flow model based on the half-change method had been performed to liberate Gentamycin from globular embeddings in polymethylmethacrylate. The Gentamycin had been determined in a micro-biological manner. The release behaviour of the polymere carrier could be controlled by adding Polyethylenglycol 400 as softener or butane dioldimethacrylate as wettener. Adding 20 vol.-% of Polyethylenglycol 400, the Gentamycin release could be increased to the 8-fold, whereas the addition of 5 vol.-% of butane dioldimethacrylate resulted in a decrease amounting to 7/8 exit value.

  16. Bone-targeted therapy for metastatic breast cancer—Where do we go from here? A commentary from the BONUS 8 meeting

    Directory of Open Access Journals (Sweden)

    Xiaofu Zhu

    2014-03-01

    Full Text Available The annual Bone and The Oncologist New Updates (BONUS 8 conference focuses on the current understanding and dilemmas in the treatment and prevention of bone metastasis in cancer, as well as novel research on bone homeostasis and cancer-induced bone loss. We present commentaries from experts for their own take on where they feel the field of bone-targeted therapies for metastatic breast cancer is moving, or needs to move, if we are to make further progress.

  17. Partial resolution of bone lesions. A child with severe combined immunodeficiency disease and adenosine deaminase deficiency after enzyme-replacement therapy

    International Nuclear Information System (INIS)

    Yulish, B.S.; Stern, R.C.; Polmar, S.H.

    1980-01-01

    A child with severe combined immunodeficiency disease and adenosine deaminase deficiency, with characteristic bone dysplasia, was treated with transfusions of frozen irradiated RBCs as a means of enzyme replacement. This therapy resulted in restoration of immunologic competence and partial resolution of the bone lesions. Although the natural history of these lesions without therapy is not known, enzyme-replacement therapy may have played a role in the resolution of this patient's bone lesions

  18. Patterns of Intraosseous Recurrence After Stereotactic Body Radiation Therapy for Coxal Bone Metastasis.

    Science.gov (United States)

    Ito, Kei; Shimizuguchi, Takuya; Nihei, Keiji; Furuya, Tomohisa; Ogawa, Hiroaki; Tanaka, Hiroshi; Sasai, Keisuke; Karasawa, Katsuyuki

    2018-01-01

    To analyze the detailed pattern of intraosseous failure after stereotactic body radiation therapy (SBRT) for coxal bone metastasis. Patients treated with SBRT to coxal bone metastasis were identified by retrospective chart review. The SBRT doses were 30 Gy or 35 Gy in 5 fractions. A margin of 5 to 10 mm was added to the gross tumor volume to create the clinical target volume. We evaluated the presence or absence of intraosseous recurrence using magnetic resonance imaging. Intraosseous recurrences were assessed as "in-field" or "marginal/out-of-field." In addition, we measured the distance between the center of the recurrent tumor and the nearest edge of the initial bone metastasis in cases of marginal/out-of-field recurrence. Seventeen patients treated for 17 coxal bone metastases were included. Median age was 64 years (range, 48-79 years). Coxal lesions involved the ilium in 14 cases, pubis in 3, and ischium in 4 (3 lesions crossed over multiple regions). Patients most commonly had renal cell carcinoma (29.4%), followed by lung, hepatic cell, and colorectal cancers (23.5%, 11.8%, and 11.8%, respectively). Median follow-up after SBRT was 13 months (range, 2-44 months). Among all 17 cases, 7 cases developed 8 intraosseous recurrences, including in-field recurrence in 1 case and marginal/out-of-field recurrences in 7 cases. Median time to intraosseous recurrence was 10 months (range, 2-35 months). Among 7 cases with marginal/out-of-field recurrence, mean distance to the center of the recurrent tumor from the nearest edge of the initial bone metastasis was 34 mm (range, 15-55 mm). Most recurrences were observed out-of-field in the same coxal bone. These results suggest that defining the optimal clinical target volume in SBRT for coxal bone metastasis to obtain sufficient local tumor control is difficult. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Bone Marrow?Derived Mesenchymal Stem Cells Enhance Bacterial Clearance and Preserve Bioprosthetic Integrity in a Model of Mesh Infection

    OpenAIRE

    Criman, Erik T.; Kurata, Wendy E.; Matsumoto, Karen W.; Aubin, Harry T.; Campbell, Carmen E.; Pierce, Lisa M.

    2016-01-01

    Background: The reported incidence of mesh infection in contaminated operative fields is as high as 30% regardless of the material used. Recently, mesenchymal stem cells (MSCs) have been shown to possess favorable immunomodulatory properties and improve tissue incorporation when seeded onto bioprosthetics. The aim of this study was to evaluate whether seeding noncrosslinked bovine pericardium (Veritas Collagen Matrix) with allogeneic bone marrow?derived MSCs improves infection resistance in v...

  20. Serial MR imaging evaluation of effects of radiation therapy on bone marrow and liver

    International Nuclear Information System (INIS)

    Yankelevitz, D.; Henschke, C.I.; Chu, F.; Hayt, D.B.; Whalen, J.P.; Cahill, P.T.

    1989-01-01

    This paper reports on baseline and serial MR imaging studies obtained on 20 patients (lung cancer and lymphoma) who were receiving radiation therapy as their only form of treatment. Quantitative and qualitative MR signal intensity measurement were made on bone marrow and liver. Additionally, changes in signal intensity were correlated with laboratory values including both complete blood count and liver function tests. The spine showed increased signal intensity on T1-weighted images. MR signal intensity increased rapidly in the first 6 weeks and continued to rise slowly thereafter. In three of 10 cases in which the liver was included in the radiotherapy field, areas of increased activity in the liver were seen on T2-weighted images. These areas were in the field of radiation and sharply demarcated from nonirradiated liver. This area of abnormality gradually returned to normal after completion of therapy

  1. Whole body vibration versus magnetic therapy on bone mineral density in elderly osteoporotic individuals.

    Science.gov (United States)

    Shanb, Alsayed Abdelhameed; Youssef, Enas Fawzy; Muaidi, Qassim Ibrahim; Alothman, Abdullah Ahmed

    2017-08-03

    Osteoporosis usually develops gradually and progresses without significant signs and symptoms. It is one of the most common musculoskeletal conditions associated with aging. To evaluate the effects of whole body vibration (WBV) or magnetic therapy in addition to standard pharmacological treatment on bone mineral density (BMD) in elderly individuals being treated for osteoporosis. Eighty-five participants, 60-75 years of age, were randomly divided into three groups. All three groups received the same standard pharmacological treatment comprised of vitamin D, calcium, and alendronate sodium. In Group I, thirty participants were also exposed to WBV for 25 minutes in each session with two sessions per week for 4 months. In Group II, thirty participants were exposed to magnetic therapy for 50 minutes in each session with two sessions per week for 4 months. In Group III, twenty-five participants received only pharmacological treatment. Dual-energy X-ray absorptiometry was used to measure BMD of the lumbar spine and femoral heads before and after interventions. Venus blood sample was drawn for analysis of calcium and vitamin D. An ANOVA test detected significant (pmagnetic therapy. Statistical t-tests detected significant (pmagnetic therapy in combination with pharmacological treatment, but no significant increase after pharmacological treatment alone. Addition of either WBV or magnetic therapy to standard pharmacological treatment for osteoporosis significantly increased BMD in elderly subjects. No significant difference in effectiveness was detected between these two alternative therapy modalities. Consequently, either WBV or magnetic therapy could be effectively applied in conjunction with pharmacological treatment to increase BMD in elderly osteoporotic patients.

  2. Testosterone therapy preserves muscle strength and power in aging men with type 2 diabete

    DEFF Research Database (Denmark)

    Magnussen, L V; Hvid, L G; Hermann, A P

    2017-01-01

    dual-energy X-ray absorptiometry (total lean body mass, lean leg mass, total fat mass, leg fat mass). Levels of total testosterone (TotalT), BioT, free testosterone (FreeT), and sex hormone-binding globulin were measured from fasting blood samples. Coefficients (b) represent the placebo-controlled mean......The purpose of the study was to evaluate whether testosterone replacement therapy improves muscle mechanical and physical function in addition to increasing lean leg mass and total lean body mass in aging men with type 2 diabetes and lowered bio-available testosterone (BioT) levels. Thirty-nine men.......9 kg, p = 0.001) and lean leg mass (b = 0.5 kg, p mass (b = -1.3 kg, p = 0.009) and leg fat mass (b = -0.7 kg, p = 0.025) decreased during testosterone replacement therapy compared with placebo. Total T (b = 14.5 nmol/L, p = 0.056), BioT (b = 7.6 nmol/L, p = 0...

  3. Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases

    International Nuclear Information System (INIS)

    Niewald, Marcus; Tkocz, Heinz-Joachim; Abel, Ulrich; Scheib, Thomas; Walter, Karin; Nieder, Carsten; Schnabel, Klaus; Berberich, Werner; Kubale, Reinhard; Fuchs, Marcus

    1996-01-01

    Purpose: In a prospective randomized trial we examined whether radiotherapy of painful bone metastases can be shortened using larger single doses without impairing effectivity. Methods and Materials: One hundred patients with painful bone metastases having no prior surgical intervention or treatment with x-ray therapy and had a median follow-up of 12 months were analyzed. The primary tumor was located in the breast in 43%, in the lung in 24%, and in the prostate in 14%. The most frequent sites of metastases were the pelvis (31%), the vertebral column (30%), and the ribs (20%). Further percentages of sites were: lower extremity 11%, upper extremity 6%, and skull 2%. Fifty-one patients received a short course radiotherapy with a total dose of 20 Gy in 1 week (daily dose 4 Gy), and 49 patients received 30 Gy in 3 weeks (daily dose 2 Gy). Results: There were no significant differences in frequency, duration of pain relief, improvement of mobility, recalcification, frequency of pathologic fractures nor survival. There was a light trend favoring 30 Gy in frequency of pain relief and recalcification. Survival was mostly influenced by primary tumor site, Karnofsky performance status, and possibly by the response to radiotherapy (pain relief). Conclusions: Because of the very short life expectancy of patients with metastatic bone disease, we now use 20 Gy in 1 week as our standard to reduce hospital stay

  4. Postnatal soluble FGFR3 therapy rescues achondroplasia symptoms and restores bone growth in mice.

    Science.gov (United States)

    Garcia, Stéphanie; Dirat, Béatrice; Tognacci, Thomas; Rochet, Nathalie; Mouska, Xavier; Bonnafous, Stéphanie; Patouraux, Stéphanie; Tran, Albert; Gual, Philippe; Le Marchand-Brustel, Yannick; Gennero, Isabelle; Gouze, Elvire

    2013-09-18

    Achondroplasia is a rare genetic disease characterized by abnormal bone development, resulting in short stature. It is caused by a single point mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3), which leads to prolonged activation upon ligand binding. To prevent excessive intracellular signaling and rescue the symptoms of achondroplasia, we have developed a recombinant protein therapeutic approach using a soluble form of human FGFR3 (sFGFR3), which acts as a decoy receptor and prevents FGF from binding to mutant FGFR3. sFGFR3 was injected subcutaneously to newborn Fgfr3(ach/+) mice-the mouse model of achondroplasia-twice per week throughout the growth period during 3 weeks. Effective maturation of growth plate chondrocytes was restored in bones of treated mice, with a dose-dependent enhancement of skeletal growth in Fgfr3(ach/+) mice. This resulted in normal stature and a significant decrease in mortality and associated complications, without any evidence of toxicity. These results describe a new approach for restoring bone growth and suggest that sFGFR3 could be a potential therapy for children with achondroplasia and related disorders.

  5. Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?

    Directory of Open Access Journals (Sweden)

    Belsing Tina Z

    2010-09-01

    Full Text Available Abstract Context Hyperthyroidism can lead to reduced bone mineral density (BMD and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear. Objective Prospective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause. Design We have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine. Results The study showed significantly (p Conclusion The results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones.

  6. Review of Preclinical and Clinical Studies of Bone Marrow-Derived Cell Therapies for Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Rosado-de-Castro

    2016-01-01

    Full Text Available Stroke is the second leading cause of mortality worldwide, causing millions of deaths annually, and is also a major cause of disability-adjusted life years. Hemorrhagic stroke accounts for approximately 10 to 27% of all cases and has a fatality rate of about 50% in the first 30 days, with limited treatment possibilities. In the past two decades, the therapeutic potential of bone marrow-derived cells (particularly mesenchymal stem cells and mononuclear cells has been intensively investigated in preclinical models of different neurological diseases, including models of intracerebral hemorrhage and subarachnoid hemorrhage. More recently, clinical studies, most of them small, unblinded, and nonrandomized, have suggested that the therapy with bone marrow-derived cells is safe and feasible in patients with ischemic or hemorrhagic stroke. This review discusses the available evidence on the use of bone marrow-derived cells to treat hemorrhagic strokes. Distinctive properties of animal studies are analyzed, including study design, cell dose, administration route, therapeutic time window, and possible mechanisms of action. Furthermore, clinical trials are also reviewed and discussed, with the objective of improving future studies in the field.

  7. An Easy Tool to Predict Survival in Patients Receiving Radiation Therapy for Painful Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff, Paulien G., E-mail: p.g.westhoff@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Graeff, Alexander de [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Monninkhof, Evelyn M. [Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht (Netherlands); Bollen, Laurens; Dijkstra, Sander P. [Department of Orthopedic Surgery, Leiden University Medical Center (Netherlands); Steen-Banasik, Elzbieta M. van der [ARTI Institute for Radiation Oncology Arnhem, Arnhem (Netherlands); Vulpen, Marco van [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Leer, Jan Willem H. [Department of Radiotherapy, University Medical Center Nijmegen, Nijmegen (Netherlands); Marijnen, Corrie A.; Linden, Yvette M. van der [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands)

    2014-11-15

    Purpose: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and patient-reported scores of pain and quality of life, to predict survival in patients with painful bone metastases. Methods and Materials: In the Dutch Bone Metastasis Study, 1157 patients were treated with radiation therapy for painful bone metastases. At randomization, physicians determined the KPS; patients rated general health on a visual analogue scale (VAS-gh), valuation of life on a verbal rating scale (VRS-vl) and pain intensity. To assess the predictive value of the variables, we used multivariate Cox proportional hazard analyses and C-statistics for discriminative value. Of the final model, calibration was assessed. External validation was performed on a dataset of 934 patients who were treated with radiation therapy for vertebral metastases. Results: Patients had mainly breast (39%), prostate (23%), or lung cancer (25%). After a maximum of 142 weeks' follow-up, 74% of patients had died. The best predictive model included sex, primary tumor, visceral metastases, KPS, VAS-gh, and VRS-vl (C-statistic = 0.72, 95% CI = 0.70-0.74). A reduced model, with only KPS and primary tumor, showed comparable discriminative capacity (C-statistic = 0.71, 95% CI = 0.69-0.72). External validation showed a C-statistic of 0.72 (95% CI = 0.70-0.73). Calibration of the derivation and the validation dataset showed underestimation of survival. Conclusion: In predicting survival in patients with painful bone metastases, KPS combined with primary tumor was comparable to a more complex model. Considering the amount of variables in complex models and the additional burden on patients, the simple model is preferred for daily use. In addition, a risk table for survival is

  8. Biomechanical properties: effects of low-level laser therapy and Biosilicate® on tibial bone defects in osteopenic rats.

    Science.gov (United States)

    Fangel, Renan; Bossini, Paulo S; Renno, Ana Cláudia; Granito, Renata N; Wang, Charles C; Nonaka, Keico O; Driusso, Patricia; Parizotto, Nivaldo A; Oishi, Jorge

    2014-12-30

    The aim of this study was to investigate the effects of laser therapy and Biosilicate® on the biomechanical properties of bone callus in osteopenic rats. Fifty female Wistar rats were equally divided into 5 groups (n=10/group): osteopenic rats with intact tibiae (SC); osteopenic rats with unfilled and untreated tibial bone defects (OC); osteopenic rats whose bone defects were treated with Biosilicate® (B); osteopenic rats whose bone defects were treated with 830-nm laser, at 120 J/cm2 (L120) and osteopenic rats whose bone defects were treated with Biosilicate® and 830-nm laser, at 120 J/cm2 (BL120). Ovariectomy (OVX) was used to induce osteopenia. A non-critical bone defect was created on the tibia of the osteopenic animals 8 weeks after OVX. In Biosilicate® groups, bone defects were completely filled with the biomaterial. For the laser therapy, an 830-nm laser, 120 J/cm2 was used. On day 14 postsurgery, rats were euthanized, and tibiae were removed for biomechanical analysis. Maximal load and energy absorption were higher in groups B and BL120, according to the indentation test. Animals submitted to low-level laser therapy (LLLT) did not show any significant biomechanical improvement, but the association between Biosilicate® and LLLT was shown to be efficient to enhance callus biomechanical properties. Conversely, no differences were found between study groups in the bending test. Biosilicate® alone or in association with low level laser therapy improves biomechanical properties of tibial bone callus in osteopenic rats.

  9. Autologous Bone Marrow Mononuclear Cell Therapy for Autism: An Open Label Proof of Concept Study

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2013-01-01

    Full Text Available Cellular therapy is an emerging therapeutic modality with a great potential for the treatment of autism. Recent findings show that the major underlying pathogenetic mechanisms of autism are hypoperfusion and immune alterations in the brain. So conceptually, cellular therapy which facilitates counteractive processes of improving perfusion by angiogenesis and balancing inflammation by immune regulation would exhibit beneficial clinical effects in patients with autism. This is an open label proof of concept study of autologous bone marrow mononuclear cells (BMMNCs intrathecal transplantation in 32 patients with autism followed by multidisciplinary therapies. All patients were followed up for 26 months (mean 12.7. Outcome measures used were ISAA, CGI, and FIM/Wee-FIM scales. Positron Emission Tomography-Computed Tomography (PET-CT scan recorded objective changes. Out of 32 patients, a total of 29 (91% patients improved on total ISAA scores and 20 patients (62% showed decreased severity on CGI-I. The difference between pre- and postscores was statistically significant (P<0.001 on Wilcoxon matched-pairs signed rank test. On CGI-II 96% of patients showed global improvement. The efficacy was measured on CGI-III efficacy index. Few adverse events including seizures in three patients were controlled with medications. The encouraging results of this leading clinical study provide future directions for application of cellular therapy in autism.

  10. Effect of estrogen/gestagen and 24R,25-dihydroxyvitamin D3 therapy on bone formation in postmenopausal women

    International Nuclear Information System (INIS)

    Thomsen, K.; Riis, B.; Christiansen, C.

    1986-01-01

    The effect of two different estrogen/gestagen regimens and 24R,25-(OH)2-cholecalciferol on bone formation was studied in a randomized trial with 144 healthy postmenopausal women. Urinary excretion (UE) of /sup 99m/technetium-diphosphonate and serum alkaline phosphatase (AP) was determined before and then once a year for 2 years of treatment. Both estimates of bone formation showed highly significant decreases (p less than .001) to normal premenopausal levels in women receiving unopposed 17 beta-estradiol or in a sequential combination with progestagen, whereas unchanged high values were found in the groups receiving 24R,25-(OH)2D3 and placebo. The data show that bone turnover increases in early postmenopausal women concomitantly with the loss of bone mass, and that hormonal substitutional therapy normalizes the total skeletal turnover as well as preventing bone loss

  11. Melanin-Covered Nanoparticles for Protection of Bone Marrow During Radiation Therapy of Cancer

    International Nuclear Information System (INIS)

    Schweitzer, Andrew D.; Revskaya, Ekaterina; Chu, Peter; Pazo, Valeria; Friedman, Matthew; Nosanchuk, Joshua D.; Cahill, Sean; Frases, Susana; Casadevall, Arturo; Dadachova, Ekaterina

    2010-01-01

    Purpose: Protection of bone marrow against radiotoxicity during radioimmunotherapy and in some cases external beam radiation therapy such as hemi-body irradiation would permit administration of significantly higher doses to tumors, resulting in increased efficacy and safety of treatment. Melanin, a naturally occurring pigment, possesses radioprotective properties. We hypothesized that melanin, which is insoluble, could be delivered to the bone marrow by intravenously administrated melanin-covered nanoparticles (MNs) because of the human body's 'self-sieving' ability, protecting it against ionizing radiation. Methods and Materials: The synthesis of MNs was performed via enzymatic polymerization of 3,4-dihydroxyphenylalanine and/or 5-S-cysteinyl-3,4-dihydroxyphenylalanine on the surface of 20-nm plain silica nanoparticles. The biodistribution of radiolabeled MNs in mice was done at 3 and 24 h. Healthy CD-1 mice (Charles River Laboratories International, Inc., Wilmington, MA) or melanoma tumor-bearing nude mice were given MNs intravenously, 50 mg/kg of body weight, 3 h before either whole-body exposure to 125 cGy or treatment with 1 mCi of 188 Re-labeled 6D2 melanin-binding antibody. Results: Polymerization of melanin precursors on the surface of silica nanoparticles resulted in formation of a 15-nm-thick melanin layer as confirmed by light scattering, transmission electron microscopy, and immunofluorescence. The biodistribution after intravenous administration showed than MN uptake in bone marrow was 0.3% and 0.2% of injected dose per gram at 3 and 24 h, respectively, whereas pre-injection with pluronic acid increased the uptake to 6% and 3% of injected dose per gram, respectively. Systemic MN administration reduced hematologic toxicity in mice treated with external radiation or radioimmunotherapy, whereas no tumor protection by MNs was observed. Conclusions: MNs or similar structures provide a novel approach to protection of bone marrow from ionizing radiation based

  12. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Peng Xue

    2013-01-01

    Full Text Available Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochrane Library were undertaken to identify studies in humans of the association between growth hormone treatment and bone mineral density in growth hormone deficient adults. Random effects model was used for this meta-analysis. Results. A total of 20 studies (including one outlier study with 936 subjects were included in our research. We detected significant overall association of growth hormone treatment with increased bone mineral density of spine, femoral neck, and total body, but some results of subgroup analyses were not consistent with the overall analyses. Conclusions. Our meta-analysis suggested that growth hormone replacement therapy could have beneficial influence on bone mineral density in growth hormone deficient adults, but, in some subject populations, the influence was not evident.

  13. Anti-leukemic therapies induce cytogenetic changes of human bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Yeh, Su-Peng; Lo, Wen-Jyi; Lin, Chiao-Lin; Liao, Yu-Min; Lin, Chen-Yuan; Bai, Li-Yuan; Liang, Ji-An; Chiu, Chang-Fang

    2012-02-01

    Both bone marrow hematopoietic cells (BM-HCs) and mesenchymal stem cells (BM-MSCs) may have cytogenetic aberrations in leukemic patients, and anti-leukemic therapy may induce cytogenetic remission of BM-HCs. The impact of anti-leukemic therapy on BM-MSCs remains unknown. Cytogenetic studies of BM-MSCs from 15 leukemic patients with documented cytogenetic abnormalities of BM-HCs were investigated. To see the influence of anti-leukemic therapy on BM-MSCs, cytogenetic studies were carried out in seven of them after the completion of anti-leukemic therapy, including anthracycline/Ara-C-based chemotherapy in two patients, high-dose busulfan/cyclophosphamide-based allogeneic transplantation in two patients, and total body irradiation (TBI)-based allogeneic transplantation in three patients. To simulate the effect of TBI in vitro, three BM-MSCs from one leukemic patient and two normal adults were irradiated using the same dosage and dosing schedule of TBI and cytogenetics were re-examined after irradiation. At the diagnosis of leukemia, two BM-MSCs had cytogenetic aberration, which were completely different to their BM-HCs counterpart. After the completion of anti-leukemic therapy, cytogenetic aberration was no longer detectable in one patient. Unexpectedly, BM-MSCs from three patients receiving TBI-based allogeneic transplantation acquired new, clonal cytogenetic abnormalities after transplantation. Similarly, complex cytogenetic abnormalities were found in all the three BM-MSCs exposed to in vitro irradiation. In conclusion, anti-leukemic treatments induce not only "cytogenetic remission" but also new cytogenetic abnormalities of BM-MSCs. TBI especially exerts detrimental effect on the chromosomal integrity of BM-MSCs and highlights the equal importance of investigating long-term adverse effect of anti-leukemic therapy on BM-MSCs as opposed to beneficial effect on BM-HCs.

  14. Growth on poly(L-lactic acid) porous scaffold preserves CD73 and CD90 immunophenotype markers of rat bone marrow mesenchymal stromal cells.

    Science.gov (United States)

    Zamparelli, Alessandra; Zini, Nicoletta; Cattini, Luca; Spaletta, Giulia; Dallatana, Davide; Bassi, Elena; Barbaro, Fulvio; Iafisco, Michele; Mosca, Salvatore; Parrilli, Annapaola; Fini, Milena; Giardino, Roberto; Sandri, Monica; Sprio, Simone; Tampieri, Anna; Maraldi, Nadir M; Toni, Roberto

    2014-10-01

    Few data are available on the effect of biomaterials on surface antigens of mammalian bone marrow-derived, adult mesenchymal stromal cells (MSCs). Since poly(L-lactic acid) or PLLA is largely used in tissue engineering of human bones, and we are developing a reverse engineering program to prototype with biomaterials the vascular architecture of bones for their bioartificial reconstruction, both in humans and animal models, we have studied the effect of porous, flat and smooth PLLA scaffolds on the immunophenotype of in vitro grown, rat MSCs in the absence of any coating, co-polymeric enrichment, and differentiation stimuli. Similar to controls on plastic, we show that our PLLA scaffold does not modify the distribution of some surface markers in rat MSCs. In particular, the maintained expression of CD73 and CD90 on two different subpopulations (small and large cells) is consistent with their adhesion to the PLLA scaffold through specialized appendages, and to their prominent content in actin. In addition, our PLLA scaffold favours retention of the intermediate filament desmin, believed a putative marker of undifferentiated state. Finally, it preserves all rat MSCs morphotypes, and allows for their survival, adhesion to the substrate, and replication. Remarkably, a subpopulation of rat MSCs grown on our PLLA scaffold exhibited formation of membrane protrusions of uncertain significance, although in a size range and morphology compatible with either motility blebs or shedding vesicles. In summary, our PLLA scaffold has no detrimental effect on a number of features of rat MSCs, primarily the expression of CD73 and CD90.

  15. Clinical observation on strontium-89-chloride therapy in elder patients with prostate cancer for palliation of pain from bone metastases

    International Nuclear Information System (INIS)

    Chen Weimin; Lin Tiansheng; Wang Shen; Chen Tanying

    2006-01-01

    Objective: To estimate clinical curative efficacy and adverse reaction of 89 Sr-chloride therapy for palliation of pain from bone metastases in the older patients with prostate cancer. Methods: 48 cases of older patients with metastatic prostate cancer with bone pain were studied after androgen deprivation therapy, 89 Sr- chloride were administrated iv for the palliative treatment of metastatic bone pain. The curative effects in patients were investigated, including palliation of pain, change of metastatic focus, the tumor sign of PSA, and the adverse reaction. Results: After 89 Sr-chloride therapy, the total palliation rate was 89.6%, inefficiency rate was 10.4%, while metastatic focus and PSA decreased to some extent. No severe adverse reaction occurred. Conclusions: It is shown that the curative efficacy of acesodyne is evident after 89 Sr-chloride therapy in older patients suffering from bone metastase with prostate cancer. It is an effective therapeutic method for the palliation of pain from bone metastases especially to the older patients with multiple metastatases. (authors)

  16. Prostate Hypofractionated Radiation Therapy: Injection of Hyaluronic Acid to Better Preserve The Rectal Wall

    International Nuclear Information System (INIS)

    Chapet, Olivier; Udrescu, Corina; Devonec, Marian; Tanguy, Ronan; Sotton, Marie-Pierre; Enachescu, Ciprian; Colombel, Marc; Azria, David; Jalade, Patrice; Ruffion, Alain

    2013-01-01

    Purpose: The aim of this study was to evaluate the contribution of an injection of hyaluronic acid (HA) between the rectum and the prostate for reducing the dose to the rectal wall in a hypofractionated irradiation for prostate cancer. Methods and Materials: In a phase 2 study, 10 cc of HA was injected between the rectum and prostate. For 16 patients, the same intensity modulated radiation therapy plan (62 Gy in 20 fractions) was optimized on 2 computed tomography scans: CT1 (before injection) and CT2 (after injection). Rectal parameters were compared: dose to 2.5 cc (D2.5), 5 cc (D5), 10 cc (D10), 15 cc (D15), and 20 cc (D20) of rectal wall and volume of rectum covered by the 90% isodose line (V90), 80% (V80), 70% (V70), 60% (V60), and 50% (V50). Results: The mean V90, V80, V70, V60, and V50 values were reduced by 73.8% (P<.0001), 55.7% (P=.0003), 43.0% (P=.007), 34% (P=.002), and 25% (P=.036), respectively. The average values of D2.5, D5, D10, D15, and D20 were reduced by 8.5 Gy (P<.0001), 12.3 Gy (P<.0001), 8.4 Gy (P=.005), 3.7 Gy (P=.026), and 1.2 Gy (P=.25), respectively. Conclusions: The injection of HA significantly limited radiation doses to the rectal wall

  17. Prostate Hypofractionated Radiation Therapy: Injection of Hyaluronic Acid to Better Preserve The Rectal Wall

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Udrescu, Corina [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Devonec, Marian [Department of Urology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Tanguy, Ronan [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Sotton, Marie-Pierre [Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Enachescu, Ciprian [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Colombel, Marc [Department of Urology, Hopital Edouard Herriot, Lyon (France); Azria, David [Department of Radiation Oncology, Centre Val d' Aurelle, Montpellier (France); Jalade, Patrice [Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Ruffion, Alain [Department of Urology, Centre Hospitalier Lyon Sud, Pierre Benite (France)

    2013-05-01

    Purpose: The aim of this study was to evaluate the contribution of an injection of hyaluronic acid (HA) between the rectum and the prostate for reducing the dose to the rectal wall in a hypofractionated irradiation for prostate cancer. Methods and Materials: In a phase 2 study, 10 cc of HA was injected between the rectum and prostate. For 16 patients, the same intensity modulated radiation therapy plan (62 Gy in 20 fractions) was optimized on 2 computed tomography scans: CT1 (before injection) and CT2 (after injection). Rectal parameters were compared: dose to 2.5 cc (D2.5), 5 cc (D5), 10 cc (D10), 15 cc (D15), and 20 cc (D20) of rectal wall and volume of rectum covered by the 90% isodose line (V90), 80% (V80), 70% (V70), 60% (V60), and 50% (V50). Results: The mean V90, V80, V70, V60, and V50 values were reduced by 73.8% (P<.0001), 55.7% (P=.0003), 43.0% (P=.007), 34% (P=.002), and 25% (P=.036), respectively. The average values of D2.5, D5, D10, D15, and D20 were reduced by 8.5 Gy (P<.0001), 12.3 Gy (P<.0001), 8.4 Gy (P=.005), 3.7 Gy (P=.026), and 1.2 Gy (P=.25), respectively. Conclusions: The injection of HA significantly limited radiation doses to the rectal wall.

  18. Early Clinical Outcomes Demonstrate Preserved Cognitive Function in Children With Average-Risk Medulloblastoma When Treated With Hyperfractionated Radiation Therapy

    International Nuclear Information System (INIS)

    Gupta, Tejpal; Jalali, Rakesh; Goswami, Savita; Nair, Vimoj; Moiyadi, Aliasgar; Epari, Sridhar; Sarin, Rajiv

    2012-01-01

    Purpose: To report on acute toxicity, longitudinal cognitive function, and early clinical outcomes in children with average-risk medulloblastoma. Methods and Materials: Twenty children ≥5 years of age classified as having average-risk medulloblastoma were accrued on a prospective protocol of hyperfractionated radiation therapy (HFRT) alone. Radiotherapy was delivered with two daily fractions (1 Gy/fraction, 6 to 8 hours apart, 5 days/week), initially to the neuraxis (36 Gy/36 fractions), followed by conformal tumor bed boost (32 Gy/32 fractions) for a total tumor bed dose of 68 Gy/68 fractions over 6 to 7 weeks. Cognitive function was prospectively assessed longitudinally (pretreatment and at specified posttreatment follow-up visits) with the Wechsler Intelligence Scale for Children to give verbal quotient, performance quotient, and full-scale intelligence quotient (FSIQ). Results: The median age of the study cohort was 8 years (range, 5–14 years), representing a slightly older cohort. Acute hematologic toxicity was mild and self-limiting. Eight (40%) children had subnormal intelligence (FSIQ <85), including 3 (15%) with mild mental retardation (FSIQ 56–70) even before radiotherapy. Cognitive functioning for all tested domains was preserved in children evaluable at 3 months, 1 year, and 2 years after completion of HFRT, with no significant decline over time. Age at diagnosis or baseline FSIQ did not have a significant impact on longitudinal cognitive function. At a median follow-up time of 33 months (range, 16–58 months), 3 patients had died (2 of relapse and 1 of accidental burns), resulting in 3-year relapse-free survival and overall survival of 83.5% and 83.2%, respectively. Conclusion: HFRT without upfront chemotherapy has an acceptable acute toxicity profile, without an unduly increased risk of relapse, with preserved cognitive functioning in children with average-risk medulloblastoma.

  19. Early Clinical Outcomes Demonstrate Preserved Cognitive Function in Children With Average-Risk Medulloblastoma When Treated With Hyperfractionated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Tejpal, E-mail: tejpalgupta@rediffmail.com [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Jalali, Rakesh [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Goswami, Savita [Department of Clinical Psychology and Psychiatry Unit, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Nair, Vimoj [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Moiyadi, Aliasgar [Division of Neuro-Surgery, Department of Surgical Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Epari, Sridhar [Department of Pathology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Sarin, Rajiv [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India)

    2012-08-01

    Purpose: To report on acute toxicity, longitudinal cognitive function, and early clinical outcomes in children with average-risk medulloblastoma. Methods and Materials: Twenty children {>=}5 years of age classified as having average-risk medulloblastoma were accrued on a prospective protocol of hyperfractionated radiation therapy (HFRT) alone. Radiotherapy was delivered with two daily fractions (1 Gy/fraction, 6 to 8 hours apart, 5 days/week), initially to the neuraxis (36 Gy/36 fractions), followed by conformal tumor bed boost (32 Gy/32 fractions) for a total tumor bed dose of 68 Gy/68 fractions over 6 to 7 weeks. Cognitive function was prospectively assessed longitudinally (pretreatment and at specified posttreatment follow-up visits) with the Wechsler Intelligence Scale for Children to give verbal quotient, performance quotient, and full-scale intelligence quotient (FSIQ). Results: The median age of the study cohort was 8 years (range, 5-14 years), representing a slightly older cohort. Acute hematologic toxicity was mild and self-limiting. Eight (40%) children had subnormal intelligence (FSIQ <85), including 3 (15%) with mild mental retardation (FSIQ 56-70) even before radiotherapy. Cognitive functioning for all tested domains was preserved in children evaluable at 3 months, 1 year, and 2 years after completion of HFRT, with no significant decline over time. Age at diagnosis or baseline FSIQ did not have a significant impact on longitudinal cognitive function. At a median follow-up time of 33 months (range, 16-58 months), 3 patients had died (2 of relapse and 1 of accidental burns), resulting in 3-year relapse-free survival and overall survival of 83.5% and 83.2%, respectively. Conclusion: HFRT without upfront chemotherapy has an acceptable acute toxicity profile, without an unduly increased risk of relapse, with preserved cognitive functioning in children with average-risk medulloblastoma.

