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Sample records for bisphosphonate treatment affects

  1. Bisphosphonate treatment affects trabecular bone apparent modulus through micro-architecture rather than matrix properties

    DEFF Research Database (Denmark)

    Ding, Ming

    2004-01-01

    and trabecular architecture independently. Conventional histomorphometry and microdamage data were obtained from the second and third lumbar vertebrae of the same dogs [Bone 28 (2001) 524]. Bisphosphonate treatment resulted in an increased apparent Young's modulus, decreased bone turnover, increased calcified...... matrix density, and increased microdamage. We could not detect any change in the effective Young's modulus of the calcified matrix in the bisphosphonate treated groups. The observed increase in apparent Young's modulus was due to increased bone mass and altered trabecular architecture rather than changes...... in the calcified matrix modulus. We hypothesize that the expected increase in the Young's modulus of the calcified matrix due to the increased calcified matrix density was counteracted by the accumulation of microdamage. Udgivelsesdato: 2004 May...

  2. Bisphosphonate Treatment and Pregnancy

    Science.gov (United States)

    ... rats given bisphosphonates during pregnancy developed calcium deficiency (hypocalcemia), which led to abnormal bone development, and also slow, difficult labor and delivery. Effects related to low calcium are not expected in ...

  3. Atypical form of active melorheostosis and its treatment with bisphosphonate

    Energy Technology Data Exchange (ETDEWEB)

    Donath, Judit; Poor, Gyula; Kiss, Csaba [National Institute of Rheumatology and Physiotherapy, 1027 Budapest (Hungary); Fornet, Bela [Semmelweis University Department of Radiology, Budapest (Hungary); Genant, Harry [University of California Department of Radiology, San Francisco, California (United States)

    2002-12-01

    We present the case of a 38-year-old man in whom extensive bilateral melorheostosis was associated with elevated serum alkaline phosphatase, swelling of the right foot and progressive deformity of the left hand, left leg and right foot. Radiography, computed tomography and bone scintigraphy were performed. Following treatment with bisphosphonate (30 mg/day of pamidronate for 6 days) infusion, the pain and swelling of his right foot showed improvement and his elevated serum alkaline phosphatase decreased. (orig.)

  4. Comparison of serum Dkk1 (Dickkopf-1) and bone mineral density in patients on bisphosphonate treatment vs no treatment.

    LENUS (Irish Health Repository)

    Memon, Adeel R

    2013-05-17

    Complex pathways affect bone metabolism at the cellular level, and a balance between osteoblast and osteoclast activity is critical to bone remodeling. One of the major pathways affecting bone metabolism is Wnt\\/β-catenin signaling, and its disturbances lead to a wide range of bone abnormalities. An important antagonist of this pathway is Dickkopf-1 (Dkk1). Higher Dkk1 levels have been associated with increased bone loss due to inhibition of Wnt pathway. Currently, bisphosphonates are the most commonly used agents to treat primary osteoporotic patients. This study demonstrates the effect of bisphosphonates on Dkk1 levels and its correlation with bone mineral density (BMD). Eighty patients with low BMD were recruited and divided into 2 groups of 40 each (bisphosphonate treatment group and control group). The mean Dkk1 level in the treatment group was significantly reduced to 2358.18 vs 3749.80 pg\\/mL in the control group (p<0.001). Pearson correlation coefficient showed negative correlation between Dkk1 and BMD at lumbar spine (r=-0.55) and femoral neck in the control group; however, no such correlation was found in the treatment group (r=-0.05). Hence, bisphosphonate therapy leads to reduction in Dkk1 levels, but it does not correlate with BMD in such patients.

  5. Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment.

    Science.gov (United States)

    Wehrhan, F; Hyckel, P; Amann, K; Ries, J; Stockmann, P; Schlegel, Ka; Neukam, Fw; Nkenke, E

    2011-05-01

    Bone-destructive disease treatments include bisphosphonates and antibodies against receptor activator for nuclear factor κB ligand (aRANKL). Osteonecrosis of the jaw (ONJ) is a side-effect. Aetiopathology models failed to explain their restriction to the jaw. The osteoproliferative transcription factor Msx-1 is expressed constitutively only in mature jaw bone. Msx-1 expression might be impaired in bisphosphonate-related ONJ. This study compared the expression of Msx-1, Bone Morphogenetic Protein (BMP)-2 and RANKL, in ONJ-affected and healthy jaw bone. An automated immunohistochemistry-based alkaline phosphatase-anti-alkaline phosphatase method was used on ONJ-affected and healthy jaw bone samples (n = 20 each): cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed to quantitatively compare Msx-1, BMP-2, RANKL and GAPDH mRNA levels. Labelling indices were significantly lower for Msx-1 (P Msx-1, 22-fold lower (P Msx-1, RANKL suppression and BMP-2 induction were consistent with the bisphosphonate-associated osteopetrosis and impaired bone remodelling in BP- and aRANKL-induced ONJ. Msx-1 suppression suggested a possible explanation of the exclusivity of ONJ in jaw bone. Functional analyses of Msx-1- RANKL interaction during bone remodelling should be performed in the future. © 2011 John Wiley & Sons A/S.

  6. Comparison of raloxifene and bisphosphonates based on adherence and treatment satisfaction in postmenopausal Asian women.

    Science.gov (United States)

    Pasion, Ellewellyn G; Sivananthan, Shanmugam K; Kung, Annie Wai-Chee; Chen, Sung-Hsiung; Chen, Yen-Jen; Mirasol, Roberto; Tay, Boon Keng; Shah, Ghazanfar Ali; Khan, Mansoor Ali; Tam, Frances; Hall, Belinda J; Thiebaud, Daniel

    2007-01-01

    We evaluated adherence with raloxifene therapy compared with daily bisphosphonate in Asian postmenopausal women at increased risk of osteoporotic fractures. In this 12-month observational study conducted in Asia (Hong Kong, Malaysia, Pakistan, Philippines, Singapore, Taiwan), 984 postmenopausal women (aged 55 years or older) were treated with raloxifene 60 mg/day (n = 707; 72%) or daily bisphosphonate (alendronate 10 mg/day; n = 206; 21%, or risedronate 5 mg/day; n = 71; 7%) during their normal course of care. Patients were assessed at baseline, 6, and 12 months. Baseline characteristics (including age, race, education, menopausal status, and baseline fractures) were comparable between the raloxifene and bisphosphonate groups. More women on raloxifene completed the study compared with those on bisphosphonate (50.2% versus 37.5%; P < 0.001). Patients also took raloxifene for a longer period than bisphosphonate (median, 356 versus 348 days; P = 0.011). Compared with those taking bisphosphonate, significantly fewer patients taking raloxifene discontinued the study because of stopping treatment (5.7% versus 10.1%, P = 0.017) or changing treatment (2.8% versus 9.7%, P < 0.001). Inconvenient dosing was reported as a primary reason for discontinuation due to stopping or changing treatment in 19 (6.9%) bisphosphonate patients compared with 0 raloxifene patients. The percentage of patients who had consumed 80% or more of their study medication was similar for raloxifene patients (48-56 weeks; 95.2%) and bisphosphonate patients (48-56 weeks; 93.3%). More raloxifene patients responded that they were satisfied with their medication than bisphosphonate patients at 48-56 weeks (P = 0.002). We concluded that Asian postmenopausal women at increased risk of osteoporotic fractures showed a greater propensity to remain on raloxifene compared with bisphosphonate. The women on raloxifene exhibited lower discontinuation rates and higher treatment satisfaction.

  7. Gastrointestinal tolerability with ibandronate after previous weekly bisphosphonate treatment

    Directory of Open Access Journals (Sweden)

    Richard Derman

    2009-09-01

    Full Text Available Richard Derman1, Joseph D Kohles2, Ann Babbitt31Department of Obstetrics and Gynecology, Christiana Hospital, Newark, DE, USA; 2Roche, Nutley, NJ, USA; 3Greater Portland Bone and Joint Specialists, Portland, ME, USAAbstract: Data from two open-label trials (PRIOR and CURRENT of women with postmenopausal osteoporosis or osteopenia were evaluated to assess whether monthly oral and quarterly intravenous (IV ibandronate dosing improved self-reported gastrointestinal (GI tolerability for patients who had previously experienced GI irritation with bisphosphonate (BP use. In PRIOR, women who had discontinued daily or weekly BP treatment due to GI intolerance received monthly oral or quarterly IV ibandronate for 12 months. The CURRENT subanalysis included women receiving weekly BP treatment who switched to monthly oral ibandronate for six months. GI symptom severity and frequency were assessed using the Osteoporosis Patient Satisfaction Questionnaire™. In PRIOR, mean GI tolerability scores increased significantly at month 1 from screening for both treatment groups (oral: 79.3 versus 54.1; IV: 84.4 versus 51.0; p < 0.001 for both. Most patients reported improvement in GI symptom severity and frequency from baseline at all post-screening assessments (>90% at Month 10. In the CURRENT subanalysis >60% of patients reported improvements in heartburn or acid reflux and >70% indicated improvement in other stomach upset at month 6. Postmenopausal women with GI irritability with daily or weekly BPs experienced improvement in symptoms with extended dosing monthly or quarterly ibandronate compared with baseline.Keywords: ibandronate, osteoporosis, bisphosphonate, gastrointestinal

  8. BISPHOSPHONATE INDUCED STRESS FRACTURE OF BILATERAL FEMUR: A CASE REPORT

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    Saidapur

    2015-08-01

    Full Text Available Osteoporosis is a common problem affecting people after 4 - 5 decade of life. There are various treatment options available for Osteoporosis and Bisphosphonates are widely used. Bisphosphonates work by blocking osteoclast mediated bone resorption and can be given in oral and injectable forms. R ecent studies have brought to light the risk of sub trochanteric stress fracture secondary to bisphosphonate therapy. Here we are presenting a case with bilateral sub trochanteric fracture following prolonged bisphosphonate therapy

  9. Gastrointestinal tolerability with ibandronate after previous weekly bisphosphonate treatment.

    Science.gov (United States)

    Derman, Richard; Kohles, Joseph D; Babbitt, Ann

    2009-01-01

    Data from two open-label trials (PRIOR and CURRENT) of women with postmenopausal osteoporosis or osteopenia were evaluated to assess whether monthly oral and quarterly intravenous (IV) ibandronate dosing improved self-reported gastrointestinal (GI) tolerability for patients who had previously experienced GI irritation with bisphosphonate (BP) use. In PRIOR, women who had discontinued daily or weekly BP treatment due to GI intolerance received monthly oral or quarterly IV ibandronate for 12 months. The CURRENT subanalysis included women receiving weekly BP treatment who switched to monthly oral ibandronate for six months. GI symptom severity and frequency were assessed using the Osteoporosis Patient Satisfaction Questionnaire. In PRIOR, mean GI tolerability scores increased significantly at month 1 from screening for both treatment groups (oral: 79.3 versus 54.1; IV: 84.4 versus 51.0; p 90% at Month 10). In the CURRENT subanalysis >60% of patients reported improvements in heartburn or acid reflux and >70% indicated improvement in other stomach upset at month 6. Postmenopausal women with GI irritability with daily or weekly BPs experienced improvement in symptoms with extended dosing monthly or quarterly ibandronate compared with baseline.

  10. Bisphosphonate-associated Osteonecrosis of the jaws and endodontic treatment: two case reports.

    Science.gov (United States)

    Goodell, Gary

    2006-01-01

    Bisphosphonates are commonly used in the management of bone diseases, such as osteoporosis and Paget's disease, and to prevent bone complications and treat malignant hypercalcemia in certain types of cancer. Although this class of drugs has clear evidence of medical efficacy, there are an, increasing number of reports of bisphosphonate-associated osteonecrosis of the jaws that have substantial implications for the patient and for the treating dentist. This article reviews proposed possible mechanisms of bisphosphonate-associated osteonecrosis of the jaws and describes two case reports where non-surgical and surgical root canal treatment were precipitating factors. Recommendations for prevention and treatment of the disease follow. Thorough history-taking and timely consultation with the patient's oral surgeon and oncologist are emphasized.

  11. Current perspectives on bisphosphonate treatment in Paget’s disease of bone

    Directory of Open Access Journals (Sweden)

    Wat WZM

    2014-11-01

    Full Text Available Winnie Zee Man Wat Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Abstract: Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic

  12. Position Statement: Drug Holiday in Osteoporosis Treatment with Bisphosphonates in South Korea

    Science.gov (United States)

    Lee, Seung Hun; Gong, Hyun Sik; Kim, Tae-Hee; Park, Si Young; Shin, Jung-Ho; Cho, Sun Wook

    2015-01-01

    Bisphosphonates have been widely used in the treatment of osteoporosis with robust data from many placebo-controlled trials demonstrating its efficacy in fracture risk reduction over 3 to 5 years of treatment. Although bisphosphonates are generally safe and well tolerated, concerns have emerged about the adverse effects related to its long-term use, including osteonecrosis of the jaw and atypical femur fractures. Because bisphosphonates are incorporated into the skeleton and continue to exert an anti-resorptive effect for a period of time after the discontinuation of drugs, the concept of a "drug holiday" has emerged, whereby the risk of adverse effects might be decreased while the patient still benefits from anti-fracture efficacy. As randomized clinical trial evidence is not yet available on who may qualify for a drug holiday, there is considerable controversy regarding the selection of candidates for the drug holiday and monitoring during a drug holiday, both of which should be based on individual assessments of risk and benefit. This statement will provide suggestions for clinicians in South Korea on the identification of possible candidates and monitoring during a bisphosphonate drug holiday. PMID:26713307

  13. Duration of treatment with bisphosphonates at the time of osteonecrosis of the jaw onset in patients with rheumatoid arthritis. Review.

    Science.gov (United States)

    Compain, H; Berquet, A; Loison-Robert, L-S; Ahossi, V; Zwetyenga, N

    2018-06-01

    Rheumatoid arthritis (RA) is a frequent and co-morbid condition. One of the main complications is induced osteoporosis. Treatments related to this complication significantly modify oral and implant management. Affected patients represent a population at intermediate risk of osteonecrosis of the jaw (ONJ). The objective was to search the literature for durations of treatment with bisphosphonates at the time of ONJ occurrence in patients with RA in order to obtain an average duration. A bibliographic search in the PubMed/Medline database was carried out using the following equation "(osteonecrosis and jaw) and rheumatoid arthritis" with no time limitation. The primary study endpoint was the duration of treatment with bisphosphonates (BP) at the time of ONJ onset in patients with RA. Twelve articles accounting for 50 patients were included. Patients had had a median of 46.8 months of treatment with BP before ONJ occurred. Mean, minimum and maximum treatment times were 48.68, 6 and 120 months, respectively. The standard deviation was 27.77 months. The median treatment duration in our cohort of patients with RA was less than that reported for osteoporosis. We therefore, recommend that practitioners take additional precautions regarding oral surgery or implant procedures, particularly in patients with RA who have been treated with BP for more than 4 years. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. Efficacy of Bisphosphonates for the Treatment of Osteoporosis in Patients with Multiple Sclerosis

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    İlke Coşkun Benlidayı

    2015-08-01

    Full Text Available Objective: The aim of this study was to evaluate the effectiveness of bisphosphonates in osteoporotic patients with multiple sclerosis. Materials and Methods: Patients with multiple sclerosis, who were started on treatment with a diagnosis of osteoporosis, at the Department of Physical Medicine and Rehabilitation, Faculty of Medicine Çukurova University, between January 2011 and January 2014, were included in this study. Patients were allocated into control (calcium-vitamin D alone and active treatment (calcium-vitamin D and bisphosphonate groups according to their medications. Response to the 12-month treatment in terms of bone mineral density (BMD values and biological marker levels were evaluated, both within and between groups. Results: The study group consisted of 29 patients (14 controls and 15 active treatment. Evaluation performed within each group revealed no significant difference between baseline and post-treatment values of BMD and biological markers in controls. However, regarding the active treatment group, a significant increase in L1-L4 T-score and 25(OHD was detected. When delta values were taken into account, comparison between groups revealed no significant difference in terms of BMD and biological marker levels. Conclusion: The effect of calcium-vitamin D alone on BMD and biologic markers was similar to that of calcium-vitamin D and bisphosphonate combination, in multiple sclerosis patients with osteoporosis. However, prospective, randomized, controlled studies are required on this issue. (Turkish Journal of Osteoporosis 2015;21: 53-7

  15. Radiographic and MR Imaging Findings of the Spine after Bisphosphonate Treatment, in a Child with Idiopathic Juvenile Osteoporosis

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    Olympia Papakonstantinou

    2015-01-01

    Full Text Available Bisphosphonates are employed with increasing frequency in various pediatric disorders, mainly associated with osteoporosis. After cessation of bisphosphonate treatment in children, skeletal radiologic changes have been documented including dense metaphyseal lines of the long bones and “bone in bone” appearance of the vertebrae. However, the evolution of these radiographic changes has not been fully explored. We describe the MR imaging appearance of the spine that, to our knowledge, has not been previously addressed in a child with idiopathic juvenile osteoporosis who had received bisphosphonates and emphasize the evolution of the radiographic findings of the spine and pelvis over a four-year period.

  16. Bisphosphonate-modified gold nanoparticles: a useful vehicle to study the treatment of osteonecrosis of the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Fanord, Fedena; Fairbairn, Korie; Bhethanabotla, Venkat; Gupta, Vinay K [Department of Chemical and Biomedical Engineering, University of South Florida, 4202 E. Fowler Avenue, ENB 118, Tampa, FL 33620 (United States); Kim, Harry [Shriners Hospitals for Children, 12502 USF Pine Drive, Tampa, FL 33612 (United States); Garces, Amanda, E-mail: vkgupta@usf.edu [Lisa Muma Weitz Microscopy and Cell Imaging, Department of Pathology and Cell Biology, University of South Florida, 12901 Bruce B Downs Boulevard, Tampa, FL 33612 (United States)

    2011-01-21

    Legg-Calve-Perthes disease (LCPD) is a juvenile form of osteonecrosis of the femoral head that presents in children aged 2-14 years. To date, there is no effective medical therapy for treating LCPD largely due to an inability to modulate the repair process, including the predominance of bone resorption. This investigation aims to evaluate the feasibility of using gold nanoparticles (GNPs) that are surface modified with a bisphosphonate compound for the treatment of osteonecrosis at the cellular level. Studies have found osteoclast-mediated resorption to be a process that contributes significantly to the pathogenesis of femoral head deformities arising from Perthes disease. Our in vitro model was designed to elucidate the effect of alendronate-(a bisphosphonate) modified GNPs, on osteoclastogenesis and osteoclast function. RAW 264.7 macrophage cells were cultured with recombinant mouse receptor activator of NF-{kappa}B ligand (RANKL), which stimulates osteoclastogenesis, and were then treated with alendronate-modified GNPs for 24, 48, and 72 h. Cell proliferation, osteoclast function, and osteoclast morphology were evaluated by trypan blue dye exclusion assay, tartrate-resistant acid phosphatase (TRAP) staining, and transmission electron microscopy (TEM) imaging. Comparative studies were performed with GNPs that were only stabilized with citrate ions and with alendronate alone. Neither osteoclastogenesis nor osteoclast function were adversely affected by the presence of the citrate-GNP. Alendronate-modified GNPs had an enhanced effect on inducing osteoclast apoptosis and impairing osteoclast function when compared to unbound alendronate populations.

  17. Bisphosphonate-modified gold nanoparticles: a useful vehicle to study the treatment of osteonecrosis of the femoral head

    International Nuclear Information System (INIS)

    Fanord, Fedena; Fairbairn, Korie; Bhethanabotla, Venkat; Gupta, Vinay K; Kim, Harry; Garces, Amanda

    2011-01-01

    Legg-Calve-Perthes disease (LCPD) is a juvenile form of osteonecrosis of the femoral head that presents in children aged 2-14 years. To date, there is no effective medical therapy for treating LCPD largely due to an inability to modulate the repair process, including the predominance of bone resorption. This investigation aims to evaluate the feasibility of using gold nanoparticles (GNPs) that are surface modified with a bisphosphonate compound for the treatment of osteonecrosis at the cellular level. Studies have found osteoclast-mediated resorption to be a process that contributes significantly to the pathogenesis of femoral head deformities arising from Perthes disease. Our in vitro model was designed to elucidate the effect of alendronate-(a bisphosphonate) modified GNPs, on osteoclastogenesis and osteoclast function. RAW 264.7 macrophage cells were cultured with recombinant mouse receptor activator of NF-κB ligand (RANKL), which stimulates osteoclastogenesis, and were then treated with alendronate-modified GNPs for 24, 48, and 72 h. Cell proliferation, osteoclast function, and osteoclast morphology were evaluated by trypan blue dye exclusion assay, tartrate-resistant acid phosphatase (TRAP) staining, and transmission electron microscopy (TEM) imaging. Comparative studies were performed with GNPs that were only stabilized with citrate ions and with alendronate alone. Neither osteoclastogenesis nor osteoclast function were adversely affected by the presence of the citrate-GNP. Alendronate-modified GNPs had an enhanced effect on inducing osteoclast apoptosis and impairing osteoclast function when compared to unbound alendronate populations.

  18. Bisphosphonate Treatment in Osteoporosis: Optimal Duration of Therapy and the Incorporation of a Drug Holiday.

    Science.gov (United States)

    Villa, Jordan C; Gianakos, Arianna; Lane, Joseph M

    2016-02-01

    Bisphosphonates are the most widely used treatment for osteoporosis. They accumulate in the bone for years, and therefore, their inhibitory effects on osteoclasts may persist after drug discontinuation. The ideal duration of therapy remains controversial. The purpose of this study is to review the literature to determine the (1) indications for drug holiday, (2) the duration of drug holiday, (3) the evaluation during drug holiday, and (4) the proper treatment and maintenance after drug holiday. A review of two electronic databases (PubMed/MEDLINE and EMBASE) was conducted using the term "(Drug holiday)," in January 29, 2015. Inclusion criteria were as follows: (1) clinical trials and case control, (2) human studies, (3) published in a peer-review journal, and (4) written in English. Exclusion criteria were as follows: (1) case reports, (2) case series, and (3) in vitro studies. The literature supports a therapeutic pause after 3-5 years of bisphosphonate treatment in patients with minor bone deficiencies and no recent fragility fracture (low risk) and in patients with moderate bone deficiencies and/or recent fragility fracture (moderate risk). In these patients, a bone health reevaluation is recommended every 1-3 years. Patients with high fracture risk should be maintained on bisphosphonate therapy without drug holiday. The duration and length of drug holiday should be individualized for each patient. Evaluation should be based on serial bone mass measurements, bone turnover rates, and fracture history evaluation. If after drug therapy, assessments show an increased risk of fracture, the patient may benefit from initiating another treatment. Raloxifene, teriparatide, or denosumab are available options.

  19. BONE TURNOVER IN OSTEOPOROTIC WOMEN DURING LONG-TERM ORAL BISPHOSPHONATES TREATMENT: IMPLICATIONS FOR TREATMENT FAILURE AND "DRUG HOLIDAY" IN THE REAL WORLD.

    Science.gov (United States)

    Liel, Yair; Plakht, Ygal; Tailakh, Muhammad Abu

    2017-07-01

    Little data exist to support concerns over bone turnover suppression during prolonged oral bisphosphonate treatment and on consequences of the recommended "drug holiday." This study was performed to assess bone resorption rates in postmenopausal osteoporotic women on prolonged oral bisphosphonate treatment and in response to switching to "drug holiday" intravenous bisphosphonate, or continuation of oral bisphosphonates. The frequency distribution of the bone resorption marker urinary deoxypyridinoline crosslinks (uDPD), was obtained retrospectively from 211 osteoporotic women attended at an academic hospital endocrine clinic, treated for >2 years with oral bisphosphonates. In some patients, uDPD was re-assessed following modification or continuation of treatment. The mean duration of oral bisphosphonates treatment was 7.2 ± 3.1 years. uDPD was within reference range for premenopausal women in 61.6% of the patients, below in 7.6% of the patients, and above upper limit in 30.8%. uDPD decreased significantly following intravenous zoledronic acid, increased significantly during "drug holiday," and slightly decreased in those continued on oral bisphosphonate treatment. In this real-world study, the majority of women on prolonged oral bisphosphonates maintained bone resorption rates within the normal reference range for premenopausal women. The likelihood for inadequate suppression was considerably greater than that of over-suppression. Implementing a "drug holiday" resulted in a marked increase in bone resorption rates. Additional studies should explore the potential role of bone turnover markers in the evaluation of patients on prolonged oral bisphosphonates and during "drug holiday" in different settings and using additional markers. BMD = bone mineral density; IQR = interquartile range; uDPD = urinary deoxypyridinoline crosslinks.

  20. Treatment of bisphosphonate related osteonecrosis following root canal therapy at the 1-year follow-up: report of two cases

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    Kaptan F

    2013-12-01

    Full Text Available Figen Kaptan,1 Meric Karapinar Kazandag,1 Ufuk Iseri21Yeditepe University, Faculty of Dentistry, Department of Endodontics, 2Department of Prosthodontics, Istanbul, TurkeyAbstract: The objective of this report was to use topical gaseous ozone as an adjunct to conventional treatment methods and to describe the multidisciplinary management of bisphosphonate associated bone necrosis, which developed following endodontic treatment. No complaints were noted by the patients at their 1-year follow-up and the treatment showed favorable prognosis.Keywords: bisphosphonate, osteonecrosis, BRONJ, endodontics, oxygen, ozone

  1. Treatment of bisphosphonate related osteonecrosis following root canal therapy at the 1-year follow-up: report of two cases.

    Science.gov (United States)

    Kaptan, Figen; Kazandag, Meric Karapinar; Iseri, Ufuk

    2013-01-01

    The objective of this report was to use topical gaseous ozone as an adjunct to conventional treatment methods and to describe the multidisciplinary management of bisphosphonate associated bone necrosis, which developed following endodontic treatment. No complaints were noted by the patients at their 1-year follow-up and the treatment showed favorable prognosis.

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

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    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.

  3. Bisphosphonates for osteoporosis in primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Rudic, Jelena; Giljaca, Vanja; Krstic, Miodrag N

    2011-01-01

    Bisphosphonates are widely used for treatment of postmenopausal osteoporosis. Patients with primary biliary cirrhosis often have osteoporosis - either postmenopausal or secondary to the liver disease. No systematic review or meta-analysis has assessed the effects of bisphosphonates for osteoporosis...

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

    Science.gov (United States)

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

    2016-05-01

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

  5. [Orthodontic treatment of patients medicated with bisphosphonates-a clinical case report].

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    Krieger, Elena; d'Hoedt, Bernd; Scheller, Herbert; Jacobs, Collin; Walter, Christian; Wehrbein, Heinrich

    2013-01-01

    Bisphosphonates (BP) are an established medication, e.g., for the prevention/therapy of osteoporosis. The effects of the changed bone metabolism for orthodontic treatments are unknown. A 66-year-old woman underwent a total oral rehabilitation. The therapy included (1) tooth extractions, (2) periodontal treatment, (3) insertion of dental implants, (4) provisional implant restorations, (5) orthodontic treatment, and (6) definite implant restorations. The orthodontic tooth movements were in- and retrusion of the upper frontal teeth, intrusion of the lower front teeth, using the dental implants as skeletal anchorage. After implant insertion and one month before beginning the orthodontic treatment, osteoporosis was diagnosed in this patient and, without notification to our facility, BP treatment was initiated by her general practitioner (alendronate oral, 70 mg/week), with an overall duration of intake of 7 months. After 13 months, the orthodontic treatment was successfully accomplished; however enlarged periodontal gaps, sclerotic bone areas, and mild apical root resorptions of the upper frontal teeth were found in this patient. Currently, there are no recommendations for orthodontic patients undergoing BP therapy. Orthodontic tooth movement in this low-risk patient with a short duration of intake and a low-dose BP medication was possible. Because of the reduced bone metabolism and the higher amount of side effects, the treatment should be performed with extremely light forces and frequent monitoring.