  20. Removing the cells from adult bone marrow derived stem cell therapy does not eliminate cardioprotection.

    Science.gov (United States)

    Yasin, Mohammed

    2013-04-01

    The debate as to whether adult stem cell therapy is regenerative or not continues. The non-regenerative benefits of adult bone marrow-derived stem cell therapy were investigated by testing whether the supernatant derived from unfractionated bone marrow mononuclear cells might be cardioprotective in an animal model of myocardial ischaemia-reperfusion injury. Regional myocardial reperfusion injury was acquired by 25 min reversible left anterior descending coronary artery (LAD) occlusion followed by 2 h reperfusion, in anaesthetized Wistar male rats. Unfractionated bone marrow mononuclear cells (BMMNC) isolated from sibling Wistar male rat whole bone marrow were phenotyped by fluorescence activated cell sorting flowcytometry for the haematopoietic stem cell surface markers c-kit, CD34, CD45 and CD133. Animals subjected to regional myocardial reperfusion injury received either 10 million BMMNC or BMMNC supernatant (BMS); both were collected in 0.5 ml phosphate-buffered saline and delivered by intravenous bolus at the onset of reperfusion. The left ventricular region distal to the LAD occlusion point was excised for measurement of myocardial infarct size and proteomic analysis, which was used to identify whether there were any differences in myocardial proteins associated with intravenous injection of either BMMNC or BMS. BMMNC were phenotyped to be c-kit(+) (7 ± 1%), CD34(+) (7 ± 1%), CD45(+) (54 ± 6%), CD133(+) (15 ± 1%). The supernatant reduced myocardial infarct size (BMS 34 ± 2%, n = 15 vs control 57 ± 2%, n = 7, P < 0.0001), which was comparable to the reduction in infarct size afforded by the injection of cells (BMMNC 33 ± 3% vs control 57 ± 2%, n = 10, P < 0.0001). Proteomics of hearts treated with either BMS or BMMNC demonstrated higher expression of (i) anti-apoptotic signal transduction protein: 14-3-3-epsilon (1.5-fold); (ii) anti-oxidants: peroxiredoxin-6 (2.1-fold); (iii) heat shock proteins: alpha B-crystallin (1.7-fold), heat shock protein 72 (2

  1. Influence of estrogen deficiency and tibolone therapy on trabecular and cortical bone evaluated by computed radiography system in rats

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Ana Carolina Bergmann de; Henriques, Helene Nara [Postgraduate Program in Pathology, Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil); Fernandes, Gustavo Vieira Oliveira [Postgraduate Program in Medical Sciences, Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil); Lima, Inaya; Oliveira, Davi Ferreira de; Lopes, Ricardo Tadeu [Nuclear Engineering Program, Federal University of Rio de Janeiro (UFRJ), RJ (Brazil); Pantaleao, Jose Augusto Soares [Maternal and Child Department, Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil); Granjeiro, Jose Mauro [Department of Cellular and Molecular Biology, Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil); Silva, Maria Angelica Guzman [Department of Pathology, Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil)

    2012-03-15

    Purpose: To verify the effects of tibolone administration on trabecular and cortical bone of ovariectomized female rats by computed radiography system (CRS). Methods: The experiment was performed on two groups of rats previously ovariectomized, one received tibolone (OVX+T) while the other did not (OVX), those groups were compared to a control group (C) not ovariectomized. Tibolone administration (1 mg/day) began thirty days after the ovariectomy and the treatment remained for five months. At last, the animals were euthanized and femurs and tibias collected. Computed radiographs of the bones were obtained and the digital images were used to determine the bone optical density and cortical thickness on every group. All results were statistically evaluated with significance set at P<0.05%. Results: Tibolone administration was shown to be beneficial only in the densitometric analysis of the femoral head, performing higher optical density compared to OVX. No difference was found in cortical bone thickness. Conclusion: Ovariectomy caused bone loss in the analyzed regions and tibolone administered in high doses over a long period showed not to be fully beneficial, but preserved bone mass in the femoral head. (author)

  2. Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Noticewala, Sonal S.; Li, Nan; Williamson, Casey W. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Hoh, Carl K. [Division of Nuclear Medicine, Department of Radiology, University of California San Diego, La Jolla, California (United States); Shen, Hanjie [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McHale, Michael T.; Saenz, Cheryl C. [Division of Gynecologic Oncology, Department of Reproductive Medicine, University of California San Diego, La Jolla, California (United States); Einck, John [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Plaxe, Steven [Division of Gynecologic Oncology, Department of Reproductive Medicine, University of California San Diego, La Jolla, California (United States); Vaida, Florin [Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California (United States); Yashar, Catheryn M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2017-03-15

    Purpose: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT). Methods and Materials: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m{sup 2}) and 14 were treated with cisplatin (40 mg/m{sup 2}) plus gemcitabine (50-125 mg/m{sup 2}) (C/G). Patients underwent {sup 18}F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and 1.5 to 6.0 months after treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV of the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extrapelvic versus pelvic ABM percentage from baseline to after treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extrapelvic BM using a 2-sided paired t test. Results: We observed a significant increase in the overall extrapelvic compensatory response after CRT (0.381; 95% confidence interval [CI]: 0.312, 0.449) and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared with C/G (P=.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (P<.001) and in those receiving C/G (P<.001), whereas extrapelvic ABM percentage was increased in patients receiving cisplatin (P<.001) and C/G (P<.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (P<.001) and C/G (P<.001). The mean SUV appeared lower in extrapelvic structures after CRT in patients treated with C/G (P=.076) but not with cisplatin (P=.942). We also observed that older age and more intense chemotherapy

  3. Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Noticewala, Sonal S.; Li, Nan; Williamson, Casey W.; Hoh, Carl K.; Shen, Hanjie; McHale, Michael T.; Saenz, Cheryl C.; Einck, John; Plaxe, Steven; Vaida, Florin; Yashar, Catheryn M.; Mell, Loren K.

    2017-01-01

    Purpose: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT). Methods and Materials: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m"2) and 14 were treated with cisplatin (40 mg/m"2) plus gemcitabine (50-125 mg/m"2) (C/G). Patients underwent "1"8F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and 1.5 to 6.0 months after treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV of the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extrapelvic versus pelvic ABM percentage from baseline to after treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extrapelvic BM using a 2-sided paired t test. Results: We observed a significant increase in the overall extrapelvic compensatory response after CRT (0.381; 95% confidence interval [CI]: 0.312, 0.449) and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared with C/G (P=.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (P<.001) and in those receiving C/G (P<.001), whereas extrapelvic ABM percentage was increased in patients receiving cisplatin (P<.001) and C/G (P<.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (P<.001) and C/G (P<.001). The mean SUV appeared lower in extrapelvic structures after CRT in patients treated with C/G (P=.076) but not with cisplatin (P=.942). We also observed that older age and more intense chemotherapy regimens were

  4. Risk factors for bone loss with prostate cancer in Korean men not receiving androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Sun-Ouck Kim

    2009-04-01

    Full Text Available PURPOSE: Preexisting bone loss in men with prostate cancer is an important issue due to the accelerated bone loss during androgen deprivation therapy (ADT. In addition, a high prostate-specific antigen (PSA level has been reported to be related to bone metabolism. This study assessed the factors associated with osteoporosis in Korean men with non-metastatic prostate cancer before undergoing ADT. MATERIAL AND METHODS: The study enrolled patients admitted for a prostate biopsy because of a high PSA or palpable nodule on a digital rectal examination. We divided the patients (n = 172 according to the results of the biopsy: group I, non-metastatic prostate cancer (n = 42 and group II, benign prostatic hypertrophy (BPH; n = 130. The lumbar bone mineral density (BMD was evaluated using quantitative computed tomography. The demographic, health status, lifestyle, body mass index (BMI, serum testosterone concentration, and disease variables in prostate cancer (Gleason score, clinical stage, and PSA were analyzed prospectively to determine their effect on the BMD. RESULTS: The estimated mean T-score was higher in group I than in group II (-1.96 ± 3.35 vs. -2.66 ± 3.20, but without statistic significance (p = 0.235. The significant factors correlated with BMD in group I were a high serum PSA (ß = -0.346, p = 0.010 and low BMI (ß = 0.345, p = 0.014 in the multiple linear regression model. Also old age (r = -0.481, p = 0.001, a high serum PSA (r = -0.571, p < 0.001, low BMI (r = 0.598, p < 0.001, and a high Gleason’s score (r = -0.319, p = 0.040 were the factors related to BMD in the correlation. The significant factors correlated with BMD in group II were old age (ß = -0.324, p = 0.001 and BMI (ß = 0.143, p = 0.014 in the multiple linear regression model. CONCLUSIONS: The risk factors for osteoporosis in men with prostate cancer include a low BMI, and elevated serum PSA. Monitoring BMD from the outset of ADT is a logical first step in the clinical

  5. Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links

    Directory of Open Access Journals (Sweden)

    Dolores Perovano Pardini

    2000-01-01

    Full Text Available CONTEXT: The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. OBJECTIVE: To study the effect of hormone replacement therapy (HRT on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN: Cohort correlational study. SETTING: Academic referral center. SAMPLE: 53 post-menopausal women, aged 48-58 years. MAIN MEASUREMENTS: Urinary pyr and d-pyr were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion measured before treatment and after 1, 2, 4 and 12 months. Bone mineral density (BMD was measured by dual energy X-ray absorptiometry (DEXA before treatment and after 12 months of HRT. RESULTS: The BMD after HRT was about 4.7% (P < 0.0004; 2% (P < 0.002; and 3% (P < 0.01 higher than the basal values in lumbar spine, neck and trochanter respectively. There were no significant correlations between pyridinium cross-links and age, weight, menopause duration and BMD. The decrease in pyr and d-pyr was progressive after HRT, reaching 28.9% (P < 0.0002, and 42% (P < 0.0002 respectively after 1 year. CONCLUSIONS: Urinary pyridinoline and deoxypyridinoline excretion decreases early in hormone replacement therapy, reflecting a decrease in the bone resorption rate, and no correlation was observed with the bone mass evaluated by densitometry.

  6. Terapia hormonal y calidad del hueso Hormone therapy and bone quality

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available La osteoporosis se reconoce como uno de los problemas de salud de la población femenina posmenopáusica, y la terapia hormonal de reemplazo (THR como una de las medidas terapéuticas efectivas para evitar la fractura. Nos propusimos mostrar la experiencia acumulada en relación con el efecto de la terapia hormonal de reemplazo sobre la calidad del hueso. En un estudio retrospectivo realizado en 42 mujeres con edades entre 40 y 59 años que asistieron a la Clínica de Climaterio y Osteoporosis y a la consulta multidisciplinaria de climaterio del Hospital Ginecoobstétrico “Ramón González Coro” entre enero de 1997 y diciembre del año 2003, se determinó la calidad ósea mediante absorciometría dual de rayos X en región lumbar (L2-L4 o por ultrasonido del calcáneo (USCAL y recibieron tratamiento continuado con terapia estrogénica (E o con estrógenos progestagenos (EP durante no menos de un año (n = 30. Las mujeres que no pudieron recibir THR fueron agrupadas y evaluadas como grupo control (n =12. Durante el tiempo de observación promedio de 2 años, las mujeres que recibieron THR mejoraron su calidad ósea en el 16,8 %, mientras que las del grupo control empeoraron en el 8 % de los casos. Estos resultados iniciales, aunque son modestos, muestran la utilidad de la THR para mejorar la calidad del hueso y la necesidad de continuar estudios que permitan definir en nuestro medio la persistencia de la mejoría ósea, así como la magnitud de la osteoporosis posmenopáusica.Osteoporosis is recognized as one of the health problems of the female postmenopausic population and the replacement hormone therapy (RHT as one of the effective therapeutical measures to prevent fracture. We proposed ourselves to show the experience accumulated in relation to the effect of the replacement hormone therapy on the bone quality. In a retrospective study conducted among 42 women aged 30-59 that attended the Climacteric and Osteoporosis Clinic and the

  7. Bone marrow derived stem cell therapy for type 2 diabetes mellitus.

    Science.gov (United States)

    Wehbe, Tarek; Chahine, Nassim Abi; Sissi, Salam; Abou-Joaude, Isabelle; Chalhoub, Louis

    2016-01-01

    In this study, 6 patients with type 2 diabetes (T2D) underwent autologous bone marrow mononuclear stem cell (BM-MNSC) infusion into the celiac and superior mesenteric arteries without pretreatment with any myeloablative or immune-suppressive therapy. Five of 6 (83%) showed normalization of their fasting glucose and the glycosylated hemoglobin (HbA1C) with significant reduction of their medication requirements. The HbA1C dropped on average 2.2 points. The three patients with diabetic complications showed improvement or stabilization and most patients reported improved energy and stamina. The durations of response varied between 6 months and 2 years. No patients had any significant adverse effects.

  8. Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology.

    Science.gov (United States)

    Gómez-Barrena, Enrique; Rosset, Philippe; Müller, Ingo; Giordano, Rosaria; Bunu, Carmen; Layrolle, Pierre; Konttinen, Yrjö T; Luyten, Frank P

    2011-06-01

    Regenerative medicine seeks to repair or replace damaged tissues or organs, with the goal to fully restore structure and function without the formation of scar tissue. Cell based therapies are promising new therapeutic approaches in regenerative medicine. By using mesenchymal stem cells, good results have been reported for bone engineering in a number of clinical studies, most of them investigator initiated trials with limited scope with respect to controls and outcome. With the implementation of a new regulatory framework for advanced therapeutic medicinal products, the stage is set to improve both the characterization of the cells and combination products, and pave the way for improved controlled and well-designed clinical trials. The incorporation of more personalized medicine approaches, including the use of biomarkers to identify the proper patients and the responders to treatment, will be contributing to progress in the field. Both translational and clinical research will move the boundaries in the field of regenerative medicine, and a coordinated effort will provide the clinical breakthroughs, particularly in the many applications of bone engineering. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  9. Radiation therapy for painful bone metastases. Aiming at optimal treatment schedules

    International Nuclear Information System (INIS)

    Murakami, Ryuji; Saito, Ryuichi; Miyazaki, Toshiyuki; Takahashi, Mutsumasa

    2001-01-01

    The purpose of this study is to evaluate the pain relief obtained by radiation therapy for painful bone metastases, with a special regard to general condition. Between June 1998 and May 2000, 54 patients with 86 painful bone metastases were treated with radiation therapy whose effects could be evaluated for a minimum period of 6 months or until death. Treatment schedules were 3 Gy/fraction/day (30-36 Gy/10-12 fractions) in usual cases (61 lesions), 4-8 Gy/fraction/day (8-20 Gy/1-5 fractions) in patients with a poor general condition (9 lesions), and 2 Gy/fraction/day (40-50 Gy/20-25 fractions) in lesions with a large radiation field (16 lesions). Complete pain relief without medication (CR) was achieved in 40 lesions (47%). Significant predictors for CR were primary site (p=0.0003), performance status (p=0.0060), pain score (p=00190), narcotic score (p<0.0001), and prognosis (p<0.0001), but no difference was found in CR among treatment schedules. No evidence of severe radiation-induced complication was seen. General condition (performance status and prognosis) has an influence on pain relief. Compared with the daily 2 Gy protocol, the daily 3 Gy protocol has the advantage of shorter treatment time. The treatment schedule should be assessed in patients with a large radiation field and/or poor general condition. Especially for the patients with poor general condition, combined pain medication should be considered. (author)

  10. Cytogenetic evidence of metastatic myxoid liposarcoma and therapy-related myelodysplastic syndrome in a bone marrow biopsy.

    Science.gov (United States)

    Rossi, Sabrina; Canal, Fabio; Licci, Stefano; Zanatta, Lucia; Laurino, Licia; Gottardi, Michele; Gherlinzoni, Filippo; Dei Tos, Angelo Paolo

    2009-07-01

    Myxoid liposarcoma exhibits a peculiar clinical behavior, with a tendency to spread to serosal membranes, distant soft tissues, and bones, even in the absence of lung metastases. Therapy-related hematological neoplasms are well-known side effects of cytotoxic chemotherapy. We describe an exceptional case of metastatic myxoid liposarcoma of the spine associated with therapy-related refractory anemia with excess of blasts in a 37-year-old woman who underwent multi-agent chemotherapy for a myxoid liposarcoma of the left thigh. Microscopic examination of the bone marrow biopsy revealed dysplastic features, with abnormal localization of immature precursors and micromegakaryocytes, and islands of undifferentiated oval small/medium-size cells, suggestive of acute myeloid leukemia arising in the setting of a myelodysplastic syndrome. Immunohistochemistry was not discriminant. Cytogenetic analyses of bone marrow aspirate disclosed the presence of 2 different rearrangements, subsequently confirmed by fluorescent in situ hybridization and was crucial in making the correct diagnosis.

  11. Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease

    DEFF Research Database (Denmark)

    Doyon, Anke; Fischer, Dagmar Christiane; Bayazit, Aysun Karabay

    2015-01-01

    Objectives: The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric...... turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity......./min/ 1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results: Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum...

  12. Treatment of Atypical Ulnar Fractures Associated with Long-Term Bisphosphonate Therapy for Osteoporosis: Autogenous Bone Graft with Internal Fixation

    Directory of Open Access Journals (Sweden)

    Yohei Shimada

    2017-01-01

    Full Text Available Long-term bisphosphonate use has been suggested to result in decreased bone remodelling and an increased risk of atypical fractures. Fractures of this nature commonly occur in the femur, and relatively few reports exist to show that they occur in other bones. Among eight previous reports of atypical ulnar fractures associated with bisphosphonate use, one report described nonunion in a patient who was treated with cast immobilization and another described ulna nonunion in one of three patients, all of whom were treated surgically with a locking plate. The remaining two surgical patients achieved bone union uneventfully following resection of the osteosclerotic lesion and iliac bone grafting before rigid fixation. We hypothesized that the discontinuation of bisphosphonate therapy, the use of teriparatide treatment, and low-intensity pulsed ultrasound (LIPUS might have been associated with fracture healing.

  13. Summary of major radiation fractionation and chemotherapy trials for organ preservation therapy in locally advanced head and neck squamous cell carcinoma.

    Science.gov (United States)

    Parsons, James T; Greene, Bruce D

    2015-01-01

    To review radiation fractionation and chemotherapy trials for patients undergoing organ preservation therapy for locally advanced head and neck squamous cell carcinoma. Radiation therapy fractionation and chemotherapy trial results as well as historical evidence are systematically reviewed. Trial results, which involve nearly 30,000 patients, have been interpreted, compared, and presented in a structured manner to demonstrate the changing approaches in treatment over the years from the 1960s to the present. The review includes data from the split-course radiation therapy era, meta-analyses of chemotherapy and radiation therapy fractionation trials, cetuximab trials, "triple-drug trials," and modern trials of induction chemotherapy followed by concomitant chemotherapy and radiation therapy. This summary will be useful to clinicians making treatment decisions today and to investigators designing trials in the future. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  14. Sheep model for osteoporosis: The effects of peripheral hormone therapy on centrally induced systemic bone loss in an osteoporotic sheep model.

    Science.gov (United States)

    Oheim, Ralf; Simon, Maciej J K; Steiner, Malte; Vettorazzi, Eik; Barvencik, Florian; Ignatius, Anita; Amling, Michael; Clarke, Iain J; Pogoda, Pia; Beil, F Timo

    2017-04-01

    Hypothalamic-pituitary disconnection (HPD) leads to low bone turnover followed by bone loss and reduced biomechanical properties in sheep. To investigate the role of peripheral hormones in this centrally induced systemic bone loss model, we planned a hormone replacement experiment. Therefore, estrogen (OHE), thyroxin (OHT) or a combination of both (OHTE) was substituted in ovariectomized HPD sheep, as both hormones are decreased in HPD sheep and are known to have a significant but yet not fully understood impact on bone metabolism. Bone turnover and structural parameters were analyzed in comparison to different control groups - untreated sheep (C), ovariectomized (O) and ovariectomized+HPD sheep (OH). We performed histomorphometric and HR-pQCT analyses nine months after the HPD procedure, as well as biomechanical testing of all ewes studied. In HPD sheep (OH) the low bone turnover led to a significant bone loss. Treatment with thyroxin alone (OHT) mainly increased bone resorption, leading to a further reduction in bone volume. In contrast, the treatment with estrogen alone (OHE) and the combined treatment with estrogen and thyroxin (OHTE) prevented HPD-induced bone loss completely. In conclusion, peripheral hormone substitution was able to prevent HPD-induced low-turnover osteoporosis in sheep. But only the treatment with estrogen alone or in combination with thyroxin was able to completely preserve bone mass and structure. These findings demonstrate the importance of peripheral hormones for a balanced bone remodeling and a physiological bone turnover. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Bone strength and management of postmenopausal fracture risk with antiresorptive therapies: considerations for women’s health practice

    Directory of Open Access Journals (Sweden)

    Cheung AM

    2016-09-01

    Full Text Available Angela M Cheung,1–3 Heather Frame,4 Michael Ho,5 Erin S Mackinnon,6 Jacques P Brown7 1Department of Medicine, University of Toronto, 2Centre of Excellence in Skeletal Health Assessment, Joint Department of Medical Imaging, University Health Network (UHN, 3Mount Sinai Hospital, University of Toronto, Toronto, ON, 4Assiniboine Clinic, Winnipeg, MB, 5University Health Network, Toronto, 6Amgen Canada, Inc, Mississauga, ON, 7Rheumatology Division, CHU de Québec Research Centre, Laval University, Quebec City, QC, Canada Abstract: Bone strength – and, hence, fracture risk – reflects the structural and material properties of the skeleton, which changes with bone turnover during aging and following effective pharmacotherapy. A variety of powerful new techniques (quantitative computed tomography, as well as peripheral quantitative computed tomography and high-resolution peripheral quantitative computed tomography provide precise images of bone structure and can be used to model the response of specific bones to different types of mechanical load. This review explores the various components of bone strength and the clinical significance of measures, such as bone mineral density, bone turnover markers, and modern imaging data, with regard to fracture risk in women with postmenopausal osteoporosis, before and after initiating antiresorptive therapy. These imaging and related techniques offer an ever-clearer picture of the changes in bone structure and bone mineral metabolism during normal aging and in osteoporosis, as well as in response to treatment. However, because the newer techniques are not yet available in routine practice, validated tools for absolute fracture risk assessment remain essential for clinical decision making. These tools, which are tailored to patient risk data in individual countries, are based on bone mineral density and other readily available clinical data. In addition, bone turnover marker measurements can be useful in

  16. SU-F-R-55: Early Detection of Treatment Induced Bone Marrow Injury During Chemoradiation Therapy Using Quantitative CT

    Energy Technology Data Exchange (ETDEWEB)

    Chen, X; Song, Y; Erickson, B; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

    2016-06-15

    Purpose: Acute hematologic toxicity associated with bone marrow injury is a common complication of chemoradiation therapy (CRT) for pelvic malignancies. In this work, we investigate the feasibility of using quantitative CT to detect bone marrow injury during CRT. Methods: Daily CTs were acquired during routine CT-guided radiation therapy using a CT-on-rails for 15 cervical cancer patients. All patients treated with a radiation dose of 45.0 to 50.4 Gy in 1.8 Gy/fraction along with chemotherapy. For each patient, the contours of bone marrow were generated in L4, L5 and sacrum on the first daily CT and then populated to other daily CTs by rigid registration using MIM (MIM Software Inc., Cleveland, OH) with manual editing if possible. A series of CT texture parameters, including Hunsfield Unit (HU) histogram, mean HU, entropy, energy, in bone marrow contours were calculated using MATLAB on each daily CT and were correlated with the completed blood counts (CBC) collected weekly for each patient. The correlations were analyzed with Pearson correlation tests. Results: For all patient data analyzed, mean HU in bone marrow decreased during CRT delivery. From the first to the last fraction the average mean HU reduction is 58.1 ± 13.6 HU (P<0.01). This decrease can be observed as early as after first 5 fractions and is strongly associated with the changes of most CBC quantities, such as the reductions of white and blood cell counts (r=0.97, P=0.001). The reduction of HU is spatially varied. Conclusion: Chemoradiation induced bone marrow injury can be detected during the delivery of CRT using quantitative CT. Chemoradiation results in reductions in mean HU, which are strongly associated with the change in the pretrial blood cell counts. Early detection of bone marrow injury with commonly available CT opens a door to improve bone marrow sparing, reducing risk of hematologic toxicity.

  17. Mid- and long-term clinical results of surgical therapy in unicameral bone cysts

    Directory of Open Access Journals (Sweden)

    Hagmann Sébastien

    2011-12-01

    Full Text Available Abstract Background Unicameral (or simple bone cysts (UBC are benign tumours most often located in long bones of children and adolescents. Pathological fractures are common, and due to high recurrence rates, these lesions remain a challenge to treat. Numerous surgical procedures have been proposed, but there is no general consensus of the ideal treatment. The aim of this investigation therefore was to study the long-term outcome after surgical treatment in UBC. Methods A retrospective analysis of 46 patients surgically treated for UBC was performed for short and mid-term outcome. Clinical and radiological outcome parameters were studied according to a modified Neer classification system. Long-term clinical information was retrieved via a questionnaire at a minimum follow-up of 10 years after surgery. Results Forty-six patients (17 female, 29 male with a mean age of 10.0 ± 4.8 years and with histopathologically confirmed diagnosis of UBC were included. Pathological fractures were observed in 21 cases (46%. All patients underwent surgery for UBC (35 patients underwent curettage and bone grafting as a primary therapy, 4 curettage alone, 3 received corticoid instillation and 4 decompression by cannulated screws. Overall recurrence rate after the first surgical treatment was 39% (18/46, second (17.4% of all patients and third recurrence (4.3% were frequently observed and were addressed by revision surgery. Recurrence was significantly higher in young and in male patients as well as in active cysts. After a mean of 52 months, 40 out of 46 cysts were considered healed. Prognosis was significantly better when recurrence was observed later than 30 months after therapy. After a mean follow-up of 15.5 ± 6.2 years, 40 patients acknowledged clinically excellent results, while five reported mild and casual pain. Only one patient reported a mild limitation of range of motion. Conclusions Our results suggest satisfactory overall long-term outcome for the

  18. Mid- and long-term clinical results of surgical therapy in unicameral bone cysts.

    Science.gov (United States)

    Hagmann, Sébastien; Eichhorn, Florian; Moradi, Babak; Gotterbarm, Tobias; Dreher, Thomas; Lehner, Burkhard; Zeifang, Felix

    2011-12-13

    Unicameral (or simple) bone cysts (UBC) are benign tumours most often located in long bones of children and adolescents. Pathological fractures are common, and due to high recurrence rates, these lesions remain a challenge to treat. Numerous surgical procedures have been proposed, but there is no general consensus of the ideal treatment. The aim of this investigation therefore was to study the long-term outcome after surgical treatment in UBC. A retrospective analysis of 46 patients surgically treated for UBC was performed for short and mid-term outcome. Clinical and radiological outcome parameters were studied according to a modified Neer classification system. Long-term clinical information was retrieved via a questionnaire at a minimum follow-up of 10 years after surgery. Forty-six patients (17 female, 29 male) with a mean age of 10.0 ± 4.8 years and with histopathologically confirmed diagnosis of UBC were included. Pathological fractures were observed in 21 cases (46%). All patients underwent surgery for UBC (35 patients underwent curettage and bone grafting as a primary therapy, 4 curettage alone, 3 received corticoid instillation and 4 decompression by cannulated screws). Overall recurrence rate after the first surgical treatment was 39% (18/46), second (17.4% of all patients) and third recurrence (4.3%) were frequently observed and were addressed by revision surgery. Recurrence was significantly higher in young and in male patients as well as in active cysts. After a mean of 52 months, 40 out of 46 cysts were considered healed. Prognosis was significantly better when recurrence was observed later than 30 months after therapy. After a mean follow-up of 15.5 ± 6.2 years, 40 patients acknowledged clinically excellent results, while five reported mild and casual pain. Only one patient reported a mild limitation of range of motion. Our results suggest satisfactory overall long-term outcome for the surgical treatment of UBC, although short-and mid

  19. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Randa; Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina, E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-05-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS.

  20. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    International Nuclear Information System (INIS)

    Tao, Randa; Allen, Pamela K.; Rodriguez, Alma; Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K.; Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey; Dabaja, Bouthaina

    2015-01-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS

  1. Multiscale registration of medical images based on edge preserving scale space with application in image-guided radiation therapy

    Science.gov (United States)

    Li, Dengwang; Li, Hongsheng; Wan, Honglin; Chen, Jinhu; Gong, Guanzhong; Wang, Hongjun; Wang, Liming; Yin, Yong

    2012-08-01

    Mutual information (MI) is a well-accepted similarity measure for image registration in medical systems. However, MI-based registration faces the challenges of high computational complexity and a high likelihood of being trapped into local optima due to an absence of spatial information. In order to solve these problems, multi-scale frameworks can be used to accelerate registration and improve robustness. Traditional Gaussian pyramid representation is one such technique but it suffers from contour diffusion at coarse levels which may lead to unsatisfactory registration results. In this work, a new multi-scale registration framework called edge preserving multiscale registration (EPMR) was proposed based upon an edge preserving total variation L1 norm (TV-L1) scale space representation. TV-L1 scale space is constructed by selecting edges and contours of images according to their size rather than the intensity values of the image features. This ensures more meaningful spatial information with an EPMR framework for MI-based registration. Furthermore, we design an optimal estimation of the TV-L1 parameter in the EPMR framework by training and minimizing the transformation offset between the registered pairs for automated registration in medical systems. We validated our EPMR method on both simulated mono- and multi-modal medical datasets with ground truth and clinical studies from a combined positron emission tomography/computed tomography (PET/CT) scanner. We compared our registration framework with other traditional registration approaches. Our experimental results demonstrated that our method outperformed other methods in terms of the accuracy and robustness for medical images. EPMR can always achieve a small offset value, which is closer to the ground truth both for mono-modality and multi-modality, and the speed can be increased 5-8% for mono-modality and 10-14% for multi-modality registration under the same condition. Furthermore, clinical application by adaptive

  2. Multiscale registration of medical images based on edge preserving scale space with application in image-guided radiation therapy

    International Nuclear Information System (INIS)

    Li Dengwang; Wan Honglin; Li Hongsheng; Chen Jinhu; Gong Guanzhong; Yin Yong; Wang Hongjun; Wang Liming

    2012-01-01

    Mutual information (MI) is a well-accepted similarity measure for image registration in medical systems. However, MI-based registration faces the challenges of high computational complexity and a high likelihood of being trapped into local optima due to an absence of spatial information. In order to solve these problems, multi-scale frameworks can be used to accelerate registration and improve robustness. Traditional Gaussian pyramid representation is one such technique but it suffers from contour diffusion at coarse levels which may lead to unsatisfactory registration results. In this work, a new multi-scale registration framework called edge preserving multiscale registration (EPMR) was proposed based upon an edge preserving total variation L1 norm (TV-L1) scale space representation. TV-L1 scale space is constructed by selecting edges and contours of images according to their size rather than the intensity values of the image features. This ensures more meaningful spatial information with an EPMR framework for MI-based registration. Furthermore, we design an optimal estimation of the TV-L1 parameter in the EPMR framework by training and minimizing the transformation offset between the registered pairs for automated registration in medical systems. We validated our EPMR method on both simulated mono- and multi-modal medical datasets with ground truth and clinical studies from a combined positron emission tomography/computed tomography (PET/CT) scanner. We compared our registration framework with other traditional registration approaches. Our experimental results demonstrated that our method outperformed other methods in terms of the accuracy and robustness for medical images. EPMR can always achieve a small offset value, which is closer to the ground truth both for mono-modality and multi-modality, and the speed can be increased 5–8% for mono-modality and 10–14% for multi-modality registration under the same condition. Furthermore, clinical application by

  3. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff, Paulien G., E-mail: p.g.westhoff@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Graeff, Alexander de [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Monninkhof, Evelyn M. [Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht (Netherlands); Pomp, Jacqueline [Department of Radiotherapy, Reinier de Graaf Gasthuis, Delft (Netherlands); Vulpen, Marco van [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Leer, Jan Willem H. [Department of Radiotherapy, University Medical Center Nijmegen, Nijmegen (Netherlands); Marijnen, Corrie A.M.; Linden, Yvette M. van der [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands)

    2015-11-01

    Purpose: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. Patients and Methods: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within the Dutch Bone Metastasis Study were used. These patients, irradiated for painful bone metastases, rated pain, QoL, and overall health at baseline and weekly afterward for 12 weeks. Using generalized estimating equations analysis, the course of QoL was studied, adjusted for primary tumor. To identify predictive variables, proportional hazard analyses were performed, taking into account death as a competing risk, and C-statistics were calculated for discriminative value. Results: In total, 722 patients (76%) responded to radiation therapy. During follow-up, responders had a better QoL in all domains compared with nonresponders. Patients with breast or prostate cancer had a better QoL than patients with lung cancer. In multivariate analysis, baseline predictors for a pain response were breast or prostate cancer as primary tumor, younger age, good performance status, absence of visceral metastases, and using opioids. The discriminative ability of the model was low (C-statistic: 0.56). Conclusions: Responding patients show a better QoL after radiation therapy for painful bone metastases than nonresponders. Our model did not have enough discriminative power to predict which patients are likely to respond to radiation therapy. Therefore, radiation therapy should be offered to all patients with painful bone metastases, aiming to decrease pain and improve QoL.

  4. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases

    International Nuclear Information System (INIS)

    Westhoff, Paulien G.; Graeff, Alexander de; Monninkhof, Evelyn M.; Pomp, Jacqueline; Vulpen, Marco van; Leer, Jan Willem H.; Marijnen, Corrie A.M.; Linden, Yvette M. van der

    2015-01-01

    Purpose: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. Patients and Methods: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within the Dutch Bone Metastasis Study were used. These patients, irradiated for painful bone metastases, rated pain, QoL, and overall health at baseline and weekly afterward for 12 weeks. Using generalized estimating equations analysis, the course of QoL was studied, adjusted for primary tumor. To identify predictive variables, proportional hazard analyses were performed, taking into account death as a competing risk, and C-statistics were calculated for discriminative value. Results: In total, 722 patients (76%) responded to radiation therapy. During follow-up, responders had a better QoL in all domains compared with nonresponders. Patients with breast or prostate cancer had a better QoL than patients with lung cancer. In multivariate analysis, baseline predictors for a pain response were breast or prostate cancer as primary tumor, younger age, good performance status, absence of visceral metastases, and using opioids. The discriminative ability of the model was low (C-statistic: 0.56). Conclusions: Responding patients show a better QoL after radiation therapy for painful bone metastases than nonresponders. Our model did not have enough discriminative power to predict which patients are likely to respond to radiation therapy. Therefore, radiation therapy should be offered to all patients with painful bone metastases, aiming to decrease pain and improve QoL.