  6. Tratamiento con bisfosfonatos y fracturas atípicas Treatment with bisphosphonates and atypical fractures

    Directory of Open Access Journals (Sweden)

    Francisco R. Spivacow

    2009-12-01

    remodeling could be the microdamage accumulation, and paradoxically the occurrence of new and atypical fractures. Until now, few cases of these unusual fractures have been reported in the international literature. All these patients shared some common characteristics, apart from the chronic use of bisphosphonates for the treatment of osteoporosis. The more frequent is the atypical location of the fractures. Since the majority happened in one or both femoral shafts, others bones such as sacrum, ischium, ribs and pubic rami could be affected. The fractures were atraumatic or caused by minimal trauma and, in some cases, it was preceded by a prodromal pain in the affected area. All cases had biochemical or histomorphometric evidence of low bone turnover. The aim of this paper is to report three new cases of patients that fulfill with the diagnostic criteria of this new entity, two of them with femoral shaft fractures and the remainder with a pelvis one.

  7. Treatment of bisphosphonate related osteonecrosis following root canal therapy at the 1-year follow-up: report of two cases

    OpenAIRE

    Kaptan, Figen; Kazandag, Meric Karapinar; Iseri, Ufuk

    2013-01-01

    Figen Kaptan,1 Meric Karapinar Kazandag,1 Ufuk Iseri21Yeditepe University, Faculty of Dentistry, Department of Endodontics, 2Department of Prosthodontics, Istanbul, TurkeyAbstract: The objective of this report was to use topical gaseous ozone as an adjunct to conventional treatment methods and to describe the multidisciplinary management of bisphosphonate associated bone necrosis, which developed following endodontic treatment. No complaints were noted by the patients at their 1-year follow-u...

  8. Inflammatory eye reactions with bisphosphonates and other osteoporosis medications

    DEFF Research Database (Denmark)

    Clark, Emma M; Durup, Darshana

    2015-01-01

    Inflammatory eye reactions (IERs) are rare but have been associated with medications to treat osteoporosis. The aim of this review is to summarize the current literature on the association between IERs and specific medications to treat osteoporosis (bisphosphonates, selective estrogen receptor...... of the information available is from spontaneous case reports and case series reporting associations between bisphosphonates and IERs. No case reports describe IERs after other anti-osteoporosis medications. Importantly, some case reports describe recurrence of the IER after affected patients were rechallenged...... with the same or another bisphosphonate, and that no reported cases resolved without discontinuation of the bisphosphonate. However, three large population-based cohort studies have shown conflicting results between osteoporosis treatments and IERs, but overall these studies suggest that IERs may actually...

  9. Optimal Timing of Bisphosphonate Administration in Combination with Samarium-153 Oxabifore in the Treatment of Painful Metastatic Bone Disease

    International Nuclear Information System (INIS)

    Rasulova, Nigora; Lyubshin, Vladimir; Arybzhanov, Dauranbek; Sagdullaev, Sh.; Krylov, Valery; Khodjibekov, Marat

    2013-01-01

    While bisphosphonates are indicated for prevention of skeletal-related events, radionuclide therapy is widely used for treatment of painful bone metastases. Combined radionuclide therapy with bisphosphonates has demonstrated improved effectiveness in achieving bone pain palliation in comparison to mono therapy with radionuclides or bisphosphonates alone. However, there are conflicting reports as to whether bisphosphonates adversely influence skeletal uptake of the bone-seeking radiotracers used for therapy. Recent studies analyzing influence of Zoledronic acid on total bone uptake of Samarium-153 EDTMP (Sm-153 EDTMP) by measuring cumulative urinary activity of Sm-153 on baseline study, as well as in combination with bisphosphonates (administrated 48 hours prior to Sm-153) did not provide any statistically significant difference in urinary excretion of Sm-153 between the two groups. It may be noted that the exact temporal sequence of bisphosphonate administration vis a vis radionuclide therapy has not yet been studied. One of the side effects of bisphosphonates is transient flare effect on bone pain. Radionuclide therapy may also have similar side effect. Keeping in view the above the current study was designed with the main objective of determining the exact timing of bisphosphonate administration in patients receiving combined therapy so as to achieve optimal efficacy of bone pain palliation. Ninety-three patients suffering from metastatic bone pain who received combination therapy with Sm-153 oxabifore (an analog of Sm-153 EDTMP) and Zoledronic acid were divided into three groups according to the timing of Zoledronic acid administration: Group I: 39 patients who received Zoledronic acid 7 or more days prior to Sm-153 oxabifore treatment; Group II: 32 patients who received Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment and Group III: 22 patients who received Zoledronic acid 7 days after Sm-153 oxabifore treatment. Sm-153 oxabifore was administered

  10. Fracture during intravenous bisphosphonate treatment in a child with osteogenesis imperfecta: an argument for a more frequent, low-dose treatment regimen.

    Science.gov (United States)

    Biggin, Andrew; Briody, Julie N; Ormshaw, Elizabeth; Wong, Karen K Y; Bennetts, Bruce H; Munns, Craig F

    2014-01-01

    Intravenous bisphosphonate therapy is the mainstay of medical treatment in osteogenesis imperfecta (OI) and has been shown to increase bone mass, decrease bone pain, improve mobility, and reduce the incidence of fractures. Sclerotic metaphyseal lines parallel to the growth plate are seen on long bone radiographs following cyclical intravenous therapy. These areas create stress risers within the bone that may act as foci for subsequent fractures as exemplified in this clinical case. An 8-year-old girl with OI sustained a distal radial fracture following 3 years of treatment with 6-monthly intravenous zoledronate. Her diagnosis, response to treatment, and subsequent fracture at a sclerotic metaphyseal line is described. Peripheral quantitative computer tomography was used to characterise the presence of multiple stress risers at the distal forearm. Trabecular bone mineral density fluctuated from 34 to 126% compared to neighbouring 2-mm regions. There remain many unanswered questions about optimal bisphosphonate treatment regimens in children with OI. The formation of stress risers following intravenous bisphosphonate treatment raises the hypothesis that a more frequent and low-dose bisphosphonate regimen would provide more uniform dosing of bone in the growing child and reduce the likelihood of fractures compared to current treatment practices.

  11. The dental implications of bisphosphonates and bone disease.

    Science.gov (United States)

    Cheng, A; Mavrokokki, A; Carter, G; Stein, B; Fazzalari, N L; Wilson, D F; Goss, A N

    2005-12-01

    In 2002/2003 a number of patients presented to the South Australian Oral and Maxillofacial Surgery Unit with unusual non-healing extraction wounds of the jaws. All were middle-aged to elderly, medically compromised and on bisphosphonates for bone pathology. Review of the literature showed similar cases being reported in the North American oral and maxillofacial surgery literature. This paper reviews the role of bisphosphonates in the management of bone disease. There were 2.3 million prescriptions for bisphosphonates in Australia in 2003. This group of drugs is very useful in controlling bone pain and preventing pathologic fractures. However, in a small number of patients on bisphosphonates, intractable, painful, non-healing exposed bone occurs following dental extractions or denture irritation. Affected patients are usually, but not always, over 55 years, medically compromised and on the potent nitrogen containing bisphosphonates pamidronate (Aredia/Pamisol), alendronate (Fosamax) and zolendronate (Zometa) for non-osteoporotic bone disease. Currently, there is no simple, effective treatment and the painful exposed bone may persist for years. The main complications are marked weight loss from difficulty in eating and severe jaw and neck infections. Possible preventive and therapeutic strategies are presented although at this time there is no evidence of their effectiveness. Dentists must ask about bisphosphonate usage for bone disease when recording medical histories and take appropriate actions to avoid the development of this debilitating condition in their patients.

  12. Influence of Bisphosphonate Treatment on Medullary Macrophages and Osteoclasts: An Experimental Study

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    Natalia Daniela Escudero

    2012-01-01

    Full Text Available Nitrogen-containing bisphosphonates are widely used for treating diverse bone pathologies. They are anticatabolic drugs that act on osteoclasts inhibiting bone resorption. It remains unknown whether the mechanism of action is by decreasing osteoclast number, impairing osteoclast function, or whether they continue to effectively inhibit bone resorption despite the increase in osteoclast number. There is increasing evidence that bisphosphonates also act on bone marrow cells like macrophages and monocytes. The present work sought to evaluate the dynamics of preosteoclast fusion and possible changes in medullary macrophage number in bisphosphonate-treated animals. Healthy female Wistar rats received olpadronate, alendronate, or vehicle during 5 weeks, and 5-bromo-2-deoxyuridine (BrdU on day 7, 28, or 34 of the experiment. Histomorphometric studies were performed to study femurs and evaluate: number of nuclei per osteoclast (N.Nu/Oc; number of BrdU-positive nuclei (N.Nu BrdU+/Oc; percentage of BrdU-positive nuclei per osteoclast (%Nu.BrdU+/Oc; medullary macrophage number (mac/mm2 and correlation between N.Nu/Oc and mac/mm2. Results showed bisphosphonate-treated animals exhibited increased N.Nu/Oc, caused by an increase in preosteoclast fusion rate and evidenced by higher N.Nu BrdU+/Oc, and significantly decreased mac/mm2. Considering the common origin of osteoclasts and macrophages, the increased demand for precursors of the osteoclast lineage may occur at the expense of macrophage lineage precursors.

  13. Healing of extraction sockets and augmented alveolar defects following 1-year treatment with bisphosphonate.

    Science.gov (United States)

    Khojasteh, Arash; Behnia, Hossein; Morad, Golnaz; Dashti, Seyedeh Ghazaleh; Dehghan, Mohammad Mehdi; Shahab, Shahriyar; Abbas, Fatemeh Mashhadi

    2013-01-01

    To assess the effect of bisphosphonates on healing of extraction sockets and augmented alveolar defects, 12 adult female mongrel dogs were assigned to 2 experimental groups and a control group. The experimental groups received oral alendronate (ALN, 3.5 mg/kg/wk) or IV pamidronate (PAM, 1 mg/kg/wk) for 12 months. Animals were randomly tested for serum C-terminal telopeptide of collagen I (CTx). The right first and second premolars were extracted. After 8 weeks, extraction sites were evaluated for healing. Subsequently, 3-wall defects were created in ridges and filled with human mineralized cortical particulate bone. Two months post-augmentation, animals were sacrificed and mandibles were collected for cone-beam computed tomography (CBCT) and histomorphometric appraisal. The obtained data were compared using 1-way ANOVA test. CTx test results in both experimental groups were comparable (alveolar bone in the PAM group and the upper rim of the alveoli in the ALN group. Histologically, bone sequestra from the PAM group demonstrated empty osteocyte lacunae, while in the ALN group areas of necrotic bone along with evidence of active bone remodeling was distinguished. Eight weeks post-augmentation, the experimental groups showed no evidence of bone formation in the augmented area, while bone formation ratio was measured to be 18.32% in the control group. The mean amount of pixel intensity calculated from the CBCT images of the ALN, PAM, and control group was 113.69 ± 11.04, 124.94 ± 4.72, and 113.69 ± 6.63, respectively. Pixel intensity in PAM-treated group was significantly higher than both other groups. This study demonstrated that 1-year treatment with ALN/PAM was associated with impairment of post-extraction and post-augmentation bone healing in dogs.

  14. Pain and quality of life of children and adolescents with osteogenesis imperfecta over a bisphosphonate treatment cycle.

    Science.gov (United States)

    Tsimicalis, Argerie; Boitor, Madalina; Ferland, Catherine E; Rauch, Frank; Le May, Sylvie; Carrier, Jaimie Isabel; Ngheim, Tracy; Bilodeau, Claudette

    2018-06-01

    The objective was to describe the pain and quality of life among children and adolescents with any osteogenesis imperfecta (OI) type over one intravenous bisphosphonate treatment cycle from a child and parental perspective. A prospective, observational study was conducted, where children and adolescents evaluated their pain intensity, location, and quality, as well as quality of life before, 1 week after treatment, and 6 months later. Quality of life was also evaluated from the parental perspective at the same three time points. Thirty-three child/parent dyads participated. The results showed that pain intensity on the 0-10 self-report scale after the Zoledronate infusion (median = 0, range = 0-6) was not different from pre (median = 2, range = 0-10) and 6-months post-scores (median = 2, range = 0-8) (p = 0.170). Children and adolescents with OI reported experiencing pain mainly in the ankles and the anterior and posterior shoulders. They selected evaluative pain descriptors such as uncomfortable (n = 16, 48%) and annoying (n = 13, 39%). Children and adolescents' functioning and quality of life did not change significantly across the bisphosphonate treatment cycle (p = 0.326), parents perceived an improvement immediately after the treatment compared to before (p = 0.016). Children and adolescents with OI experience mild, yet complex pain localized across several body areas. There is little fluctuation in the pain intensity and functioning of children with OI undergoing bisphosphonate treatment. What is Known: • Acute and chronic musculoskeletal pain remains a major issue in OI. • Pain has a negative impact on quality of life. What is New: • New and unpublished methods and findings describing the pain and quality of life of children and adolescents with OI over one intravenous bisphosphonate treatment cycle from a child- and parental-proxy perspective. • Children and adolescents with OI experience pain intensity that is mild, yet

  15. The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta.

    Science.gov (United States)

    Biggin, Andrew; Zheng, Linda; Briody, Julie N; Coorey, Craig P; Munns, Craig F

    2015-01-01

    Intravenous bisphosphonate therapy is the first-line treatment in moderate-to-severe osteogenesis imperfecta (OI), but there are varied treatment protocols with little data on long-term efficacy. This study evaluates the clinical outcomes when transitioning from active bisphosphonate treatment to maintenance therapy. A retrospective review was conducted on 17 patients before treatment, following active treatment (zoledronate 0.05 mg/kg 6-monthly or pamidronate 6-9 mg/kg/year) and after establishment on maintenance treatment for more than 2 years (zoledronate 0.025 mg/kg 6-monthly or pamidronate lean tissue mass increased during active treatment. These improvements were maintained during the period of maintenance treatment. Vertebral height improved in fractured thoracic vertebrae from pre-treatment to active therapy and improved further during maintenance treatment. Metacarpal cortical thickness and relative cortical area also increased over the treatment periods. Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of active treatment at the doses stated above. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI. © 2015 S. Karger AG, Basel.