  5. Radiodensitometric and DXA analyses for the measurement of bone mineral density after systemic alendronate therapy

    International Nuclear Information System (INIS)

    Lucisano, Marilia Pacifico; Nelson-Filho, Paulo; Silva, Raquel Assed Bezerra da; Silva, Lea Assed Bezerra da; Battaglino, Ricardo; Watanabe, Plauto Christopher Aranha

    2013-01-01

    Precise techniques for the measurement of maxillary bone mineral density (BMD) are useful for the early diagnosis of systemic diseases. The aim of this study was to compare in vivo the efficacy of dual energy x-ray absorptiometry (DXA) and radiographic densitometry for the measurement of BMD after systemic administration of sodium alendronate. Wistar rats were randomly allocated to a control group (n = 5), which received distilled water, and a sodium alendronate group (n = 8), which received two doses of chemically pure sodium alendronate (1 mg/kg) per week. After 8 weeks, the animals were euthanized, the tibias were removed, and the BMD of the proximal tibial metaphysis was analyzed radiographically and by DXA. The data were subjected to statistical analysis by the Kruskal-Wallis test at a significance level of 5%. Both of the techniques revealed that the alendronate-treated group had a significantly higher BMD (p < 0.05) than the control group after 8 weeks of treatment. Comparing the groups with and without alendronate therapy revealed increases of 14.9% and 29.6% in BMD, as detected radiographically and by DXA, respectively. In conclusion, both of the methods were able to detect an increase in BMD of the proximal tibial metaphysis after alendronate therapy. (author)

  6. Radiodensitometric and DXA analyses for the measurement of bone mineral density after systemic alendronate therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lucisano, Marilia Pacifico; Nelson-Filho, Paulo; Silva, Raquel Assed Bezerra da; Silva, Lea Assed Bezerra da, E-mail: nelson@forp.usp.br [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Fac. de Odontologia. Dept. de Clinica Pediatrica, Preventiva e Odontologia Comunitaria; Morse, Leslie [Department of Physical Medicine and Rehabilitation, School of Medicine, Harvard Univ., Boston, MA (United States); Battaglino, Ricardo [Department of Skeletal Biology, Forsyth Institute, Cambridge, MA (United States); Watanabe, Plauto Christopher Aranha [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Fac. de Odontologia. Dept. de Morfologia, Estomacologia e Fisiologia

    2013-05-15

    Precise techniques for the measurement of maxillary bone mineral density (BMD) are useful for the early diagnosis of systemic diseases. The aim of this study was to compare in vivo the efficacy of dual energy x-ray absorptiometry (DXA) and radiographic densitometry for the measurement of BMD after systemic administration of sodium alendronate. Wistar rats were randomly allocated to a control group (n = 5), which received distilled water, and a sodium alendronate group (n = 8), which received two doses of chemically pure sodium alendronate (1 mg/kg) per week. After 8 weeks, the animals were euthanized, the tibias were removed, and the BMD of the proximal tibial metaphysis was analyzed radiographically and by DXA. The data were subjected to statistical analysis by the Kruskal-Wallis test at a significance level of 5%. Both of the techniques revealed that the alendronate-treated group had a significantly higher BMD (p < 0.05) than the control group after 8 weeks of treatment. Comparing the groups with and without alendronate therapy revealed increases of 14.9% and 29.6% in BMD, as detected radiographically and by DXA, respectively. In conclusion, both of the methods were able to detect an increase in BMD of the proximal tibial metaphysis after alendronate therapy. (author)

  7. Fat Composition Changes in Bone Marrow During Chemotherapy and Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Carmona, Ruben; Pritz, Jakub [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Bydder, Mark [Department of Radiology, University of California San Diego Medical Center, San Diego, California (United States); Gulaya, Sachin; Zhu, He; Williamson, Casey W. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Welch, Christian S. [Department of Radiology, University of California San Diego Medical Center, San Diego, California (United States); Vaida, Florin [Biostatistics and Bioinformatics, Department of Family and Preventive Medicine, University of California San Diego Medical Center, San Diego, California (United States); Bydder, Graeme [Department of Radiology, University of California San Diego Medical Center, San Diego, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2014-09-01

    Purpose: To quantify changes in bone marrow fat fraction and determine associations with peripheral blood cell counts. Methods and Materials: In this prospective study, 19 patients received either highly myelotoxic treatment (radiation therapy plus cisplatin, 5-fluorouracil mitomycin C [FU/MMC], or cisplatin/5-FU/cetuximab) or less myelotoxic treatment (capecitabine-radiation therapy or no concurrent chemotherapy). Patients underwent MR imaging and venipuncture at baseline, midtreatment, and posttreatment visits. We performed mixed effects modeling of the mean proton density fat fraction (PDFF[%]) by linear time, treatment, and vertebral column region (lumbar [L]4-sacral [S]2 vs thoracic [T]10-L3 vs cervical[C]3-T9), while controlling for cumulative mean dose and other confounders. Spearman rank correlations were performed by white blood cell (WBC) counts versus the differences in PDFF(%) before and after treatment. Results: Cumulative mean dose was associated with a 0.43% per Gy (P=.004) increase in PDFF(%). In the highly myelotoxic group, we observed significant changes in PDFF(%) per visit within L4-S2 (10.1%, P<.001) and within T10-L3 (3.93%, P=.01), relative to the reference C3-T9. In the less myelotoxic group, we did not observe significant changes in PDFF(%) per visit according to region. Within L4-S2, we observed a significant difference between treatment groups in the change in PDFF(%) per visit (5.36%, P=.04). Rank correlations of the inverse log differences in WBC versus the differences in PDFF(%) overall and within T10-S2 ranged from 0.69 to 0.78 (P<.05). Rank correlations of the inverse log differences in absolute neutrophil counts versus the differences in PDFF(%) overall and within L4-S2 ranged from 0.79 to 0.81 (P<.05). Conclusions: Magnetic resonance imaging fat quantification is sensitive to marrow composition changes that result from chemoradiation therapy. These changes are associated with peripheral blood cell counts. This study supports a

  8. Fat Composition Changes in Bone Marrow During Chemotherapy and Radiation Therapy

    International Nuclear Information System (INIS)

    Carmona, Ruben; Pritz, Jakub; Bydder, Mark; Gulaya, Sachin; Zhu, He; Williamson, Casey W.; Welch, Christian S.; Vaida, Florin; Bydder, Graeme; Mell, Loren K.

    2014-01-01

    Purpose: To quantify changes in bone marrow fat fraction and determine associations with peripheral blood cell counts. Methods and Materials: In this prospective study, 19 patients received either highly myelotoxic treatment (radiation therapy plus cisplatin, 5-fluorouracil mitomycin C [FU/MMC], or cisplatin/5-FU/cetuximab) or less myelotoxic treatment (capecitabine-radiation therapy or no concurrent chemotherapy). Patients underwent MR imaging and venipuncture at baseline, midtreatment, and posttreatment visits. We performed mixed effects modeling of the mean proton density fat fraction (PDFF[%]) by linear time, treatment, and vertebral column region (lumbar [L]4-sacral [S]2 vs thoracic [T]10-L3 vs cervical[C]3-T9), while controlling for cumulative mean dose and other confounders. Spearman rank correlations were performed by white blood cell (WBC) counts versus the differences in PDFF(%) before and after treatment. Results: Cumulative mean dose was associated with a 0.43% per Gy (P=.004) increase in PDFF(%). In the highly myelotoxic group, we observed significant changes in PDFF(%) per visit within L4-S2 (10.1%, P<.001) and within T10-L3 (3.93%, P=.01), relative to the reference C3-T9. In the less myelotoxic group, we did not observe significant changes in PDFF(%) per visit according to region. Within L4-S2, we observed a significant difference between treatment groups in the change in PDFF(%) per visit (5.36%, P=.04). Rank correlations of the inverse log differences in WBC versus the differences in PDFF(%) overall and within T10-S2 ranged from 0.69 to 0.78 (P<.05). Rank correlations of the inverse log differences in absolute neutrophil counts versus the differences in PDFF(%) overall and within L4-S2 ranged from 0.79 to 0.81 (P<.05). Conclusions: Magnetic resonance imaging fat quantification is sensitive to marrow composition changes that result from chemoradiation therapy. These changes are associated with peripheral blood cell counts. This study supports a

  9. Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results

    International Nuclear Information System (INIS)

    Poll, L.W.; Koch, J.A.; Scherer, A.; Boerner, D.; Moedder, U.; Dahl, S. vom; Niederau, C.; Haeussinger, D.; Willers, R.

    2001-01-01

    Objective:. Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. Patients and design:. Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. Results:. Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). Conclusions:. MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non- homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021). (orig.)

  10. Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results

    Energy Technology Data Exchange (ETDEWEB)

    Poll, L.W.; Koch, J.A.; Scherer, A.; Boerner, D.; Moedder, U. [Duesseldorf Univ. (Germany). Inst. fuer Diagnostische Radiologie; Dahl, S. vom; Niederau, C.; Haeussinger, D. [Duesseldorf Univ. (Germany). Medizinische Fakultaet; Willers, R. [Duesseldorf Univ. (Germany). Rechenzentrum

    2001-09-01

    Objective:. Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. Patients and design:. Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. Results:. Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). Conclusions:. MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non- homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021). (orig.)

  11. How are teeth better than bone? An investigation of dental tissue diagenesis and state of preservation at a histological scale (with photo catalogue

    Directory of Open Access Journals (Sweden)

    Hege I. Hollund

    2014-07-01

    Full Text Available Teeth are often the preferred substrate for isotopic and genetic assays in archaeological research. Teeth can yield isotopic signals from different periods of an individual's lifetime, useful in dietary reconstruction, climate research, and investigation into mobility of people and animals in the past. Additionally, it is generally accepted that teeth preserve biomolecules (e.g. DNA, collagen and isotopic signals better. Despite the importance of dental tissue in archaeological research, no systematic study has been carried out concerning diagenetic alterations at histological scale. This article reports the results of a thorough histological characterisation of post-mortem alterations observed in 34 ancient teeth. Such alterations are well described in bone whereas similar analyses of teeth are scant and highlight the need for diagenetic screening before analysis. Micrographs have been made, illustrating typical diagenetic features occurring within the dental tissues cementum, dentine and enamel including bioerosion, cracking, etching and staining. The photo catalogue produced can be used within fields such as archaeology, forensics and palaeontology.

  12. Time course of bone mineral density changes during 4-year rituximab therapy in postmenopausal women with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    T. A. Raskina

    2015-01-01

    Full Text Available Objective: to estimate the time course of bone mineral density (BMD changes during 4-year rituximab (RTM therapy in postmenopausal women with rheumatoid arthritis (RA.Subjects and methods. Seventy-nine postmenopausal women with a valid diagnosis of RA were followed up. According to the basic therapy option, all the patients were allocated into two groups: 1 44 patients who received combination therapy with RTM and methotrexate (MT; 2 35 patients who had MT monotherapy. BMD was estimated by dual-energy X-ray absorptiometry using an Excell XR-46 stationary dualenergy X-ray bone densitometer (Norland, USA.Results. There was a statistically significant increase in femoral neck BMD and T score as compared to the baseline values in the RTM group after 3 years of follow-up. The MT monotherapy group showed no statistically significant densitometric changes in the femoral neck. The similar positive BMD changes were observed 4 years following RTM and MT therapy.Conclusion. Following 2 therapy cycles, femoral neck BMD parameters were noted to be stabilized in the patients with RA. After 3 therapy cycles, there was a positive densitometric change that remained by the fourth therapy cycle.

  13. Bone metastases of differentiated thyroid cancer: the importance of early diagnosis and {sup 131}I therapy on prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Zanotti-Fregonara, P. [CEA, DSV, I2BM, SHFJ, UMNRC, Orsay (France); Rubello, D. [Santa Maria Misericordia Hosp, Rovigo (Italy); Hindie, E. [Hop StLouis, Paris (France)

    2008-07-01

    Complete text of publication follows: Distant metastases are found at diagnosis or during follow-up in 10%-15% of patients with differentiated thyroid cancer. Bone is the second most commonly involved site. Patients with bone metastases, whether isolated or associated with lung metastases, have a markedly poor prognosis. Ten-year survival rates range from 13% to 21%. Given such poor prognosis, the use of {sup 131}I therapy has been questioned. However, it might well be that poor prognosis of bone metastases can be overcome if {sup 131}I therapy is delivered at an early stage, when tumor burden is small, as previously demonstrated for pulmonary metastases. A review of a large series of patients showed that only rarely were bone metastases diagnosed at an early stage. Among 109 patients with bone metastases reported by Bernier et al., only 4 had both radioiodine uptake and a negative standard radiography examination. Similarly, Durante et al. reported that only 8 of 115 patients had negative radiography findings at presentation. Prognosis may improve if bone metastases are detected earlier. In a recent study, bone metastases were first detected by {sup 131}I scanning in 8 of 16 patients, when complementary radiologic studies were negative. Six of these patients showed an excellent response to {sup 131}I therapy. Today, the nuclear medicine community is well armed for this challenge toward earlier diagnosis. Postsurgery thyroid remnant ablation is more widely used. The {sup 131}I whole body scan associated with thyroid remnant ablation after thyroidectomy has a major role in early diagnosis of functioning distant metastases at a time when complementary imaging techniques (CT, MRI, bone scanning) are often still showing negative findings. Early diagnosis of specific {sup 131}I-avid bone foci will be improved with the advent and generalization of SPECT/CT. When early diagnosis is achieved, repeated {sup 131}I therapy can be effective by targeting not only visible

  14. Bone metastases of differentiated thyroid cancer: the importance of early diagnosis and 131I therapy on prognosis

    International Nuclear Information System (INIS)

    Zanotti-Fregonara, P.; Rubello, D.; Hindie, E.

    2008-01-01

    Complete text of publication follows: Distant metastases are found at diagnosis or during follow-up in 10%-15% of patients with differentiated thyroid cancer. Bone is the second most commonly involved site. Patients with bone metastases, whether isolated or associated with lung metastases, have a markedly poor prognosis. Ten-year survival rates range from 13% to 21%. Given such poor prognosis, the use of 131 I therapy has been questioned. However, it might well be that poor prognosis of bone metastases can be overcome if 131 I therapy is delivered at an early stage, when tumor burden is small, as previously demonstrated for pulmonary metastases. A review of a large series of patients showed that only rarely were bone metastases diagnosed at an early stage. Among 109 patients with bone metastases reported by Bernier et al., only 4 had both radioiodine uptake and a negative standard radiography examination. Similarly, Durante et al. reported that only 8 of 115 patients had negative radiography findings at presentation. Prognosis may improve if bone metastases are detected earlier. In a recent study, bone metastases were first detected by 131 I scanning in 8 of 16 patients, when complementary radiologic studies were negative. Six of these patients showed an excellent response to 131 I therapy. Today, the nuclear medicine community is well armed for this challenge toward earlier diagnosis. Postsurgery thyroid remnant ablation is more widely used. The 131 I whole body scan associated with thyroid remnant ablation after thyroidectomy has a major role in early diagnosis of functioning distant metastases at a time when complementary imaging techniques (CT, MRI, bone scanning) are often still showing negative findings. Early diagnosis of specific 131 I-avid bone foci will be improved with the advent and generalization of SPECT/CT. When early diagnosis is achieved, repeated 131 I therapy can be effective by targeting not only visible metastases but also those still too small

  15. Bone marrow sparing in intensity modulated proton therapy for cervical cancer: Efficacy and robustness under range and setup uncertainties

    International Nuclear Information System (INIS)

    Dinges, Eric; Felderman, Nicole; McGuire, Sarah; Gross, Brandie; Bhatia, Sudershan; Mott, Sarah; Buatti, John; Wang, Dongxu

    2015-01-01

    Background and purpose: This study evaluates the potential efficacy and robustness of functional bone marrow sparing (BMS) using intensity-modulated proton therapy (IMPT) for cervical cancer, with the goal of reducing hematologic toxicity. Material and methods: IMPT plans with prescription dose of 45 Gy were generated for ten patients who have received BMS intensity-modulated X-ray therapy (IMRT). Functional bone marrow was identified by 18 F-flourothymidine positron emission tomography. IMPT plans were designed to minimize the volume of functional bone marrow receiving 5–40 Gy while maintaining similar target coverage and healthy organ sparing as IMRT. IMPT robustness was analyzed with ±3% range uncertainty errors and/or ±3 mm translational setup errors in all three principal dimensions. Results: In the static scenario, the median dose volume reductions for functional bone marrow by IMPT were: 32% for V 5Gy , 47% for V 10Gy , 54% for V 20Gy , and 57% for V 40Gy , all with p < 0.01 compared to IMRT. With assumed errors, even the worst-case reductions by IMPT were: 23% for V 5Gy , 37% for V 10Gy , 41% for V 20Gy , and 39% for V 40Gy , all with p < 0.01. Conclusions: The potential sparing of functional bone marrow by IMPT for cervical cancer is significant and robust under realistic systematic range uncertainties and clinically relevant setup errors

  16. Bone Marrow Sparing in Intensity Modulated Proton Therapy for Cervical Cancer: Efficacy and Robustness under Range and Setup Uncertainties

    Science.gov (United States)

    Dinges, Eric; Felderman, Nicole; McGuire, Sarah; Gross, Brandie; Bhatia, Sudershan; Mott, Sarah; Buatti, John; Wang, Dongxu

    2015-01-01

    Background and Purpose This study evaluates the potential efficacy and robustness of functional bone marrow sparing (BMS) using intensity-modulated proton therapy (IMPT) for cervical cancer, with the goal of reducing hematologic toxicity. Material and Methods IMPT plans with prescription dose of 45 Gy were generated for ten patients who have received BMS intensity-modulated x-ray therapy (IMRT). Functional bone marrow was identified by 18F-flourothymidine positron emission tomography. IMPT plans were designed to minimize the volume of functional bone marrow receiving 5–40 Gy while maintaining similar target coverage and healthy organ sparing as IMRT. IMPT robustness was analyzed with ±3% range uncertainty errors and/or ±3mm translational setup errors in all three principal dimensions. Results In the static scenario, the median dose volume reductions for functional bone marrow by IMPT were: 32% for V5GY, 47% for V10Gy, 54% for V20Gy, and 57% for V40Gy, all with p<0.01 compared to IMRT. With assumed errors, even the worst-case reductions by IMPT were: 23% for V5Gy, 37% for V10Gy, 41% for V20Gy, and 39% for V40Gy, all with p<0.01. Conclusions The potential sparing of functional bone marrow by IMPT for cervical cancer is significant and robust under realistic systematic range uncertainties and clinically relevant setup errors. PMID:25981130

  17. Effect of an estrogen-deficient state and alendronate therapy on bone loss resulting from experimental periapical lesions in rats.

    Science.gov (United States)

    Xiong, Haofei; Peng, Bin; Wei, Lili; Zhang, Xiaolei; Wang, Li

    2007-11-01

    The aim of the research was to evaluate the impact of an estrogen-deficient state and alendronate (ALD) therapy on bone loss resulting from experimental periapical lesions in rats. Periapical lesions were induced on ovariectomized (OVX) and sham-ovariectomized (Sham) rats. After sample preparation, histologic and radiographic examination for periapical bone loss area and an enzyme histochemical test for tartrate-resistant acid phosphatase (TRAP) were performed. The results showed that OVX significantly increased bone loss resulting from periradicular lesions. After daily subcutaneous injection of ALD, the bone loss area and the number of TRAP-positive cells (osteoclasts) were reduced. These findings suggested that alendronate may protect against increased bone loss from experimental periapical lesions in estrogen-deficient rats. Given recent recognition of adverse effects of bisphosphonates, including an increased risk for osteonecrosis, the findings from this study should not be interpreted as a new indication for ALD treatment. However, they may offer insight into understanding and predicting outcomes in female postmenopausal patients already on ALD therapy for medical indications.

  18. Hypofractionated Intensity Modulated Radiation Therapy in Combined Modality Treatment for Bladder Preservation in Elderly Patients With Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Turgeon, Guy-Anne [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Souhami, Luis, E-mail: luis.souhami@muhc.mcgill.ca [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Cury, Fabio L.; Faria, Sergio L.; Duclos, Marie [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Sturgeon, Jeremy [Department of Medical Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Kassouf, Wassim [Department of Urology, McGill University Health Centre, Montreal, Quebec (Canada)

    2014-02-01

    Purpose/Objective(s): To review our experience with bladder-preserving trimodality treatment (TMT) using hypofractionated intensity modulated radiation therapy (IMRT) for the treatment of elderly patients with muscle-invasive bladder cancer. Methods and Materials: Retrospective study of elderly patients treated with TMT using hypofractionated IMRT (50 Gy in 20 fractions) with concomitant weekly radiosensitizing chemotherapy. Eligibility criteria were as follows: age ≥70 years, a proven diagnosis of muscle-invasive transitional cell bladder carcinoma, stage T2-T3N0M0 disease, and receipt of TMT with curative intent. Response rate was assessed by cystoscopic evaluation and bladder biopsy. Results: 24 patients with a median age of 79 years were eligible. A complete response was confirmed in 83% of the patients. Of the remaining patients, 1 of them underwent salvage cystectomy, and no disease was found in the bladder on histopathologic assessment. After a median follow-up time of 28 months, of the patients with a complete response, 2 patients had muscle-invasive recurrence, 1 experienced locoregional failure, and 3 experienced distant metastasis. The overall and cancer-specific survival rates at 3 years were 61% and 71%, respectively. Of the surviving patients, 75% have a disease-free and functioning bladder. All patients completed hypofractionated IMRT, and 19 patients tolerated all 4 cycles of chemotherapy. Acute grade 3 gastrointestinal or genitourinary toxicities occurred in only 4% of the patients, and acute grade 3 or 4 hematologic toxicities, liver toxicities, or both were experienced by 17% of the cohort. No patient experienced grade 4 gastrointestinal or genitourinary toxicity. Conclusions: Hypofractionated IMRT with concurrent radiosensitizing chemotherapy appears to be an effective and well-tolerated curative treatment strategy in the elderly population and should be considered for patients who are not candidates for cystectomy or who wish to avoid

  19. New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes

    Science.gov (United States)

    Senni, Michele; Paulus, Walter J.; Gavazzi, Antonello; Fraser, Alan G.; Díez, Javier; Solomon, Scott D.; Smiseth, Otto A.; Guazzi, Marco; Lam, Carolyn S. P.; Maggioni, Aldo P.; Tschöpe, Carsten; Metra, Marco; Hummel, Scott L.; Edelmann, Frank; Ambrosio, Giuseppe; Stewart Coats, Andrew J.; Filippatos, Gerasimos S.; Gheorghiade, Mihai; Anker, Stefan D.; Levy, Daniel; Pfeffer, Marc A.; Stough, Wendy Gattis; Pieske, Burkert M.

    2014-01-01

    The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed. PMID:25104786

  20. Modeling the effect of levothyroxine therapy on bone mass density in postmenopausal women: a different approach leads to new inference

    Directory of Open Access Journals (Sweden)

    Tavangar Seyed

    2007-06-01

    Full Text Available Abstract Background The diagnosis, treatment and prevention of osteoporosis is a national health emergency. Osteoporosis quietly progresses without symptoms until late stage complications occur. Older patients are more commonly at risk of fractures due to osteoporosis. The fracture risk increases when suppressive doses of levothyroxine are administered especially in postmenopausal women. The question is; "When should bone mass density be tested in postmenopausal women after the initiation of suppressive levothyroxine therapy?". Standard guidelines for the prevention of osteoporosis suggest that follow-up be done in 1 to 2 years. We were interested in predicting the level of bone mass density in postmenopausal women after the initiation of suppressive levothyroxine therapy with a novel approach. Methods The study used data from the literature on the influence of exogenous thyroid hormones on bone mass density. Four cubic polynomial equations were obtained by curve fitting for Ward's triangle, trochanter, spine and femoral neck. The behaviors of the models were investigated by statistical and mathematical analyses. Results There are four points of inflexion on the graphs of the first derivatives of the equations with respect to time at about 6, 5, 7 and 5 months. In other words, there is a maximum speed of bone loss around the 6th month after the start of suppressive L-thyroxine therapy in post-menopausal women. Conclusion It seems reasonable to check bone mass density at the 6th month of therapy. More research is needed to explain the cause and to confirm the clinical application of this phenomenon for osteoporosis, but such an approach can be used as a guide to future experimentation. The investigation of change over time may lead to more sophisticated decision making in a wide variety of clinical problems.

  1. Bone Marrow Cell Therapy on 1,2-Dimethylhydrazine (DMH)-Induced Colon Cancer in Rats.

    Science.gov (United States)

    El-Khadragy, Manal F; Nabil, Heba M; Hassan, Basmaa N; Tohamy, Amany A; Waaer, Hanaa F; Yehia, Hany M; Alharbi, Afra M; Moneim, Ahmed Esmat Abdel

    2018-01-01

    Stem cell based therapies are being under focus due to their possible role in treatment of various tumors. Bone marrow stem cells believed to have anticancer potential and are preferred for their activities by stimulating the immune system, migration to the site of tumor and ability for inducting apoptosis in cancer cells. The current study was aimed to investigate the tumor suppressive effects of bone marrow cells (BMCs) in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats. The rats were randomly allocated into four groups: control, BMCs alone, DMH alone and BMCs with DMH. BMCs were injected intrarectally while DMH was injected subcutaneously at 20 mg/kg body weight once a week for 15 weeks. Histopathological examination and gene expression of survivin, β-catenin and multidrug resistance-1 (MDR-1) by real-time reverse transcription-polymerase chain reaction (RT-PCR) in rat colon tissues. This is in addition to oxidative stress markers in colon were performed across all groups. The presence of aberrant crypt foci was reordered once histopathological examination of colon tissue from rats which received DMH alone. Administration of BMCs into rats starting from zero-day of DMH injection improved the histopathological picture which showed a clear improvement in mucosal layer, few inflammatory cells infiltration periglandular and in the lamina propria. Gene expression in rat colon tissue demonstrated that BMCs down-regulated survivin, β-catenin, MDR-1 and cytokeratin 20 genes expression in colon tissues after colon cancer induction. Amelioration of the colon status after administration of MSCs has been evidenced by a major reduction of lipid peroxidation, nitric oxide, and increasing of glutathione content and superoxide dismutase along with catalase activities. Our findings demonstrated that BMCs have tumor suppressive effects in DMH-induced colon cancer as evidenced by down-regulation of survivin, β-catenin, and MDR-1 genes and enhancing the antioxidant

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

    Energy Technology Data Exchange (ETDEWEB)

    Cadieux, Catherine L., E-mail: ccadieux@umail.iu.edu [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN (United States); DesRosiers, Colleen [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN (United States); McMullen, Kevin [Department of Radiation Oncology, IU Health Methodist Hospital, Indianapolis, IN (United States)

    2016-10-01

    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 4.125 Gy with a range of 1.085 to 6.228 Gy. The risk estimate for these patients ranged from 0.16% to 0.93%. The average total lifetime risk estimate for the bladder in all patients is 0.22% and the average total lifetime risk estimate for the remainder organs in all patients is 1.25%. In conclusions, proper shielding created from multileaf collimators (MLCs), blocks, and shields should always be used when possible.

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

    International Nuclear Information System (INIS)

    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 4.125 Gy with a range of 1.085 to 6.228 Gy. The risk estimate for these patients ranged from 0.16% to 0.93%. The average total lifetime risk estimate for the bladder in all patients is 0.22% and the average total lifetime risk estimate for the remainder organs in all patients is 1.25%. In conclusions, proper shielding created from multileaf collimators (MLCs), blocks, and shields should always be used when possible.

  4. Recruitment of bone marrow derived cells during anti-angiogenic therapy in GBM : Bone marrow derived cell in GBM

    NARCIS (Netherlands)

    Boer, Jennifer C.; Walenkamp, Annemiek M. E.; den Dunnen, Wilfred F. A.

    2014-01-01

    Glioblastoma (GBM) is a highly vascular tumor characterized by rapid and invasive tumor growth, followed by oxygen depletion, hypoxia and neovascularization, which generate a network of disorganized, tortuous and permeable vessels. Recruitment of bone marrow derived cells (BMDC) is crucial for

  5. In vivo confocal microscopy of conjunctiva in preservative-free timolol 0.1% gel formulation therapy for glaucoma.

    Science.gov (United States)

    Frezzotti, Paolo; Fogagnolo, Paolo; Haka, Gentiana; Motolese, Ilaria; Iester, Michele; Bagaglia, Simone A; Mittica, Pietro; Menicacci, Cristina; Rossetti, Luca; Motolese, Eduardo

    2014-03-01

    To evaluate the effects at 1 year of preservative-free timolol gel and preserved timolol eye drops on conjunctiva and tear parameters. Forty patients with primary open-angle glaucoma or ocular hypertension were randomized to the two treatment groups and compared with 20 healthy age-matched controls. Clinical tests (IOP, Schirmer I test, and lacrimal film break-up time BUT) and in vivo conjunctival confocal microscopy (IVCM) were performed in all patients at baseline and after 12 months. IVCM (HRT II Rostock Cornea Module; Heidelberg Engineering GmbH, Heidelberg, Germany) was performed after topical anaesthesia in the four cardinal locations and at the corresponding limbus to analyse conjunctiva cells. The main IVCM outcomes were goblet cell density and epithelial regularity. IVCM and clinical parameters were similar in the three groups at baseline. After 12 months, intra-epithelial goblet cell density was significantly lower in the preserved (48.25 ± 7.70) than in the preservative-free beta-blocker group (86.83 ± 22.17, p preserved beta-blocker medication group than in the preservative-free beta-blocker group (p preserved timolol (respectively, 11.3 ± 2.97 and 8.12 ± 0.99) compared with preservative-free timolol (16.8 ± 1.83 and 11.27 ± 1.27, p preservative-free beta-blocker gel induces less changes at ocular surface than preserved beta-blockers, a fact that should be considered to obtain less adverse effects and maximal adherence to treatment in a chronic condition such as glaucoma. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  6. The potential of mangosteen (Garcinia mangostana peel extract, combined with demineralized freeze-dried bovine bone xenograft, to reduce ridge resorption and alveolar bone regeneration in preserving the tooth extraction socket

    Directory of Open Access Journals (Sweden)

    Utari Kresnoadi

    2017-01-01

    Conclusion: The induction of MPEs and DFBBX is effective in reducing inflammation, lowering osteoclasts, decreasing alveolar bone resorption, and also increasing BMP2 expression and alveolar bone regeneration.

  7. Changes of bone mineral density and related parameters in patients of hyperthyroidism before and after 131I therapy

    International Nuclear Information System (INIS)

    Gao Jibing; Cai Shanwu; Huang Haiquan; Lv Xuefeng; Chen Jizhong; Li Xuguang

    2005-01-01

    Objective: To investigate the changes of bone metabolism in patients with hyperthyroidism before and after 131 I therapy. Methods: The serum levels of TT 3 , TT 4 , sensitive thyroid-stimulating hormone (sTSH), bone gla protein (BGP), parathyroid hormone (PTH) and calcitonin (CT) of 58 patients with hyperthyroidism were measured and also the serum alkaline phosphatase (ALP), calcium (Ca) and phosphorus (P) levels. The bone mineral density (BMD) of the forearm, lumbar (L 2 -L 4 ) and femur was obtained by dual photon X-ray before and after 131 I therapy. Results: 1) Both BMD between the patients treated after 6 months, and before treatment, also the BMD between various 131 I treated group and no response group had significant differences (P 3 level before therapy was positively correlative to the serum BGP (r=0.4113, t=2.9896, P 3 and CT/PTH radio (r=0.3613, t=2.6836, P 131 I therapy (authors)

  8. Fractionation of Palliative Radiation Therapy for Bone Metastases in Ontario: Do Practice Guidelines Guide Practice?

    Energy Technology Data Exchange (ETDEWEB)

    Ashworth, Allison [Division of Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Queen' s University, Kingston, Ontario (Canada); Cancer Center of Southeastern Ontario, Kingston, Ontario (Canada); Kong, Weidong [Division of Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Queen' s University, Kingston, Ontario (Canada); Chow, Edward [Sunnybrook Regional Cancer Centre, Toronto, Ontario (Canada); Mackillop, William J., E-mail: william.mackillop@krcc.on.ca [Division of Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Queen' s University, Kingston, Ontario (Canada); Cancer Center of Southeastern Ontario, Kingston, Ontario (Canada)

    2016-01-01

    Purpose: To evaluate the effect of a provincial practice guideline on the fractionation of palliative radiation therapy for bone metastases (PRT.B) in Ontario. Methods and Materials: The present retrospective study used electronic treatment records linked to Ontario's population-based cancer registry. Hierarchical multivariable regression analysis was used to evaluate temporal trends in the use of single fractions (SFs), controlling for patient-related factors associated with the use of SFs. Results: From 1984 to 2012, 43.9% of 161,835 courses of PRT.B were administered as SFs. The percentage of SF courses was greater for older patients (age <50 years, 39.8% vs age >80 years, 52.5%), those with a shorter life expectancy (survival >12 months, 36.9% vs < 1 month, 53.6%), and those who lived farther from a radiation therapy center (<10 km, 42.1% vs > 50 km, 47.3%). The percentage of SFs to spinal fields was lower than that to other skeletal sites (31.5% vs 57.1%). The percentage of SFs varied among the cancer centers (range, 26.0%-67.8%). These differences were all highly significant in the multivariable analysis (P<.0001). In 2004, Cancer Care Ontario released a practice guideline endorsing the use of SFs for uncomplicated bone metastases. The rate of use of SFs increased from 42.3% in the pre-guideline period (1999-2003) to 52.6% in the immediate post-guideline period (2004-2007). However, it subsequently decreased again to 44.0% (2009-2012). These temporal trends were significant after controlling for patient-related factors in the multivariable analysis (P<.0001). Large intercenter variations in the use of SFs persisted after publication of the guideline. Conclusions: The publication of an Ontario practice guideline endorsing the use of SF PRT.B was associated with only a transient increase in the use of SFs in Ontario and did little to reduce intercenter variations in fractionation.

  9. Alpha-1 antitrypsin gene therapy prevented bone loss in ovariectomy induced osteoporosis mouse model

    Science.gov (United States)

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at meno...

  10. Sphincter preservation with pre-operative radiation therapy (RT) and coloanal anastomosis: long term follow-up

    International Nuclear Information System (INIS)

    Wagman, Raquel; Minsky, Bruce D.; Cohen, Alfred M.; Guillem, Jose G.; Paty, Philip B.

    1997-01-01

    36 patients, cumulative local failure as a component of failure was crude: 17%, and 5-Yr actuarial: 21%. The 5-yr actuarial disease free survival was 60% and overall survival was 64%. A total of 9 Pts. were excluded from the analysis of sphincter function (8 underwent an APR, and 1: unresectable liver mets). In the remaining 27 eligible pts. sphincter function was: excellent: 59%, good: 26%, fair: 15%, and poor: 0%. The median number of bowel movements was 2 (range: 0-8). CONCLUSION: Our data suggest that pre-operative RT allows sphincter preservation in 77% of pts. who would otherwise require an APR and 85% have good to excellent sphincter function. Given the moderate local failure rate we now routinely use pre-operative combined modality therapy plus post-op chemotherapy for pts. with clinical T3 disease

  11. Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease

    DEFF Research Database (Denmark)

    Sezer, Orhan; Beksac, Meral; Hajek, Roman

    2017-01-01

    This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles...... from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P...... with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival....

  12. Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease.

    Science.gov (United States)

    Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

    2015-01-01

    The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6-18 years with an estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity.

  13. Phenotypic characterization of the bone marrow stem cells used in regenerative cellular therapy

    International Nuclear Information System (INIS)

    Macias Abraham, Consuelo; Valle Perez, Lazaro O del; Baganet Cobas, Aymara

    2011-01-01

    Regenerative medicine is a novel therapeutic method with broad potential for the treatment of various illnesses, based on the use of bone marrow (BM) stem cells, whose phenotypic characterization is limited. The paper deals with the expression of different cell membrane markers in mononuclear BM cells from 14 patients who underwent autologous cell therapy, obtained by medullary puncture and mobilization to peripheral blood, with the purpose of characterizing the different types of cells present in that heterogeneous cellular population and identifying the adhesion molecules involved in their adhesion. A greater presence was observed of adherent stem cells from the marrow stroma in mononuclear cells obtained directly from the BM; a larger population of CD90 +c ells in mononuclear cells from CD34 -/ CD45 -p eripheral blood with a high expression of molecules CD44 and CD62L, which suggests a greater presence of mesenchymal stem cells (MSC) in mobilized cells from the marrow stroma. The higher levels of CD34 +c ells in peripheral blood stem cells with a low expression of molecules CD117 -a nd DR -s uggests the presence of hematopoietic stem cells, hemangioblasts and progenitor endothelial cells mobilized to peripheral circulation. It was found that mononuclear cells from both the BM and peripheral blood show a high presence of stem cells with expression of adhesion molecule CD44 (MMC marker), probably involved in their migration, settling and differentiation

  14. Involved field radiation therapy for Hodgkin's disease autologous bone marrow transplantation regimens

    International Nuclear Information System (INIS)

    Pezner, Richard D.; Nademanee, Auayporn; Niland, Joyce C.; Vora, Nayana; Forman, Stephen J.