  16. [Osteonecrosis of the jaws and bisphosphonates].

    Science.gov (United States)

    Junod, A F; Carrel, J-P; Richter, M; Vogt-Ferrier, N

    2005-11-02

    Widely prescribed, bisphosphonates inhibit bone resorption. They are not metabolised and have long half-lives. Two cases of osteonecrosis of the jaws have recently been attributed to bisphosphonates at the University Hospital of Geneva. The recent literature reveals more than a hundred similar cases throughout the world. Bone exposure appears spontaneously or after dental care. Treatment of the osteonecrosis is controversial and cure very difficult. This pathology is usually seen in patients on chemotherapy, steroids and i.v. bisphosphonates, but is sometimes seen with low-dose p.o. bisphosphonates. In view of the strong association between bisphosphonate therapy and osteonecrosis of the jaw, specialists have recommended dental and oral evaluation during bisphosphonate therapy as well as for several years after drug discontinuation.

  17. BISPHOSPHONATE - RELATED MUCOSITIS (BRM: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Pavel Stanimirov

    2017-03-01

    Full Text Available Bisphosphonates (BPs are the most widely used and effective antiresorptive agents for the treatment of diseases in which there is an increase in osteoclastic resorption, including post-menopausal osteoporosis, Paget’s disease, and tumor-associated osteolysis. Oral and maxillofacial surgeons are well aware of the side effects of bisphosphonates and mainly with bisphosphonate-related osteonecrosis of the jaws (BRONJ. Less known are the mucosal lesions associated with the use of these agents. In the scientific literature, there are only few reports of mucosal lesions due to the direct contact of the oral form of BPs with the mucosa (bisphosphonate-related mucositis. They are mostly related to improper use of bisphosphonate tablets that are chewed, sucked or allowed to melt in the mouth before swallowing. Lesions are atypical and need to be differentiated from other mucosal erosions. We present a case of bisphosphonate-related mucositis due to the improper use of alendronate.

  18. Cost effectiveness of denosumab compared with oral bisphosphonates in the treatment of post-menopausal osteoporotic women in Belgium.

    Science.gov (United States)

    Hiligsmann, Mickaël; Reginster, Jean-Yves

    2011-10-01

    Denosumab has recently been shown to be well tolerated, to increase bone mineral density (BMD) and to significantly reduce the risk of hip, vertebral and non-vertebral fractures in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial. It is becoming increasingly important to evaluate not only the therapeutic value of a new drug but also the cost effectiveness compared with the most relevant treatment alternatives. The objective of this study was to estimate the cost effectiveness of denosumab compared with oral bisphosphonates (branded and generic drugs) in the treatment of post-menopausal osteoporotic women in Belgium. Cost effectiveness of 3 years of treatment with denosumab was compared with branded risedronate and branded and generic alendronate using an updated version of a previously validated Markov microsimulation model. The model was populated with relevant cost, adherence and epidemiological data for Belgium from a payer perspective and the results were presented as costs per QALY gained (&U20AC;, year 2009 values). Analyses were performed in populations (aged ≥60 years) in which osteoporosis medications are currently reimbursed in many European countries, i.e. those with BMD T-score of -2.5 or less or prevalent vertebral fracture. Patients receiving denosumab were assumed to have a 46% lower risk of discontinuation than those receiving oral bisphosphonates, and the effect of denosumab after treatment cessation was assumed to decline linearly to zero over a maximum of 1 year. Denosumab was cost effective compared with all other therapies, assuming a willingness to pay of &U20AC;40 000 per QALY gained. In particular, denosumab was found to be cost effective compared with branded alendronate and risedronate at a threshold value of &U20AC;30 000 per QALY and denosumab was dominant (i.e. lower cost and greater effectiveness) compared with risedronate from the age of 70 years in women with a T-score of -2.5 or

  19. Report of a Rare Case of Gorham-Stout Disease of Both Shoulders: Bisphosphonate Treatment and Shoulder Replacement

    Directory of Open Access Journals (Sweden)

    Eike Garbers

    2011-01-01

    Full Text Available Massive osteolysis known as Gorham-Stout disease is a rare idiopathic disorder typically affecting long bones in a unifocal pattern. Angiomatosis is strongly connected to the osteolysis. Weather angiomatosis is the cause or the result of osteolysis is subject of intense discussion (Kawasaki et al. (2003, Möller et al. (1999, Radhakrishnan and Rockson (2008. There are about 200 cases described since 1955. Our patient is a 77-year-old female patient with osteolyses of both shoulders involving the proximal humerus, lateral clavicle, and the glenoid. Under bisphosphonate therapy, the progressive osteolysis stopped on the right side and showed progression on the left. With the patient complaining about severe rest pain and impaired function, we performed surgical reconstruction by implantation of total shoulder prosthesis three months after onset of symptoms. Our case shows a possibility of primary and early surgical reconstruction with good clinical outcome.

  20. Eleven years of experience with bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2012-12-01

    Full Text Available Jun Iwamoto,1 Yoshihiro Sato,2 Mitsuyoshi Uzawa,3 Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, 2Department of Neurology, Mitate Hospital, Fukuoka, 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanAbstract: We report the 11-year follow-up of a man with osteogenesis imperfecta type I who was treated with bisphosphonates and alfacalcidol. A 36-year-old Japanese man with osteogenesis imperfecta type I who had frequently experienced painful fragility fractures consulted our clinic because of chronic back pain. The patient had multiple morphometric vertebral fractures and a low bone mineral density (BMD at the lumbar spine. The patient was treated with cyclical etidronate 200 mg, for 2 weeks every 3 months, plus alfacalcidol 1 µg daily, for 2 years; and alendronate 5 mg daily or 35 mg weekly, plus alfacalcidol 1 µg daily for 9 years. After 11 years of treatment, BMD at the lumbar spine increased by 6.4%, following a 20.3% reduction in serum alkaline phosphatase. Serum calcium, phosphorus, and intact parathyroid hormone levels remained within the normal ranges. Three clinical fractures occurred at two ribs and the metacarpus, and two morphometric vertebral fractures occurred at the thoracic spine during the 11-year treatment period, but the patient experienced no adverse effects. Thus, the present case report shows the long-term outcome and safety of bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I.Keywords: etidronate, alendronate, fragility fracture, bone mineral density, osteogenesis imperfecta

  1. Bisphosphonates for treatment of Complex Regional Pain Syndrome type 1: A systematic literature review and meta-analysis of randomized controlled trials versus placebo.

    Science.gov (United States)

    Chevreau, Maxime; Romand, Xavier; Gaudin, Philippe; Juvin, Robert; Baillet, Athan

    2017-07-01

    Complex Regional Pain Syndrome Type 1 is a severely disabling pain syndrome with no definite established treatment. We have performed a systematic literature review and meta-analysis of all randomized controlled trials to assess the benefit of bisphosphonates on pain and function in patients with Complex Regional Pain Syndrome Type 1. A systematic literature search was performed in the Medline, Embase and Cochrane databases. Two authors selected independently blinded randomized trials comparing bisphosphonates to placebo on short-term (J30 to J40) and medium term pain (M2-M3), safety and function in patients with CRPS 1. The methodological quality of the studies was analyzed. Data were aggregated using the method of the inverse of the variance. 258 articles were identified. Four trials of moderate to good quality comprising 181 patients (90 in the bisphosphonate group and 91 in the placebo group) were included in this meta-analysis. Short-term pain Visual Analog Scale was significantly lower in the bisphosphonate group versus the placebo group (SMD=-2.6, 95%CI [-1.8, -3.4], Ppain (SMD=-2.5, 95%CI [-1.4, -3.6], Ppain in patients with Complex Regional Pain Syndrome type 1. Other studies are needed to determine their effectiveness. Copyright © 2017. Published by Elsevier SAS.

  2. How much we know about bisphosphonate lesions

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    Pešić Zoran

    2016-01-01

    Full Text Available Introduction: Bisphosphonate drugs are used in the treatment of the osteoporosis and malignant processes in the bone tissue. As a result of this use bisphosphonate lesions are formed in bone tissue and oral mucosis, which representing a remarkable therapeutic problem. The aim of this study was to determine how many dentists in general practice are familiar with the character, diagnosis and therapy bisphosphonate lesions. Material and Methods: An anonymous questionnaire of 13 questions was conducted in dental practices in Nis County in the period from October 2015 to December 2015. The obtained data were statistically analyzed. Results: A total of 60% dentists knew what drugs are used in the treatment of osteoporosis and malignant processes in the bones. 25% knew what the bisphosphonate bone lesions are . 66, 6% of dentists knewn what is the prevention of bisphosphonate lesions. 63.3% of dentists are aware of the complications bisphosphonate lesions. Conclusion: Dentists in general practices are insufficiently familiar with the character, diagnosis and treatment of bisphosphonate lesions. We should activate all entities that participate in more continuous medical education, in order to achieve a higher level of prevention of these therapeutic ungrateful lesions.

  3. Bisphosphonate-Linked TrkB Agonist: Cochlea-Targeted Delivery of a Neurotrophic Agent as a Strategy for the Treatment of Hearing Loss.

    Science.gov (United States)

    Kempfle, Judith S; Nguyen, Kim; Hamadani, Christine; Koen, Nicholas; Edge, Albert S; Kashemirov, Boris A; Jung, David H; McKenna, Charles E

    2018-04-18

    Hearing loss affects more than two-thirds of the elderly population, and more than 17% of all adults in the U.S. Sensorineural hearing loss related to noise exposure or aging is associated with loss of inner ear sensory hair cells (HCs), cochlear spiral ganglion neurons (SGNs), and ribbon synapses between HCs and SGNs, stimulating intense interest in therapies to regenerate synaptic function. 7,8-Dihydroxyflavone (DHF) is a selective and potent agonist of tropomyosin receptor kinase B (TrkB) and protects the neuron from apoptosis. Despite evidence that TrkB agonists can promote survival of SGNs, local delivery of drugs such as DHF to the inner ear remains a challenge. We previously demonstrated in an animal model that a fluorescently labeled bisphosphonate, 6-FAM-Zol, administered to the round window membrane penetrated the membrane and diffused throughout the cochlea. Given their affinity for bone mineral, including cochlear bone, bisphosphonates offer an intriguing modality for targeted delivery of neurotrophic agents to the SGNs to promote survival, neurite outgrowth, and, potentially, regeneration of synapses between HCs and SGNs. The design and synthesis of a bisphosphonate conjugate of DHF (Ris-DHF) is presented, with a preliminary evaluation of its neurotrophic activity. Ris-DHF increases neurite outgrowth in vitro, maintains this ability after binding to hydroxyapatite, and regenerates synapses in kainic acid-damaged cochlear organ of Corti explants dissected in vitro with attached SGNs. The results suggest that bisphosphonate-TrkB agonist conjugates have promise as a novel approach to targeted delivery of drugs to treat sensorineural hearing loss.

  4. Adjuvant bisphosphonates in early breast cancer

    DEFF Research Database (Denmark)

    Hadji, P; Coleman, R E; Wilson, C

    2016-01-01

    Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have...... regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature...... was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus...

  5. Current state of orthodontic patients under Bisphosphonate therapy

    Science.gov (United States)

    2013-01-01

    Background Bisphosphonates are a common medication for the prevention and therapy of osteoporosis, but are also applied for tumor diseases. They affect bone metabolism, and therefore also orthodontic treatments, but how it does has yet not been definitively clarified. Therefore, the aim of this research was to evaluate and demonstrate the reported effects and the current state of scientific research regarding orthodontic treatment and bisphosphonate medication exclusively in humans. Material and methods A systematic research of the literature for selected keywords in the Medline database (Pubmed) as well as a manual search was conducted. The following search terms were used: ‘Bisphosphonate’ in combination with: orthodontic, orthodontic treatment, tooth movement. Findings To date, only nine reported patients (case reports/series) and one original article (retrospective cohort study) regarding orthodontic treatment under bisphosphonate medication in humans have been published. Decelerated tooth movement with increased side effects (especially in high-risk patients) and longer treatment duration was reported in some articles. Patients with initial spacing or extraction cases had a higher risk of incomplete space closure and poor root parallelism. Conclusions Orthodontic tooth movement under bisphosphonate medication is possible, especially in low-risk patients (low dose and short period of intake). But the treatment is still not predictable, especially in high-risk patients. Therefore, the altered bone metabolism and higher extent of side effects should be considered in treatment planning, especially in extraction cases or high-risk patients. Regardless, longer treatment duration, decelerated tooth movement, and more side effects, e.g., incomplete space closure and poor root parallelism, should be expected, especially in extraction cases or space closure. PMID:23556517

  6. Psychometric evaluation of the Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q™, a novel measure to assess satisfaction with bisphosphonate treatment in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Shikiar Richard

    2006-07-01

    Full Text Available Abstract Background The Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q is a new measure of patient satisfaction with bisphosphonate treatment for osteoporosis. The objective of this study was to evaluate the psychometric characteristics of the OPSAT-Q. Methods The OPSAT-Q contains 16 items in four subscales: Convenience, Confidence with Daily Activities, Side Effects, and Overall Satisfaction. All four subscale scores and an overall composite satisfaction score (CSS can be computed. The OPSAT-Q, Osteoporosis Targeted Quality of Life (OPTQoL, and sociodemographic/clinical questionnaires, including 3 global items on convenience, functioning and side effects, were self-administered to women with osteoporosis or osteopenia recruited from four US clinics. Analyses included item and scale performance, internal consistency reliability, reproducibility, and construct validity. Reproducibility was measured using the intraclass correlation coefficient (ICC via a follow-up questionnaire completed by participants 2 weeks post baseline. Results 104 women with a mean age of 65.1 years participated. The majority were Caucasian (64.4%, living with someone (74%, and not currently employed (58.7%. 73% had osteoporosis and 27% had osteopenia. 80% were taking weekly bisphosphonates and 18% were taking daily medication (2% missing data. On a scale of 0–100, individual patient subscale scores ranged from 17 to 100 and CSS scores ranged from 44 to 100. All scores showed acceptable internal consistency reliability (Cronbach's alpha > 0.70 (range 0.72 to 0.89. Reproducibility ranged from 0.62 (Daily Activities to 0.79 (Side Effects for the subscales; reproducibility for the CSS was 0.81. Significant correlations were found between the OPSAT-Q subscales and conceptually similar global measures (p Conclusion The findings from this study confirm the validity and reliability of the OPSAT-Q and support the proposed composition of four subscales and a composite