    1995-01-01

    From 1986 through 1992, involved-field radiation therapy (IF-RT) was administered to 29 of 86 patients with recurrent Hodgkin's disease (HD) who received a high-dose cyclophosphamide/etoposide regimen with autologous bone marrow transplantation (A-BMT). Patients without a significant history of prior RT received total body irradiation (TBI), initially as a single dose 5-7.5 Gy, and subsequently with fractionated TBI (F-TBI) delivering 12 Gy. Previously irradiated patients received a high-dose BCNU regimen instead of TBI. IF-RT was employed selectively, usually for sites of bulky disease (> 5 cm). IF-RT doses were typically 20 Gy at 2 Gy per fraction for TBI patients and 30-40 Gy at 1.8-2.0 Gy per fraction for non-TBI Patients. Fatal complications developed in four patients while second malignancies have developed in two. The region which received IF-RT was the site of first recurrence in only two cases (7%). With a median follow-up of 28 months, the two-year disease-free survival rate was 44%. For the 22 patients treated by either F-TBI or high-dose BCNU, the 2-year disease-free survival rate was 50% with a median follow up of 29 months. Selective use of IF-RT may increase the chances of complete remission and disease free survival in HD patients with a history of bulky disease

  15. Endothelial Nitric Oxide Synthase Overexpression Restores the Efficiency of Bone Marrow Mononuclear Cell-Based Therapy

    Science.gov (United States)

    Mees, Barend; Récalde, Alice; Loinard, Céline; Tempel, Dennie; Godinho, Marcia; Vilar, José; van Haperen, Rien; Lévy, Bernard; de Crom, Rini; Silvestre, Jean-Sébastien

    2011-01-01

    Bone marrow-derived mononuclear cells (BMMNCs) enhance postischemic neovascularization, and their therapeutic use is currently under clinical investigation. However, cardiovascular risk factors, including diabetes mellitus and hypercholesterolemia, lead to the abrogation of BMMNCs proangiogenic potential. NO has been shown to be critical for the proangiogenic function of BMMNCs, and increased endothelial NO synthase (eNOS) activity promotes vessel growth in ischemic conditions. We therefore hypothesized that eNOS overexpression could restore both the impaired neovascularization response and decreased proangiogenic function of BMMNCs in clinically relevant models of diabetes and hypercholesterolemia. Transgenic eNOS overexpression in diabetic, atherosclerotic, and wild-type mice induced a 1.5- to 2.3-fold increase in postischemic neovascularization compared with control. eNOS overexpression in diabetic or atherosclerotic BMMNCs restored their reduced proangiogenic potential in ischemic hind limb. This effect was associated with an increase in BMMNC ability to differentiate into cells with endothelial phenotype in vitro and in vivo and an increase in BMMNCs paracrine function, including vascular endothelial growth factor A release and NO-dependent vasodilation. Moreover, although wild-type BMMNCs treatment resulted in significant progression of atherosclerotic plaque in ischemic mice, eNOS transgenic atherosclerotic BMMNCs treatment even had antiatherogenic effects. Cell-based eNOS gene therapy has both proangiogenic and antiatherogenic effects and should be further investigated for the development of efficient therapeutic neovascularization designed to treat ischemic cardiovascular disease. PMID:21224043

  16. Impact of Drug Therapy, Radiation Dose, and Dose Rate on Renal Toxicity Following Bone Marrow Transplantation

    International Nuclear Information System (INIS)

    Cheng, Jonathan C.; Schultheiss, Timothy E.; Wong, Jeffrey Y.C.

    2008-01-01

    Purpose: To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). Methods and Materials: A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age ≥18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. Results: Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. Conclusion: A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function

  17. Quantitative determination of bone mineral concentrations using quotient densitometry in patients under long-term anticonvulsant therapy

    International Nuclear Information System (INIS)

    Schulz, H.

    1980-01-01

    The effect on bone mineral concentration of anticonvulsive long-term therapy was investigated in order to find out if there is a relation between the occurence and extent of osteomalacial lesions on the one hand and the type and time of application of anticonvulsants. The hydroxyl apatite content was determined by X-ray densitometry. The method is considered to be suitable for yearly skeletal monitoring of epilepticians treated with anticonvulsants. (orig./HP) [de

  18. Tissue engineering for lateral ridge augmentation with recombinant human bone morphogenetic protein 2 combination therapy: a case report.

    Science.gov (United States)

    Mandelaris, George A; Spagnoli, Daniel B; Rosenfeld, Alan L; McKee, James; Lu, Mei

    2015-01-01

    This case report describes a tissue-engineered reconstruction with recombinant human bone morphogenetic protein 2/acellular collagen sponge (rhBMP-2/ ACS) + cancellous allograft and space maintenance via Medpor Contain mesh in the treatment of a patient requiring maxillary and mandibular horizontal ridge augmentation to enable implant placement. The patient underwent a previously unsuccessful corticocancellous bone graft at these sites. Multiple and contiguous sites in the maxilla and in the mandibular anterior, demonstrating advanced lateral ridge deficiencies, were managed using a tissue engineering approach as an alternative to autogenous bone harvesting. Four maxillary and three mandibular implants were placed 9 and 10 months, respectively, after tissue engineering reconstruction, and all were functioning successfully after 24 months of follow-up. Histomorphometric analysis of a bone core obtained at the time of the maxillary implant placement demonstrated a mean of 76.1% new vital bone formation, 22.2% marrow/cells, and 1.7% residual graft tissue. Tissue engineering for lateral ridge augmentation with combination therapy requires further research to determine predictability and limitations.

  19. Diagnostic problems of MRI in studying the effect of G-CSF therapy in bone marrow of patients with malignoma

    International Nuclear Information System (INIS)

    Layer, G.; Sander, W.; Traeber, F.; Block, W.; Koenig, R.; Vahlensieck, M.; Schild, H.H.; Ko, Y.; Ziske, C.G.

    2000-01-01

    Aim. To study the effect of G-CSF therapy directly by MRI and 1 H MRS in the lumbar and femoral bone marrow and differentiate between malignant bone marrow infiltration (MBMI) and reconversion of red marrow. Methods. Thirteen patients could be examined twice, before and during G-CSF medication and another six only during treatment. T1 weighted spin-echo and opposed-phase gradient-echo images as well as the spectroscopic data (T2 values, water content) were analysed. Results. After G-CSF a pathologic bone marrow signal intensity was seen in 8/13 (lumbar) and 11/13 (femoral) patients respectively. The majority of the signal alterations were diffuse (6 and 8), the minority focal (2 and 3). If a patient was successfully stimulated, a significant increase in water content occurred (21% lumbar, 34% femoral). T2 values did not change significantly, nor did they correlate with the stimulation success. Conclusions. MR tomography and -spectroscopy are suitable to detect lumbar and femoral bone marrow stimulation by G-CSF quantitatively and qualitatively. The changes may simulate MBMI. The adequate judgement of G-CSF treated bone marrow without pretherapeutic images is not possible. (orig.) [de

  20. Radionuclide bone scintigraphy in early detection of avascular osteonecrosis occurred in recovered SARS patients after hormone therapy

    International Nuclear Information System (INIS)

    Wang Qian; Huang Lili; Qin Shuling; Wang Yu; Nie Yuxin; Liang Tiejun; Zhang Caiqun; Zhao Yamei

    2005-01-01

    Objective: To analyze the characteristics of bone scintigraphy in patients who recovered from the severe acute respiratory syndrome (SARS), and to evaluate the clinical value of bone scintigraphy in the early diagnosis of avascular osteonecrosis (AVN) after hormone therapy. Methods: Bone scintigraphy was performed in 66 SARS patients. Among them 54 underwent MRI in bilateral hips and knees. Both images were compared and followed up clinically. Results: Abnormal scintigraphy was found in 30 (45.5%) of the 66 recovered SARS patients. Total 82 foci were found in hip, knee, ankle, elbow, shoulder, wrist and the middle of the tibia. Hip and knee joints were the most involved sites. 25 patients with 71 lesions were symptomatic, whereas 11 in 5 patients were asymptomatic, lesions in 8 patients were multifocal. The lesions found in scintigraphy and MRI were concordant in 92.6% of the joints. But more lesions could be detected by bone scintigraphy. Conclusions: SARS patients have a high occurrence of AVN, usually involved in multiple sites. Bone scintigraphy should be the first choice method used for early detection of AVN. (authors)

  1. Possible mechanisms of retinal function recovery with the use of cell therapy with bone marrow-derived stem cells

    Directory of Open Access Journals (Sweden)

    Rubens Camargo Siqueira

    2010-10-01

    Full Text Available Bone marrow has been proposed as a potential source of stem cells for regenerative medicine. In the eye, degeneration of neural cells in the retina is a hallmark of such widespread ocular diseases as age-related macular degeneration (AMD and retinitis pigmentosa. Bone marrow is an ideal tissue for studying stem cells mainly because of its accessibility. Furthermore, there are a number of well-defined mouse models and cell surface markers that allow effective study of hematopoiesis in healthy and injured mice. Because of these characteristics and the experience of bone marrow transplantation in the treatment of hematological disease such as leukemia, bone marrow-derived stem cells have also become a major tool in regenerative medicine. Those cells may be able to restore the retina function through different mechanisms: A cellular differentiation, B paracrine effect, and C retinal pigment epithelium repair. In this review, we described these possible mechanisms of recovery of retinal function with the use of cell therapy with bone marrow-derived stem cells.

  2. Treatment with vacuum-assisted closure and cryo-preserved homologous de-epidermalised dermis of complex traumas to the lower limbs with loss of substance, and bones and tendons exposure.

    Science.gov (United States)

    Brandi, C; Grimaldi, L; Nisi, G; Silvestri, A; Brafa, A; Calabrò, M; D'Aniello, C

    2008-12-01

    Lower-limb injuries with loss of tissue and exposure of bones and tendons are an increasing problem. The condition of the wound locally and the patient in general does not always allow immediate and adequate coverage of the structures exposed by the trauma. Therefore, new therapeutic solutions are needed. A reduction in the time that bones and tendons are exposed is essential to achieve complete healing of bone fractures, with reduced risks of infection and less disabling outcomes. The effectiveness of vacuum-assisted closure (VAC) therapy in supporting wound healing and of cryopreserved homologous de-epidermalised dermis (DED) in providing an effective template for re-epithelialisation has been previously reported. We carried out a study to evaluate the effectiveness of the synergistic and combined use of the two methodologies. Eighteen patients with traumatic loss of tissue in the lower limbs, involving exposure of bone and tendon structures, were enrolled in the study. All participants had local, general contraindications to first-instance reconstructions, or both. All patients received a combination of VAC therapy and DED implants. Granulation tissue was obtained in all wounds, with complete coverage of exposed structures. No infections were detected in the cohort, and all patients were prepared for further necessary reconstructive treatments. In our experience, the combination of VAC therapy and DED could, in selected cases, constitute an effective treatment for complex lower limb traumatic injuries with bone and tendon exposure.

  3. Hypothalamic Leptin Gene Therapy Reduces Bone Marrow Adiposity in ob/ob Mice Fed Regular and High Fat Diets

    Directory of Open Access Journals (Sweden)

    Laurence B Lindenmaier

    2016-08-01

    Full Text Available Low bone mass is often associated with increased bone marrow adiposity. Since osteoblasts and adipocytes are derived from the same mesenchymal stem cell progenitor, adipocyte formation may increase at the expense of osteoblast formation. Leptin is an adipocyte-derived hormone known to regulate energy and bone metabolism. Genetic (e.g., leptin deficiency and high fat diet-induced (e.g., leptin resistance obesity are associated with increased marrow adipose tissue (MAT and reduced bone formation. Short-duration studies suggest that leptin treatment reduces MAT and increases bone formation in leptin-deficient ob/ob mice fed a regular diet. Here, we determined the long-duration impact of increased hypothalamic leptin on marrow adipocytes and osteoblasts in ob/ob mice using recombinant adeno-associated virus (rAAV gene therapy. In a first study, eight- to ten-week-old male ob/ob mice were randomized into 4 groups: (1 untreated, (2 rAAV-Lep, (3 rAAV-green fluorescent protein (rAAV-GFP, or (4 pair-fed to rAAV-Lep. For vector administration, mice were placed in a Kopf stereotaxic apparatus, and injected intracerebroventricularly with either rAAV-Lep or rAAV-GFP (9 × 107 particles in 1.5 µl. The mice were maintained for 30 weeks following vector administration. In a second study, the impact of increased hypothalamic leptin levels on MAT was determined in mice fed high fat diets. Eight- to ten-week-old male ob/ob mice were randomized into 2 groups and treated with either rAAV-Lep or rAAV-GFP. At 7 weeks post-vector administration, half the mice in each group were switched to a high fat diet for 8 weeks. Wild type (WT controls included age-matched mice fed regular or high fat diet. Hypothalamic leptin gene therapy increased osteoblast perimeter and osteoclast perimeter with minor change in cancellous bone architecture. The gene therapy decreased MAT levels in ob/ob mice fed regular or high fat diet to values similar to WT mice fed regular diet. These

  4. No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone

    International Nuclear Information System (INIS)

    Peterse, Elisabeth F. P.; Cleven, Arjen H. G.; De Jong, Yvonne; Briaire-de Bruijn, Inge; Fletcher, Jonathan A.; Danen, Erik H. J.; Cleton-Jansen, Anne-Marie; Bovée, Judith V. M. G.

    2016-01-01

    Chondrosarcoma is a malignant cartilage forming bone tumour for which no effective systemic treatment is available. Previous studies illustrate the need for a better understanding of the role of the IGF pathway in chondrosarcoma to determine if it can be a target for therapy, which was therefore explored in this study. Expression of mediators of IGF1R signalling and phosphorylation status of IRS1 was determined in chondrosarcoma cell lines by qRT-PCR and western blot. The effect of activation and inhibition of IGF1R signalling on downstream targets was assessed by western blot. Ten chondrosarcoma cell lines were treated with OSI-906 (IGF1R and IR dual inhibitor) after which cell proliferation and migration were determined by a viability assay and the xCELLigence system, respectively. In addition, four chondrosarcoma cell lines were treated with a combination of doxorubicin and OSI-906. By immunohistochemistry, IGF1R expression levels were determined in tissue microarrays of 187 cartilage tumours and ten paraffin embedded cell lines. Mediators of IGF1R signalling are heterogeneously expressed and phosphorylated IRS1 was detected in 67 % of the tested chondrosarcoma cell lines, suggesting that IGF1R signalling is active in a subset of chondrosarcoma cell lines. In the cell lines with phosphorylated IRS1, inhibition of IGF1R signalling decreased phosphorylated Akt levels and increased IGF1R expression, but it did not influence MAPK or S6 activity. In line with these findings, treatment with IGF1R/IR inhibitors did not impact proliferation or migration in any of the chondrosarcoma cell lines, even upon stimulation with IGF1. Although synergistic effects of IGF1R/IR inhibition with doxorubicin are described for other cancers, our results demonstrate that this was not the case for chondrosarcoma. In addition, we found minimal IGF1R expression in primary tumours in contrast to the high expression detected in chondrosarcoma cell lines, even if both were derived from the

  5. No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone.

    Science.gov (United States)

    Peterse, Elisabeth F P; Cleven, Arjen H G; De Jong, Yvonne; Briaire-de Bruijn, Inge; Fletcher, Jonathan A; Danen, Erik H J; Cleton-Jansen, Anne-Marie; Bovée, Judith V M G

    2016-07-14

    Chondrosarcoma is a malignant cartilage forming bone tumour for which no effective systemic treatment is available. Previous studies illustrate the need for a better understanding of the role of the IGF pathway in chondrosarcoma to determine if it can be a target for therapy, which was therefore explored in this study. Expression of mediators of IGF1R signalling and phosphorylation status of IRS1 was determined in chondrosarcoma cell lines by qRT-PCR and western blot. The effect of activation and inhibition of IGF1R signalling on downstream targets was assessed by western blot. Ten chondrosarcoma cell lines were treated with OSI-906 (IGF1R and IR dual inhibitor) after which cell proliferation and migration were determined by a viability assay and the xCELLigence system, respectively. In addition, four chondrosarcoma cell lines were treated with a combination of doxorubicin and OSI-906. By immunohistochemistry, IGF1R expression levels were determined in tissue microarrays of 187 cartilage tumours and ten paraffin embedded cell lines. Mediators of IGF1R signalling are heterogeneously expressed and phosphorylated IRS1 was detected in 67 % of the tested chondrosarcoma cell lines, suggesting that IGF1R signalling is active in a subset of chondrosarcoma cell lines. In the cell lines with phosphorylated IRS1, inhibition of IGF1R signalling decreased phosphorylated Akt levels and increased IGF1R expression, but it did not influence MAPK or S6 activity. In line with these findings, treatment with IGF1R/IR inhibitors did not impact proliferation or migration in any of the chondrosarcoma cell lines, even upon stimulation with IGF1. Although synergistic effects of IGF1R/IR inhibition with doxorubicin are described for other cancers, our results demonstrate that this was not the case for chondrosarcoma. In addition, we found minimal IGF1R expression in primary tumours in contrast to the high expression detected in chondrosarcoma cell lines, even if both were derived from the

  6. Bone marrow-sparing intensity-modulated radiation therapy for Stage I seminoma

    International Nuclear Information System (INIS)

    Zilli, Thomas; Boudreau, Chantal; Doucet, Robert; Alizadeh, Moein; Lambert, Carole; Van Nguyen, Thu; Taussky, Daniel

    2011-01-01

    Background. A direct association between radiotherapy dose, side-effects and secondary cancers has been described in patients with seminoma. A treatment planning study was performed in order to compare computed tomography-based traditional radiotherapy (CT-tRT) versus bone marrow-sparing intensity-modulated radiation therapy (BMS-IMRT) in patients with Stage I seminoma. Material and methods. We optimized in 10 patients a CT-tRT and a BMS-IMRT treatment plan to deliver 20 Gy to the para-aortic nodes. CT-tRT and IMRT consisted of anteroposterior-posterioranterior parallel-opposed and seven non-opposed coplanar fields using 16 and 6-MV photon energies, respectively. Dose-Volume Histograms for clinical target volume (CTV), planning target volume (PTV) and organs at risk (OARs) were compared for both techniques using Wilcoxon matched-pair signed rank-test. Results. Dmean to CTV and PTV were similar for both techniques, even if CT-tRT showed a slightly improved target coverage in terms of PTV-D95% (19.7 vs. 19.5 Gy, p 0.005) and PTV-V95% (100 vs. 99.7%, p = 0.011) compared to BMS-IMRT. BMS-IMRT resulted in a significant reduction (5.2 Gy, p = 0.005) in the Dmean to the active bone marrow (ABM). The V100% and V75% of the OARs were reduced with BMS-IMRT by: ABM-V100% = 51.7% and ABM-V75% = 42.3%; bowel-V100% = 15.7% and bowel-V75% = 16.8%; stomach-V100% = 22% and stomach-V75% = 27.7%; pancreas-V100% = 37.1% and pancreas-V75% = 35.9% (p = 0.005 for all variables). Conclusions. BMS-IMRT reduces markedly the dose to the OARs compared to CT-tRT. This should translate into a reduction in acute and long-term toxicity, as well as into the risk of secondary solid and hematological cancers

  7. Impact of Conventional Medical Therapy on Bone Mineral Density and Bone Turnover in Adult Patients with X-Linked Hypophosphatemia

    DEFF Research Database (Denmark)

    Shanbhogue, Vikram Vinod; Hansen, Stinus; Jørgensen, Niklas Rye

    2018-01-01

    X-linked hypophosphatemia (XLH) is a rare, inheritable disorder manifesting as rickets in children and osteomalacia in adults. While conventional medical treatment with oral phosphate and alfacalcidol is recommended in childhood, it is undecided whether adults should continue therapy. The aim...

  8. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    Directory of Open Access Journals (Sweden)

    Guihong Li

    2016-01-01

    Full Text Available Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  9. Induced hemocompatibility and bone formation as biological scaffold for cell therapy implant

    Directory of Open Access Journals (Sweden)

    Keng-Liang Ou

    2016-06-01

    Full Text Available Although stem cells can become almost any type of specialized cell in the human body and may have the potential to generate replacement cells for tissues and organs, the transplantation of these cells are hindered by immune rejection and teratoma formation. However, scientists have found a promising solution for these problems-they have discovered the ability to isolate stem cells from a patient’s umbilical cord blood or bone marrow. Even more recently, small stem cells, such as spore-like stem cells, Blastomere-Like Stem Cells (BLSCs, and Very-Small Embryonic-Like stem cells (VSELs isolated directly from the peripheral blood have beeninvestigated as a novel approach to stem cell therapy as they can be isolated directly from the peripheral blood. A newly-discovered population of multipotent stem cells in this class has been dubbed StemBios (SB cells. The potential therapeutic uses of such stem cells have been explored in many ways, one of which includes dental remodeling and construction. Using adult stem cells, scientists have engineered and cultivated teeth in mice that may one day be used for human implantation.It follows that such regeneration may be possible, to a certain degree, in human patients as well. This idea leads to the present study on the effect of SB cell therapy on early osseointegrationof dental implants. Titanium (Ti dental implants have been proven to be a reliable and predictable treatment for restoration of edentulous regions. The osseointegration process can be described in two stages: primary stability (mechanical stability and secondary stability (biological stability. The mechanical stabilization of the implant reflects the interaction between the bone density and the features of the implant designs and can be determined after implant insertion. Alternatively,the biological stabilization of the implant is a physiologic healing process. It is couple to the biological interaction between the external surface of the

  10. Bone Marrow-Derived Mononuclear Cell Therapy in Papain-Induced Experimental Pulmonary Emphysema

    Directory of Open Access Journals (Sweden)

    Mariana N. Machado

    2018-02-01

    Full Text Available Murine papain-induced emphysema is a model that reproduces many of the features found in patients. Bone marrow-derived mononuclear cells (BMMC have already been used to repair the alveolar epithelium in respiratory diseases, but not in the papain model. Thus, we hypothesized that BMMC could prevent the pathophysiological processes in papain-induced experimental emphysema. Female BALB/c mice received intratracheal instillation of 50 μL of saline (S groups or papain (P groups, 10 IU/50 μl of saline on days 1 and 7 of the experimental protocol. On the 14th day, 2 × 106 BMMC of male BALB/c mice (SC21 and PC21 or saline (SS21 and PS21 were injected by the jugular vein. Analyses were done on days 14 (S14 and P14 and 21 (SS21, PS21, SC21, and PC21 of the protocol. qPCR evaluated the presence of the Y chromosome in the lungs of BMMC recipient animals. Functional residual capacity (FRC, alveolar diameter, cellularity, elastic fiber content, concentrations of TNF-α, IL-1β, IL-6, MIP-2, KC, IFN-γ, apoptosis, mRNA expression of the dual oxidase (DUOX1 and DUOX2, production of H2O2 and DUOX activity were evaluated in lung tissue. We did not detect the Y chromosome in recipients' lungs. FRC, alveolar diameter, polymorphonuclear cells (PMN and levels of KC, MIP-2, and IFN-γ increased in P14 and PS21 groups; the changes in the latter were reverted by BMMC. TNF-α, IL-1β e IL-6 were similar in all groups. The amount of elastic fibers was smaller in P14 and PS21 than in other groups, and BMMC did not increase it in PC21 mice. PS21 animals showed increased DUOX activity and mRNA expression for DUOX1 and 2. Cell therapy reverted the activity of DUOX and mRNA expression of DUOX1. BMMC reduced mRNA expression of DUOX2. Apoptosis index was elevated in PS21 mice, which was reduced by cell therapy in PC21. Static compliance, viscoelastic component of elastance and pressure to overcome viscoelasticity were increased in P14 and PS21 groups. These changes and the

  11. Course of Quality of Life After Radiation Therapy for Painful Bone Metastases: A Detailed Analysis From the Dutch Bone Metastasis Study

    International Nuclear Information System (INIS)

    Westhoff, Paulien G.; Verdam, Mathilde G.E.; Oort, Frans J.; Jobsen, Jan J.; Vulpen, Marco van; Leer, Jan Willem H.; Marijnen, Corrie A.M.; Graeff, Alexander de; Linden, Yvette M. van der

    2016-01-01

    Purpose: To study the course of quality of life (QoL) after radiation therapy for painful bone metastases. Patients and Methods: The Dutch Bone Metastasis Study randomized 1157 patients with painful bone metastases between a single fraction of 8 Gy and 6 fractions of 4 Gy between 1996 and 1998. The study showed a comparable pain response of 74%. Patients filled out weekly questionnaires for 13 weeks, then monthly for 2 years. In these analyses, physical, psychosocial, and functional QoL domain scores and a score of general health were studied. Mixed modeling was used to model the course of QoL and to study the influence of several characteristics. Results: In general, QoL stabilized after 1 month. Psychosocial QoL improved after treatment. The level of QoL remained stable, steeply deteriorating at the end of life. For most QoL domains, a high pain score and intake of opioids were associated with worse QoL, with small effect sizes (−0.11 to −0.27). A poor performance score was associated with worse functional QoL, with a medium effect size (0.41). There is no difference in QoL between patients receiving a single fraction of 8 Gy and 6 fractions of 4 Gy, except for a temporary worsening of physical QoL after 6 fractions. Conclusion: Although radiation therapy for painful bone metastases leads to a meaningful pain response, most domains of QoL do not improve after treatment. Only psychosocial QoL improves slightly after treatment. The level of QoL is related to the actual survival, with a rather stable course of QoL for most of the remaining survival time and afterward a sharp decrease, starting only a few weeks before the end of life. Six fractions of 4 Gy lead to a temporary worse physical QoL compared with a single fraction of 8 Gy.

  12. Course of Quality of Life After Radiation Therapy for Painful Bone Metastases: A Detailed Analysis From the Dutch Bone Metastasis Study

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff, Paulien G., E-mail: p.g.westhoff@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Department of Radiotherapy, Radboud University Medical Center, Nijmegen (Netherlands); Verdam, Mathilde G.E. [Department of Medical Psychology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Oort, Frans J. [Research Institute of Child Development and Education, Department of Medical Psychology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Jobsen, Jan J. [Department of Radiotherapy, Medisch Spectrum Twente, Enschede (Netherlands); Vulpen, Marco van [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Leer, Jan Willem H. [Department of Radiotherapy, Radboud University Medical Center, Nijmegen (Netherlands); Marijnen, Corrie A.M. [Department of Radiotherapy, Leiden University Medical Center, Leiden (Netherlands); Graeff, Alexander de [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Linden, Yvette M. van der [Department of Radiotherapy, Leiden University Medical Center, Leiden (Netherlands)

    2016-08-01

    Purpose: To study the course of quality of life (QoL) after radiation therapy for painful bone metastases. Patients and Methods: The Dutch Bone Metastasis Study randomized 1157 patients with painful bone metastases between a single fraction of 8 Gy and 6 fractions of 4 Gy between 1996 and 1998. The study showed a comparable pain response of 74%. Patients filled out weekly questionnaires for 13 weeks, then monthly for 2 years. In these analyses, physical, psychosocial, and functional QoL domain scores and a score of general health were studied. Mixed modeling was used to model the course of QoL and to study the influence of several characteristics. Results: In general, QoL stabilized after 1 month. Psychosocial QoL improved after treatment. The level of QoL remained stable, steeply deteriorating at the end of life. For most QoL domains, a high pain score and intake of opioids were associated with worse QoL, with small effect sizes (−0.11 to −0.27). A poor performance score was associated with worse functional QoL, with a medium effect size (0.41). There is no difference in QoL between patients receiving a single fraction of 8 Gy and 6 fractions of 4 Gy, except for a temporary worsening of physical QoL after 6 fractions. Conclusion: Although radiation therapy for painful bone metastases leads to a meaningful pain response, most domains of QoL do not improve after treatment. Only psychosocial QoL improves slightly after treatment. The level of QoL is related to the actual survival, with a rather stable course of QoL for most of the remaining survival time and afterward a sharp decrease, starting only a few weeks before the end of life. Six fractions of 4 Gy lead to a temporary worse physical QoL compared with a single fraction of 8 Gy.

  13. Long-term follow-up in patients treated with larynx preservation approach using sequential chemotherapy and radiation therapy: the Memorial Hospital experience

    Energy Technology Data Exchange (ETDEWEB)

    Maluf, Fernando; Sherman, Eric J.; Bosl, George J.; Pfister, David G. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Medicine. Div. of Solid Tumor Oncology; Kraus, Dennis H.; Shaha, Ashok; Shah, Jatin P. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States).Dept. of Surgery. Head and Neck Service; Zelefsky, Michael J. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Radiation Oncology]. E-mail: pfisterd@mskcc.org

    2000-06-01

    While many combined modality, organ preservation programs are reported in the literature, few provide long-term follow-up with functional outcomes. The goal of this report is to provide this outcome data for patients treated with a sequential chemotherapy/radiotherapy (CT/RT) approach - the only strategy successfully compared to surgery and RT in randomized trials to date - treated at our institution with a median follow-up of over 10 years. Eligible patients had advanced, resectable, histologically-confirmed squamous cell carcinomas of larynx or pharynx for which standard surgical management would have jeopardized the larynx. Treatment occurred as part of three consecutive larynx preservation protocols and consisted of three cycles of induction, cisplatin-based chemotherapy followed, if the primary site had a major response, by definitive dose radiation therapy (65-70 Gy to sites of initial disease bulk) via conventional fractionation (1.8-2 Gy fraction). If the tumor did not respond to the induction chemotherapy or persisted after radiation therapy, appropriate locoregional treatment was pursued. Response to induction chemotherapy, initial rendered disease-free rate, local control with a functional larynx (without any surgery except biopsy to the primary site, permanent tracheostomy or gastrostomy - LCLP), and actuarial survival rates were calculated. A multivariate assessment of prognostic variables was performed using Cox-proportional hazards model to evaluate for predictors of successful larynx preservation. One hundred and ten patients (109 evaluable) with cancer of the larynx (40%), hypopharynx (29%), and oropharynx (30%) were enrolled from 1983 to 1990. The median age was 60 years With a median Karnofsky Performance Status of 80%. The stage of the patients consisted of 33% T4, 74% node positive, and 69% stage IV. The major response rate at the primary site to induction chemotherapy was 74% (complete response in 36%). Seventy-eight percent were rendered

  14. Preservation of sexual function in young prostate cancer patients after radiation therapy: a positive factor in choice of a treatment modality

    International Nuclear Information System (INIS)

    Nicolaou, Nicos; Bruner, Deborah Watkins; Hanks, G.E.; Hanlon, Alex

    1996-01-01

    Purpose/Objective: To assess the effect of definitive radiation therapy (RT) without androgen deprivation, on the sexual function and quality of life of young prostate cancer patients as compared to age matched controls, using the Sexual Adjustment Questionnaire (SAQ), in order to assist future patients in making informed choices when deciding between surgery and radiation therapy. Methods and Materials: Forty five patients between 50 and 65 years of age at time of diagnosis (mean age 60 years), were treated with RT at Fox Chase Cancer Center (FCCC) from 1/1/89 to 12/31/93 for biopsy proven, T1-T3 clinically localized prostatic adenocarcinoma. Mean age at time of present assessment was 63 years. Their pre- and post-treatment sexual function and quality of life were assessed and compared to 47 age matched controls (mean age 60 years) using a modified version of the SAQ. Results: Mean and median follow up of the RT group was 31 months. Potency rate was 85% ((40(47))) in controls and pre-treatment potency rate was 91% ((41(45))) in RT group. Post-treatment overall potency rate in RT group was 67% ((30(45))). Preservation of potency in initially potent patients treated with RT, was 73% ((30(41))). The RT group was significantly inferior to the control group regarding sexual arousal, function and frequency of sexual activity but not in sexual desire and enjoyment or the importance placed on sexual activity. Conclusion: (1) Sexual potency is preserved in 73% of young sexually active men treated with RT for prostate cancer which is at least as good as the best reports after never sparing prostatectomy and far superior to the 0-10% rates of sexual potency preservation after non-nerve sparing prostatectomy. (2) The 27% of patients who lose sexual potency after RT, generally retain sexual desire and enjoyment indicating a favorable situation for rehabilitation. (3) The 27% loss of sexual potency may be artificially high without a known correction factor for those who would

  15. Long-term follow-up in patients treated with larynx preservation approach using sequential chemotherapy and radiation therapy: the Memorial Hospital experience

    International Nuclear Information System (INIS)

    Maluf, Fernando; Sherman, Eric J.; Bosl, George J.; Pfister, David G.; Kraus, Dennis H.; Shaha, Ashok; Shah, Jatin P.; Zelefsky, Michael J.

    2000-01-01

    While many combined modality, organ preservation programs are reported in the literature, few provide long-term follow-up with functional outcomes. The goal of this report is to provide this outcome data for patients treated with a sequential chemotherapy/radiotherapy (CT/RT) approach - the only strategy successfully compared to surgery and RT in randomized trials to date - treated at our institution with a median follow-up of over 10 years. Eligible patients had advanced, resectable, histologically-confirmed squamous cell carcinomas of larynx or pharynx for which standard surgical management would have jeopardized the larynx. Treatment occurred as part of three consecutive larynx preservation protocols and consisted of three cycles of induction, cisplatin-based chemotherapy followed, if the primary site had a major response, by definitive dose radiation therapy (65-70 Gy to sites of initial disease bulk) via conventional fractionation (1.8-2 Gy fraction). If the tumor did not respond to the induction chemotherapy or persisted after radiation therapy, appropriate locoregional treatment was pursued. Response to induction chemotherapy, initial rendered disease-free rate, local control with a functional larynx (without any surgery except biopsy to the primary site, permanent tracheostomy or gastrostomy - LCLP), and actuarial survival rates were calculated. A multivariate assessment of prognostic variables was performed using Cox-proportional hazards model to evaluate for predictors of successful larynx preservation. One hundred and ten patients (109 evaluable) with cancer of the larynx (40%), hypopharynx (29%), and oropharynx (30%) were enrolled from 1983 to 1990. The median age was 60 years With a median Karnofsky Performance Status of 80%. The stage of the patients consisted of 33% T4, 74% node positive, and 69% stage IV. The major response rate at the primary site to induction chemotherapy was 74% (complete response in 36%). Seventy-eight percent were rendered

  16. Retrospective Analysis of the Outcome of Ridge Preservation with Anorganic Bovine Bone Minerals: Microcomputed Tomographic Assessment of Wound Healing in Grafted Extraction Sockets.

    Science.gov (United States)

    Bakhshalian, Neema; Freire, Marcelo; Min, Seiko; Wu, Ivy; Zadeh, Homayoun H

    A total of 68 extraction sockets were grafted with anorganic bovine bone mineral and covered by dense polytetrafluoroethylene membrane. Quantitative analysis of three-dimensional microcomputed tomography imaging of core samples retrieved after a mean of 21.0 ± 14.2 weeks revealed 40.1% bone volume fraction (bone volume [BV]/total volume [TV]) and 12% residual graft. Evidence of de novo bone formation was observed in the form of discrete islands of newly formed bone in direct apposition to graft particles, separated from parent bone. Anterior sockets exhibited a significantly higher percentage of residual graft compared to premolar sockets (P = .05). The BV/TV and percentage of residual graft correlated well with histomorphometric analysis of the same sites, but not with implant outcomes.

  17. Improvement of Lumbar Bone Mass after Infliximab Therapy in Crohn’s Disease Patients

    Directory of Open Access Journals (Sweden)

    Marina Mauro

    2007-01-01

    Full Text Available BACKGROUND: Patients with Crohn’s disease (CD have a high risk of developing osteoporosis, but the mechanisms underlying bone mass loss are unclear. Elevated proinflammatory cytokines, such as tumour necrosis factor-alpha (TNFα, have been implicated in the pathogenesis of bone resorption.

  18. BEYOND GLYCEMIC CONTROL IN DIABETES MELLITUS: EFFECTS OF INCRETIN-BASED THERAPY ON BONE METABOLISM

    Directory of Open Access Journals (Sweden)

    ELENA eCECCARELLI

    2013-06-01

    Full Text Available Diabetes mellitus (DM and osteoporosis (OP are common disorders with a significant health burden, and an increase in fracture risk has been described both in type 1 (T1DM and in type 2 (T2DM diabetes. The pathogenic mechanisms of impaired skeletal strength in diabetes remain to be clarified in details and they are only in part reflected by a variation in bone mineral density (BMD. In T2DM, the occurrence of low bone turnover together with a decreased osteoblast activity and compromised bone quality has been shown. Of note, some antidiabetic drugs (e.g. tiazolidinediones, insulin may deeply affect bone metabolism. In addition, the recently introduced class of incretin-based drugs (i.e. GLP-1 receptor agonists and DPP-4 inhibitors is expected to exert potentially beneficial effects on bone health, possibly due to a bone anabolic activity of GLP-1, that can be either direct or indirect through the involvement of thyroid C cells.Here we will review the established as well as the putative effects of incretin hormones and of incretin-based drugs on bone metabolism, both in preclinical models and in man, taking into account that such therapeutic strategy may be effective not only to achieve a good glycemic control, but also to improve bone health in diabetic patients.

  19. Effects of low‑level laser therapy on osteoblastic bone formation and ...

    African Journals Online (AJOL)

    were compared. Conclusion: Histologically, LLLT stimulated bone formation, as revealed by analysis after the retention period. LLLT during expansion may accelerate bone healing. Key words: Bio‑stimulation, laser, rapid maxillary expansion. Date of Acceptance: 12‑Jan‑2015. Address for correspondence: Dr. M Demirkol,.

  20. Massage therapy during early postnatal life promotes greater lean mass and bone growth, mineralization, and strength in juvenile and young adult rats.

    Science.gov (United States)

    Chen, H; Miller, S; Shaw, J; Moyer-Mileur, L

    2009-01-01

    The objects of this study were to investigate the effects of massage therapy during early life on postnatal growth, body composition, and skeletal development in juvenile and young adult rats. Massage therapy was performed for 10 minutes daily from D6 to D10 of postnatal life in rat pups (MT, n=24). Body composition, bone area, mineral content, and bone mineral density were measured by dual energy X-ray absorptiometry (DXA); bone strength and intrinsic stiffness on femur shaft were tested by three-point bending; cortical and cancellous bone histomorphometric measurements were performed at D21 and D60. Results were compared to age- and gender-matched controls (C, n=24). D21 body weight, body length, lean mass, and bone area were significantly greater in the MT cohort. Greater bone mineral content was found in male MT rats; bone strength and intrinsic stiffness were greater in D60 MT groups. At D60 MT treatment promoted bone mineralization by increasing trabecular mineral apposition rate in male and endosteal mineral surface in females, and also improved micro-architecture by greater trabeculae width in males and decreasing trabecular separation in females. In summary, massage therapy during early life elicited immediate and prolonged anabolic effects on postnatal growth, lean mass and skeletal developmental in a gender-specific manner in juvenile and young adult rats.

  1. Psychometric evaluation of the Polish adaptation of the Hill-Bone Compliance to High Blood Pressure Therapy Scale.

    Science.gov (United States)

    Uchmanowicz, Izabella; Jankowska-Polańska, Beata; Chudiak, Anna; Szymańska-Chabowska, Anna; Mazur, Grzegorz

    2016-05-10

    Development of simple instruments for the determination of the level of adherence in patients with high blood pressure is the subject of ongoing research. One such instrument, gaining growing popularity worldwide, is the Hill-Bone Compliance to High Blood Pressure Therapy. The aim of this study was to adapt and to test the reliability of the Polish version of Hill-Bone Compliance to High Blood Pressure Therapy Scale. A standard guideline was used for the translation and cultural adaptation of the English version of the Hill-Bone Compliance to High Blood Pressure Therapy Scale into Polish. The study included 117 Polish patients with hypertension aged between 27 and 90 years, among them 53 men and 64 women. Cronbach's alpha was used for analysing the internal consistency of the scale. The mean score in the reduced sodium intake subscale was M = 5.7 points (standard deviation SD = 1.6 points). The mean score in the appointment-keeping subscale was M = 3.4 points (standard deviation SD = 1.4 points). The mean score in the medication-taking subscale was M = 11.6 points (standard deviation SD = 3.3 points). In the principal component analysis, the three-factor system (1 - medication-taking, 2 - appointment-keeping, 3 - reduced sodium intake) accounted for 53 % of total variance. All questions had factor loadings > 0.4. The medication-taking subscale: most questions (6 out of 9) had the highest loadings with Factor 1. The appointment-keeping subscale: all questions (2 out of 2) had the highest loadings with Factor 2. The reduced sodium intake subscale: most questions (2 out of 3) had the highest loadings with Factor 3. Goodness of fit was tested at chi(2) = 248.87; p High Blood Pressure Therapy Scale proved to be suitable for use in the Polish population. Use of this screening tool for the assessment of adherence to BP treatment is recommended.

  2. Clinical study of 89Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms

    International Nuclear Information System (INIS)

    Liu Yajie; Wang Shubin; Guo Yiling; Chen Zuowei; Zhang Yingnan

    2005-01-01

    Objective: To evaluate the curative effect and side effects of 89 Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms. Methods: Ninety-seven patients were divided into 4 groups respectively: group A, 89 Sr + nicotinamide + carbogen (24 patients); group B, 89 Sr + nicotinamide(22 patients); group C, 89 Sr + carbogen (25 patients); group D, 89 Sr, (26 patients). 89 SrCl was intravenously injected at a dose of 1.48-2.22 MBq/kg. Nicotinamide was taken orally 1 hour before 89 SrCl injection, 6 g/day, tid, d1-d5. Aspiration of carbogen(95%O 2 + 5%CO 2 ) gases, 6 L/min, 10 minutes, qd, d1-d5. Results: The effective rate of pain control and QOL improvement in A group were higher than in groups B, C and D (91.7% VS 77.3%, 76.0% and 69.2%, P=0.048). The lesions assessed by SPECT imaging in every group was not significantly different at three months after treatment. I to II degree toxic effect on bone marrow appeared in every group and there were no significantly inter-group differences. Conclusions: Combinative therapy using 89 Sr + nicotinamide + carbogen is more effective to treat multiple metastatic bone pain and for improvement of QOL. The side effects are not increased. (authors)

  3. Investigation of a Novel PLGA/CaP Scaffold in the Healing of Tooth Extraction Sockets to Alveolar Bone Preservation in Humans.

    Science.gov (United States)

    Araujo-Pires, Ana Claudia; Mendes, Vanessa Cristina; Ferreira-Junior, Osny; Carvalho, Paulo Sérgio Perri; Guan, Limin; Davies, John Edward

    2016-06-01

    It is expected that 40% to 60% of initial alveolar bone volume will be lost up to 6 months after tooth extraction. OsteoScaf(TM) (TRT, Toronto, ON, Canada) (poly (DL-lactide-co-glycololide/calcium phosphate [PLGA/CaP] scaffold) is a novel bone substitute material and represents a promising alternative for maintaining alveolar bone integrity in this clinical scenario. Here it was hypothesized that OsteoScaf would reduce alveolar bone lost after tooth extraction in patient, acting as a clot-retention device. A total of 10 patients (32 sockets) were included in the study, of which 16 sockets were grafted with OsteoScaf and 16 were used as control (coagulum alone). Cone beam computed tomography (CBCT) was performed both immediately following extraction and also at 120 days postoperatively, at which time biopsy samples were also harvested for histological analyses. Quantitative analysis of CBCT showed less bone resorption in the OsteoScaf groups, being 10.5% to 14.4% less bone lost in the center of the socket, 15.4% in the buccal region, and 12.6% in the palatal. Qualitative histological analysis showed new bone tissue in direct apposition to the scaffold - demonstrating its osteoconductive nature. OsteoScaf diminished the expected bone lost during the postextraction remodeling of the alveolar bone ridge at 120 days postextraction. © 2015 Wiley Periodicals, Inc.

  4. A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wu Weigang; Zheng Qixin; Guo Xiaodong; Sun Jianhua; Liu Yudong, E-mail: Zheng-qx@163.co [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

    2009-12-15

    In the world, bone tuberculosis is still very difficult to treat and presents a challenge to clinicians. In this study, we utilized 3D printing technology to fabricate a programmed release multi-drug implant for bone tuberculosis therapy. The construction of the drug implant was a multi-layered concentric cylinder divided into four layers from the center to the periphery. Isoniazid and rifampicin were distributed individually into the different layers in a specific sequence of isoniazid-rifampicin-isoniazid-rifampicin. The drug release assays in vitro and in vivo showed that isoniazid and rifampicin were released orderly from the outside to the center to form the multi-drug therapeutic alliance, and the peak concentrations of drugs were detected in sequence at 8 to 12 day intervals. In addition, no negative effect on the proliferation of rabbit bone marrow mesenchymal stem cells was detected during the cytocompatibility assay. Due to its ideal pharmacologic action and cytocompatibility, the programmed release multi-drug implant with a complex construction fabricated by 3D printing technology could be of interest in prevention and treatment of bone tuberculosis.

  5. Overall response rates to radiation therapy for patients with painful uncomplicated bone metastases undergoing initial treatment and retreatment

    International Nuclear Information System (INIS)

    Bedard, Gillian; Hoskin, Peter; Chow, Edward

    2014-01-01

    Introduction: Radiation therapy has been shown to successfully palliate bone metastases. A number of systematic reviews and large clinical trials have reported response rates for initial treatment and retreatment. Objective: To determine overall response rates of patients with painful uncomplicated bone metastases undergoing initial treatment and retreatment. Methods: Intent-to-treat and evaluable patient statistics from a systematic review of palliative radiotherapy trials for initial treatment of bone metastases and a randomized clinical trial of retreatment were pooled and analyzed to determine the overall response rates for patients receiving initial treatment and retreatment. Results: In the intent-to-treat calculation, 71–73% of patients had an overall response to radiation treatment and in the evaluable patient population; 85–87% of patients did so. Response rates varied slightly whether patients underwent single or multiple fractions in initial treatment or retreatment. Conclusions: Single and multiple fraction radiation treatment yielded very similar overall response rates. Patients treated with a single fraction for both initial and repeat radiation experience almost identical overall response to those patients treated with multiple fraction treatment. It is therefore recommended that patients with uncomplicated painful bone metastases be treated with a single 8 Gy fraction of radiation at both the initial treatment and retreatment

  6. A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy

    International Nuclear Information System (INIS)

    Wu Weigang; Zheng Qixin; Guo Xiaodong; Sun Jianhua; Liu Yudong

    2009-01-01

    In the world, bone tuberculosis is still very difficult to treat and presents a challenge to clinicians. In this study, we utilized 3D printing technology to fabricate a programmed release multi-drug implant for bone tuberculosis therapy. The construction of the drug implant was a multi-layered concentric cylinder divided into four layers from the center to the periphery. Isoniazid and rifampicin were distributed individually into the different layers in a specific sequence of isoniazid-rifampicin-isoniazid-rifampicin. The drug release assays in vitro and in vivo showed that isoniazid and rifampicin were released orderly from the outside to the center to form the multi-drug therapeutic alliance, and the peak concentrations of drugs were detected in sequence at 8 to 12 day intervals. In addition, no negative effect on the proliferation of rabbit bone marrow mesenchymal stem cells was detected during the cytocompatibility assay. Due to its ideal pharmacologic action and cytocompatibility, the programmed release multi-drug implant with a complex construction fabricated by 3D printing technology could be of interest in prevention and treatment of bone tuberculosis.

  7. Targeting sphingosine-1-phosphate lyase as an anabolic therapy for bone loss.

    Science.gov (United States)

    Weske, Sarah; Vaidya, Mithila; Reese, Alina; von Wnuck Lipinski, Karin; Keul, Petra; Bayer, Julia K; Fischer, Jens W; Flögel, Ulrich; Nelsen, Jens; Epple, Matthias; Scatena, Marta; Schwedhelm, Edzard; Dörr, Marcus; Völzke, Henry; Moritz, Eileen; Hannemann, Anke; Rauch, Bernhard H; Gräler, Markus H; Heusch, Gerd; Levkau, Bodo

    2018-05-01

    Sphingosine-1-phosphate (S1P) signaling influences bone metabolism, but its therapeutic potential in bone disorders has remained unexplored. We show that raising S1P levels in adult mice through conditionally deleting or pharmacologically inhibiting S1P lyase, the sole enzyme responsible for irreversibly degrading S1P, markedly increased bone formation, mass and strength and substantially decreased white adipose tissue. S1P signaling through S1P 2 potently stimulated osteoblastogenesis at the expense of adipogenesis by inversely regulating osterix and PPAR-γ, and it simultaneously inhibited osteoclastogenesis by inducing osteoprotegerin through newly discovered p38-GSK3β-β-catenin and WNT5A-LRP5 pathways. Accordingly, S1P 2 -deficient mice were osteopenic and obese. In ovariectomy-induced osteopenia, S1P lyase inhibition was as effective as intermittent parathyroid hormone (iPTH) treatment in increasing bone mass and was superior to iPTH in enhancing bone strength. Furthermore, lyase inhibition in mice successfully corrected severe genetic osteoporosis caused by osteoprotegerin deficiency. Human data from 4,091 participants of the SHIP-Trend population-based study revealed a positive association between serum levels of S1P and bone formation markers, but not resorption markers. Furthermore, serum S1P levels were positively associated with serum calcium , negatively with PTH , and curvilinearly with body mass index. Bone stiffness, as determined through quantitative ultrasound, was inversely related to levels of both S1P and the bone formation marker PINP, suggesting that S1P stimulates osteoanabolic activity to counteract decreasing bone quality. S1P-based drugs should be considered as a promising therapeutic avenue for the treatment of osteoporotic diseases.

  8. CHANGES OF BONE MINERAL DENSITY DURING FOUR-YEAR RITUXIMAB AND METHOTREXATE THERAPY IN POSTMENOPAUSAL WOMEN WITH RHEUMATOID ARTHRITIS

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    T. A. Raskina

    2016-01-01

    Full Text Available Objective: to estimate the changes of bone mineral density (BMD  at the femoral neck and lumbar spine during fouryear combination  therapy with rituximab (RTM  and methotrexate (MT in postmenopausal women with rheumatoid arthritis (RA.Subjects and methods. 79 postmenopausal women with a documented diagnosis of RA were followed up. They were divided into two groups according to the basic treatment:  1 44 patients received combination  therapy with RTM and MT; 2 36 patients had MT monotherapy. BMD was assessed by dual-energy X-ray absorptiometry using an Excell XR-46 stationary dual-energy X-ray bone densitometer  (Norland, USA once per year (over 48 months.Results and discussion. The group of patients receiving RTM and MT achieved a statistically significant increase in femoral neck BMD after 36 months of therapy. Statistically significant changes in femoral neck BMD were not revealed in the patients who had MT monotherapy. Lumbar spine BMD was decreased during MT monotherapy, but it remained stable in the RTM + MT group throughout  the 48-month follow-up.Conclusion. Thirty-six-month combination  treatment with RTM and MT provides positive changes in femoral neck BMD, which persists within 48 months after treatment initiation.  Lumbar spine BMD remained stable in the patients receiving RTM and MT.

  9. Fertility preservation with ovarian stimulation and time to treatment in women with stage II-III breast cancer receiving neoadjuvant therapy.

    Science.gov (United States)

    Chien, A Jo; Chambers, Julia; Mcauley, Fiona; Kaplan, Tessa; Letourneau, Joseph; Hwang, Jimmy; Kim, Mi-Ok; Melisko, Michelle E; Rugo, Hope S; Esserman, Laura J; Rosen, Mitchell P

    2017-08-01

    To determine whether fertility preservation with ovarian stimulation (OS) results in treatment delay in breast cancer (BC) patients receiving neoadjuvant therapy (NAT). This is a retrospective study of women screened for the prospective neoadjuvant ISPY2 trial at the University of California San Francisco. All patients were years old, p = 0.06), and more likely to be childless (79.4 vs 31.2%, p 40 days, with no significant difference between STIM and control groups (mean 39.8 days vs 40.9 days, p = 0.75). Mean time from diagnosis to fertility consultation was 16.3 days. With median follow-up of 79 months, 16 (19.5%) patients have recurred or died from BC. Rates of pCR, recurrence, and death were similar in both groups. Six of 34 STIM patients have undergone embryo transfer, resulting in one patient with two live births. Fertility preservation with OS can be performed in the neoadjuvant setting without delay in initiation of systemic therapy and should be discussed with all early-stage BC patients of reproductive age.

  10. Exercise therapy for bone and muscle health: an overview of systematic reviews.

    Science.gov (United States)

    Hagen, Kåre Birger; Dagfinrud, Hanne; Moe, Rikke Helene; Østerås, Nina; Kjeken, Ingvild; Grotle, Margreth; Smedslund, Geir

    2012-12-19

    Musculoskeletal conditions (MSCs) are widely prevalent in present-day society, with resultant high healthcare costs and substantial negative effects on patient health and quality of life. The main aim of this overview was to synthesize evidence from systematic reviews on the effects of exercise therapy (ET) on pain and physical function for patients with MSCs. In addition, the evidence for the effect of ET on disease pathogenesis, and whether particular components of exercise programs are associated with the size of the treatment effects, was also explored. We included four common conditions: fibromyalgia (FM), low back pain (LBP), neck pain (NP), and shoulder pain (SP), and four specific musculoskeletal diseases: osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis (AS), and osteoporosis (OP). We first included Cochrane reviews with the most recent update being January 2007 or later, and then searched for non-Cochrane reviews published after this date. Pain and physical functioning were selected as primary outcomes. We identified 9 reviews, comprising a total of 224 trials and 24,059 patients. In addition, one review addressing the effect of exercise on pathogenesis was included. Overall, we found solid evidence supporting ET in the management of MSCs, but there were substantial differences in the level of research evidence between the included diagnostic groups. The standardized mean differences for knee OA, LBP, FM, and SP varied between 0.30 and 0.65 and were significantly in favor of exercise for both pain and function. For NP, hip OA, RA, and AS, the effect estimates were generally smaller and not always significant. There was little or no evidence that ET can influence disease pathogenesis. The only exception was for osteoporosis, where there was evidence that ET increases bone mineral density in postmenopausal women, but no significant effects were found for clinically relevant outcomes (fractures). For LBP and knee OA, there was evidence

  11. Exercise therapy for bone and muscle health: an overview of systematic reviews

    Directory of Open Access Journals (Sweden)

    Hagen Kåre

    2012-12-01

    Full Text Available Abstract Background Musculoskeletal conditions (MSCs are widely prevalent in present-day society, with resultant high healthcare costs and substantial negative effects on patient health and quality of life. The main aim of this overview was to synthesize evidence from systematic reviews on the effects of exercise therapy (ET on pain and physical function for patients with MSCs. In addition, the evidence for the effect of ET on disease pathogenesis, and whether particular components of exercise programs are associated with the size of the treatment effects, was also explored. Methods We included four common conditions: fibromyalgia (FM, low back pain (LBP, neck pain (NP, and shoulder pain (SP, and four specific musculoskeletal diseases: osteoarthritis (OA, rheumatoid arthritis (RA, ankylosing spondylitis (AS, and osteoporosis (OP. We first included Cochrane reviews with the most recent update being January 2007 or later, and then searched for non-Cochrane reviews published after this date. Pain and physical functioning were selected as primary outcomes. Results We identified 9 reviews, comprising a total of 224 trials and 24,059 patients. In addition, one review addressing the effect of exercise on pathogenesis was included. Overall, we found solid evidence supporting ET in the management of MSCs, but there were substantial differences in the level of research evidence between the included diagnostic groups. The standardized mean differences for knee OA, LBP, FM, and SP varied between 0.30 and 0.65 and were significantly in favor of exercise for both pain and function. For NP, hip OA, RA, and AS, the effect estimates were generally smaller and not always significant. There was little or no evidence that ET can influence disease pathogenesis. The only exception was for osteoporosis, where there was evidence that ET increases bone mineral density in postmenopausal women, but no significant effects were found for clinically relevant outcomes

  12. Autologous bone marrow-derived stem cell therapy in heart disease: discrepancies and contradictions.

    Science.gov (United States)

    Francis, Darrel P; Mielewczik, Michael; Zargaran, David; Cole, Graham D

    2013-10-09

    Autologous bone marrow stem cell therapy is the greatest advance in the treatment of heart disease for a generation according to pioneering reports. In response to an unanswered letter regarding one of the largest and most promising trials, we attempted to summarise the findings from the most innovative and prolific laboratory. Amongst 48 reports from the group, there appeared to be 5 actual clinical studies ("families" of reports). Duplicate or overlapping reports were common, with contradictory experimental design, recruitment and results. Readers cannot always tell whether a study is randomised versus not, open-controlled or blinded placebo-controlled, or lacking a control group. There were conflicts in recruitment dates, criteria, sample sizes, million-fold differences in cell counts, sex reclassification, fractional numbers of patients and conflation of competitors' studies with authors' own. Contradictory results were also common. These included arithmetical miscalculations, statistical errors, suppression of significant changes, exaggerated description of own findings, possible silent patient deletions, fractional numbers of coronary arteries, identical results with contradictory sample sizes, contradictory results with identical sample sizes, misrepresented survival graphs and a patient with a negative NYHA class. We tabulate over 200 discrepancies amongst the reports. The 5 family-flagship papers (Strauer 2002, STAR, IACT, ABCD, BALANCE) have had 2665 citations. Of these, 291 citations were to the pivotal STAR or IACT-JACC papers, but 97% of their eligible citing papers did not mention any discrepancies. Five meta-analyses or systematic reviews covered these studies, but none described any discrepancies and all resolved uncertainties by undisclosed methods, in mutually contradictory ways. Meta-analysts disagreed whether some studies were randomised or "accepter-versus-rejecter". Our experience of presenting the discrepancies to journals is that readers may

  13. Monoclonal antibody-purged bone marrow transplantation therapy for multiple myeloma.

    Science.gov (United States)

    Anderson, K C; Andersen, J; Soiffer, R; Freedman, A S; Rabinowe, S N; Robertson, M J; Spector, N; Blake, K; Murray, C; Freeman, A

    1993-10-15

    Forty patients with plasma cell dyscrasias underwent high-dose chemoradiotherapy and either anti-B-cell monoclonal antibody (MoAb)-treated autologous, anti-T-cell MoAb-treated HLA-matched sibling allogeneic or syngeneic bone marrow transplantation (BMT). The majority of patients had advanced Durie-Salmon stage myeloma at diagnosis, all were pretreated with chemotherapy, and 17 had received prior radiotherapy. At the time of BMT, all patients demonstrated good performance status with Karnofsky score of 80% or greater and had less than 10% marrow tumor cells; 34 patients had residual monoclonal marrow plasma cells and 38 patients had paraprotein. Following high-dose chemoradiotherapy, there were 18 complete responses (CR), 18 partial responses, one non-responder, and three toxic deaths. Granulocytes greater than 500/microL and untransfused platelets greater than 20,000/microL were noted at a median of 23 (range, 12 to 46) and 25 (range, 10 to 175) days posttransplant (PT), respectively, in 24 of the 26 patients who underwent autografting. In the 14 patients who received allogeneic or syngeneic grafts, granulocytes greater than 500/microL and untransfused platelets greater than 20,000/microL were noted at a median of 19 (range, 12 to 24) and 16 (range, 5 to 32) days PT, respectively. With 24 months median follow-up for survival after autologous BMT, 16 of 26 patients are alive free from progression at 2+ to 55+ months PT; of these, 5 patients remain in CR at 6+ to 55+ months PT. With 24 months median follow-up for survival after allogeneic and syngeneic BMT, 8 of 14 patients are alive free from progression at 8+ to 34+ months PT; of these, 5 patients remain in CR at 8+ to 34+ months PT. This therapy has achieved high response rates and prolonged progression-free survival in some patients and proven to have acceptable toxicity. However, relapses post-BMT, coupled with slow engraftment post-BMT in heavily pretreated patients, suggest that such treatment strategies

  14. Thoracic radiation therapy before autologous bone marrow transplantation in relapsed or refractory Hodgkin's disease

    International Nuclear Information System (INIS)

    Tsang, R.W.; Gospodarowicz, M.K.; Sutcliffe, S.B.; Crump, M.; Keating, A.

    1999-01-01

    The aim of this study was to assess the relationship between radiation therapy (RT) and treatment-related mortality in patients receiving high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT) for recurrent/refractory Hodgkin's disease (HD). Between December 1986 and December 1992, 59 patients previously treated at the Princess Margaret Hospital underwent HDCT (etoposide 60 mg/kg, melphalan 160 mg/m 2 ) and ABMT, performed for refractory (13 patients) or relapsed (46 patients) HD. RT was incorporated in the salvage treatment with the intent to achieve complete control of disease prior to ABMT. RT was given before ABMT in 33 patients, and after ABMT in 4 patients. Treatment-related (TR) mortality was defined as any death occurring within 100 days of ABMT. Autopsies were performed for all patients with TR deaths. With a median follow-up of 4.6 years (range 1.2-7.4 years), the actuarial overall survival was 41%±14% at 5 years. We observed 37 deaths, and 10 of these were TR deaths. Among the 24 patients who received thoracic RT before ABMT, there were 8 TR deaths, 3 of these solely attributable to radiation pneumonitis. The remaining 5 TR deaths all had respiratory failure with complicating sepsis as a major medical problem. The interval from RT to ABMT was shorter for 8 patients dying of TR death (mean 37 days; range 0-103 days), than for the 16 survivors (mean 105 days; range 0-263 days) (P=0.026). Among 9 patients with ABMT within 50 days of thoracic RT, 6 had TR death. In contrast, among the 35 patients without thoracic RT (26 no RT, 9 non-thoracic RT), there were only 2 TR deaths. The 4 patients treated with mantle RT post-ABMT had no serious pulmonary complications. The use of thoracic RT before HDCT and ABMT was associated with a high post-transplant mortality rate. It was most evident in patients who received thoracic RT within 50 days prior to ABMT, or when the target volume included large volume of lung. We recommend that the use of

  15. Combined bilateral idiopathic necrosis of the humerus and femur heads: Bone scan, X-ray, CT, and MRI findings

    International Nuclear Information System (INIS)

    Piepenburg, R.; Hahn, K.; Doll, G.; Grimm, J.

    1992-01-01

    Untreated aseptic bone necroses close to a joint commonly leads to severe secondary arthrosis and destruction of the joint within a short time. Therefore, only a diagnosis in an early stage of the disease offers the chance of a successful joint- preserving therapy. In cases of clinically suspected aseptic bone necrosis but still negative or doubtful X-ray findings, bone scans or MRI are reliable methods of verifying the diagnosis. (orig./MG) [de

  16. Parathyroid hormone related to bone regeneration in grafted and nongrafted tooth extraction sockets in rats.

    Science.gov (United States)

    Kuroshima, Shinichiro; Al-Salihi, Zeina; Yamashita, Junro

    2013-02-01

    The quality and quantity of bone formed in tooth extraction sockets impact implant therapy. Therefore, the establishment of a new approach to enhance bone formation and to minimize bone resorption is important for the success of implant therapy. In this study, we investigated whether intermittent parathyroid hormone (PTH) therapy enhanced bone formation in grafted sockets. Tooth extractions of the maxillary first molars were performed in rats, and the sockets were grafted with xenograft. Intermittent PTH was administered either for 7 days before extractions, for 14 days after extractions, or both. The effect of PTH therapy on bone formation in the grafted sockets was assessed using microcomputed tomography at 14 days after extractions. PTH therapy for 7 days before extractions was not effective to augment bone fill, whereas PTH therapy for 14 days after operation significantly augmented bone formation in the grafted sockets. Intermittent PTH therapy starting right after tooth extractions significantly enhanced bone fill in the grafted sockets, suggesting that PTH therapy can be a strong asset for the success of the ridge preservation procedure.

  17. Effect of growth hormone therapy and puberty on bone and body composition in children with idiopathic short stature and growth hormone deficiency.

    Science.gov (United States)

    Högler, Wolfgang; Briody, Julie; Moore, Bin; Lu, Pei Wen; Cowell, Christopher T

    2005-11-01

    The state of bone health and the effect of growth hormone (GH) therapy on bone and body composition in children with idiopathic short stature (ISS) are largely unknown. A direct role of GH deficiency (GHD) on bone density is controversial. Using dual-energy X-ray absorptiometry, this study measured total body bone mineral content (TB BMC), body composition, and volumetric bone mineral density (vBMD) at the lumbar spine (LS) and femoral neck (FN) in 77 children (aged 3-17 years) with ISS (n = 57) and GHD (n = 20). Fifty-five children (GHD = 13) receiving GH were followed over 24 months including measurement of bone turnover. At diagnosis, size-corrected TB BMC SDS was greater (P bone relation, as assessed by the BMC/lean mass (LTM) ratio SDS was not different between groups. During GH therapy, prepubertal GHD children gained more height (1.58 [0.9] SDS) and LTM (0.87 [0.63] SDS) compared to prepubertal ISS children (0.75 [0.27] and 0.17 [0.25] SDS, respectively). Percent body fat decreased in GHD (-5.94% [4.29]) but not in ISS children. Total body BMC accrual was less than predicted in all groups accompanied by an increase in bone turnover. Puberty led to the greatest absolute, but not relative, increments in weight, LTM, BMI, bone mass, and LSvBMD. Our results show that children with ISS and GHD differ in their response to GH therapy in anthropometry, body composition, and bone measures. Despite low vBMD values at diagnosis in both prepubertal groups, size-corrected regional or TB bone data were generally within the normal range and did not increase during GH therapy in GHD or ISS children. Growth hormone had great effects on the growth plate and body composition with subsequent gains in height, LTM, bone turnover, and bone mass accrual, but no benefit for volumetric bone density over 2 years.

  18. Results after therapy of pain from bone metastases with Samarium-153 in our centers in Lima, Peru

    International Nuclear Information System (INIS)

    Alvarado, N.; Eskenazi, S.; Valle, M.P.; Montoya, J.; Castro, M.; Montiel, L.; Velarde, V.; Jauregui, I.; Cueto, C.

    2004-01-01

    Full text: 105 patients with bone metastases from prostate and breast cancer; between 42 and 78 years age (median 61 years) were evaluated. Patients had intense pain that could not be managed with combinations of analgesic and anti tumoral drugs. All patients received 1.2 mCi/kg of Samarium-153 intravenously as treatment for pain due to bony metastases. The isotope obtained from atomic reactor placed in Lima - Peru, was provided by Peruvian Nuclear Energy Institute (IPEN). One week before therapy, all the patients had a bone scan study with Tc99m-MDP that showed the presence of multiple bone metastases with high blastic activity. Haematology and biochemical parameter checked were: Creatinine ( 150,000 mm3), Leukocytes (> 5,000 mm3), Red cells (>3,500,000 mm3). No problems were encountered during intravenous administration of the radioisotope. The side effects after treatment were: Primary effects: 16 cases of nausea, 2 of vomiting, 3 of headache, 28 had increment of pain, 6 had flushing. 50 patients did not have the primary symptoms. Secondary effects: 3 Patients showed drop in leukocyte count between 2nd and 3rd week of therapy. Red cells showed 10-15% decrease between 6th to 8th week. Platelets showed a decrease of about 15% with one peak between 1st and 2nd week post Samarium therapy. Data was analysed using an analogue visual scale of the pain with values from 0 - 10 (0-no pain; 10-maximum pain) and in the same way using the E.C.O.G. scale (Eastern Cooperative Oncology Group) in relationship with the Karnofsky index in order to establish functional recovery for each patient. The decrease of pain was seen between 4th-7th days (average 8 days). A second dose was given after 60 days in 12 patients and a third dose in 3 cases.11 patients died due to different causes between 30 - 60 days post treatment. The analgesic dose came down significantly in 80% of patients. We conclude that palliative therapy of metastatic bone pain in Peru is possible with radionuclides. It

  19. Association of Trabecular Bone Score with Inflammation and Adiposity in Patients with Psoriasis: Effect of Adalimumab Therapy

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    José L. Hernández

    2016-01-01

    Full Text Available Studies on trabecular bone score (TBS in psoriasis are lacking. We aim to assess the association between TBS and inflammation, metabolic syndrome features, and serum adipokines in 29 nondiabetic patients with psoriasis without arthritis, before and after 6-month adalimumab therapy. For that purpose, adjusted partial correlations and stepwise multivariable linear regression analysis were performed. No correlation was found between TBS and disease severity. TBS was negatively associated with weight, BMI, waist perimeter, fat percentage, and systolic and diastolic blood pressure before and after adalimumab. After 6 months of therapy, a negative correlation between TBS and insulin resistance (p=0.02 and leptin (p=0.01 and a positive correlation with adiponectin were found (p=0.01. The best set of predictors for TBS values at baseline were female sex (p=0.015, age (p=0.05, and BMI (p=0.001. The best set of predictors for TBS following 6 months of biologic therapy were age (p=0.001, BMI (p<0.0001, and serum adiponectin levels (p=0.027. In conclusion, in nondiabetic patients with moderate-to-severe psoriasis, TBS correlates with metabolic syndrome features and inflammation. This association is still present after 6 months of adalimumab therapy. Moreover, serum adiponectin levels seem to be an independent variable related to TBS values, after adalimumab therapy.

  20. Wood preservation

    Science.gov (United States)

    Kevin Archer; Stan Lebow

    2006-01-01

    Wood preservation can be interpreted to mean protection from fire, chemical degradation, mechanical wear, weathering, as well as biological attack. In this chapter, the term preservation is applied more restrictively to protection from biological hazards.

  1. A mineral-rich extract from the red marine algae Lithothamnion calcareum preserves bone structure and function in female mice on a Western-style diet.

    Science.gov (United States)

    Aslam, Muhammad Nadeem; Kreider, Jaclynn M; Paruchuri, Tejaswi; Bhagavathula, Narasimharao; DaSilva, Marissa; Zernicke, Ronald F; Goldstein, Steven A; Varani, James

    2010-04-01

    The purpose of this study was to determine whether a mineral-rich extract derived from the red marine algae Lithothamnion calcareum could be used as a dietary supplement for prevention of bone mineral loss. Sixty C57BL/6 mice were divided into three groups based on diet: the first group received a high-fat Western-style diet (HFWD), the second group was fed the same HFWD along with the mineral-rich extract included as a dietary supplement, and the third group was used as a control and was fed a low-fat rodent chow diet (AIN76A). Mice were maintained on the respective diets for 15 months. Then, long bones (femora and tibiae) from both males and females were analyzed by three-dimensional micro-computed tomography (micro-CT) and (bones from female mice) concomitantly assessed in bone strength studies. Tartrate-resistant acid phosphatase (TRAP), osteocalcin, and N-terminal peptide of type I procollagen (PINP) were assessed in plasma samples obtained from female mice at the time of sacrifice. To summarize, female mice on the HFWD had reduced bone mineralization and reduced bone strength relative to female mice on the low-fat chow diet. The bone defects in female mice on the HFWD were overcome in the presence of the mineral-rich supplement. In fact, female mice receiving the mineral-rich supplement in the HFWD had better bone structure/function than did female mice on the low-fat chow diet. Female mice on the mineral-supplemented HFWD had higher plasma levels of TRAP than mice of the other groups. There were no differences in the other two markers. Male mice showed little diet-specific differences by micro-CT.

  2. Reduced quantitative ultrasound bone mineral density in HIV-infected patients on antiretroviral therapy in Senegal.

    Directory of Open Access Journals (Sweden)

    Amandine Cournil

    Full Text Available BACKGROUND: Bone status in HIV-infected patients on antiretroviral treatment (ART is poorly documented in resource-limited settings. We compared bone mineral density between HIV-infected patients and control subjects from Dakar, Senegal. METHODS: A total of 207 (134 women and 73 men HIV-infected patients from an observational cohort in Dakar (ANRS 1215 and 207 age- and sex-matched controls from the general population were enrolled. Bone mineral density was assessed by quantitative ultrasound (QUS at the calcaneus, an alternative to the reference method (i.e. dual X-absorptiometry, often not available in resource-limited countries. RESULTS: Mean age was 47.0 (±8.5 years. Patients had received ART for a median duration of 8.8 years; 45% received a protease inhibitor and 27% tenofovir; 84% had undetectable viral load. Patients had lower body mass index (BMI than controls (23 versus 26 kg/m(2, P<0.001. In unadjusted analysis, QUS bone mineral density was lower in HIV-infected patients than in controls (difference: -0.36 standard deviation, 95% confidence interval (CI: -0.59;-0.12, P = 0.003. Adjusting for BMI, physical activity, smoking and calcium intake attenuated the difference (-0.27, CI: -0.53;-0.002, P = 0.05. Differences in BMI between patients and controls explained a third of the difference in QUS bone mineral density. Among patients, BMI was independently associated with QUS bone mineral density (P<0.001. An association between undetectable viral load and QUS bone density was also suggested (β = 0.48, CI: 0.02;0.93; P = 0.04. No association between protease inhibitor or tenofovir use and QUS bone mineral density was found. CONCLUSION: Senegalese HIV-infected patients had reduced QUS bone mineral density in comparison with control subjects, in part related to their lower BMI. Further investigation is needed to clarify the clinical significance of these observations.