  7. A systematic review of the role of bisphosphonates in metastatic disease.

    Science.gov (United States)

    Ross, J R; Saunders, Y; Edmonds, P M; Patel, S; Wonderling, D; Normand, C; Broadley, K

    2004-01-01

    significant in studies that lasted over a year 0.59 [0.39-0.88]. Bisphosphonates significantly increased the time to first SRE but did not affect survival. Subanalyses were performed for disease groups, drugs and route of administration. Most evidence supports the use of intravenous aminobisphosphonates. For adjuvant use of bisphosphonates, Clodronate, given to patients with primary operable breast cancer and no metastatic disease, significantly reduced the number of patients developing bone metastases. This benefit was not maintained once regular administration had been discontinued. Two trials reported significant survival advantages in the treated groups. Bisphosphonates reduce the number of bone metastases in patients with both early and advanced breast cancer. Bisphosphonates are well tolerated with a low incidence of side-effects. Economic modelling showed that for acute hypercalcaemia, drugs with the longest cumulative duration of normocalcaemia were most cost-effective. Zoledronate 4 mg was the most costly, but most cost-effective treatment. For skeletal morbidity, Markov models estimated that the overall cost of bisphosphonate therapy to prevent an SRE was GBP250 and GBP1500 per event for patients with breast cancer and multiple myeloma, respectively. Bisphosphonate treatment is sometimes cost-saving in breast cancer patients where fractures are prevented. High dose aminobisphosphonates are most effective for the treatment of acute hypercalcaemia and delay time to relapse. Bisphosphonates significantly reduce SREs and delay the time to first SRE in patients with bony metastatic disease but do not affect survival. Benefit is demonstrated after administration for at least 6-12 months. The greatest body of evidence supports the use of intravenous aminobisphosphonates. Further evidence is required to support use in the adjuvant setting.

  8. Treatment of hemimandibular paresthesia in a patient with bisphosphonate-related osteonecrosis of the jaw (BRONJ) by combining surgical resection and PRGF-Endoret.

    Science.gov (United States)

    Anitua, E; Begoña, L; Orive, G

    2013-12-01

    We report a case of a 50-year-old patient with bisphosphonate-related osteonecrosis of the jaws (BRONJs) whose symptoms included severe pain and hemimandibular paraesthesia. The treatment included resection of necrotic bone and the application of plasma rich in growth factors (PRGF(®)-Endoret(®)). We closed the ulcer in the soft tissue and her pain and paraesthesia improved. One year postoperatively sensitivity was totally recovered, pain was absent and bone was partially regenerated. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  9. [The treatment of Paget's disease of bone with second-generation bisphosphonates via intravenous infusion].

    Science.gov (United States)

    Arboleya, L; Sánchez, J; Iglesias, G; Arranz, J L

    1993-12-01

    We compared the biochemical effects and safety of pamidronate (30 mg a day for 3 consecutive days) versus clodronate (300 mg a day for 3 consecutive days) via intravenous infusion in 14 patients with Paget's disease of bone (PDB). Both drugs induced a decrease in serum alkaline phosphatase levels as well as the elimination of hydroxyproline from urine, an effect most marked in the group treated with pamidronate. The response was maintained for 6 months after the infusion in the majority of the patients. No relevant side effects were found, except post-infusion febricula and in one patient, self-limiting thrombopenia 6 months after the infusion. We conclude that the intravenous infusion of either of the two drugs may constitute a safe and effective alternative for treatment of PDB with marked biochemical activity or resistant to conventional therapy.

  10. Pleiotropic effects of bisphosphonates on osteosarcoma.

    Science.gov (United States)

    Ohba, Tetsuro; Cates, Justin M M; Cole, Heather A; Slosky, David A; Haro, Hirotaka; Ichikawa, Jiro; Ando, Takashi; Schwartz, Herbert S; Schoenecker, Jonathan G

    2014-06-01

    Osteosarcoma is the most common primary malignant tumor of bone and accounts for half of all primary skeletal malignancies in children and teenagers. The prognosis for patients who fail or progress on first-line chemotherapy protocols is poor, therefore, additional adjuvant therapeutic strategies are needed. A recent feasibility study has demonstrated that the nitrogen-containing bisphosphonate zoledronic acid (ZOL) can be combined safely with conventional chemotherapy. However, the pharmacodynamics of bisphosphonate therapy is not well characterized. Osteosarcoma is a highly angiogenic tumor. Recent reports of the anti-angiogenic effects of bisphosphonates prompted us to determine whether nitrogen-containing bisphosphonate (ZOL and alendronate) treatment attenuates osteosarcoma growth by inhibition of osteoclast activity, tumor-mediated angiogenesis, or direct inhibitory effects on osteosarcoma. Here, we demonstrate that bisphosphonates directly inhibit VEGFR2 expression in endothelial cells, as well as endothelial cell proliferation and migration. Additionally, bisphosphonates also decrease VEGF-A expression in osteosarcoma (K7M3) cells, resulting in reduced stimulation of endothelial cell migration in co-culture assays. ZOL also decreases VEGFR1 expression in aggressive osteosarcoma cell lines (K7M3, 143B) and induces apoptosis of these cells, but has negligible effects on less aggressive osteosarcoma cell lines (K12 and TE85). In vivo ZOL treatment results in significant reduction in osteosarcoma-initiated angiogenesis and tumor growth in a murine model of osteosarcoma. In conclusion, bisphosphonates have diverse growth inhibitory effects on osteosarcoma through: (1) activation of apoptosis and inhibition of cell proliferation, (2) inhibition of VEGF-A and VEGFR1 expression by tumor cells, (3) inhibition of tumor-induced angiogenesis, and (4) direct inhibitory actions on endothelial cells. Published by Elsevier Inc.

  11. Bisphosphonate ISS Flight Experiment

    Science.gov (United States)

    LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey; Shapiro, Jay; Lang, Thomas; Shackleford, Linda; Smith, Scott M.; Evans, Harlan; Spector, Elizabeth; Ploutz-Snyder, Robert; hide

    2014-01-01

    The bisphosphonate study is a collaborative effort between the NASA and JAXA space agencies to investigate the potential for antiresorptive drugs to mitigate bone changes associated with long-duration spaceflight. Elevated bone resorption is a hallmark of human spaceflight and bed rest (common zero-G analog). We tested whether an antiresorptive drug in combination with in-flight exercise would ameliorate bone loss and hypercalcuria during longduration spaceflight. Measurements include DXA, QCT, pQCT, and urine and blood biomarkers. We have completed analysis of 7 crewmembers treated with alendronate during flight and the immediate postflight (R+week) data collection in 5 of 10 controls without treatment. Both groups used the advanced resistive exercise device (ARED) during their missions. We previously reported the pre/postflight results of crew taking alendronate during flight (Osteoporosis Int. 24:2105-2114, 2013). The purpose of this report is to present the 12-month follow-up data in the treated astronauts and to compare these results with preliminary data from untreated crewmembers exercising with ARED (ARED control) or without ARED (Pre-ARED control). Results: the table presents DXA and QCT BMD expressed as percentage change from preflight in the control astronauts (18 Pre-ARED and the current 5 ARED-1-year data not yet available) and the 7 treated subjects. As shown previously the combination of exercise plus antiresorptive is effective in preventing bone loss during flight. Bone measures for treated subjects, 1 year after return from space remain at or near baseline values. Except in one region, the treated group maintained or gained bone 1 year after flight. Biomarker data are not currently available for either control group and therefore not presented. However, data from other studies with or without ARED show elevated bone resorption and urinary Ca excretion while bisphosphonate treated subjects show decreases during flight. Comparing the two control

  12. Bisphosphonates and osteonecrosis of the jaw.

    Science.gov (United States)

    Shannon, Jodi; Shannon, John; Modelevsky, Steven; Grippo, Anne A

    2011-12-01

    Bisphosphonates are used worldwide as a successful treatment for people with osteoporosis, which is the major underlying cause of fractures in postmenopausal women and older adults. These agents are successful at increasing bone mass and bone trabecular thickness, decreasing the risk of fracture, and decreasing bone pain, enabling individuals to have better quality of life. Bisphosphonates are also used to treat multiple myeloma, bone metastasis, and Paget's disease; however, bisphosphonate treatment may result in negative side effects, including osteonecrosis of the jaw (ONJ). ONJ involves necrotic, exposed bone in the jaw, pain, possible secondary infection, swelling, painful lesions, and various dysesthesias, although less-severe cases may be asymptomatic. First-generation bisphosphonates, which do not contain nitrogen, are metabolized into a nonfunctional, cytotoxic analogue of adenosine triphosphate and cause osteoclast death by starvation. Second-generation bisphosphonates are nitrogen-containing agents; these inhibit osteoclast vesicular trafficking, membrane ruffling, morphology, and cytoskeletal arrangement by inhibiting farnesyl diphosphate synthase in the mevalonate pathway. Physicians treating older adults with osteoporosis and cancer should work together with dental practitioners, pharmacists, and other clinicians to inform individuals receiving bisphosphonates of their possible side effects and to suggest precautionary steps that may minimize the risk of osteonecrosis, particularly of the jaw. These include practicing good oral hygiene; scheduling regular dental examinations and cleanings; and cautioning people who are scheduling treatment for periodontal disease, oral and maxillofacial therapy, endodontics, implant placement, restorative dentistry, and prosthodontics. Recommendations for management of people with ONJ include an oral rinse, such as chlorhexidine, and antibiotics. © 2011, Copyright the Authors Journal compilation © 2011, The American

  13. A review of the clinical implications of bisphosphonates in dentistry.

    Science.gov (United States)

    Borromeo, G L; Tsao, C E; Darby, I B; Ebeling, P R

    2011-03-01

    Bisphosphonates are drugs that suppress bone turnover and are commonly prescribed to prevent skeletal related events in malignancy and for benign bone diseases such as osteoporosis. Bisphosphonate associated jaw osteonecrosis (ONJ) is a potentially debilitating, yet poorly understood condition. A literature review was undertaken to review the dental clinical implications of bisphosphonates. The present paper briefly describes the postulated pathophysiology of ONJ and conditions with similar clinical presentations. The implications of bisphosphonates for implantology, periodontology, orthodontics and endodontics are reviewed. Whilst bisphosphonates have potential positive applications in some clinical settings, periodontology particularly, further clinical research is limited by the risk of ONJ. Prevention and management are reviewed, including guidelines for reducing cumulative intravenous bisphosphonate dose, cessation of bisphosphonates prior to invasive dental treatment or after ONJ development, and the use of serum beta-CTX-1 in assessing risk. In the context of substantial uncertainty, the implications of bisphosphonate use in the dental clinical setting are still being determined. © 2010 Australian Dental Association.

  14. Clinical strategies to address patients' concerns in osteoporosis management with bisphosphonates.

    Science.gov (United States)

    Cole, Raymond E

    2011-03-01

    Approximately 44 million Americans either have, or are at risk of developing, osteoporosis, a disease associated with an increased risk of fracture and, consequently, morbidity and mortality. Osteoporosis affects 20% to 30% of postmenopausal women, and resulting fractures pose a major economic burden, with estimated annual direct costs ranging from $17 billion to $19 billion. Hip fractures account for the majority of costs (~60%) because they often require costly long-term follow-up care in addition to the direct costs of initial treatment. Screening, diagnosis, and disease management are of paramount importance when treating patients at risk for osteoporosis. The National Osteoporosis Foundation recommends that all postmenopausal women be evaluated for osteoporosis risk factors and that all women aged ≥ 65 years undergo bone mineral density testing. Once the primary care physician has identified a patient at risk for osteoporosis-related fracture, the physician must decide whether and how to treat the patient (ie, nonpharmacologic or pharmacologic options). Bisphosphonates are the first-line pharmacologic treatment for women aged ≥ 50 years with postmenopausal osteoporosis. Bisphosphonates-which have a favorable safety and tolerability profile in clinical trials-have shown efficacy in reducing fractures. However, achieved real world effectiveness is very much dependent on good treatment adherence by the patient. Media attention to rare adverse events has motivated some patients to deliberate nonadherence. Physicians should screen patients for contraindications and adverse event risk factors, educate them on the risks of fracture and benefits and risks of treatment, and monitor them during therapy. To assist primary care physicians in clinical decision making for women at risk for or with confirmed osteoporosis, this article presents a review of the guidelines for the diagnosis and treatment of postmenopausal osteoporosis, recent long-term efficacy data for

  15. The bisphosphonates: risks and benefits of long term use

    DEFF Research Database (Denmark)

    Hermann, Anne Pernille; Abrahamsen, Bo

    2013-01-01

    Bisphosphonates are widely used globally as the main treatment for osteoporosis. Both safety and efficacy have only been rigorously evaluated in studies of relatively short duration (3-5 years), with smaller extension studies. The evidence for benefit beyond five years in intervention studies...... is limited and does not include proven efficacy against nonvertebral fractures. Observational studies suggest a sustained benefit against hip fractures. Bisphosphonates are stored in the skeleton for months to years, depending on the degree of bone turnover and the binding properties of the bisphosphonate...

  16. Leucocyte-rich and platelet-rich fibrin for the treatment of bisphosphonate-related osteonecrosis of the jaw: a prospective feasibility study.