  3. Periodontal Therapy in Dogs Using Bone Augmentation Products Marketed for Veterinary Use.

    Science.gov (United States)

    Angel, Molly

    Periodontal disease is extremely common in companion animal practice. Patients presenting for a routine oral examination and prophylaxis may be found to have extensive periodontal disease and attachment loss. Vertical bone loss is a known sequela to periodontal disease and commonly involves the distal root of the mandibular first molar. This case report outlines two dogs presenting for oral examination and prophylaxis with general anesthesia. Both patients did not have any clinical symptoms of periodontal disease other than halitosis. Both patients were diagnosed with three-walled vertical bone loss defects of one or both mandibular first molars utilizing dental radiography as well as periodontal probing, measuring, and direct visual inspection. These defects were consistent with periodontal disease index stage 4 (>50% attachment loss). The lesions were treated with appropriate root planing and debridement. Bone augmentation products readily available and marketed for veterinary use were then utilized to fill the defects to promote both the re-establishment of normal alveolar bone height and periodontal ligament reattachment to the treated surface. Follow-up assessment and owner dedication is critical to treatment outcome. Both patients' 6 mo follow-up examinations radiographically indicated bone repair and replacement with visible periodontal ligament space.

  4. Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

    Energy Technology Data Exchange (ETDEWEB)

    Tomar, Geetanjali B.; Srivastava, Rupesh K.; Gupta, Navita; Barhanpurkar, Amruta P.; Pote, Satish T. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Jhaveri, Hiral M. [Department of Periodontics and Oral Implantology, Dr. D.Y. Patil Dental College and Hospital, Pune (India); Mishra, Gyan C. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Wani, Mohan R., E-mail: mohanwani@nccs.res.in [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India)

    2010-03-12

    Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs are easy to isolate, homogenous and proliferate faster than bone marrow MSCs without any growth factor. Importantly, gingival MSCs display stable morphology and do not loose MSC characteristic at higher passages. In addition, gingival MSCs maintain normal karyotype and telomerase activity in long-term cultures, and are not tumorigenic. Thus, we reveal that human gingiva is a better source of MSCs than bone marrow, and large number of functionally competent clinical grade MSCs can be generated in short duration for cell therapy in regenerative medicine and tissue engineering.

  5. Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

    International Nuclear Information System (INIS)

    Tomar, Geetanjali B.; Srivastava, Rupesh K.; Gupta, Navita; Barhanpurkar, Amruta P.; Pote, Satish T.; Jhaveri, Hiral M.; Mishra, Gyan C.; Wani, Mohan R.

    2010-01-01

    Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs are easy to isolate, homogenous and proliferate faster than bone marrow MSCs without any growth factor. Importantly, gingival MSCs display stable morphology and do not loose MSC characteristic at higher passages. In addition, gingival MSCs maintain normal karyotype and telomerase activity in long-term cultures, and are not tumorigenic. Thus, we reveal that human gingiva is a better source of MSCs than bone marrow, and large number of functionally competent clinical grade MSCs can be generated in short duration for cell therapy in regenerative medicine and tissue engineering.

  6. Aneurysmal bone cyst of the mandible managed by conservative surgical therapy with preoperative embolization

    Energy Technology Data Exchange (ETDEWEB)

    An, Seo Young [School of Dentistry, Kyungpook National University, Daegu (Korea, Republic of)

    2012-03-15

    A 9-year-old girl visited our hospital, complaining of a rapid-growing and rigid swelling on the left posterior mandibular area. Panoramic radiograph showed a moderately defined multilocular honeycomb appearance involving the left mandibular body. CT scan revealed an expansile, multilocular osteolytic lesion and multiple fluid levels within cystic spaces. Bone scan demonstrated increased radiotracer uptake and angiography showed a highly vascularized lesion. The lesion was suspected as aneurysmal bone cyst (ABC) and preoperative embolization was performed, which minimize the extent of operation and the surgical complication. The lesion was treated by surgical curettage and lateral decortication with repositioning. No additional treatment such as a surgical reconstruction or bone graft was needed. Early diagnosis of ABC is very important and appropriate treatment should be performed considering several factors such as age, surgical complication, and possibility of recurrence.

  7. Bone marrow necrosis in a patient with acute promyelocytic leukemia during re-induction therapy with arsenic trioxide.

    Science.gov (United States)

    Ishitsuka, Kenji; Shirahashi, Akihiko; Iwao, Yasuhiro; Shishime, Mikiko; Takamatsu, Yasushi; Takatsuka, Yoshifusa; Utsunomiya, Atae; Suzumiya, Junji; Hara, Syuji; Tamura, Kazuo

    2004-04-01

    Arsenic trioxide (As2O3) therapy at a daily dose of 0.15 mg/kg was given to a 60-yr-old Japanese male with refractory acute promyelocytic leukemia. White blood cell (WBC) of 6.6 x 10(3)/microl increased to 134 x 10(3)/microl following the administration of As2O3. Daily hydroxyurea (HU), and 6-mercaptopurine (6-MP) were added on days 7 and 19, respectively. Both HU and 6-MP were discontinued on day 28, when WBC declined to 54.0 x 10(3)/microl. He developed unexplained fever and profound cytopenia requiring multiple blood products transfusions. Bone marrow examination on day 42 revealed massive necrosis. Pharmacokinetics confirmed a mean maximum plasma arsenic concentration (Cpmax) and a half-life time (t1/2) of 6.9 microm and 3.2 h, respectively, in the therapeutic range. This is the first case of bone marrow necrosis after standard-dose As2O3 therapy.

  8. Labeling of MDP with {sup 188}Re for bone tumour therapy

    Energy Technology Data Exchange (ETDEWEB)

    Barbezan, Angelica B.; Osso Junior, Joao A., E-mail: jaosso@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    {sup 188}Re is one of the most attractive radioisotopes for a variety of therapeutic applications in nuclear medicine, due to its physical decay properties, such as {beta}{sup -} emission of 2.12 MeV, {gamma} emission of 155 keV and half life of 16.9 hours. Biphosphonates are potent inhibitors of osteoclastic bone resorption and are effective in several diseases that cause bone fragility and bone metastases. Because of these characteristics, labeled biphosphonates have been studied for bone pathologies, also acting as palliation of bone pain in case of metastasis.The aim of this study was to optimize the labeling of a phosphonate-MDP (Sodium Methylene Diphosphonate) with {sup 188}Re for use in bone pain palliation. {sup 188}Re was obtained by eluting a {sup 188}W-{sup 188}Re generator from POLATOM. The labeling was performed at room temperature using MDP, SnCl{sub 2} as reducing agent and ascorbic acid. The variables studied were: Mass of ligand (3, 6 and 10 mg), reducing agent mass (5, 7, 10 and 11 mg), ascorbic acid mass (1, 3, 5 and 6 mg), pH (1 and 2) and time of reaction (15, 60, 120, 360 and 4320 minutes), that also reflected the stability of the radiopharmaceutical. The radiochemical control, that also measures the labeling efficiency was evaluated by paper chromatography using Whatman 3MM paper and the solvents acetone and 0.9%NaCl. The best formulation was the following: Mass of ligand MDP: 10 mg, mass of SnCl{sub 2}: 5 mg, ascorbic acid mass: 3 mg, time of reaction: 30 minutes, pH: 1. Under optimum conditions, {sup 188}Re MDP radiolabeling yield was 98,07% and the radiopharmaceutical was stable up to 72 h. (author)

  9. Autologous Bone Marrow Stem Cell Infusion (AMBI therapy for Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Rajkumar JS

    2007-01-01

    Full Text Available Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

  10. Effects of a Combination Therapy of Sclerostin Antibody III and Raloxifene on Bone Formation Markers in Ovariectomized Rats

    International Nuclear Information System (INIS)

    Allam, H. I. G.

    2016-01-01

    Objective: To determine the systemic effect of sclerostin monoclonal antibody (Scl-AbIII) administration on markers of bone formation and compare it with a combination of sclerostin antibody and raloxifene. Study Design: Experimental study. Place and Duration of Study: Medical College Animal House at King Khaled University Hospital, Riyadh, Saudi Arabia, from January to November 2014. Methodology: Forty-five female rats were divided into 5 groups equally; 1 control group and 4 groups of ovariectomized (OVX) rats: control OVX rats and OVX rats treated by Scl-AbIII, raloxifene or Scl-AbIII+raloxifene one month after ovariectomy, continued for 4 weeks. At the end of treatment, serum levels of Bone Specific Alkaline Phosphatase (BSAP), alkaline phosphatase, osteocalcin, Insulin-like Growth Factor-1 (IGF-1), Parathyroid Hormone (PTH), Ca/sup 2+/ and phosphorus were measured. Uterus was weighed and body weight change was calculated. Results: Scl-AbIII or raloxifene treatment produced significant increase of serum BSAP, osteocalcin, IGF-1, PTH and Ca/sup 2+/ levels. Raloxifene, either alone or combined with Scl-AbIII attenuated the decrease in uterus wet weight, and the increase in body weight seen in OVX rats. Combination therapy of Scl-AbIII, and raloxifene produced significant increase of serum alkaline phosphatase, osteocalcin and IGF-1 levels than treatment with either Scl-AbIII or raloxifene alone. Conclusion: Combination therapy of Scl-AbIII and raloxifene is an attractive strategy to enhance bone formation and can offer better gain over treatment with either one of them alone. Confirmation of these preliminary observations must await careful long-term studies. (author)

  11. Protective effect of bone marrow mesenchymal stem cells combined with erythropoietin therapy on spinal cord injury rat model

    Directory of Open Access Journals (Sweden)

    Peng Xie

    2016-01-01

    Full Text Available Objective: To study the protective effect of bone marrow mesenchymal stem cells combined with erythropoietin therapy on spinal cord injury rat model. Methods: SD rats were selected as experimental animals, spinal cord injury rat model was built by striking spinal cord with Hatteras Instruments PCI3000, and model rats were divided into control group, bone marrow mesenchymal stem cells (BMSCs group, erythropoietin (EPO group and BMSCs combined with EPO group according to different treatment methods. Then number of apoptotic cells in spinal cord tissue, contents of neural markers and neurotrophic factors as well as expression of apoptosis and injury molecules was detected. Results: Number of apoptotic cells as well as mRNA contents of Caspase-3 and c-fos of BMSCs group, EPO group and BMSCs+EPO group was lower than those of control group, and number of apoptotic cells as well as mRNA contents of Caspase-3 and c-fos of BMSCs+EPO group were lower than those of BMSCs group and EPO group; mRNA contents of NF-200 and MBP as well as protein contents of NGF and BDNF in spinal cord tissue of BMSCs group, EPO group and BMSCs+EPO group were higher than those of control group, and mRNA contents of NF-200 and MBP as well as protein contents of NGF and BDNF in spinal cord tissue of BMSCs+EPO group were higher than those of BMSCs group and EPO group. Conclusions: Bone marrow mesenchymal stem cells combined with erythropoietin therapy can inhibit cell apoptosis in the injured spinal cord tissue, increase neurotrophic factor levels and inhibit apoptosis and injury molecule expression; it has protective effect on spinal cord injury.

  12. Influence of low-level laser therapy on the healing of human bone maxillofacial defects: A systematic review.

    Science.gov (United States)

    Santinoni, Carolina Dos Santos; Oliveira, Hiskell Francine Fernandes; Batista, Victor Eduardo de Souza; Lemos, Cleidiel Aparecido Araujo; Verri, Fellippo Ramos

    2017-04-01

    This systematic review evaluates the effectiveness of low-level laser therapy (LLLT) to enhance maxillofacial area bone repair. A comprehensive search of studies published up to February 2017 and listed in PubMed/MEDLINE, Scopus, and Cochrane Library databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The 15 selected studies evaluated a total of 374 patients (mean age, 28.5years) who were treated with LLLT. Gallium-arsenide (GaAs) and gallium aluminium arsenide (GaAlAs) were the most commonly used devices, and LLLT parameters varied greatly. Wavelengths varied from 500 to 1000nm. Tooth extraction, distraction osteogenesis, maxillary expansion, periodontal defects, orthodontic movement and maxillary cystic defects were evaluated. From the 15 selected studies, six evaluated bone repair (primary outcomes). Of these, four studies showed improvement in bone formation after using LLLT, two demonstrated improved results for only one follow up period, and one showed no additional benefits. The other 9 studies evaluated secondary parameters related to healing (secondary outcomes) in the maxillofacial area after applying LLLT, including anti-inflammatory, analgesic, and healing accelerator effects, and quality of life related to oral health. There were no adverse or negative effects of LLLT reported. Within the limitation of this review, a possible improvement in bone density can be found when LLLT is applied postoperatively in maxillofacial bony defects. LLLT also seems to promote anti-inflammatory and analgesic effects and accelerate healing, as well as enhance quality of life related to oral health. However, LLLT use protocols need to be standardized before more specific conclusions can be drawn about this subject. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Enzymatic maceration of bone

    DEFF Research Database (Denmark)

    Uhre, Marie-Louise; Eriksen, Anne Marie; Simonsen, Kim Pilkjær

    2015-01-01

    and afterwards macerated by one of the two methods. DNA extraction was performed to see the effect of the macerations on DNA preservation. Furthermore, the bone pieces were examined in a stereomicroscope to assess for any bone damage. The results demonstrated that both methods removed all flesh/soft tissue from...... the bones. The DNA analysis showed that DNA was preserved on all the pieces of bones which were examined. Finally, the investigation suggests that enzyme maceration could be gentler on the bones, as the edges appeared less frayed. The enzyme maceration was also a quicker method; it took three hours compared...

  14. Treatment of Bone Metastases with Radium-223 in Patients with Castration Resistant Prostate Cancer (CRPC): Alternative or Complementary to Innovative Molecular Therapies?

    International Nuclear Information System (INIS)

    Bombardieri, Emilio

    2013-01-01

    The skeletal metastatic disease is a real clinical problem. Approximately 70% of patients with prostate or breast cancer and 35% of those with advanced lung, thyroid, and kidney cancers will develop skeletal metastases, which cause considerable morbidity. Several options are available for treatment, to be used either alone or in various combinations: hormones in case of hormone-sensitive tumours, chemotherapy, biphosphonates, external beam radiation therapy, surgery (in pathologic or impending fracture), bone-seeking radiopharmceuticals, and also molecular therapies. Focusing our attention to patients with prostate cancer, 50% of patients with bone metastases develop skeletal related events (SREs) such as: severe pain, pathologic fractures, spinal compression syndrome, malignant hypercalcemia, bone marrow suppression. All these SREs require adequate therapy since generally determine several functional impairments and worsen the prognosis. It is well known that skeletal complications reduce the quality of life affecting different aspects, physical, functional end emotional. SREs are associated also with lower survival

  15. Predicting changes in flow category in patients with severe aortic stenosis and preserved left ventricular ejection fraction on medical therapy.

    Science.gov (United States)

    Ngiam, Jinghao Nicholas; Kuntjoro, Ivandito; Tan, Benjamin Y Q; Sim, Hui-Wen; Kong, William K F; Yeo, Tiong-Cheng; Poh, Kian-Keong

    2017-11-01

    Controversy surrounds the prognosis and management of patients with paradoxical low-flow severe aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF). It was not certain if patients in a particular flow category remained in the same category as disease progressed. We investigated whether there were switches in categories and if so, their predictors. Consecutive subjects (n = 203) with isolated severe AS and paired echocardiography (>180 days apart) were studied. They were divided into 4 groups, based on their flow categories and if they progressed on subsequent echocardiography to switch or remain in the same flow category. Univariate analyses of clinical and echocardiographic parameters identified predictors of these changes in flow category. One hundred eighteen were normal flow (SVI ≥ 35 mL/m 2 ), while 85 were low flow on index echocardiography. In the patients with normal flow, 33% switched to low flow. This was associated with higher valvuloarterial impedance (Zva, P 4.77 mm Hg/mL/m 2 , AUC = 0.81 [95% CI:0.75-0.87, P < .001]). In patients with low flow, 25% switched to normal flow, which was associated with lower Zva and higher SAC and the switch was predicted by a higher initial mean transaortic pressure gradient. A significant number of patients switched flow categories in severe AS with preserved LVEF on subsequent echocardiography. Changes in flow were reflected by respective changes in Zva and SAC. Identifying echocardiographic predictors of a switch in category may guide prognostication and management of such patients. © 2017, Wiley Periodicals, Inc.

  16. Impact of chemotherapy and definitive radiotherapy for laryngeal preservation. A comparative study of concurrent chemoradiotherapy and induction chemotherapy followed by radiation therapy

    International Nuclear Information System (INIS)

    Hiraga, Yukihiro; Kou, Junichi

    2013-01-01

    During the past 23 years, from June 1989 to December 2012, our treatment paradigm for head and neck squamous cell carcinoma (HNSCC) had involved comprehensive use of chemotherapy and radiation therapy followed by surgery. Between 1989 and 2005, chemotherapy using fluorouracil and carboplatin had been administered via intravenous drip infusion as induction chemotherapy (ICT), and more recently between 2006 and 2012 as concurrent chemoradiotherapy (CCRT). In the present study, we examined the superiority of definitive CCRT (dCCRT) over the ICT followed by definitive radiotherapy (ICT-dRT) as to the impact on the treatment of HNSCC with the stage-categories of T2-T4a, retrospectively analyzing survival rates and laryngeal preservation rates at the 3-year point between the two groups. The number of patients assigned for this study was 76, all of whom were previously untreated, and of whom 51 suffered from laryngeal carcinoma and 25 from hypopharyngeal carcinoma: 21 with Stage II, 25 with Stage III, 23 with Stage IV A, 7 with Stage IV C. The three-year overall survival rate and cause-specific survival rate were 54.5%, 73.5% in the ICT-dRT group and 69.2%, 80.5% in the dCCRT group, respectively, both of which statistically had no difference. But the dCCRT was found to contribute to obtaining a higher rate of laryngeal preservation than that of the ICT-dRT in T2 and T3 but not in T4a. In conclusion, dCCRT showed more significant efficacy for organ preservation on T2 and T3 HNSCC than ICT-dRT. (author)

  17. Patterns of failure following bone marrow transplantation for metastatic breast cancer: the role of consolidative local therapy

    International Nuclear Information System (INIS)

    Shah, Amit B.; Hartsell, William F.; Ghalie, Richard; Kaizer, Herbert

    1995-01-01

    Purpose: The purpose of this analysis is to evaluate the patterns of failure and the role of local therapy in conjunction with bone marrow transplantation (BMT) for metastatic or recurrent breast cancer. Methods and Materials: Between June 1986 and November 1991, 46 patients with hormone unresponsive metastatic or recurrent breast cancer underwent high dose chemotherapy (HDC) with hematopoietic stem cell support. The most commonly used preparative regimen consisted of thiotepa (750 mg/m 2 ), cisplatin (150 mg/m 2 ), and cyclophosphamide (120 mg/kg) followed by autologous BMT. Consolidative surgery or irradiation was considered in patients whose cancer responded to BMT and had localized sites of disease. Results: Six patients (13%) died of BMT-related complications. Of the remaining 40 patients, 22 were candidates for consolidative therapy, and 18 of those patients received consolidative irradiation (17 patients) or surgery (1 patient) to one or more sites. At median follow-up of 27 months (range, 20-78), 12 of 18 (67%) patients have continuous local control at the 22 consolidated sites (1 of 4 controlled at chest wall sites, 7 of 8 at regional nodal sites, 7 of 7 at localized bone sites, and 1 of 3 at lung/mediastinal sites). Toxicity of consolidative irradiation was mainly limited to myelosuppression in 6 of 17 patients. Two patients did not complete the consolidative local therapy, one because of hematologic toxicity and one because of rapid systemic tumor progression during treatment. Conclusion: In patients with localized areas of extravisceral metastases, consolidative irradiation is feasible with acceptable hematologic toxicity. Consolidative irradiation can result in continuous local control, especially in isolated bone metastases and in regional nodal sites; however, the advantage is less clear in patients undergoing consolidative irradiation for chest wall failures. Because distant visceral metastases still remain a major site of failure after this HDC

  18. Singing can improve speech function in aphasics associated with intact right basal ganglia and preserve right temporal glucose metabolism: Implications for singing therapy indication.

    Science.gov (United States)

    Akanuma, Kyoko; Meguro, Kenichi; Satoh, Masayuki; Tashiro, Manabu; Itoh, Masatoshi

    2016-01-01

    Clinically, we know that some aphasic patients can sing well despite their speech disturbances. Herein, we report 10 patients with non-fluent aphasia, of which half of the patients improved their speech function after singing training. We studied ten patients with non-fluent aphasia complaining of difficulty finding words. All had lesions in the left basal ganglia or temporal lobe. They selected the melodies they knew well, but which they could not sing. We made a new lyric with a familiar melody using words they could not name. The singing training using these new lyrics was performed for 30 minutes once a week for 10 weeks. Before and after the training, their speech functions were assessed by language tests. At baseline, 6 of them received positron emission tomography to evaluate glucose metabolism. Five patients exhibited improvements after intervention; all but one exhibited intact right basal ganglia and left temporal lobes, but all exhibited left basal ganglia lesions. Among them, three subjects exhibited preserved glucose metabolism in the right temporal lobe. We considered that patients who exhibit intact right basal ganglia and left temporal lobes, together with preserved right hemispheric glucose metabolism, might be an indication of the effectiveness of singing therapy.

  19. Is cardiac resynchronization therapy an option in heart failure patients with preserved ejection fraction? Justification for the ongoing KaRen project.

    Science.gov (United States)

    Donal, Erwan; Lund, Lars; Linde, Cecilia; Daubert, Jean-Claude

    2010-01-01

    The relevance of electrical and mechanical dyssynchrony has been demonstrated in heart failure with reduced ejection fraction. Preserved ejection fraction is present in as many as 50% of patients with chronic heart failure. Recent small studies suggest that both electrical and mechanical left ventricular dyssynchrony are sometimes present in patients with heart failure and preserved ejection fraction (HFPEF). These data remain controversial and a robust validation of this hypothesis has to be achieved. In the present paper, we review in detail the concepts and try to justify the ongoing KaRen registry. This is a prospective, multicentre, international, observational study to characterize the prevalence of electrical or mechanical dyssynchrony in HFPEF and the resultant effect on prognosis. Patients are enrolled currently at the time of an acute congestive episode. The diagnosis of HFPEF is made according to clinical data, natriuretic peptides and echocardiography for the measurement of ejection fraction. Once stabilized, patients return for a hospital check-up. They undergo clinical and biological evaluation, electrocardiography and Doppler echocardiography. Thereafter, patients are followed every six months, for at least 18 months for mortality, and heart failure-related and non-cardiovascular hospitalizations. KaRen aims to characterize electrical and mechanical dyssynchrony and to assess its prognostic impact in HFPEF. The results may improve our understanding of HFPEF and generate answers to the question of whether or not dyssynchrony could be a target for cardiac resynchronization therapy in HFPEF. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  20. A quantitative study of bone repair after endodontic therapy on digital subtraction radiography

    International Nuclear Information System (INIS)

    Kim, Jae Duk

    1997-01-01

    This study was performed to prepare the quantitative method of judging the sensitive prognosis of chronic apical periodontitis as early as possible. The subjects were 25 cases with periapical radiolucencies of which were treated with endodontic treatment. Serial radiographs were taken by standardized method longitudinally. The density slice function of digital radiographic system were employed for quantitative and longitudinal assessment of the radiolucent area and the condensing osteitis simultaneously. Obtained results were as follows: 1. The amount of bone repair after endodontic treatment could be detected quantitatively by the density slice function of digital radiographic system. 2. Within the 6-week period after root canal filling, the prognosis could be evaluated by assessment both radiolucent area and condensing osteitis on digital radiographic system. 3. The pattern of bone repair showed peripheral type in most cases from the 6th week after root canal filling. 4. In longitudinal change, bone repair showed two patterns; the succeeding reduction of radiolucent area showing the increase of condensing osteitis in size till 6th week and following by static state or reduction tendency and the reduction following the initial increase of both areas. 5. Cases with pulpitis by trauma showed initial increase of condensing osteitis at 2nd week, marked reduction of radiolucent area and condensing osteitis at 6th week, and approximately normal bone state at 8th week after root canal filling.

  1. A quantitative study of bone repair after endodontic therapy on digital subtraction radiography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Duk [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Chosun University, Kwangju (Korea, Republic of)

    1997-08-15

    This study was performed to prepare the quantitative method of judging the sensitive prognosis of chronic apical periodontitis as early as possible. The subjects were 25 cases with periapical radiolucencies of which were treated with endodontic treatment. Serial radiographs were taken by standardized method longitudinally. The density slice function of digital radiographic system were employed for quantitative and longitudinal assessment of the radiolucent area and the condensing osteitis simultaneously. Obtained results were as follows: 1. The amount of bone repair after endodontic treatment could be detected quantitatively by the density slice function of digital radiographic system. 2. Within the 6-week period after root canal filling, the prognosis could be evaluated by assessment both radiolucent area and condensing osteitis on digital radiographic system. 3. The pattern of bone repair showed peripheral type in most cases from the 6th week after root canal filling. 4. In longitudinal change, bone repair showed two patterns; the succeeding reduction of radiolucent area showing the increase of condensing osteitis in size till 6th week and following by static state or reduction tendency and the reduction following the initial increase of both areas. 5. Cases with pulpitis by trauma showed initial increase of condensing osteitis at 2nd week, marked reduction of radiolucent area and condensing osteitis at 6th week, and approximately normal bone state at 8th week after root canal filling.

  2. High-dose therapy and autologous bone marrow transplantation for Hodgkin's disease patients with relapses potentially treatable by radical radiation therapy

    International Nuclear Information System (INIS)

    Pezner, Richard D.; Nademanee, Auayporn; Forman, Stephen J.

    1995-01-01

    Purpose: A retrospective review evaluated the results of autologous bone marrow transplantation (A-BMT) for patients with relapsed Hodgkin's disease (HD) who were potentially treatable by radical radiation therapy (RRT). Methods and Materials: Evaluated patient cases met the following criteria: initial treatment with chemotherapy (with or without involved field radiation therapy 20 Gy to spinal cord); HD at time of salvage therapy limited to lymph nodes, Waldeyer's ring, liver, spleen, direct extension sites, and/or one lung. Results: There were 23 A-BMT patients treated between 1986 and 1991 who fulfilled the criteria. Three (13%) patients died from treatment-related complications and eight (35%) developed nonfatal Grade 3-4 complications. The 3-year actuarial disease-free survival rate was 61%. The 3-year disease-free survival rate was 55% for the nine patients with at least one prior disease-free interval (DFI) > 12 months, 67% for nine patients with DFI 0.10). These results are comparable to retrospective studies of RRT results in selected relapsed HD patients. Conclusions: Long-term disease-free survival is frequently possible with either A-BMT or RRT appropriately selected relapsed HD patients. In considering treatment options, important prognostic factors include initial stage of disease, number of prior relapses, DFI, and extent of relapsed disease

  3. A definition of “uncomplicated bone metastases” based on previous bone metastases radiation trials comparing single-fraction and multi-fraction radiation therapy

    Directory of Open Access Journals (Sweden)

    Paul M. Cheon

    2015-03-01

    “Uncomplicated” bone metastases can be defined as: presence of painful bone metastases unassociated with impending or existing pathologic fracture or existing spinal cord or cauda equina compression. Therefore, MF and SF have equal efficacy in patients with such bone metastases.

  4. Dosimetric Implications of an Injection of Hyaluronic Acid for Preserving the Rectal Wall in Prostate Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Udrescu, Corina [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Tanguy, Ronan [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Ruffion, Alain [Department of Urology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology, Centre Val d' Aurelle, Montpellier (France); Sotton, Marie-Pierre [Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Devonec, Marian [Department of Urology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Colombel, Marc [Department of Urology, Hopital Edouard Herriot, Lyon (France); Jalade, Patrice [Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology, Centre Val d' Aurelle, Montpellier (France)

    2014-02-01

    Purpose: This study assessed the contribution of ahyaluronic acid (HA) injection between the rectum and the prostate to reducing the dose to the rectal wall in stereotactic body radiation therapy (SBRT). Methods and Materials: As part of a phase 2 study of hypofractionated radiation therapy (62 Gy in 20 fractions), the patients received a transperineal injection of 10 cc HA between the rectum and the prostate. A dosimetric computed tomographic (CT) scan was systematically performed before (CT1) and after (CT2) the injection. Two 9-beam intensity modulated radiation therapy-SBRT plans were optimized for the first 10 patients on both CTs according to 2 dosage levels: 5 × 6.5 Gy (PlanA) and 5 × 8.5 Gy (PlanB). Rectal wall parameters were compared with a dose–volume histogram, and the prostate–rectum separation was measured at 7 levels of the prostate on the center line of the organ. Results: For both plans, the average volume of the rectal wall receiving the 90% isodose line (V90%) was reduced up to 90% after injection. There was no significant difference (P=.32) between doses received by the rectal wall on CT1 and CT2 at the base of the prostate. This variation became significant from the median plane to the apex of the prostate (P=.002). No significant differences were found between PlanA without HA and PlanB with HA for each level of the prostate (P=.77, at the isocenter of the prostate). Conclusions: HA injection significantly reduced the dose to the rectal wall and allowed a dose escalation from 6.5 Gy to 8.5 Gy without increasing the dose to the rectum. A phase 2 study is under way in our department to assess the rate of acute and late rectal toxicities when SBRT (5 × 8.5 Gy) is combined with an injection of HA.

  5. Dosimetric Implications of an Injection of Hyaluronic Acid for Preserving the Rectal Wall in Prostate Stereotactic Body Radiation Therapy

    International Nuclear Information System (INIS)

    Chapet, Olivier; Udrescu, Corina; Tanguy, Ronan; Ruffion, Alain; Fenoglietto, Pascal; Sotton, Marie-Pierre; Devonec, Marian; Colombel, Marc; Jalade, Patrice; Azria, David

    2014-01-01

    Purpose: This study assessed the contribution of ahyaluronic acid (HA) injection between the rectum and the prostate to reducing the dose to the rectal wall in stereotactic body radiation therapy (SBRT). Methods and Materials: As part of a phase 2 study of hypofractionated radiation therapy (62 Gy in 20 fractions), the patients received a transperineal injection of 10 cc HA between the rectum and the prostate. A dosimetric computed tomographic (CT) scan was systematically performed before (CT1) and after (CT2) the injection. Two 9-beam intensity modulated radiation therapy-SBRT plans were optimized for the first 10 patients on both CTs according to 2 dosage levels: 5 × 6.5 Gy (PlanA) and 5 × 8.5 Gy (PlanB). Rectal wall parameters were compared with a dose–volume histogram, and the prostate–rectum separation was measured at 7 levels of the prostate on the center line of the organ. Results: For both plans, the average volume of the rectal wall receiving the 90% isodose line (V90%) was reduced up to 90% after injection. There was no significant difference (P=.32) between doses received by the rectal wall on CT1 and CT2 at the base of the prostate. This variation became significant from the median plane to the apex of the prostate (P=.002). No significant differences were found between PlanA without HA and PlanB with HA for each level of the prostate (P=.77, at the isocenter of the prostate). Conclusions: HA injection significantly reduced the dose to the rectal wall and allowed a dose escalation from 6.5 Gy to 8.5 Gy without increasing the dose to the rectum. A phase 2 study is under way in our department to assess the rate of acute and late rectal toxicities when SBRT (5 × 8.5 Gy) is combined with an injection of HA

  6. The effect of permanent grafting materials on the preservation of the buccal bone plate after tooth extraction: an experimental study in the dog.

    LENUS (Irish Health Repository)

    Bashara, Haitham

    2012-08-01

    The aim of the present study was to evaluate the effects of a novel bone substitute system (Natix(®)), consisting of porous titanium granules (PTG) and a bovine-derived xenograft (Bio-Oss(®)), on hard tissue remodelling following their placement into fresh extraction sockets in dogs.

  7. Evaluation of radiation therapy for bone metastases: pain relief and quality of life

    International Nuclear Information System (INIS)

    Gilbert, H.A.; Kagan, A.R.; Nussbaum, H.; Rao, A.R.; Satzman, J.; Chan, P.; Allen, B.; Forsythe, A.

    1977-01-01

    The records of 158 patients irradiated for bone metastases were reviewed to evaluate the effectiveness of pain relief and to judge the effect of treatment on overall quality of life. Within 3 months 73% of the sites treated had pain relief, with 55 to 65% having sustained relief up to 1 year or death. Of patients surviving more than 3 months, 63% maintained a satisfactory quality of life and were able to take care of most personal needs. The median survival of all patients was 1 year from initial treatment for bone metastasis. Radiation dose and the primary tumor site do not seem to be significant prognostic factors for initial pain relief or quality of life

  8. Testosterone therapy preserves muscle strength and power in aging men with type 2 diabetes - a randomized controlled trial

    DEFF Research Database (Denmark)

    Magnussen, Line Velling; Hvid, Lars Næsby; Hermann, Anne Pernille

    2017-01-01

    dual-energy X-ray absorptiometry (total lean body mass, lean leg mass, total fat mass, leg fat mass). Levels of total testosterone (TotalT), BioT, free testosterone (FreeT), and sex hormone-binding globulin were measured from fasting blood samples. Coefficients (b) represent the placebo-controlled mean......The purpose of the study was to evaluate whether testosterone replacement therapy improves muscle mechanical and physical function in addition to increasing lean leg mass and total lean body mass in aging men with type 2 diabetes and lowered bio-available testosterone (BioT) levels. Thirty-nine men.......9 kg, p = 0.001) and lean leg mass (b = 0.5 kg, p mass (b = -1.3 kg, p = 0.009) and leg fat mass (b = -0.7 kg, p = 0.025) decreased during testosterone replacement therapy compared with placebo. Total T (b = 14.5 nmol/L, p = 0.056), BioT (b = 7.6 nmol/L, p = 0...

  9. Early changes in parameters of bone and mineral metabolism during therapy for hyper- and hypothyroidism.

    Science.gov (United States)

    Sabuncu, T; Aksoy, N; Arikan, E; Ugur, B; Tasan, E; Hatemi, H

    2001-01-01

    The effects of thyroid hormones on various organs and metabolic systems have been the focus of intensive research. In this study we investigated the mechanisms of the changes in some parameters of bone and mineral metabolism before and during treatment of hyper- and hypothyroidism. Our study groups were as follows; 1) Untreated hyperthyroid patients (n= 38), 2) Hyperthyroid patients treated for three months (n=21), 3) Untreated hypothyroid patients (n=27), 4) Hypothyroid patients treated for three months (n= 20), and 5) Euthyroid control subjects (age, weight, sex and menopausal status matched) (n = 47). As expected, the mean serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and urinary Ca/creatinine and deoxypyridinoline (D-Pyr)/creatinine levels were higher in group-1 than in the control group. Serum PTH level was lower in group-1 than in group-5. However, after treatment for three months (group-2) we found that the serum and urinary levels of these parameters (except ALP) were not different than in the control group. Group-3 and group-4 did not show any differences in these parameters compared with group-5. Covariance analysis showed that urinary D-Pyr excretion had a positive, independent relationship to the serum free T3 level and age (P hyperthyroid patients, and with the treatment, particularly, in the period of first three months the bone resorption markers decrease rapidly. If the treatment is maintained the decrease slows, becoming more gradual. However, bone formation markers like ALP remain high in hyperthyroid patients during the treatment. In the light of this data, it is possible to conclude that osteoblastic activity lasts longer in hyperthyroidism. On the other hand, we demonstrated that these bone formation and resorption markers do not seem to be different in hypothyroid patients, even during the treatment, compared to the euthyroid controls.

  10. Long-term results of positron emission tomography-directed management of the neck in node-positive head and neck cancer after organ preservation therapy.

    Science.gov (United States)

    Sjövall, Johanna; Chua, Benjamin; Pryor, David; Burmeister, Elizabeth; Foote, Matthew C; Panizza, Benedict; Burmeister, Bryan H; Porceddu, Sandro V

    2015-03-01

    The current study presents the long-term results from a study designed to evaluate a restaging positron emission tomography (PET) directed policy whereby neck dissections were omitted in all node positive head and neck squamous cell carcinoma (N+HNSCC) patients with PET-negative lymph nodes after definitive radiotherapy (RT), with or without chemotherapy. A post-therapy nodal response assessment with PET and computed tomography (CT) was performed in patients who achieved a complete response at the primary site after definitive radiotherapy. Patients with PET-negative lymph nodes were observed regardless of residual CT abnormalities. One hundred and twelve patients, the majority of whom (83 patients, 74%) had oropharyngeal primaries, were treated on protocol. Median follow-up was 62months. Negative and positive predictive values for the restaging PET was 97.1% and 77.8% respectively, with only one patient who was PET-negative after treatment experiencing an isolated nodal relapse. PET-guided management of the neck following organ preservation therapy effectively spares neck dissections in patients with N+HNSCC without compromising isolated nodal control or overall survival. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  11. Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy.