    Science.gov (United States)

    Kim, Jin-Woo; Kim, Sun-Jong; Kim, Myung-Rae

    2014-11-01

    Our aim was to assess the feasibility of using leucocyte-rich and platelet-rich fibrin (L-PRF) for the treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a single group study. After treatment with L-PRF, the response of each patient was recorded 1 month and 4 months postoperatively. Further assessments were made of the site, stage, concentration of c-terminal crosslinked telopepide of type 1 collagen, and actinomycosis. Among the total of 34 patients, 26 (77%) showed complete resolution, 6 (18%) had delayed resolution, and 2 (6%) showed no resolution. There was a significant association between the response to treatment and the stage of BRONJ (p=0.002) but no other significant associations were detected. This study has shown that it is feasible to use L-PRF for the treatment of BRONJ, but the effectiveness cannot be judged with this study design. Randomised prospective trials are needed to confirm this. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  17. Bisphosphonate-related osteonecrosis of the jaw: specificities

    Directory of Open Access Journals (Sweden)

    Siri Paulo

    2014-09-01

    Full Text Available Bisphosphonate-related osteonecrosis of the jaws (BRONJ is a severe complication that has recently emerged in patients treated with intravenous bisphosphonates for malignant diseases. This complication usually presents after a minor local trauma during a dental treatment. Several etiopathogenic mechanisms of this pathological condition have been proposed, but no model can explain all morphological changes observed at the macroscopic and microscopic level. BRONJ is likely to be related to direct toxicity in the bone and soft tissue cells, due to nitrogen-containing bisphosphonates. This review elucidates the clinical indications and mechanism of action of bisphosphonates, reports some clinical diagnostic criteria for BRONJ, describe the histopathological criteria for BRONJ diagnosis, the potential triggering pathways and the available treatment strategies.

  18. Risk factors influencing the duration of treatment with bisphosphonates until occurrence of an osteonecrosis of the jaw in 963 cancer patients.

    Science.gov (United States)

    Gabbert, Tatjana I; Hoffmeister, Bodo; Felsenberg, Dieter

    2015-04-01

    Osteonecrosis of the jaw (ONJ) is an adverse effect that is associated with bisphosphonate (BP) use. Little data are available on risk factors influencing the time of treatment until an osteonecrosis occurs. From 1 Dec 2004 until 21 Sep 2012, the German Register collected all patients with validated diagnoses of ONJ (N = 1,229) that were reported to the national pharmaco-vigilance system or to the Register directly. We analysed 963 patients with cancerous disease and an ONJ during i.v. BP treatment. Duration of BP treatment until first diagnosis of ONJ and Kaplan-Meier curves of ONJ-free survival were analysed stratified by gender, type of BP and type of cancer. Main indications for BP treatment were breast cancer (36%), multiple myeloma (24%), prostate cancer (16%) and kidney cancer (4%). Men suffered from their ONJ earlier than women. A total of 780 patients (81%) had their ONJ during zoledronate treatment, 93 (10%) under pamidronate and 90 (9%) under ibandronate treatment. ONJ-free survival in single BP users was significantly longer in pamidronate-treated patients than in zoledronate or ibandronate users. Ibandronate users had the shortest median duration of treatment (17 months), similar to that of zoledronate users (21.5 months). Sequential prescription of two different BPs prolonged the period of overall BP treatment until an ONJ occurred. Time of BP treatment was shortest in patients with kidney cancer. Age or a concomitant osteoporosis did not influence the time to event of an ONJ. Systemic risk factors such as gender play a significant role in certain subgroups only. Comparative analysis of different cancer patients helps the treating oncologist/dentist to identify patients with a more imminent risk to develop an ONJ (i.e. kidney cancer, ibandronate/zoledronate use).

  19. Jaw osteonecrosis related to bisphosphonate therapy: a severe secondary disorder.

    Science.gov (United States)

    Dannemann, C; Grätz, K W; Riener, M O; Zwahlen, R A

    2007-04-01

    Bisphosphonate-related osteonecrosis of the jaws (BON), first described in 2003, is gaining importance due to the increasing indication spectrum of bisphosphonate therapy [S. Takeyama, M. Ito, H. Shinoda, A novel bisphosphonate, TRK-530, for periodontitis, Bone 38 (2006) 31-31; M. Tagil, A. W-Dahl, J. Astrand, D. Little, S. Toksvig-Larsen, Decreasing the catabolic response by a single bisphosphonate infusion shortens the healing time in hemicallotasis operations, Bone 38 (2006) 84-85; E. Rodriguez, M.C. Duran, L.M. Rodriguez, R. Ros, M.R. Aleman, M. Rodriguez-Gaspar, A.M. Lopez, E. Garcia-Valdecasas, F. Santolaria, Intravenous (IV) bisphosphonates for osteopenic cancer survivor women: an alternative treatment, Bone 38 (2006) 72-73; D.G. Little, K. Ward, P. Kiely, M.C. Bellemore, J. Briody, C.T. Cowell, Bisphosphonate rescue in distraction osteogenesis: a case series, Bone 38 (2006) 80-80; R. Marx, Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic, J. Oral Maxillofac. Surg. 61 (2003) 1115-1118]. BON patients suffering from varying bony defects and symptoms are extremely restricted in their quality of life. Due to a limited knowledge of the aetiology of BON efficient evidence-based treatment strategies are lacking. Until now 23 patients with bisphosphonate-related osteonecrosis have been admitted to the Department of Cranio-Maxillofacial Surgery of the University of Zurich. A complete history has been recorded. All patients underwent clinical and radiographic examination. CT scans and MRI have been performed in selected cases. All patients had in common that, before signs of BON were observed, a local traumatic incidence had occurred. All patients showed signs of infection which could be remarkably reduced by antibacterial treatment. Furthermore, the period of bisphosphonate treatment was found to be one of the significant factors causing bisphosphonate-related osteonecrosis of the jaws. The aetiology of BON

  20. Intravenous aminohydroxypropylidene bisphosphonate does not modify 99mTc-hydroxymethylene bisphosphonate bone scintigraphy. A prospective study

    International Nuclear Information System (INIS)

    Macro, M.; Bouvard, G.; Le Gangneux, E.; Colin, T.; Loyau, G.

    1995-01-01

    Bisphosphonates have market affinity for bone that makes them useful in both the treatment and imaging of bone lesions. Bone scintigraphy is very sensitive for the detection of bone metastases, which can cause life-threatening hypercalcemia requiring emergency treatment. This prospective study was done to determine whether intravenous administration of pamidronate, a second-generation bisphophonate used to treat hypercalcemia, affects the affinity of the radiopharmaceutical 99m technetium-labeled hydroxymethylene bisphosphonate (99m Tc- HMDP) for bone and bone lesions. Six patients with metastatic bone disease and five with Paget's disease of bone had a 99m Tc-HMDP bone scan before and two to four days after an intravenous infusion of pamidronate. The number and activity of metastatic bone lesions were unchanged after pamidronate, even when the second bone scan was done only 24 hours after the pamidronate infusion. Our data suggest that emergency treatment of life-threatening hypercalcemia by intravenous pamidronate does not decrease the sensitivity of subsequent bone scanning done to detect bone metastases. (authors). 17 refs. 1 tab. 2 figs

  1. Oroantral fistula from bisphosphonate induced osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    Henry Sharp

    2010-07-01

    Full Text Available Bisphosphonates like alendronic acid, disodium etidronate, and risedronate are effective for preventing postmenopausal and corticosteroid induced osteoporosis. They are also useful in the treatment of Paget’s disease, hypercalcaemia of malignancy and in bony metastases. However osteonecrosis of the jaw has been reported following intravenous bisphosphonate use and rarely in those taking them orally.Increasingly, oroantral fistulae have been shown to occur as sequelae of bisphosphonate-induced osteonecrosis of the jaw and this case report highlights a patient that presented to our ENT department and required sinus surgery in collaboration with maxillofacial surgeons.This case report aims to raise awareness among ENT surgeons to these patients on bisphosphonates that could present to them with sinus disease from oroantral fistulae. There is an on-going audit in the maxillofacial community on this emerging trend.

  2. Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis.

    Science.gov (United States)

    Katsumi, Hidemasa; Tanaka, Yutaro; Hitomi, Kaori; Liu, Shu; Quan, Ying-Shu; Kamiyama, Fumio; Sakane, Toshiyasu; Yamamoto, Akira

    2017-08-17

    To improve the transdermal bioavailability and safety of alendronate (ALN), a nitrogen-containing bisphosphonate, we developed self-dissolving microneedle arrays (MNs), in which ALN is loaded only at the tip portion of micron-scale needles by a dip-coating method (ALN(TIP)-MN). We observed micron-scale pores in rat skin just after application of ALN(TIP)-MN, indicating that transdermal pathways for ALN were created by MN. ALN was rapidly released from the tip of MNs as observed in an in vitro release study. The tip portions of MNs completely dissolved in the rat skin within 5 min after application in vivo. After application of ALN(TIP)-MN in mice, the plasma concentration of ALN rapidly increased, and the bioavailability of ALN was approximately 96%. In addition, the decrease in growth plate was effectively suppressed by this efficient delivery of ALN in a rat model of osteoporosis. Furthermore, no skin irritation was observed after application of ALN(TIP)-MN and subcutaneous injection of ALN, while mild skin irritation was induced by whole-ALN-loaded MN (ALN-MN)-in which ALN is contained in the whole of the micron-scale needles fabricated from hyaluronic acid-and intradermal injection of ALN. These findings indicate that ALN(TIP)-MN is a promising transdermal formulation for the treatment of osteoporosis without skin irritation.

  3. Bisphosphonates and osteonecrosis of jaws

    Directory of Open Access Journals (Sweden)

    Geetha Vijay

    2012-01-01

    The purpose of the present article is to enlighten the dental fraternity about this frequently prescribed class of drugs with regard to its types and mode of action, and the implication of bisphosphonates-induced ONJ.

  4. Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study

    NARCIS (Netherlands)

    L. Herrera (Lizbeth); I. Leal (Ingrid); F. Lapi (Francesco); M.J. Schuemie (Martijn); V. Arcoraci (Vincenzo); F. Cipriani (Francesco); E. Sessa (E.); A. Vaccheri (Alberto); C. Piccinni (C.); T. Staniscia (Tommaso); A. Vestri (Annarita); M. Di Bari (M.); G. Corrao (Giovanni); A. Zambon (A.); D Gregori (Dario); F. Carle (F.); M.C.J.M. Sturkenboom (Miriam); G. Mazzaglia (Giampiero); G. Trifirò (Gianluca)

    2015-01-01

    textabstractSummary: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with

  5. A retrospective clinical and radiographic study on healing of periradicular lesions in patients taking oral bisphosphonates.

    Science.gov (United States)

    Hsiao, Angela; Glickman, Gerald; He, Jianing

    2009-11-01

    Bisphosphonates have been related to impaired bone remodeling. The impact of oral bisphosphonates on periradicular healing has not been studied. The purpose of this study was to evaluate the healing of periradicular lesions in patients taking oral bisphosphonates after root canal therapy. Thirty-four teeth with preoperative periradicular radiolucencies were identified in patients undergoing oral bisphosphonate therapy. These cases were examined clinically and radiographically to determine treatment outcome. Thirty-eight control teeth were selected from a pool of patients not taking bisphosphonates. Nonsurgical root canal treatment and retreatment was performed by endodontic residents and undergraduate dental students at Baylor College of Dentistry using nonstandardized protocols. In the bisphosphonate group, 73.5% of the lesions healed, whereas the control cases had a healing rate of 81.6%. There was no statistically significant difference between the groups (p > 0.05). The results of this preliminary short-term study suggest that patients taking long-term oral bisphosphonates can expect a satisfactory outcome with evidence of periradicular healing after conventional root canal treatment. Thus, root canal treatment may be considered a safe and realistic alternative to extraction in patients on bisphosphonate therapy.

  6. Eliminating the need for fasting with oral administration of bisphosphonates

    DEFF Research Database (Denmark)

    Pazianas, Michael; Abrahamsen, Bo; Ferrari, Serge

    2013-01-01

    or beverages create complexes that cannot be absorbed. For this reason, they must be taken on an empty stomach, and a period of up to 2 hours must elapse before the consumption of any food or drink other than plain water. This routine is not only inconvenient but can lead to discontinuation of treatment......Bisphosphonates are the major treatment of choice for osteoporosis, given that they are attached preferentially by bone and significantly reduce the risk of fractures. Oral bisphosphonates are poorly absorbed (usually less than 1% for nitrogen-containing bisphosphonates) and when taken with food......, and when mistakenly taken with food, may result in misdiagnosis of resistance to or failure of treatment. The development of an enteric-coated delayed-release formulation of risedronate with the addition of the calcium chelator, ethylenediaminetetraacetic acid (EDTA), a widely used food stabilizer...

  7. Characteristics of patients initiating raloxifene compared to those initiating bisphosphonates

    Directory of Open Access Journals (Sweden)

    Wang Sara

    2008-12-01

    Full Text Available Abstract Background Both raloxifene and bisphosphonates are indicated for the prevention and treatment of postmenopausal osteoporosis, however these medications have different efficacy and safety profiles. It is plausible that physicians would prescribe these agents to optimize the benefit/risk profile for individual patients. The objective of this study was to compare demographic and clinical characteristics of patients initiating raloxifene with those of patients initiating bisphosphonates for the prevention and treatment of osteoporosis. Methods This study was conducted using a retrospective cohort design. Female beneficiaries (45 years and older with at least one claim for raloxifene or a bisphosphonate in 2003 through 2005 and continuous enrollment in the previous 12 months and subsequent 6 months were identified using a collection of large national commercial, Medicare supplemental, and Medicaid administrative claims databases (MarketScan®. Patients were divided into two cohorts, a combined commercial/Medicare cohort and a Medicaid cohort. Within each cohort, characteristics (demographic, clinical, and resource utilization of patients initiating raloxifene were compared to those of patients initiating bisphosphonate therapy. Group comparisons were made using chi-square tests for proportions of categorical measures and Wilcoxon rank-sum tests for continuous variables. Logistic regression was used to simultaneously examine factors independently associated with initiation of raloxifene versus a bisphosphonate. Results Within both the commercial/Medicare and Medicaid cohorts, raloxifene patients were younger, had fewer comorbid conditions, and fewer pre-existing fractures than bisphosphonate patients. Raloxifene patients in both cohorts were less likely to have had a bone mineral density (BMD screening in the previous year than were bisphosphonate patients, and were also more likely to have used estrogen or estrogen/progestin therapy in the

  8. Osteoclasts but not osteoblasts are affected by a calcified surface treated with zoledronic acid in vitro

    International Nuclear Information System (INIS)

    Schindeler, Aaron; Little, David G.

    2005-01-01

    Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. Recent interest has centered on the effects of bisphosphonates on osteoblasts. Chronic dosing of osteoblasts with solubilized bisphosphonates has been reported to enhance osteogenesis and mineralization in vitro. However, this methodology poorly reflects the in vivo situation, where free bisphosphonate becomes rapidly bound to mineralized bone surfaces. To establish a more clinically relevant cell culture model, we cultured bone cells on calcium phosphate coated quartz discs pre-treated with the potent nitrogen-containing bisphosphonate, zoledronic acid (ZA). Binding studies utilizing [ 14 C]-labeled ZA confirmed that the bisphosphonate bound in a concentration-dependent manner over the 1-50 μM dose range. When grown on ZA-treated discs, the viability of bone-marrow derived osteoclasts was greatly reduced, while the viability and mineralization of the osteoblastic MC3T3-E1 cell line were largely unaffected. This suggests that only bone resorbing cells are affected by bound bisphosphonate. However, this system does not account for transient exposure to unbound bisphosphonate in the hours following a clinical dosing. To model this event, we transiently treated osteoblasts with ZA in the absence of a calcified surface. Osteoblasts proved highly resistant to all transitory treatment regimes, even when utilizing ZA concentrations that prevented mineralization and/or induced cell death when dosed chronically. This study represents a pharmacologically more relevant approach to modeling bisphosphonate treatment on cultured bone cells and implies that bisphosphonate therapies may not directly affect osteoblasts at bone surfaces

  9. Tooth alterations in areas of bisphosphonate-induced osteonecrosis.

    Science.gov (United States)

    de Camargo Moraes, Paulo; Silva, Carolina Amália Barcellos; Soares, Andresa Borges; Passador-Santos, Fabrício; Corrêa, Maria Elvira Pizzigatti; de Araújo, Ney Soares; de Araújo, Vera Cavalcanti

    2015-03-01

    Osteonecrosis of the jaw is a potential side effect when using bisphosphonates. Most studies on the effects of bisphosphonates on teeth have been conducted in vitro or in animal models of tooth development. Therefore, the aim of this study was to describe alterations found in human teeth extracted from areas of bisphosphonate-induced osteonecrosis. Using a retrospective study design, 16 teeth from 13 patients were extracted from areas of bisphosphonate-induced osteonecrosis during surgical debridement. The specimens were decalcified and embedded in paraffin. A series of 5-μm sections were prepared, stained with hematoxylin and eosin (H&E) and observed under a light microscope. The majority of the patients were female (53.85 %), with a mean age of 60.23 ± 13.18 years. Zoledronate (IV) was the most common bisphosphonate used (92.3 %), over a mean period of 2 years. The commonest alteration observed was hypercementosis (87.5 %), followed by pulpar necrosis (81.25 %), pulp stones attached to the dentine and loose pulp stones in the pulp chamber and root canals in addition to linear calcifications (68.75 %), dentinoid/osteoid material formation (18.75 %), and dental ankylosis (6.25 %). Patients undergoing bisphosphonate therapy present diverse tooth alterations, which should be closely monitored by clinicians to prevent complications. It is paramount that the teeth involved in oral lesions are always examined. Attention should be drawn to the need to establish preventive measures, in terms of dental treatment, for patients prior to starting bisphosphonate therapy.

  10. Bisphosphonate-Related Osteonecrosis of the Jaw: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Eder Alberto Sigua-Rodriguez

    2014-01-01

    Full Text Available Bisphosphonates (BPs are a class of drugs used to treat osteoporosis and malignant bone metastasis. BPs show high binding capacity to the bone matrix, especially in sites of active bone metabolism. The American Society for Bone and Mineral Research defines BRONJ as “an area of exposed bone in the maxillofacial region that has not healed within 8 weeks after identification by a healthcare provider in a patient who is receiving or has been exposed to a bisphosphonate and has not had radiation therapy to the craniofacial region.” Bisphosphonate-related osteonecrosis of the jaw (BRONJ can adversely affect quality of life, as it may produce significant morbidity. The American Association of Oral and Maxillofacial Surgeons (AAOMS considers as vitally important that information on BRONJ be disseminated to other dental and medical specialties. The purpose of this work is to offer a perspective on how dentists should manage patients on BPs, to show the benefits of accurately diagnosing BRONJ, and to present diagnostic aids and treatments strategies for the condition.

  11. Heart failure in patients treated with bisphosphonates

    DEFF Research Database (Denmark)

    Grove, E L; Abrahamsen, B; Vestergaard, P

    2013-01-01

    The aim of this study was to investigate the occurrence of heart failure in patients treated with bisphosphonates.......The aim of this study was to investigate the occurrence of heart failure in patients treated with bisphosphonates....

  12. New Dimensional Staging of Bisphosphonate-Related Osteonecrosis of the Jaw Allowing a Guided Surgical Treatment Protocol: Long-Term Follow-Up of 266 Lesions in Neoplastic and Osteoporotic Patients from the University of Bari

    Directory of Open Access Journals (Sweden)

    Simonetta Franco

    2014-01-01

    Full Text Available Bisphosphonate-related osteonecrosis of the jaw (BRONJ is the most serious side effect in patients receiving bisphosphonates (BPs for neoplastic disease and osteoporosis. The aim of this study is to propose a new dimensional stage classification, guiding the surgical treatment of BRONJ patients, and to evaluate the success rate of this new management. From 2004 to 2013, 203 neoplastic and osteoporotic patients with 266 BRONJ lesions were referred to the Odontostomatology Unit of the University of Bari. All patients underwent surgery after suspension of BPs therapy and antibiotic treatment. The surgical procedure was complemented by piezosurgery and followed by the application of hyaluronate and amino acids. The new dimensional staging suggests the choice of the surgical approach, and allows the prediction of postoperative complications and soft and hard tissues healing time, guiding the surgical treatment protocol. This protocol could be a successful management strategy for BRONJ, considering the low recurrences rate and the good stabilisation of the surgical sites observed after a long-term follow-up.

  13. Urea dimethacrylates functionalized with bisphosphonate/bisphosphonic acid for improved dental materials

    OpenAIRE

    Güven, Melek Naz; Guven, Melek Naz; Akyol, Ece; Duman, Fatma Demir; Acar, Havva Yağcı; Acar, Havva Yagci; Karahan, Özlem; Karahan, Ozlem; Avcı, Duygu; Avci, Duygu

    2017-01-01

    Incorporation of bisphosphonate/bisphosphonic acid groups in dental monomer structures should increase interaction of these monomers with dental tissue as these groups have strong affinity for hydroxyapatite. Therefore, new urea dimethacrylates functionalized with bisphosphonate (1a, 1b) and bisphosphonic acid (2a, 2b) groups are synthesized and evaluated for dental applications. Monomers 1a and 1b are synthesized from 2isocyanatoethyl methacrylate (IEM) and two bisphosphonated amines (BPA1 a...

  14. Efficacy of alendronate, a bisphosphonate, in the treatment of AVN of the hip. A prospective open-label study.

    Science.gov (United States)

    Agarwala, S; Jain, D; Joshi, V R; Sule, A

    2005-03-01

    To study the efficacy of alendronate, in the treatment of avascular necrosis (AVN) of the hip. Sixty patients with AVN of the hip (100 hips with AVN) were studied. The follow-up period ranged from 3 months to 5 yr. The most common cause of AVN was steroids. Parameters studied were walking time, standing time, pain and disability on a visual analogue scale (VAS), range of motion of the hip, X-ray and MRI of the hip. All patients were treated with alendronate 10 mg/day (or 70 mg/week) along with 500-1000 mg of daily calcium and vitamin D supplements, and were advised to avoid weight-bearing. NSAIDs and analgesics were permitted as needed and were recorded. Forty-one patients (71 AVN hips) with AVN have been followed up for a minimum of 1 yr, 24 patients (42 AVN hips) for 2 yr and 21 patients (37 AVN hips) for more than 2 yr (average 37 month). Fourteen patients have been followed up for less than 1 yr (3-9 months). Significant reduction in pain and disability scores (P 0.001). Radiologically, the hips either stabilized in the same grade or progressed by one grade. MRI showed a decrease in marrow oedema in most cases at the 1-yr follow-up. Six patients (10 hips) required surgery and there were two (three hips) dropouts. The drug was well tolerated and there was a reduction in NSAID requirement. Alendronate reduces pain, improves function and retards AVN progression. Early surgical intervention can be avoided in most patients.

  15. The Pharmacological Profile of a Novel Highly Potent Bisphosphonate, OX14 (1-Fluoro-2-(Imidazo-[1,2-α]Pyridin-3-yl)-Ethyl-Bisphosphonate).

    Science.gov (United States)

    Lawson, Michelle A; Ebetino, Frank H; Mazur, Adam; Chantry, Andrew D; Paton-Hough, Julia; Evans, Holly R; Lath, Darren; Tsoumpra, Maria K; Lundy, Mark W; Dobson, Roy Lm; Quijano, Michael; Kwaasi, Aaron A; Dunford, James E; Duan, Xuchen; Triffitt, James T; Jeans, Gwyn; Russell, R Graham G

    2017-09-01

    Bisphosphonates are widely used in the treatment of clinical disorders characterized by increased bone resorption, including osteoporosis, Paget's disease, and the skeletal complications of malignancy. The antiresorptive potency of the nitrogen-containing bisphosphonates on bone in vivo is now recognized to depend upon two key properties, namely mineral binding affinity and inhibitory activity on farnesyl pyrophosphate synthase (FPPS), and these properties vary independently of each other in individual bisphosphonates. The better understanding of structure activity relationships among the bisphosphonates has enabled us to design a series of novel bisphosphonates with a range of mineral binding properties and antiresorptive potencies. Among these is a highly potent bisphosphonate, 1-fluoro-2-(imidazo-[1,2 alpha]pyridin-3-yl)-ethyl-bisphosphonate, also known as OX14, which is a strong inhibitor of FPPS, but has lower binding affinity for bone mineral than most of the commonly studied bisphosphonates. The aim of this work was to characterize OX14 pharmacologically in relation to several of the bisphosphonates currently used clinically. When OX14 was compared to zoledronate (ZOL), risedronate (RIS), and minodronate (MIN), it was as potent at inhibiting FPPS in vitro but had significantly lower binding affinity to hydroxyapatite (HAP) columns than ALN, ZOL, RIS, and MIN. When injected i.v. into growing Sprague Dawley rats, OX14 was excreted into the urine to a greater extent than the other bisphosphonates, indicating reduced short-term skeletal uptake and retention. In studies in both Sprague Dawley rats and C57BL/6J mice, OX14 inhibited bone resorption, with an antiresorptive potency equivalent to or greater than the comparator bisphosphonates. In the JJN3-NSG murine model of myeloma-induced bone disease, OX14 significantly prevented the formation of osteolytic lesions (p < 0.05). In summary, OX14 is a new, highly potent bisphosphonate with lower bone binding

  16. Atypical femur fractures associated with bisphosphonates: from prodrome to resolution

    Directory of Open Access Journals (Sweden)

    Braulio Sastre-Jala

    2015-10-01

    Full Text Available Atypical fractures related to the prolonged use of bisphosphonates are caused by low energy mechanisms and are characterized by oblique and transverse lines and frequent bilateralism. We present a clinical case of a patient who we believe illustrates, both in clinical and radiological aspects, the new definition of atypical femur fracture related to treatment using bisphosphonates treated conservatively and successfully with discharge and teriparatide 20 mcg/80 mcl s.c./24h. The appearance of painful symptoms in the upper thigh, especially if bilateral, in patients treated with bisphosphonates for long periods of time, makes it necessary to dismiss bone lesions that might otherwise suggest atypical fracture. In those cases where the fracture is incomplete, restoring bone metabolism through the administration of teriparatide 20 mcg/80 mcl s.c./24h could prevent displaced fractures.

  17. Bisphosphonate-Related Osteonecrosis of the Jaws. A Severe Side Effect of Bisphosphonate Therapy

    Directory of Open Access Journals (Sweden)

    Zuzana Janovská

    2012-01-01

    Full Text Available Bisphosphonates (BP are potent inhibitors of bone resorption used mainly in the treatment of metastatic bone disease and osteoporosis. By inhibiting bone resorption, they prevent complications as pathological fracture, pain, tumor-induced hypercalcemia. Even though patient’s benefit of BP therapy is huge, various side effects may develop. Bisphosphonate-related osteonecrosis of the jaws (BRONJ is among the most serious ones. Oncologic patients receiving high doses of BP intravenously are at high risk of BRONJ development. BPs impair bone turnover leading to compromised bone healing which may result in the exposure of necrotic bone in the oral cavity frequently following tooth extraction or trauma of the oral mucosa. Frank bone exposure may be complicated by secondary infection leading to osteomyelitis development with various symptoms and radiological findings. In the management of BRONJ, conservative therapy aiming to reduce the symptoms plays the main role. In patients with extensive bone involvement resective surgery may lead to complete recovery, provided that the procedure is correctly indicated. Since the treatment of BRONJ is difficult, prevention is the main goal. Therefore in high risk patients dental preventive measures should be taken prior to bisphosphonate administration. This requires adequate communication between the prescribing physician, the patient and the dentist.

  18. [Ibandronate in the treatment of postmenopausal osteoporosis].