    Science.gov (United States)

    Tschernutter, M; Schlichtenbrede, F C; Howe, S; Balaggan, K S; Munro, P M; Bainbridge, J W B; Thrasher, A J; Smith, A J; Ali, R R

    2005-04-01

    The Royal College of Surgeons (RCS) rat is a well-characterized model of autosomal recessive retinitis pigmentosa (RP) due to a defect in the retinal pigment epithelium (RPE). It is homozygous for a null mutation in the gene encoding , a receptor tyrosine kinase found in RPE cells, that is required for phagocytosis of shed photoreceptor outer segments. The absence of Mertk results in accumulation of outer segment debris. This subsequently leads to progressive loss of photoreceptor cells. In order to evaluate the efficacy of lentiviral-mediated gene replacement therapy in the RCS rat, we produced recombinant VSV-G pseudotyped HIV-1-based lentiviruses containing a murine Mertk cDNA driven by a spleen focus forming virus (SFFV) promoter. The vector was subretinally injected into the right eye of 10-day-old RCS rats; the left eye was left untreated as an internal control. Here, we present a detailed assessment of the duration and extent of the morphological rescue and the resulting functional benefits. We examined animals at various time points over a period of 7 months by light and electron microscopy, and electroretinography. We observed correction of the phagocytic defect, slowing of photoreceptor cell loss and preservation of retinal function for up to 7 months. This study demonstrates the potential of gene therapy approaches for the treatment of retinal degenerations caused by defects specific to the RPE and supports the use of lentiviral vectors for the treatment of such disorders.

  12. Software preservation

    Directory of Open Access Journals (Sweden)

    Tadej Vodopivec

    2011-01-01

    Full Text Available Comtrade Ltd. covers a wide range of activities related to information and communication technologies; its deliverables include web applications, locally installed programs,system software, drivers, embedded software (used e.g. in medical devices, auto parts,communication switchboards. Also the extensive knowledge and practical experience about digital long-term preservation technologies have been acquired. This wide spectrum of activities puts us in the position to discuss the often overlooked aspect of the digital preservation - preservation of software programs. There are many resources dedicated to digital preservation of digital data, documents and multimedia records,but not so many about how to preserve the functionalities and features of computer programs. Exactly these functionalities - dynamic response to inputs - render the computer programs rich compared to documents or linear multimedia. The article opens the questions on the beginning of the way to the permanent digital preservation. The purpose is to find a way in the right direction, where all relevant aspects will be covered in proper balance. The following questions are asked: why at all to preserve computer programs permanently, who should do this and for whom, when we should think about permanent program preservation, what should be persevered (such as source code, screenshots, documentation, and social context of the program - e.g. media response to it ..., where and how? To illustrate the theoretic concepts given the idea of virtual national museum of electronic banking is also presented.

  13. Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease.

    Science.gov (United States)

    Whiting, Rebecca E H; Jensen, Cheryl A; Pearce, Jacqueline W; Gillespie, Lauren E; Bristow, Daniel E; Katz, Martin L

    2016-05-01

    CLN2 disease is one of a group of lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene that cause an insufficiency or complete lack of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein degradation, and lack of this enzyme results in the accumulation of protein-rich autofluorescent lysosomal storage bodies in numerous cell types including neurons throughout the central nervous system and the retina. CLN2 disease is characterized primarily by progressive loss of neurological functions and vision as well as generalized neurodegeneration and retinal degeneration. In children the progressive loss of neurological functions typically results in death by the early teenage years. A Dachshund model of CLN2 disease with a null mutation in TPP1 closely recapitulates the human disorder with a progression from disease onset at approximately 4 months of age to end-stage at 10-11 months. Delivery of functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of the recombinant protein or by a single administration of a TPP1 gene therapy vector to the CSF, significantly delays the onset and progression of neurological signs and prolongs life span but does not prevent the loss of vision or modest retinal degeneration that occurs by 11 months of age. In this study we found that in dogs that received the CSF gene therapy treatment, the degeneration of the retina and loss of retinal function continued to progress during the prolonged life spans of the treated dogs. Eventually the normal cell layers of the retina almost completely disappeared. An exception was the ganglion cell layer. In affected dogs that received TPP1 gene therapy to the CSF and survived an average of 80 weeks, ganglion cell axons were present in numbers comparable to those of normal Dachshunds of similar age. The selective preservation of the retinal ganglion cells suggests

  14. Effect of Thyrotropin Suppression Therapy on Bone in Thyroid Cancer Patients

    OpenAIRE

    Papaleontiou, Maria; Hawley, Sarah T.; Haymart, Megan R.

    2015-01-01

    Background. The thyroid cancer incidence is rising. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy. Also, its potential skeletal effects remain a concern to physicians caring for thyroid cancer patients. We conducted a review of published data to evaluate existing studies focusing on the skeletal effects of thyrotropin suppression therapy in thyroid cancer patients. Materials and Methods. A systematic search of the PubMed, O...

  15. The Use of Backscattered Electron Imaging and Transmission Electron Microscopy to Assess Bone Architecture and Mineral Loci: Effect of Intermittent Slow-Release Sodium Fluoride Therapy

    Science.gov (United States)

    Zerwekh, Joseph E.; Bellotto, Dennis; Prostak, Kenneth S.; Hagler, Herbert K.; Pak, Charles Y. C.

    1996-04-01

    Backscattered electron imaging (BEI) and transmission electron microscopy (TEM) were used to examine the effects of treatment with intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate on bone architecture and crystallinity. Examination was performed in nondecalcified biopsies obtained from patients following up to four years of therapy (placebo or SRNaF) and compared to pretreatment biopsies from each patient, as well as to bone from young, normal subjects. BEI images disclosed increased areas of recent bone formation following fluoride administration. There was no evidence of a mineralization defect in any biopsy and both cortical and trabecular architecture remained normal. TEM analysis demonstrated intrafibrillar platelike crystals and extrafibrillar needlelike crystals for both the pre- and post-treatment biopsies as well as for the bone from young normal subjects. There was no evidence of increased crystal size or of an increase in extrafibrillar mineral deposition. These observations suggest that intermittent SRNaF and continuous calcium therapy exerts an anabolic action on the skeleton not accompanied by a mineralization defect or an alteration of bone mineral deposition. The use of BEI and TEM holds promise for the study of the pathophysiology and treatment of metabolic bone diseases.

  16. Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction

    Science.gov (United States)

    Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L.; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R.; Kohn, Donald B.

    2012-01-01

    Gene therapy (GT) for adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada−/−). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist. PMID:22833548

  17. Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

    Science.gov (United States)

    Carbonaro, Denise A; Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R; Kohn, Donald B

    2012-11-01

    Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist.

  18. A randomized trial of three single - dose radiation therapy regimens in the treatment of metastatic bone pain

    International Nuclear Information System (INIS)

    Jeremic, Branislav; Shibamoto, Yuta; Acimovic, Ljubisa; Milicic, Biljana; Milisavljevic, Slobodan; Nikolic, Nebojsa; Aleksandrovic, Jasna; Igrutinovic, Ivan

    1998-01-01

    Purpose: To investigate efficacy of three single dose radiation therapy (RT) regimens in the treatment of painful bone metastasis. Material and Methods: Patient self-assessment by using pain chart enabled evaluation of response to treatment that consisted of either one of the three single fractions of 4 Gy (group I; n = 109), 6 Gy (group II; n = 108), or 8 Gy (group III; n = 110). Results: Patients in groups II and III had higher complete response rate than those in group I, but not significantly, and with no difference between group II and III. However, both patients in group II (73%) and group III (78%) had significantly higher overall response rates when compared to those observed in group I (59%) (I vs II, p = 0.025; I vs III, p = 0.0019), and with no difference between groups II and III (p 0.39). Patients in group III had shortest time to the occurrence of any pain relief which was significantly better than those observed in group I (Welch's t-test, p = 0.012), with no difference between group I and II and group II and III, respectively. There was no difference between the three treatment groups in duration of response and retreatment rate. No effect of histology or metastatic site treated was found. No pathological fractures or spinal cord compressions were observed during the 8 weeks post-RT. Conclusion: Results of this study seem to confirm that 8 Gy could be considered as probably 'lowest' optimal single fraction RT in the treatment of painful bone metastasis, although single fraction RT of 4 Gy should not be easily discarded due to its applicability in specific cases. Since single fraction RT of 6 Gy achieved results not different from that obtained with 8 Gy, further studies are warranted in order to get more informations about 'lowest' optimal single fraction RT in the treatment of painful bone metastasis

  19. Efficacy of estrogen replacement therapy (ERT) on uterine growth and acquisition of bone mass in patients with Turner syndrome.

    Science.gov (United States)

    Nakamura, Tomomi; Tsuburai, Taku; Tokinaga, Aya; Nakajima, Izumi; Kitayama, Reiko; Imai, Yuichi; Nagata, Tomoko; Yoshida, Hiroshi; Hirahara, Fumiki; Sakakibara, Hideya

    2015-01-01

    Estrogen replacement therapy (ERT) is necessary for uterine development and bone mass acquisition in women with Turner syndrome (TS) suffering from ovarian insufficiency. However, adequate ERT regimens have not yet been established. The aim of this study was to evaluate the efficacy of ERT for both uterine development and bone mass acquisition. One hundred TS patients from Yokohama City University Hospital (88 with primary amenorrhea (PA) and 12 patients with spontaneous menstrual cycles (MC)) were enrolled after obtaining consent. Clinical profiles, uterine length (UL) measured by ultrasonic examination, and bone mineral density (BMD) of the lumbar vertebrae (L2-4) assessed by DEXA were evaluated. At the time of the first visit, the ULs of patients in the PA group were significantly shorter than those in the MC group. After receiving ERT, there were no significant differences in UL between patients with PA and MC. Forty-seven patients for whom the ERT initiation age was known were investigated to clarify the influence on BMD. The results showed that the BMD in the late initiation (18 years or older) group at the latest visit (0.770 ± 0.107 g/cm2: n = 16) was significantly lower than that in the early initiation (under 18 years) group (0.858 ± 0.119 g/cm2: n = 21) or the MC group (0.941 ± 0.118 g/cm2: n = 10). No significant differences were seen between the early initiation and MC group. ERT was effective in increasing UL and BMD. However, early initiation of ERT is necessary to increase BMD.

  20. Bone marrow transplantation and other treatment after radiation injury

    International Nuclear Information System (INIS)

    Balner, H.

    1977-01-01

    This review deals mainly with current concepts about bone marrow transplantation as therapy for serious radiation injury. Such injury can be classified according to the following broadly defined dose ranges: (1) the supralethal range, leading mainly to the cerebral and intestinal syndromes; (2) the potentially lethal or therapeutic range which causes the bone marrow syndrome, and (3) the sublethal range which rarely leads to injury requiring therapy. The bone marrow syndrome of man and animals is discussed in detail. The optimal therapy for this syndrome is bone marrow transplantation in conjunction with conventional supportive treatment. The principal complications of such therapy are Graft versus Host Disease and a slow recovery of the recipient's immune system. Concerted research activities in a number of institutions have led to considerable progress in the field of bone marrow transplantation. Improved donor selection, new techniques for stem-cell separation and preservation, as well as effective barrier-nursing and antibiotic decontamination, have made bone marrow transplantation an accepted therapy for marrow depression, including the aplasia caused by excessive exposure to radiation. The review also contains a number of guidelines for the handling of serious radiation accidents. (Auth.)

  1. A Simple and Effective Daily Pain Management Method for Patients Receiving Radiation Therapy for Painful Bone Metastases

    International Nuclear Information System (INIS)

    Andrade, Regiane S.; Proctor, Julian W.; Slack, Robert; Marlowe, Ursula; Ashby, Karlotta R.; Schenken, Larry L.

    2010-01-01

    Purpose: The incidence of painful bone metastases increases with longer survival times. Although external beam radiation therapy (EBRT) is an effective palliative treatment, it often requires several days from the start of treatment to produce a measurable reduction in pain scores and a qualitative amelioration of patient pain levels. Meanwhile, the use of analgesics remains the best approach early on in the treatment course. We investigated the role of radiation therapists as key personnel for collecting daily pain scores to supplement assessments by physician and oncology nursing staff and manage pain more effectively during radiation treatment. Methods and Materials: Daily pain scores were obtained by the radiation therapists for 89 patients undertaking a total of 124 courses of EBRT for bone metastases and compared with pretreatment pain scores. The majority of patients (71%) were treated to 30 Gy (range, 20-37.5) in 10 fractions (range, 8-15 fractions). Results: One hundred nineteen treatment courses (96%) were completed. Pain scores declined rapidly to 37.5%, 50%, and 75% of the pretreatment levels by Days 2, 4, and 10, respectively. Pain was improved in 91% of patients with only 4% of worse pain at the end of treatment. Improved pain scores were maintained in 83% of patients at 1-month follow-up, but in 35% of them, the pain was worse than at the end of treatment. Conclusions: Collection of daily pain scores by radiation therapists was associated with an effective reduction in pain scores early on during EBRT of painful osseous metastases.

  2. Radiological changes of bones and soft tissues after irradiation therapy in patients with Wilms' tumor and neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, Hiroaki; Okabe, Ikuo

    1989-04-01

    Late effects of tele cobalt 60 therapy on bones and soft tissues were studied radiologically in 24 patients with neuroblastoma and Wilms' tumor. The degree of changes in spinal bodies was influenced by the dose of irradiation as well as the age of patients at the time of irradiation. In patients who had 15 to 19 Gy of irradiation at the ages under one year old, a moderate to severe degree of changes was observed. Many patients showed atrophies of iliac bone, ribs, and erector spinae and psoas muscles on the side of the irradiation. In patients who were equal to or over 12 y.o. at the time of the examination, the degree of atrophy of erector spinae muscles on the side of the irradiation was greater than that of the patients who were less than 12 y.o.. Scoliosis was observed in 71% of patients and it had a tendency to aggravate at puberty. Because there was a significant correlation between the degree of scoliosis and the severity of the atrophic erector spinae muscle, the latter was thought to contribute much to the development of the former. At present, all patients are living with no limitation of their daily activities and no one needs medical care. (author).

  3. 3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications

    OpenAIRE

    Asa'ad, Farah; Pagni, Giorgio; Pilipchuk, Sophia P.; Giann?, Aldo Bruno; Giannobile, William V.; Rasperini, Giulio

    2016-01-01

    To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopted to lessen the need for such invasive approaches, it utilizes bone grafting materials, which have limitations that could negatively affect the qu...

  4. First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy.

    Science.gov (United States)

    Yoshida, Nao; Kobayashi, Ryoji; Yabe, Hiromasa; Kosaka, Yoshiyuki; Yagasaki, Hiroshi; Watanabe, Ken-Ichiro; Kudo, Kazuko; Morimoto, Akira; Ohga, Shouichi; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kato, Koji; Suzuki, Ritsuro; Ohara, Akira; Kojima, Seiji

    2014-12-01

    The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86-90) versus 92% (90-94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54-59) versus 87% (85-90); Paplastic anemia. Copyright© Ferrata Storti Foundation.

  5. Effects of Growth Hormone Therapy on Bone Mass, Metabolic Balance, and Well-Being in Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    van den Heijkant, Silvia; Hoorweg-Nijman, Gera; Huisman, Jaap; Drent, Madeleine; van der Pal, Heleen; Kaspers, Gert-Jan; Delemarre-van de Waal, Henriette

    2011-01-01

    Growth hormone deficiency (GHD), mostly after cranial radiotherapy (CRT), may lead to several negative effects. Young adult survivors of acute lymphoblastic leukemia (ALL) could benefit from GH therapy in different ways. Twenty ALL survivors (17.1 +/- 4.3 y after diagnosis) with low bone mineral

  6. New bisphosphonate labeled with Iodine-131 for the palliative therapy for bone metastases pain

    International Nuclear Information System (INIS)

    Prats Capote, Anaís; Perera Pintado, Alejandro; León, Mariela; Hernández González, Ignacio; Leyva Montaña, René; Mocelo Castell, Raúl; O'Reilly, Beatriz; Calderón, Osmar; Griffith Pérez, Yoel; García Batle, Marisé; Rodríguez Tanty, Chryslaine

    2016-01-01

    The aim of this work was to obtain new bisphosphonate marked with 131I suitable for palliative treatment of bone metastases pain characteristics. Materials and Methods: It started with aromatic amino acids and the synthesis consisted of three stages: 1) Protection of amino groups by acetylation; 2) phosphonation protected amino acids with a mixture of phosphorous acid and phosphorus pentachloride; 3) Lack of protection of the amino groups by basic hydrolysis. The compounds obtained were characterized by IR, 1H NMR, RMN13-C mass. Los spectrometry bisphosphonic acids obtained were labeled with 131I using chloramine T and iodogen as oxidants. Stability of labeled compounds in aqueous solution was studied serum. 3 mg of 2-amino-3- (4-hydroxyphenyl) -1-hydroxypropyl-1,1-bisphosphonic acid labeled of 131I were administered to male wistar rats (170-190 g) through a lateral tail vein. The scintigraphic study was conducted at 2, 6 and 12 hours. Results: The yield of the reactions of the amino group protection four compounds ranged from 75 to 80%, while the phosphonation was between 50 and 60%. The radiochemical purity of 2-amino-3- (4-hydroxyphenyl) -1-hydroxypropyl-1,1- bisphosphonic acid labeled with 131I was (91.5 ± 1.4)% and its stability was satisfactory for 72h. Scintigraphic images suggest excretion by the kidneys of the compound and from 12 h post-administration begin to visualize bone structures of the animal, suggesting that the compound exhibits affinity for these tissues. Conclusions: A novel synthesis method with modifications that yielded the sodium salts of bisphosphonic acids starting from the respective aromatic amino acids was developed. 2-amino-3- (4-hydroxyphenyl) -1-hydroxypropyl-1,1-bisphosphonic acid 131I labeled was stable up to 72h and showed affinity for bone tissue. (author)

  7. Radiation Therapy for Bone Metastases from Hepatocellular Carcinoma: Effect of Radiation Dose Escalation

    International Nuclear Information System (INIS)

    Kim, Tae Gyu; Park, Hee Chul; Lim, Do Hoon

    2011-01-01

    To evaluate the extent of pain response and objective response to palliative radiotherapy (RT) for bone metastases from hepatocellular carcinoma according to RT dose. From January 2007 to June 2010, palliative RT was conducted for 103 patients (223 sites) with bone metastases from hepatocellular carcinoma. Treatment sites were divided into the high RT dose and low RT dose groups by biologically effective dose (BED) of 39 Gy10. Pain responses were evaluated using the numeric rating scale. Pain scores before and after RT were compared and categorized into 'Decreased', 'No change' and 'increased'. Radiological objective responses were categorized into complete response, partial response, stable disease and progression using modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria; the factors predicting patients' survival were analyzed. The median follow-up period was 6 months (range, 0 to 46 months), and the radiologic responses existed in 67 RT sites (66.3%) and 44 sites (89.8%) in the high and low RT dose group, respectively. A dose-response relationship was found in relation to RT dose (p=0.02). Pain responses were 75% and 65% in the high and low RT dose groups, respectively. However, no statistical difference in pain response was found between the two groups (p=0.24). There were no differences in the toxicity profiles between the high and low RT dose groups. Median survival from the time of bone metastases diagnosis was 11 months (range, 0 to 46 months). The Child-Pugh classification at the time of palliative RT was the only significant predictive factor for patient survival after RT. Median survival time was 14 months under Child-Pugh A and 2 months under Child-Pugh B and C. The rate of radiologic objective response was higher in the high RT dose group. Palliative RT with a high dose would provide an improvement in patient quality of life through enhanced tumor response, especially in patients with proper liver function.

  8. Improving Soldier Recovery from Catastrophic Bone Injuries: Developing an Animal Model for Standardizing the Bone Reparative Potential of Emerging Progenitor Cell Therapies

    Science.gov (United States)

    2011-08-01

    cell matrix will anchor the developing bone of the outer cortical shell to the surface of intact cortical bone. •Between day 4-7, the three...periosteum so that by day 21 an outer cortical shell, well anchored to the cortical bone at the base of the arch, provides the major structureal support of...tibia was dissected free of the femur, ankle , and overlying skin, and sufficient muscle was retained to not disrupt the fracture zone. The sample was

  9. Digital preservation

    CERN Document Server

    Deegan, Marilyn

    2013-01-01

    Digital preservation is an issue of huge importance to the library and information profession right now. With the widescale adoption of the internet and the rise of the world wide web, the world has been overwhelmed by digital information. Digital data is being produced on a massive scale by individuals and institutions: some of it is born, lives and dies only in digital form, and it is the potential death of this data, with its impact on the preservation of culture, that is the concern of this book. So how can information professionals try to remedy this? Digital preservation is a complex iss

  10. Bone size and volumetric density in women with anorexia nervosa receiving estrogen replacement therapy and in women recovered from anorexia nervosa.

    Science.gov (United States)

    Karlsson, M K; Weigall, S J; Duan, Y; Seeman, E

    2000-09-01

    Anorexia nervosa is associated with bone loss during adulthood, but may also delay skeletal growth and mineral accrual during growth. We asked the following questions. 1) Is anorexia nervosa associated with reduced bone size and reduced volumetric bone mineral density (vBMD)? 2) Is estrogen replacement therapy (ERT) or recovery from anorexia nervosa associated with normal bone size and vBMD? Using dual-energy x-ray absorptiometry, we measured bone size and vBMD of the third lumbar vertebra and femoral neck in a cross-sectional study of 161 female patients: 77 with untreated anorexia nervosa, 58 with anorexia nervosa receiving ERT, 26 recovered from anorexia nervosa, and 205 healthy age-matched controls. Results were expressed as the SD or z-score (mean +/- SEM). Deficits in vertebral body and femoral neck width in untreated women were -1.0 +/- 0.1 and -0.3 +/- 0.1 SD (P anorexia nervosa is due to reduced bone size and reduced vBMD. Although causality cannot be inferred in cross-sectional studies, the data are consistent with the view that malnutrition may contribute to reduced bone size, whereas estrogen deficiency may reduce vBMD. The use of ERT early in disease is a reasonable component of management if the chance of recovery appears remote.

  11. [Stress reactions in bones of the foot in sport: diagnosis, assessment and therapy].

    Science.gov (United States)

    Miltner, O

    2013-06-01

    Stress reactions and stress fractures are defined as structural damage to bone caused by repetitive stress or stereotypical loading. The balance between loading and unloading of bone is disrupted in stress reactions and stress fractures through the sport-specific demands and by the exogenous or endogenous risk factors present. In sports orthopedics the localization of stress reactions and stress fractures are subdivided into high risk fractures and low risk fractures. Conventional diagnostic radiology can initially be inconclusive. With symptoms persisting over 2 weeks further diagnostics using magnetic resonance imaging (MRI) should be performed. In the area of the foot stress reactions and stress fractures can often occur bilaterally or multifocally and most commonly affect the second metatarsals followed by the third metatarsals. Fractures of the fifth metatarsal, second metatarsal base, medial malleolus as well as navicular and sesamoid fractures are high risk fractures requiring special clinical and radiological monitoring. Basically, conservative treatment using the 2-phase model is the treatment of choice. In delayed union or severe pain surgical treatment is indicated.

  12. Controlling Adult Stem Cell Behavior Using Nanodiamond-Reinforced Hydrogel: Implication in Bone Regeneration Therapy.

    Science.gov (United States)

    Pacelli, Settimio; Maloney, Ryan; Chakravarti, Aparna R; Whitlow, Jonathan; Basu, Sayantani; Modaresi, Saman; Gehrke, Stevin; Paul, Arghya

    2017-07-26

    Nanodiamonds (NDs) have attracted considerable attention as drug delivery nanocarriers due to their low cytotoxicity and facile surface functionalization. Given these features, NDs have been recently investigated for the fabrication of nanocomposite hydrogels for tissue engineering. Here we report the synthesis of a hydrogel using photocrosslinkable gelatin methacrylamide (GelMA) and NDs as a three-dimensional scaffold for drug delivery and stem cell-guided bone regeneration. We investigated the effect of different concentration of NDs on the physical and mechanical properties of the GelMA hydrogel network. The inclusion of NDs increased the network stiffness, which in turn augmented the traction forces generated by human adipose stem cells (hASCs). We also tested the ability of NDs to adsorb and modulate the release of a model drug dexamethasone (Dex) to promote the osteogenic differentiation of hASCs. The ND-Dex complexes modulated gene expression, cell area, and focal adhesion number in hASCs. Moreover, the integration of the ND-Dex complex within GelMA hydrogels allowed a higher retention of Dex over time, resulting in significantly increased alkaline phosphatase activity and calcium deposition of encapsulated hASCs. These results suggest that conventional GelMA hydrogels can be coupled with conjugated NDs to develop a novel platform for bone tissue engineering.

  13. Urine Preservative

    Science.gov (United States)

    Smith, Scott M. (Inventor); Nillen, Jeannie (Inventor)

    2001-01-01

    Disclosed is CPG, a combination of a chlorhexidine salt (such as chlorhexidine digluconate, chlorhexidine diacetate, or chlorhexidine dichloride) and n-propyl gallate that can be used at ambient temperatures as a urine preservative.

  14. Musculoskeletal Complications and Bone Metastases in Breast Cancer Patients Undergoing Estrogen Deprivation Therapy

    Science.gov (United States)

    2016-10-01

    tissue (MAT) in estrogen deficient mice. Epidemiological studies have demonstrated a strong link between obesity and increased breast cancer...the accrual of MAT is dramatically accelerated with obesity , estrogen deprivation, glucocorticoid use, chemotherapy, and radiation therapy...Tucson, AZ 2005 – 2006 Graduate Research Assistant, McKnight Brain Institute, Neural Systems, Memory and Aging (NSMA), Department of Psychology

  15. High-dose therapy followed by bone marrow transplantation for relapsed follicular non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Schouten, IC; Raemaekers, JJM; Kluin-Nelemans, HC; vanKamp, H; Mellink, WAM; vantVeer, MB

    1996-01-01

    Purpose: To analyze whether, in addition to survival, and disease-free survival progression-free interval after transplantation would be longer than the last progression-free interval before transplantation, supporting the argument that high-dose therapy may change the biologic behavior of the

  16. Effects of insulin therapy on porosity, non-enzymatic glycation and mechanical competence in the bone of rats with type 2 diabetes mellitus.

    Science.gov (United States)

    Campbell, G M; Tiwari, S; Picke, A-K; Hofbauer, C; Rauner, M; Morlock, M M; Hofbauer, L C; Glüer, C-C

    2016-10-01

    Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and optimal treatment strategies remain unclear. We studied the effects of diabetes and insulin therapy on non-enzymatic glycation (NEG), cortical porosity (Ct.Po) and biomechanics of the bone tissue in Zucker Diabetic Fatty (ZDF) rats. Eleven-week old ZDF diabetic and non-diabetic rats were given insulin to achieve glycaemic control or vehicle seven days per week over twelve weeks (insulin dose adapted individually 0.5 international units (IU) at week 1 to 13.0IU at week 12). The right femora were excised, micro-CT scanned, and tested in 3-point bending to measure biomechanics. NEG of the midshaft was determined from bulk fluorescence. Diabetes led to increased NEG (+50.1%, p=0.001) and Ct.Po (+22.9%, p=0.004), as well as to reduced mechanical competence (max. stress: -14.2%, p=0.041, toughness: -29.7%, p=0.016) in the bone tissue. NEG and Ct.Po both correlated positively to serum glucose (NEG: R(2)=0.41, p1, Ct.Po: R(2)=0.34, p=0.003) and HbA1c (NEG: R(2)=0.42, p1, Ct.Po: R(2)=0.28, p=0.008) levels, while NEG correlated negatively with bone biomechanics (elastic modulus: R(2)=0.21, p=0.023, yield stress: R(2)=0.17, p=0.047). Twelve weeks of insulin therapy had no significant effect on NEG or Ct.Po, and was unable to improve the mechanical competence of the bone tissue. A reduction of mechanical competence was observed in the bone tissue of the diabetic rats, which was explained in part by increased collagen NEG. Twelve weeks of insulin therapy did not alter NEG, Ct.Po or bone biomechanics. However, significant correlations between NEG and serum glucose and HbA1c were observed, both of which were reduced with insulin therapy. This suggests that a longer duration of insulin therapy may be required to reduce the NEG of the bone collagen and restore the mechanical competence of diabetic bone. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Risk of Subsequent Leukemia After a Solid Tumor in Childhood: Impact of Bone Marrow Radiation Therapy and Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Allodji, Rodrigue S., E-mail: rodrigue.allodji@gustaveroussy.fr [Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif (France); Gustave Roussy, Villejuif (France); Paris Sud University, Orsay (France); Schwartz, Boris; Veres, Cristina; Haddy, Nadia; Rubino, Carole; Le Deley, Marie-Cécile; Labbé, Martine; Diop, Fara; Jackson, Angela; Dayet, Florent; Benabdennebi, Aymen; Llanas, Damien; Vu Bezin, Jérémi [Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif (France); Gustave Roussy, Villejuif (France); Paris Sud University, Orsay (France); Chavaudra, Jean; Lefkopoulos, Dimitri [Gustave Roussy, Villejuif (France); Deutsch, Eric [Gustave Roussy, Villejuif (France); Inserm, UMR 1030, Villejuif (France); Oberlin, Odile [Gustave Roussy, Villejuif (France); Vathaire, Florent de; Diallo, Ibrahima [Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif (France); Gustave Roussy, Villejuif (France); Paris Sud University, Orsay (France)

    2015-11-01

    Purpose: To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer. Methods and Materials: We analyzed data from a case-control study with 35 cases and 140 controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis. Results: Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trend became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m{sup 2}. Conclusions: Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.

  18. Risk of Subsequent Leukemia After a Solid Tumor in Childhood: Impact of Bone Marrow Radiation Therapy and Chemotherapy

    International Nuclear Information System (INIS)

    Allodji, Rodrigue S.; Schwartz, Boris; Veres, Cristina; Haddy, Nadia; Rubino, Carole; Le Deley, Marie-Cécile; Labbé, Martine; Diop, Fara; Jackson, Angela; Dayet, Florent; Benabdennebi, Aymen; Llanas, Damien; Vu Bezin, Jérémi; Chavaudra, Jean; Lefkopoulos, Dimitri; Deutsch, Eric; Oberlin, Odile; Vathaire, Florent de; Diallo, Ibrahima

    2015-01-01

    Purpose: To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer. Methods and Materials: We analyzed data from a case-control study with 35 cases and 140 controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis. Results: Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trend became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m"2. Conclusions: Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.

  19. G-CSF therapy with mobilization of bone marrow stem cells for myocardial recovery after acute myocardial infarction - a relevant treatment?

    DEFF Research Database (Denmark)

    Ripa, R.S.; Kastrup, J.

    2008-01-01

    -CSF treatment. Current controversies in interpretation of the results include 1) importance of direct cardiac effect of G-CSF vs indirect through bone marrow stem and progenitor cell mobilization, 2) importance of timing of G-CSF therapy, 3) importance of G-CSF dose, and 4) importance of cell types mobilized...... from the bone-marrow. Cell-based therapies to improve cardiac function remain promising and further experimental and clinical studies are warranted to determine the future role of G-CSF Udgivelsesdato: 2008/6......This review of adjunctive therapy with subcutaneous granulocyte-colony stimulating factor (G-CSF) to patients with acute myocardial infarction (AMI) focus on the cardioprotective effects and potential mechanisms of G-CSF and discuss the therapeutic potential of G-CSF. All clinical trials published...

  20. Combined endodontic therapy and periapical surgery with MTA and bone graft in treating palatogingival groove.

    Science.gov (United States)

    Mittal, Mudit; Vashisth, Pallavi; Arora, Rachita; Dwivedi, Swati

    2013-04-18

    A 37-year-old male patient reported to our department with chief complaint of pain and pus discharge from the labial marginal gingiva in the maxillary right lateral incisor region since last 4 months. Clinically, the tooth was hypersensitive to percussion and palpation but failed to respond to pulp sensitivity testing. After periodontal probing, a palatal groove was observed which started at the cingulum and travelled apically and laterally, associated with a pocket depth of 8 mm. Occlusal radiograph showed circumscribed radiolucency measuring 5 mm×7 mm in diameter at the apex of the tooth. A clinical diagnosis of chronic apical abscess was established. The case was treated with a combination of mineral trioxide aggregate and bone graft. At the 6-month follow-up visit, the tooth showed progressive healing without sinus track and sulcular bleeding.

  1. Investigation of mineral distribution in bone by synchrotron X-ray fluorescence microscopy after tibolone therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lima, I. [Rio de Janeiro State Univ., Nova Friburgo, RJ (Brazil). Dept. of Mechanical Engineering and Energy; Federal Univ. of Rio de Janeiro, RJ (Brazil). Nuclear Instrumentation Lab. - COPPE; Carvalho, A.C.B.; Henriques, H.N.; Guzman-Silva, M.A. [Fluminense Federal Univ., Niteroi, RJ (Brazil). Lab. of Experimental Pathology; Sales, E.; Lopes, R.T. [Federal Univ. of Rio de Janeiro, RJ (Brazil). Nuclear Instrumentation Lab. - COPPE; Granjeiro, J.M. [Fluminense Federal Univ., Niteroi, RJ (Brazil). Dept. of Cellular and Molecular Biology

    2011-07-01

    Tibolone is a synthetic steroid with estrogenic, androgenic, and progestagenic properties used for the prevention of postmenopausal osteoporosis and treatment of climacteric symptoms. Tibolone shows almost no action on breast and endometrium, which are target-organs for estrogens and progesterone activity. The aim of this work was to investigate the spatial distribution of calcium and zinc minerals in the femoral head of ovariectomized rat in order to evaluate the effects of the long-term administration of tibolone. For that purpose X-ray microfluorescence was used with synchrotron radiation imaging technique which was performed at Brazilian Light Synchrotron Laboratory, Campinas, SP. Minerals were not homogeneously distributed in trabecular bone areas; a higher concentration of calcium in the trabecular regions at femoral heads was found in ovariectomized and tibolone-treated rats compared to ovariectomized and control groups. (orig.)

  2. USO DO ENXERTO ÓSSEO CORTICAL BOVINO CONSERVADO EM GLICERINA A 98% NA OSTEOTOMIA FEMORAL EM GATOS USE BOVINE CORTICAL BONE, PRESERVED IN 98% GLICERIN IN FEMORAL OSTEOTOMY IN CATS.

    Directory of Open Access Journals (Sweden)

    Lucia Helena de Carvalho Penha

    2008-12-01

    . The objective of this study was to evaluate clinically and radiographically the efficacy of xenografts as a substitute for methalic implants. Animals were divided into two groups: five young cats and five adult cats. Clinically, the weight-bearing on the operated limb was observed the day after surgery in all animals, with complete remission of lameness at 15 days and bone union in 16.6 weeks. In five young animals, in two of them, the grafts were fractured carrying a serious bone bending without fracture of feline femur. In the last two young cats, remodeling was noted in mean time of 75 days or 10.7 weeks. In five adult cats, all of them suffered overriding of the fragments of osteotomized bone with various degrees, where two cases were considered severe cases dut to fracture of feline femur without bone bending. In the three remaining animals with slightly overriding, one was a case of delayed union, one suffered tow surgical procedures due to graft fracture and one did not show a radiographic exuberant bone callus, with remodeling at 110 days. The use of the bonive xenograft preserved in 98% glycerol in young and adult cats used as intramedularry nails was perfectly employed, offering mechanical support in time of bone consolidation in all of 10 animals.

    KEY WORDS: Cortical bovine graft, cats, femur, fracture, osteotomy.

  3. A bone marrow toxicity model for 223Ra alpha-emitter radiopharmaceutical therapy

    International Nuclear Information System (INIS)

    Hobbs, Robert F; Song Hong; Sgouros, George; Watchman, Christopher J; Bolch, Wesley E; Aksnes, Anne-Kirsti; Ramdahl, Thomas; Flux, Glenn D

    2012-01-01

    Ra-223, an α-particle emitting bone-seeking radionuclide, has recently been used in clinical trials for osseous metastases of prostate cancer. We investigated the relationship between absorbed fraction-based red marrow dosimetry and cell level-dosimetry using a model that accounts for the expected localization of this agent relative to marrow cavity architecture. We show that cell level-based dosimetry is essential to understanding potential marrow toxicity. The GEANT4 software package was used to create simple spheres representing marrow cavities. Ra-223 was positioned on the trabecular bone surface or in the endosteal layer and simulated for decay, along with the descendants. The interior of the sphere was divided into cell-size voxels and the energy was collected in each voxel and interpreted as dose cell histograms. The average absorbed dose values and absorbed fractions were also calculated in order to compare those results with previously published values. The absorbed dose was predominantly deposited near the trabecular surface. The dose cell histogram results were used to plot the percentage of cells that received a potentially toxic absorbed dose (2 or 4 Gy) as a function of the average absorbed dose over the marrow cavity. The results show (1) a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity; and (2) that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity resulted in only a small increase in potential marrow toxicity (i.e. the number of cells receiving more than 4 or 2 Gy), for a range of average marrow cavity absorbed doses from 1 to 20 Gy. The results from the trabecular model differ markedly from a standard absorbed fraction method while presenting comparable average dose values. These suggest that increasing the amount of radioactivity may not substantially increase the risk of toxicity, a result unavailable to the

  4. Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with turner syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Cintron, Dahima; Rodriguez-Gutierrez, Rene; Serrano, Valentina; Latortue-Albino, Paula; Erwin, Patricia J; Murad, Mohammad Hassan

    2017-02-01

    Patients with Turner syndrome have adverse bone and cardiovascular outcomes from chronic estrogen deficiency. Hence, long-term estrogen replacement therapy is the cornerstone treatment. The estimates of its effect and optimal use, however, remain uncertain. We aimed to summarize the benefits and harms of estrogen replacement therapy on bone, cardiovascular, vasomotor and quality of life outcomes in patients with Turner syndrome. A comprehensive search of four databases was performed from inception through January 2016. Randomized clinical trials and observational cohort studies studying the effect of estrogen replacement therapy in patients with Turner syndrome under the age of 40 were included. Independently and in duplicate reviewers selected studies, extracted data and assessed risk of bias. Subgroup analyses were based on route of administration and type of estrogen formulation. Twenty-five studies at moderate to high risk of bias (12 randomized trials, 13 cohort studies) with 771 patients were included. Using random-effects models, estrogen replacement therapy showed an increase in bone mineral density [weighted mean change from baseline 0.09 g/cm2 (0.04-0.14)] that differed by type of estrogen but not route of administration. Oral estrogen replacement therapy showed a higher increase in high density lipoprotein cholesterol levels when compared to transdermal [weighted mean difference 9.33 mg/dl (4.82-13.85)] with no significant effect on other lipid fractions. The current evidence suggests possible benefit of estrogen replacement therapy on bone mineral density and high density lipoprotein cholesterol. Whether this improvement translates into changes in patient important outcomes (cardiovascular events or fractures) remains uncertain. Larger randomized clinical trials with direct comparisons on patient important outcomes are necessary.

  5. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A

    1999-01-01

    The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone....... The weak response at the distal forearm during antiresorptive treatment has restricted the use of bone densitometry at this region. We describe a new model for bone densitometry at the distal forearm, by which the response obtained is comparable to the response in other regions where bone densitometry...... is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n = 69), a 1-year...

  6. Musculoskeletal Complications and Bone Metastases in Breast Cancer Patients Undergoing Estrogen Deprivation Therapy

    Science.gov (United States)

    2017-10-01

    Laura E. Wright, Ph.D. 5e. TASK NUMBER E-Mail: laewrig@iu.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES...8. PERFORMING ORGANIZATION REPORT NUMBER Indiana University School of Medicine 980 West Walnut Street R3 Room C132 Indianapolis, IN 46202 9...13. SUPPLEMENTARY NOTES 14. ABSTRACT Between 25-50% of women treated with endocrine therapies develop musculoskeletal toxicities that result in

  7. Systemic sarcoidosis with bone marrow involvement responding to therapy with adalimumab: a case report

    OpenAIRE

    Patel, Supen R

    2009-01-01

    Abstract Introduction Sarcoidosis is an inflammatory disorder characterized by the presence of non-caseating granulomas in affected organs. The presence of CD4-positive T lymphocytes and macrophages in affected organs suggests an ongoing immune response. Systemic corticosteroids remain the mainstay of treatment, but therapy is often limited by adverse effects. This is the first report of the use of adalimumab (HUMIRA®, Abbott Laboratories, North Chicago, IL, USA), an anti-tumor necrosis facto...

  8. Therapy assessment of bone metastatic disease in the era of {sup 223}radium

    Energy Technology Data Exchange (ETDEWEB)

    Etchebehere, Elba; Brito, Ana Emilia [The University of Campinas, Division of Nuclear Medicine, Campinas (Brazil); Rezaee, Alireza; Langsteger, Werner [St. Vincent' s Hospital, Department of Nuclear Medicine and Endocrinology, PET - CT Center LINZ, Ordensklinikum, Linz (Austria); Beheshti, Mohsen [St. Vincent' s Hospital, Department of Nuclear Medicine and Endocrinology, PET - CT Center LINZ, Ordensklinikum, Linz (Austria); Paracelsus Medical University, Department of Nuclear Medicine and Endocrinology, Salzburg (Austria)

    2017-08-15

    Defining an optimal imaging modality for assessment of therapy and the best time of evaluation are pivotal for ideal patient's management. {sup 223}Ra (Xofigo registered, formerly Alpharadin) has been approved by the FDA and European Medicines Agency for treatment of metastatic castration-resistant prostate cancer with painful osseous involvement. PET/CT imaging using various radiotracers such as {sup 18}F-FDG, {sup 18}F-FCH, {sup 68}Ga-PSMA and {sup 18}F-NaF have been investigated to mitigate the limitations of conventional imaging modalities. Diagnostic radiotracers that have properties similar to a therapeutic radiotracer will precisely assess of the possibility and efficacy of a treatment; this is the theranostic concept. An example of a diagnostic test employed for selecting targeted therapy is the combined use of {sup 18}F-fluoride PET/CT for evaluation of possible therapy with {sup 223}Ra. This review examines the most recent publications related to this topic. (orig.)

  9. Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Newman, Neil B.; Sidhu, Manpreet K.; Baby, Rekha [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Moss, Rebecca A.; Nissenblatt, Michael J. [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Chen, Ting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Lu, Shou-En [Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, New Jersey (United States); Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States)

    2016-04-01

    Purpose/Objective(s): To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. Methods and Materials: We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. Results: During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Conclusions: Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

  10. Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy.

    Science.gov (United States)

    Newman, Neil B; Sidhu, Manpreet K; Baby, Rekha; Moss, Rebecca A; Nissenblatt, Michael J; Chen, Ting; Lu, Shou-En; Jabbour, Salma K

    2016-04-01

    To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Comparative study of cryopreserved bone tissue and tissue preserved in a 98% glycerol solution Estudo comparativo entre o tecido ósseo criopreservado e o conservado em glicerol a 98%

    Directory of Open Access Journals (Sweden)

    Arlete Mazzini Miranda Giovani

    2006-01-01

    Full Text Available OBJECTIVE: To compare the bone graft cryopreservation method (at -80ºC with a preservation method using a 98% glycerol solution at room temperature (10ºC-35ºC, by testing the antibacterial and fungal effects of 98% glycerol and comparatively analyzing the observed histological changes resulting from the use of both methods. METHOD: This study was of 30 samples of trabecular bone tissue from 10 patients undergoing total hip arthroplasty. Each femoral head provided 3 samples that were randomized into 3 groups, namely, the control group, the cryopreserved group, and the group preserved in a 98% glycerol at room temperature for 1 year. The samples were submitted to histomorphologic, cell feasibility, and microbiologic analyses. The results were statistically analyzed using the McNemar test, with a statistical significance index of 0.05. RESULTS: Values obtained using the McNemar test to compare probability distributions of histomorphologic variables (mature or lamellar bone, immature bone, and necrosis and cell feasibility (osteoblasts and osteoclasts indicated that there is no difference between the distributions of variables under the 3 experimental conditions. Microbiological analysis of the 98% glycerol solution and bone fragments from samples stored for 1 year at room temperature did not show bacterial or fungal growth. The histological and microbiological investigation were performed at 2 different time points: immediately after the sample processing and after 1 year. CONCLUSION: The method used to preserve bone grafts kept in 98% glycerol at room temperature (10ºC-35ºC was similar to cryopreservation in terms of bone matrix preservation; no bacteria or fungi were found in the samples.OBJETIVO: Comparar o método da criopreservação de enxertos ósseos (- 80º C com o da conservação em glicerol a 98% em temperatura ambiente (10º C a 35º C, testando os efeitos antibacterianos e antifúngicos do glicerol a 98% e analisando

  12. Combined bilateral idiopathic necrosis of the humerus and femur heads: Bone scan, X-ray, CT, and MRI findings. Kombinierte beidseitige idiopathische Nekrose der Humerus- und Femurkoepfe: Skelettszintigraphie, Roentgen-, CT- und MRT-Befunde

    Energy Technology Data Exchange (ETDEWEB)

    Piepenburg, R.; Hahn, K. (Mainz Univ. (Germany). Klinik fuer Nuklearmedizin); Doll, G. (Mainz Univ. (Germany). Klinik fuer Roentgendiagnostik); Grimm, J. (Mainz Univ. (Germany). Orthopaedische Klinik)

    1992-12-01

    Untreated aseptic bone necroses close to a joint commonly leads to severe secondary arthrosis and destruction of the joint within a short time. Therefore, only a diagnosis in an early stage of the disease offers the chance of a successful joint- preserving therapy. In cases of clinically suspected aseptic bone necrosis but still negative or doubtful X-ray findings, bone scans or MRI are reliable methods of verifying the diagnosis. (orig./MG).

  13. 3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications

    Science.gov (United States)

    Asa'ad, Farah; Giannì, Aldo Bruno; Giannobile, William V.; Rasperini, Giulio

    2016-01-01

    To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopted to lessen the need for such invasive approaches, it utilizes bone grafting materials, which have limitations that could negatively affect the quality of bone formation. To overcome the drawbacks of routinely employed grafting materials, bone graft substitutes such as 3D scaffolds have been recently investigated in the dental field. In this review, we highlight different biomaterials suitable for 3D scaffold fabrication, with a focus on “3D-printed” ones as bone graft substitutes that might be convenient for various applications related to implant therapy. We also briefly discuss their possible adoption for periodontal regeneration. PMID:27366149

  14. 3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications

    Directory of Open Access Journals (Sweden)

    Farah Asa’ad

    2016-01-01

    Full Text Available To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopted to lessen the need for such invasive approaches, it utilizes bone grafting materials, which have limitations that could negatively affect the quality of bone formation. To overcome the drawbacks of routinely employed grafting materials, bone graft substitutes such as 3D scaffolds have been recently investigated in the dental field. In this review, we highlight different biomaterials suitable for 3D scaffold fabrication, with a focus on “3D-printed” ones as bone graft substitutes that might be convenient for various applications related to implant therapy. We also briefly discuss their possible adoption for periodontal regeneration.

  15. Emittance preservation

    Energy Technology Data Exchange (ETDEWEB)

    Kain, V; Arduini, G; Goddard, B; Holzer, B J; Jowett, J M; Meddahi, M; Mertens, T; Roncarolo, F; Schaumann, M; Versteegen, R; Wenninger, J [European Organization for Nuclear Research, Geneva (Switzerland)

    2012-07-01

    Emittance measurements during the LHC proton run 2011 indicated a blow-up of 20 % to 30 % from LHC injection to collisions. This presentation will show the emittance preservation throughout the different parts of the LHC cycle and discuss the current limitations on emittance determination. An overview of emittance preservation through the injector complex as function of bunch intensity will also be given. Possible sources for the observed blow-up and required tests in 2012 will be presented. Possible improvements of emittance diagnostics and analysis tools for 2012 will be shown.

  16. Impact of bone turnover markers and/or educational information on persistence to oral bisphosphonate therapy: a community setting-based trial.

    Science.gov (United States)

    Silverman, S L; Nasser, K; Nattrass, S; Drinkwater, B

    2012-03-01

    We examined how the use of bone turnover markers and educational information affects persistence of bisphosphonate use in osteoporotic patients. We found that reporting bone turnover results and/or educational information did not affect persistence. Long-term adherence and persistence to osteoporosis medication are poor. We examined whether reporting of bone turnover marker results, education about osteoporosis, or a combination of both would increase persistence to oral bisphosphonates. Two hundred and forty women who were 5 years postmenopausal with BMD at least 2.0 standard deviations below normal were recruited for the study. All women were given a new prescription for alendronate and randomly assigned to one of four groups: (1) bone marker results at baseline, 3 and 12 months; (2) educational materials every month and a membership in the National Osteoporosis Foundation; (3) bone marker and educational information; and (4) control, no information other than usual care. Persistence among randomization groups was tested using survival analysis adjusting for the delay between intervention methods. Of those filling their initial prescription, 95.5% refilled their prescription at the end of the first month, 87% at 3 months, 82% at 6 months, and 78% at 10 months. Overall persistence through 12 months was 54%. There was no difference found among the four groups for persistence time using (p > 0.58). Providing bone turnover marker results is not an effective way to enhance early compliance and persistence with drug therapy. While the women in our study felt that bone marker results and educational information were helpful to them, there was no difference in persistence between those who received either bone marker information and/or educational information and those who did not. Because of the unexpected rate of primary nonadherence, this study may be underpowered.

  17. Particle Therapy Using Protons or Carbon Ions for Unresectable or Incompletely Resected Bone and Soft Tissue Sarcomas of the Pelvis

    Energy Technology Data Exchange (ETDEWEB)

    Demizu, Yusuke, E-mail: y_demizu@nifty.com [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Jin, Dongcun; Sulaiman, Nor Shazrina; Nagano, Fumiko; Terashima, Kazuki; Tokumaru, Sunao [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Akagi, Takashi [Department of Radiation Physics, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Fujii, Osamu [Department of Radiation Oncology, Hakodate Goryokaku Hospital, Hakodate, Hokkaido (Japan); Daimon, Takashi [Department of Biostatistics, Hyogo College of Medicine, Nishinomiya, Hyogo (Japan); Sasaki, Ryohei [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Fuwa, Nobukazu [Department of Radiation Oncology, Ise Red Cross Hospital, Ise, Mie (Japan); Okimoto, Tomoaki [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan)

    2017-06-01

    Purpose: To retrospectively analyze the treatment outcomes of particle therapy using protons or carbon ions for unresectable or incompletely resected bone and soft tissue sarcomas (BSTSs) of the pelvis. Methods and Materials: From May 2005 to December 2014, 91 patients with nonmetastatic histologically proven unresectable or incompletely resected pelvic BSTSs underwent particle therapy with curative intent. The particle therapy used protons (52 patients) or carbon ions (39 patients). All patients received a dose of 70.4 Gy (relative biologic effectiveness) in 32 fractions (55 patients) or 16 fractions (36 patients). Results: The median patient age was 67 years (range 18-87). The median planning target volume (PTV) was 455 cm{sup 3} (range 108-1984). The histologic type was chordoma in 53 patients, chondrosarcoma in 14, osteosarcoma in 10, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma in 5, and other in 9 patients. Of the 91 patients, 82 had a primary tumor and 9 a recurrent tumor. The median follow-up period was 32 months (range 3-112). The 3-year rate of overall survival (OS), progression-free survival (PFS), and local control was 83%, 72%, and 92%, respectively. A Cox proportional hazards model revealed that chordoma histologic features and a PTV of ≤500 cm{sup 3} were significantly associated with better OS, and a primary tumor and PTV of ≤500 cm{sup 3} were significantly associated with better PFS. Ion type and number of fractions were not significantly associated with OS, PFS, or local control. Late grade ≥3 toxicities were observed in 23 patients. Compared with the 32-fraction protocol, the 16-fraction protocol was associated with significantly more frequent late grade ≥3 toxicities (18 of 36 vs 5 of 55; P<.001). Conclusions: Particle therapy using protons or carbon ions was effective for unresectable or incompletely resected pelvic BSTS, and the 32-fraction protocol was effective and relatively less toxic. Nevertheless, a

  18. The effects of L-thyroxin replacement therapy on bone minerals and body composition in hypothyroid children

    OpenAIRE

    Salama, Hassan M.; El-Dayem, Soha A.; Yousef, Hala; Fawzy, Ashraf; Abou-Ismail, Laila; El-lebedy, Dalia

    2010-01-01

    Introduction Prolonged treatment with levothyroxine 4 (L-T4) is a well known risk factor for osteoporosis. Patients on L-T4 replacement occasionally have a subnormal TSH, which carries a risk of development of bone loss. Thyroid hormones directly affect bone cells, stimulating osteoclastic and osteoblastic activity with a predominance of bone resorption and decrease of bone mineral density (BMD). Material and methods The study included 35 hypothyroid patients with mean age 11.57 ±5.06, while ...

  19. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    Science.gov (United States)

    Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

  20. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    Directory of Open Access Journals (Sweden)

    Ryan C Curtis

    Full Text Available Clinical studies using definitive-intent stereotactic radiation therapy (SRT for the local treatment of canine osteosarcoma (OSA have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy. Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA and parathyroid hormone (PTH are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total. Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis 8 weeks after radiation in the combined (ZA/PTH treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

  1. Role of the nurse in preserving patients' independence.

    Science.gov (United States)

    Maxwell, Cathy

    2007-01-01

    Patients with metastatic bone disease may be treated with bisphosphonates to reduce or delay skeletal complications including pathologic fracture, radiotherapy to bone, and hypercalcemia of malignancy. Nurses can provide important education to patients and support or encourage the use of bisphosphonates throughout therapy. Literature and congress reports were reviewed for relevant efficacy information on bisphosphonates and adverse events that may occur during bisphosphonate therapy. Bisphosphonates can provide meaningful benefits to patients, and zoledronic acid is now approved for the treatment of bone metastases secondary to any solid tumor. To optimize care, nurses can monitor pain scores, changes in mobility, adverse events, and serum creatinine levels. A useful tool for recording these parameters is a patient diary. The nurse should fill out the diary at each patient visit and compare it with baseline information before treatment is administered. Patients should also be counseled on the importance of adequate hydration, good dental hygiene, the need for calcium and vitamin D supplements, and how to best manage potential side effects. Bisphosphonates are effective in reducing and delaying skeletal complications, and zoledronic acid has demonstrated significant efficacy in preventing skeletal complications across a wide range of solid tumors and multiple myeloma. Nurses play an important role in enabling patients to optimize bisphosphonate therapy and in supporting patients to continue treatment to preserve their functional independence.

  2. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi

    2010-08-01

    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  3. Improving the dose-myelotoxicity correlation in radiometabolic therapy of bone metastases with {sup 153}Sm-EDTMP

    Energy Technology Data Exchange (ETDEWEB)

    Pacilio, Massimiliano; Basile, Chiara [Azienda Ospedaliera San Camillo Forlanini, Rome (Italy). Dept. of Medical Physics; Ventroni, Guido; Mango, Lucio [Azienda Ospedaliera San Camillo Forlanini, Rome (Italy). Dept. of Nuclear Medicine; Ialongo, Pasquale [Azienda Ospedaliera San Camillo Forlanini, Rome (Italy). Dept. of Radiology; Becci, Domenico [University of Rome, Health Physics Postgraduate School, Rome (Italy)

    2014-02-15

    {sup 153}Sm-ethylene diamine tetramethylene phosphonic acid ({sup 153}Sm-EDTMP) is widely used to palliate pain from bone metastases, and is being studied for combination therapy beyond palliation. Conceptually, red marrow (RM) dosimetry allows myelotoxicity to be predicted, but the correlation is poor due to dosimetric uncertainty, individual sensitivity and biological effects from previous treatments. According to EANM guidelines, basic dosimetric procedures have been studied to improve the correlation between dosimetry and myelotoxicity in {sup 153}Sm-EDTMP therapy. RM dosimetry for 33 treatments of bone metastases from breast, prostate and lung tumours was performed prospectively (with {sup 99m}Tc-MDP) and retrospectively, acquiring whole-body scans early and late after injection. The {sup 153}Sm-EDTMP activity was calculated by prospective dosimetry based on measured skeletal uptake and full physical retention, with the RM absorbed dose not exceeding 3.8 Gy. Patient-specific RM mass was evaluated by scaling in terms of body weight (BW), lean body mass (LBM) and trabecular volume (TV) estimated from CT scans of the L2-L4 vertebrae. Correlations with toxicity were determined in a selected subgroup of 27 patients, in which a better correlation between dosimetry and myelotoxicity was expected. Skeletal uptakes of {sup 99m}Tc and {sup 153}Sm (Tc{sub %} and Sm{sub %}) were well correlated. The median Sm{sub %} was higher in prostate cancer (75.3 %) than in lung (60.5 %, p = 0.005) or breast (60.8 %, p = 0.008). PLT and WBC nadirs were not correlated with administered activity, but were weakly correlated with uncorrected RM absorbed doses, and the correlation improved after rescaling in terms of BW, LBM and TV. Most patients showed transient toxicity (grade 1-3), which completely and spontaneously recovered over a few days. Using TV, RM absorbed dose was in the range 2-5 Gy, with a median of 312 cGy for PLT in patients with toxicity and 247 cGy in those with no

  4. Bone marrow involvement in Gaucher disease at MRI: what long-term evolution can we expect under enzyme replacement therapy?

    International Nuclear Information System (INIS)

    Fedida, Benjamin; Touraine, Sebastien; Laredo, Jean-Denis; Stirnemann, Jerome; Belmatoug, Nadia; Petrover, David

    2015-01-01

    To study the long-term evolution of the bone marrow burden (BMB) score at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy (ERT). Forty patients treated for GD were retrospectively studied in a referral centre. BMB scores were assessed on spine and femur MR examinations performed between January 2003 and June 2014. The long-term evolution of the BMB scores was analyzed using a linear mixed model. A total of 121 MRI examinations were performed during the study period with a mean follow-up of 7.1 years ± 5.6, an average rate of 3.1 MR examinations ± 1.7 per patient and an interval of 2.3 years ± 1.1 between examinations. Patients had received ERT during 12 years on average ± 6.7. The trend of BMB scores with time decreased significantly by 15 % (P = 0.008) during the total study period and 39 % (P = 0.01) during the first 5 years of treatment. No changes in BMB scores were observed after five years of treatment. In Gaucher patients, the trend of MRI BMB scores with time decreased significantly under ERT the first 5 years of treatment before a long-term stabilization. (orig.)

  5. Impact of laser therapy on the condition of oral cavity mucosa in chemotherapy treated patients who underwent bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Tomasz Krzysztof Bąk

    2017-08-01

    Full Text Available Patological disorders within oral mucosa (so called mucositis are the most common stomatological complications among chemotherapy treated leukemic patients scheduled for bone marrow transplantation. Early diagnosis of such oral disorders leads to numerous side effects, decreasing quality of life and systemic complications is required. Furthermore, most patients require analgesic treatment, very often using narcotic pain medications. Presently the largest role of prevention and treatment of mucositis is preventative dentistry along with maintaining strict oral hygiene. This course of action aims to reduce pain and prevention of infections. Investigation of novel non-invasive therapeutic methods that could improve treatment outcomes seems justified. Among the most promising methods, the Low-level Laser Therapy (LLLT treatment demonstrates many beneficial effects for patients suffering from chemotherapy complications. It promotes mucosal healing and helps improve patients' quality of life. These advantages may be a result of a LLLT anti-inflammatory and analgesic effect. LLLT also promotes tissue regeneration through chemical changes in cells (cell repair. In recent clinical studies conducted on a group of patients with oral mucositis, the significant acceleration of mentioned disorders regression was noted. Moreover, reduction of pain after application of LLLT was recorded. Discussed in the article LLLT is easily accessible for clinical practice . Mentioned arguments justify a wider use of such a tool in non-invasive treatment of acute oral cavity inflammation.

  6. Prospective Study of Functional Bone Marrow-Sparing Intensity Modulated Radiation Therapy With Concurrent Chemotherapy for Pelvic Malignancies

    International Nuclear Information System (INIS)

    Liang Yun; Bydder, Mark; Yashar, Catheryn M.; Rose, Brent S.; Cornell, Mariel; Hoh, Carl K.; Lawson, Joshua D.; Einck, John; Saenz, Cheryl; Fanta, Paul; Mundt, Arno J.; Bydder, Graeme M.

    2013-01-01

    Purpose: To test the hypothesis that intensity modulated radiation therapy (IMRT) can reduce radiation dose to functional bone marrow (BM) in patients with pelvic malignancies (phase IA) and estimate the clinical feasibility and acute toxicity associated with this technique (phase IB). Methods and Materials: We enrolled 31 subjects (19 with gynecologic cancer and 12 with anal cancer) in an institutional review board-approved prospective trial (6 in the pilot study, 10 in phase IA, and 15 in phase IB). The mean age was 52 years; 8 of 31 patients (26%) were men. Twenty-one subjects completed 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) simulation and magnetic resonance imaging by use of quantitative IDEAL (IDEAL IQ; GE Healthcare, Waukesha, WI). The PET/CT and IDEAL IQ were registered, and BM subvolumes were segmented above the mean standardized uptake value and below the mean fat fraction within the pelvis and lumbar spine; their intersection was designated as functional BM for IMRT planning. Functional BM-sparing vs total BM-sparing IMRT plans were compared in 12 subjects; 10 were treated with functional BM-sparing pelvic IMRT per protocol. Results: In gynecologic cancer patients, the mean functional BM V 10 (volume receiving ≥10 Gy) and V 20 (volume receiving ≥20 Gy) were 85% vs 94% (P 18 F-fluorodeoxyglucose-PET/CT and IDEAL IQ. The efficacy of BM-sparing IMRT is being tested in a phase II trial.

  7. Predictors of Fracture Risk and Bone Mineral Density in Men with Prostate Cancer on Androgen Deprivation Therapy

    Directory of Open Access Journals (Sweden)

    Katherine Neubecker

    2011-01-01

    Full Text Available Decrease of bone mineral density (BMD and fracture risk is increased in men with prostate cancer receiving androgen deprivation therapy (ADT. We looked at possible predictors of decreased BMD and increased fracture risk in men with prostate cancer; most of whom were on ADT. In a retrospective study, we analyzed serum, BMD, and clinical risk factors used in the Fracture Risk Assessment (FRAX tool and others in 78 men with prostate cancer with reported height loss. The subjects were divided in two groups: 22 men with and 56 without vertebral fractures. 17 of the 22 men with vertebral fractures on spine X-rays did not know they had a vertebral fracture. Of those 17 men, 9 had not previously qualified for treatment based on preradiograph FRAX score calculated with BMD, and 6 based on FRAX calculated without BMD. Performing spine films increased the predictive ability of FRAX for vertebral fracture. Vertebral fracture was better predicted by FRAX for other osteoporotic fractures than FRAX for hip fractures. The inclusion of BMD in FRAX calculations did not affect the predictive ability of FRAX. The PSA level showed a positive correlation with lumbar spine BMD and accounted for about 9% of spine BMD.

  8. Bone marrow involvement in Gaucher disease at MRI: what long-term evolution can we expect under enzyme replacement therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Fedida, Benjamin; Touraine, Sebastien; Laredo, Jean-Denis [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Stirnemann, Jerome [Universite Paris-Diderot Hopital Bichat, AP-HP, Department of Biostatistics and Medical Data Processing, INSERM UMR 738, Paris (France); Geneva University Hospital, Division of General Internal Medicine, Faculty of Medicine, Geneva (Switzerland); Belmatoug, Nadia [Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France); Hopital Beaujon, AP-HP, Department of Internal Medicine, Clichy (France); Petrover, David [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France)

    2015-10-15

    To study the long-term evolution of the bone marrow burden (BMB) score at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy (ERT). Forty patients treated for GD were retrospectively studied in a referral centre. BMB scores were assessed on spine and femur MR examinations performed between January 2003 and June 2014. The long-term evolution of the BMB scores was analyzed using a linear mixed model. A total of 121 MRI examinations were performed during the study period with a mean follow-up of 7.1 years ± 5.6, an average rate of 3.1 MR examinations ± 1.7 per patient and an interval of 2.3 years ± 1.1 between examinations. Patients had received ERT during 12 years on average ± 6.7. The trend of BMB scores with time decreased significantly by 15 % (P = 0.008) during the total study period and 39 % (P = 0.01) during the first 5 years of treatment. No changes in BMB scores were observed after five years of treatment. In Gaucher patients, the trend of MRI BMB scores with time decreased significantly under ERT the first 5 years of treatment before a long-term stabilization. (orig.)

  9. Bone mass regulation of leptin and postmenopausal osteoporosis with obesity.

    Science.gov (United States)

    Legiran, Siswo; Brandi, Maria Luisa

    2012-09-01

    Leptin has been known to play a role in weight regulation through food intake and energy expenditure. Leptin also has an important role in bone metabolism. The role of leptin is determined by leptin receptors, either central or peripheral to the bones. We discuss the role of leptin on bone and molecular genetics of osteoporosis in postmenopausal obese women. The role of leptin in bone preserves bone mineral density (BMD) through increased OPG levels leading to bind RANKL, resulting in reducing osteoclast activity. The estrogen role on bone is also mediated by RANKL and OPG. In postmenopausal women who have estrogen deficiency, it increases the rate of RANKL, which increases osteoclastogenesis. Obese individuals who have a high level of leptin will be effected by bone protection. There are similarities in the mechanism between estrogen and leptin in influencing the process of bone remodeling. It may be considered that the role of estrogen can be replaced by leptin. Molecular genetic aspects that play a role in bone remodeling, such as leptin, leptin receptors, cytokines (e.g. RANK, RANKL, and OPG), require further study to be useful, especially regarding osteoporosis therapy based on genetic analysis.

  10. Preserving Functional Lung Using Perfusion Imaging and Intensity-Modulated Radiation Therapy for Advanced-Stage Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Shioyama, Yoshiyuki; Jang, Si Young; Liu, H. Helen; Guerrero, Thomas; Wang, Xuanmin; Gayed, Isis W.; Erwin, William D.; Liao, Zhongxing; Chang, Joe Y.; Jeter, Melenda; Yaremko, Brian P.; Borghero, Yerko O.; Cox, James D.; Komaki, Ritsuko; Mohan, Radhe

    2007-01-01

    Purpose: To assess quantitatively the impact of incorporating functional lung imaging into intensity-modulated radiation therapy planning for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen patients with advanced-stage NSCLC who underwent radiotherapy were included in this study. Before radiotherapy, each patient underwent lung perfusion imaging with single-photon-emission computed tomography and X-ray computed tomography (SPECT-CT). The SPECT-CT was registered with simulation CT and was used to segment the 50- and 90-percentile hyperperfusion lung (F50 lung and F90 lung). Two IMRT plans were designed and compared in each patient: an anatomic plan using simulation CT alone and a functional plan using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the two types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Results: In incorporating perfusion information in IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in the functional plan were 2.2 and 4.2 Gy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, and >20 Gy in the functional plans were 7.1%, 6.0%, and 5.1%, respectively, for F50 lung, and 11.7%, 12.0%, and 6.8%, respectively, for F90 lung. A greater degree of sparing of the functional lung was achieved for patients with large perfusion defects compared with those with relatively uniform perfusion distribution. Conclusion: Function-guided IMRT planning appears to be effective in preserving functional lung in locally advanced-stage NSCLC patients

  11. Renal function preservation with pioglitazone or with basal insulin as an add-on therapy for patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Chang, Yu-Hung; Hwu, Der-Wei; Chang, Dao-Ming; An, Ling-Wang; Hsieh, Chang-Hsun; Lee, Yau-Jiunn

    2017-06-01

    Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed. Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included. A total of 1002 patients were enrolled (pioglitazone: 559, detemir: 264, glargine: 179). After propensity score matching, there were 105 patients with matchable baseline characteristics in each group. After a mean of 3.5 years of follow-up, the pioglitazone group showed a greater HbA1c reduction than the detemir group and the glargine group. Despite patients in all three groups exhibiting significant body weight gain, those in the pioglitazone group and the glargine group showed greater body weight increases than the patients in the detemir group (2.1, 1.6 and 0.8 kg, respectively, p 1.79-3.88) and 3.13 (95% CI 2.01-4.87), respectively. Our study first showed that treatment with both pioglitazone and basal insulin improved glycemic control, while only pioglitazone treatment was observed to be advantageous in terms of preserving renal function when used as an add-on therapy for patients with type 2 DM in whom sulfonylurea and metformin regimens failed.

  12. Low-dose hydrocortisone (HC) replacement therapy is associated with improved bone remodeling balance in hypopituitary subjects

    LENUS (Irish Health Repository)

    Behan, L A

    2011-06-01

    The effect of commonly used glucocorticoid replacement regimens on bone health in hypopituitary subjects is not well known. We aimed to assess the effect of 3 hydrocortisone (HC) replacement dose regimens on bone turnover in this group.10 hypopituitary men with severe ACTH deficiency were randomised in a crossover design to 3 HC dose regimens, Dose A (20mg mane, 10mg tarde), Dose B (10mg twice daily) and Dose C (10mg mane, 5mg tarde). Following 6 weeks of each regimen participants underwent fasting sampling of bone turnover markers.Data from matched controls were used to produce a Z score for subject bone formation and resorption markers and to calculate the bone remodeling balance (formation Z score-resorption Z score) and turnover index ((formation Z + resorption Z)\\/2). A positive bone remodeling balance with increased turnover is consistent with a favourable bone cycle. Data are expressed as median (range).The Pro Collagen Type 1 Peptide (PINP) bone formation Z-score was significantly increased in Dose C, (1.805 (-0.6-10.24)) compared to Dose A (0.035 (-1.0-8.1)) p<0.05 while there was no difference in the C-terminal crosslinking telopeptide (CTx) resorption Z score. The bone remodeling balance was significantly lower for dose A -0.02 (-1.05-4.12) compared to dose C 1.13 (0.13-6.4) (p<0.05). Although there was a trend to an increased bone turnover index with the lower dose regimen, this was not statistically significant.Low dose HC replacement (10mg mane\\/5 mg tarde) was associated with increased bone formation and improved bone remodeling balance which is associated with a more favourable bone cycle. This may have a long term beneficial effect on bone health.

  13. Lifestyle guidelines for managing adverse effects on bone health and body composition in men treated with androgen deprivation therapy for prostate cancer: an update.

    Science.gov (United States)

    Owen, P J; Daly, R M; Livingston, P M; Fraser, S F

    2017-06-01

    Men treated with androgen deprivation therapy (ADT) for prostate cancer are prone to multiple treatment-induced adverse effects, particularly with regard to a deterioration in bone health and altered body composition including decreased lean tissue mass and increased fat mass. These alterations may partially explain the marked increased risk in osteoporosis, falls, fracture and cardiometabolic risk that has been observed in this population. A review was conducted that assessed standard clinical guidelines for the management of ADT-induced adverse effects on bone health and body composition in men with prostate cancer. Currently, standard clinical guidelines exist for the management of various bone and metabolic ADT-induced adverse effects in men with prostate cancer. However, an evaluation of the effectiveness of these guidelines into routine practice revealed that men continued to experience increased central adiposity, and, unless pharmacotherapy was instituted, accelerated bone loss and worsening glycaemia occurred. This review discusses the current guidelines and some of the limitations, and proposes new recommendations based on emerging evidence regarding the efficacy of lifestyle interventions, particularly with regard to exercise and nutritional factors, to manage ADT-related adverse effects on bone health and body composition in men with prostate cancer.

  14. Development of a Nomogram Model Predicting Current Bone Scan Positivity in Patients Treated with Androgen-Deprivation Therapy for Prostate Cancer

    Science.gov (United States)

    Gotto, Geoffrey T.; Yu, Changhong; Bernstein, Melanie; Eastham, James A.; Kattan, Michael W.

    2014-01-01

    Purpose: To develop a nomogram predictive of current bone scan positivity in patients receiving androgen-deprivation therapy (ADT) for advanced prostate cancer; to augment clinical judgment and highlight patients in need of additional imaging investigations. Materials and methods: A retrospective chart review of bone scan reco