    Science.gov (United States)

    Lakatos, Péter

    2008-10-01

    Postmenopausal osteoporosis affects 7-10% of the population of developed countries. During the past decade, a number of new therapeutical modalities have been made available. Among these, bisphosphonates mean the mainstay of medical treatment. Ibandronate belongs to the amino-bisphosphonate group of these drugs. Amino-bisphosphonates act via the mevalonate metabolic pathway, thus, inhibiting protein prenylation. Several clinical studies have shown a significant reduction in the fracture risk of osteoporotic patients treated with ibandronate. This compound can be administered orally once a month or intravenously once in every 3 months. Longer dosing intervals stimulate patient compliance, and consequently increase efficacy and cost effectiveness.

  19. BISPHOSPHONATES IN LANGERHANS CELL HISTIOCYTOSIS: AN INTERNATIONAL RETROSPECTIVE CASE SERIES

    Directory of Open Access Journals (Sweden)

    Deepak Chellapandian

    2016-07-01

    Full Text Available Background: Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH, which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH. To date, there are no large international studies to describe their role in treating bone lesions of LCH. Method: We conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation. Results: Ten patients (77% had a single system bone disease, and 3 (23% had bone lesions as part of multisystem disease. Median follow-up time post-bisphosphonate therapy was 4.6 years (range, 0.8 to 8.2 years. Treatment with bisphosphonates was associated with significant pain relief in almost all patients. Twelve  (92% achieved resolution of active bone lesions, and 10 out of them had no active disease for a median of 3.5 years (range, 0.8 to 5 years. One patient did not respond. No major adverse effects were reported in this series.  Conclusion: Bisphosphonates are well-tolerated drugs that can significantly improve bone pain and induce remission in active bone LCH. Future prospective studies evaluating the role of bisphosphonates in LCH are warranted.

  20. Are long-term bisphosphonate users a reality?

    DEFF Research Database (Denmark)

    Abrahamsen, B

    2012-01-01

    The prevalence of long-term bisphosphonate use may be low due to low refill compliance and gaps in treatment. An analysis of the prescription history of 58,674 bisphosphonate users in Denmark found that only 2.8 % had received ten dose years of treatment or above. INTRODUCTION: This study aims...... to describe the demographics of present bisphosphonate (BP) users, to determine the prevalence of long-term BP use, and to establish if long-term use (a 10-year history of osteoporosis treatment) translated to ten dose years of bisphosphonate prescriptions filled, given the propensity for treatment gaps...... more than ten dose years of a BP. For any osteoporosis drug, 3.0 % had received ten dose years or more, while 23.2 % had received between 5 and 10 years of treatment. CONCLUSION: Long-term users with ten dose years or more of a BP are rare due to periods of low compliance and gaps, with a discrepancy...

  1. Bisphosphonates and risk of cardiovascular events: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Dae Hyun Kim

    Full Text Available Some evidence suggests that bisphosphonates may reduce atherosclerosis, while concerns have been raised about atrial fibrillation. We conducted a meta-analysis to determine the effects of bisphosphonates on total adverse cardiovascular (CV events, atrial fibrillation, myocardial infarction (MI, stroke, and CV death in adults with or at risk for low bone mass.A systematic search of MEDLINE and EMBASE through July 2014 identified 58 randomized controlled trials with longer than 6 months in duration that reported CV events. Absolute risks and the Mantel-Haenszel fixed-effects odds ratios (ORs and 95% confidence intervals (CIs of total CV events, atrial fibrillation, MI, stroke, and CV death were estimated. Subgroup analyses by follow-up duration, population characteristics, bisphosphonate types, and route were performed.Absolute risks over 25-36 months in bisphosphonate-treated versus control patients were 6.5% versus 6.2% for total CV events; 1.4% versus 1.5% for atrial fibrillation; 1.0% versus 1.2% for MI; 1.6% versus 1.9% for stroke; and 1.5% versus 1.4% for CV death. Bisphosphonate treatment up to 36 months did not have any significant effects on total CV events (14 trials; ORs [95% CI]: 0.98 [0.84-1.14]; I2 = 0.0%, atrial fibrillation (41 trials; 1.08 [0.92-1.25]; I2 = 0.0%, MI (10 trials; 0.96 [0.69-1.34]; I2 = 0.0%, stroke (10 trials; 0.99 [0.82-1.19]; I2 = 5.8%, and CV death (14 trials; 0.88 [0.72-1.07]; I2 = 0.0% with little between-study heterogeneity. The risk of atrial fibrillation appears to be modestly elevated for zoledronic acid (6 trials; 1.24 [0.96-1.61]; I2 = 0.0%, not for oral bisphosphonates (26 trials; 1.02 [0.83-1.24]; I2 = 0.0%. The CV effects did not vary by subgroups or study quality.Bisphosphonates do not have beneficial or harmful effects on atherosclerotic CV events, but zoledronic acid may modestly increase the risk of atrial fibrillation. Given the large reduction in fractures with bisphosphonates, changes in

  2. Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates.

    Science.gov (United States)

    Arponen, Heidi; Vuorimies, Ilkka; Haukka, Jari; Valta, Helena; Waltimo-Sirén, Janna; Mäkitie, Outi

    2015-03-01

    Cranial base pathology is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to improve bone strength, could also prevent the development of craniocervical junction pathology (basilar impression, basilar invagination, or platybasia) in children with OI. In this single-center retrospective study the authors analyzed the skull base morphology from lateral skull radiographs and midsagittal MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39 bisphosphonate-treated OI patients. The results were compared with age-matched normative values and with findings in 70 OI patients who were not treated with bisphosphonates. In addition to cross-sectional data, longitudinal data were available from 22 patients with an average follow-up period of 7.6 years. The patients, who had OI types I, III, IV, VI, and VII, had been treated with zoledronic acid, pamidronate, or risedronate for 3.2 years on average. Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic regression analysis suggested a higher risk of basilar impression or invagination in patients with severe OI (OR 22.04) and/or older age at initiation of bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with longer duration of treatment (OR 0.28). No significant associations between age, height, or cumulative bisphosphonate dose and the risk for cranial base anomaly were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed development of cranial base pathology in patients treated with bisphosphonates but the differences from the untreated group were not statistically significant. These findings indicate that cranial base pathology may develop despite bisphosphonate treatment. Early initiation of bisphosphonate treatment may delay development of craniocervical junction pathology

  3. Low-intensity continuous ultrasound triggers effective bisphosphonate anticancer activity in breast cancer.

    Science.gov (United States)

    Tardoski, Sophie; Ngo, Jacqueline; Gineyts, Evelyne; Roux, Jean-Paul; Clézardin, Philippe; Melodelima, David

    2015-11-18

    Ultrasound (US) is a non-ionizing pressure wave that can produce mechanical and thermal effects. Bisphosphonates have demonstrated clinical utility in bone metastases treatment. Preclinical studies suggest that bisphosphonates have anticancer activity. However, bisphosphonates exhibit a high affinity for bone mineral, which reduces their bioavailability for tumor cells. Ultrasound has been shown to be effective for drug delivery but in interaction with gas bubbles or encapsulated drugs. We examined the effects of a clinically relevant dose of bisphosphonate zoledronate (ZOL) in combination with US. In a bone metastasis model, mice treated with ZOL+US had osteolytic lesions that were 58% smaller than those of ZOL-treated animals as well as a reduced skeletal tumor burden. In a model of primary tumors, ZOL+US treatment reduced by 42% the tumor volume, compared with ZOL-treated animals. Using a fluorescent bisphosphonate, we demonstrated that US forced the release of bisphosphonate from the bone surface, enabling a continuous impregnation of the bone marrow. Additionally, US forced the penetration of ZOL within tumors, as demonstrated by the intratumoral accumulation of unprenylated Rap1A, a surrogate marker of ZOL antitumor activity. Our findings made US a promising modality to trigger bisphosphonate anticancer activity in bone metastases and in primary tumors.

  4. Use of bisphosphonate therapy for osteoporosis in childhood and adolescence.

    Science.gov (United States)

    Batch, J A; Couper, J J; Rodda, C; Cowell, C T; Zacharin, M

    2003-03-01

    Congenital and acquired forms of osteoporosis in childhood and adolescence can result in morbidity from fracture and pain in childhood, and place an individual at significant risk for problems in adult life. A range of therapies exist for the prevention and treatment of osteoporosis, including optimization of daily calcium intake, adequate vitamin D status, weight-bearing exercise, treatment with sex steroids where delayed puberty is a problem and, more recently, use of bisphosphonate therapy. Intravenous pamidronate therapy (a bisphosphonate) has been shown to reduce fractures and improve bone density in children with osteogenesis imperfecta, and might prove to be of benefit in other osteoporotic conditions in childhood. However, a number of issues regarding the optimal use of bisphosphonate therapy in children and adolescents remain to be resolved, including total annual dose and frequency and duration of administration. Bisphosphonate therapy should, therefore, be used only in the context of a well-run clinical programme with specialist knowledge in the management of osteopenic disorders in childhood.

  5. Osteonecrose dos maxilares associada ao uso de bisfosfonatos: importante complicação do tratamento oncológico Bisphosphonate-associated jaws osteonecrosis: an important complication of oncology treatment

    Directory of Open Access Journals (Sweden)

    Marco Antonio T. Martins

    2009-02-01

    Full Text Available Os bisfosfonatos são um grupo de medicamentos utilizados no tratamento de doenças malignas metastáticas e em outras doenças ósseas como osteoporose e doença de Paget. A despeito dos seus benefícios, uma importante complicação denominada de osteonecrose dos maxilares vem sendo observada nos pacientes usuários crônicos dos bisfosfonatos que se caracteriza clinicamente por exposições ósseas na região maxilofacial persistente, acompanhadas de osteomielite, geralmente sintomáticas e cujo tratamento é complexo. Este estudo tem por objetivo revisar a literatura sobre a osteonecrose associada ao uso dos bisfosfonatos, em especial, em oncologia, no período de 2003 a 2008. Serão apresentados e discutidos os fatores de risco, aspectos etiopatogênicos, clínicos, imagenológicos, terapêuticos e preventivos desta doença. Devido à dificuldade de tratamento da osteonecrose associada aos bisfosfonatos, o foco deve ser a prevenção, sendo o ideal a eliminação de quadros infecciosos orais antes da terapia com os bisfosfonatos ter sido iniciada e minimizar traumas em boca após o uso destes medicamentos.Bisphosphonates are drugs used in the treatment of malignant metastatic diseases and in other bone lesions such as osteoporosis and Paget´s disease. Besides their benefits, jaw osteonecrosis, an important side effect, has been observed in long-term users of these drugs. Jaw osteonecrosis is clinically characterized by prolonged maxillary and mandible bone exposure accompanied by osteomyelitis. These lesions are usually symptomatic and difficult to treat. This study has the objective of reviewing publications from 2003 to 2008 about bisphosphonate-associated jaw osteonecrosis, in particular in relation to oncology. Risk factors, and etiopathological, clinical, radiographic, therapeutic, and preventive aspects of this condition are presented and discussed. Due to the difficulty to treat this disease, the focus must be prevention, with the

  6. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ali Murat Tatlı

    2013-01-01

    Full Text Available Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient’s history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage.

  7. Clinical Aspects, Imaging Features, and Considerations on Bisphosphonate-Related Osteonecrosis Risk in a Pediatric Patient with Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Fábio Wildson Gurgel Costa

    2014-01-01

    Full Text Available Osteogenesis imperfecta (OI is a rare hereditary condition caused by changes in collagen metabolism. It is classified into four types according to clinical, genetic, and radiological criteria. Clinically, bone fragility, short stature, blue sclerae, and locomotion difficulties may be observed in this disease. OI is often associated to severe dental problems, such as dentinogenesis imperfecta (DI and malocclusions. Radiographically, affected teeth may have crowns with bulbous appearance, accentuated constriction in the cementoenamel junction, narrowed roots, large root canals due to defective dentin formation, and taurodontism (enlarged pulp chambers. There is no definitive cure, but bisphosphonate therapy is reported to improve bone quality; however, there is a potential risk of bisphosphonate-related osteonecrosis of the jaw. In this study we report a case of OI in a male pediatric patient with no family history of OI who was receiving ongoing treatment with intravenous perfusion of bisphosphonate and who required dental surgery. In addition, we discussed the clinical and imaging findings and briefly reviewed the literature.

  8. In vitro comparison of new bisphosphonic acids and zoledronate effects on human gingival fibroblasts viability, inflammation and matrix turnover.

    Science.gov (United States)

    De Colli, Marianna; Tortorella, Paolo; Marconi, Guya Diletta; Agamennone, Mariangela; Campestre, Cristina; Tauro, Marilena; Cataldi, Amelia; Zara, Susi

    2016-11-01

    Bisphosphonates (BPs) are drugs clinically used in resorptive diseases. It was already proved that some clinically relevant BPs can inhibit a class of enzymes called matrix metalloproteinases (MMPs), required during tissue remodelling. Combining the arylsulfonamide function with the bisphosphonic group, several compounds were synthesized to obtain selective inhibitors of MMPs. The aim of the present study was to compare the effect of zoledronic acid (ZA), the most potent bisphosphonate available as therapy, with new sulfonamide containing BPs in an in vitro model of human gingival fibroblasts (HGFs). Western blot was used to measure procollagen I, β1 integrin MMP-8 and MMP-9, phase contrast and MTT for cell viability; L-lactate-dehydrogenase (LDH) measurement was performed for toxicity evaluation and ELISA for prostaglandin E 2 (PGE 2 ) secretion assessment. When compared with ZA, the treatment with the newly synthesized compounds shows increasing viability, procollagen I expression and decreased expression of β1 integrin in HGFs. Higher levels of released LDH, PGE 2 and MMP-9 expression are recorded in ZA-treated HGFs. Increased levels of MMP-8 are recorded in newly synthesized compounds-treated samples. These findings allowed to conclude that new tested BPs did not affect HGFs viability and adhesion, did not induce cellular toxicity, were not responsible for inflammatory event induction and could preserve the physiological matrix turnover. It could be hypothesized that the new molecules were better tolerated by soft tissues, resulting in lesser side effects.

  9. Determinants of change in bone mineral density and fracture risk during bisphosphonate holiday.

    Science.gov (United States)

    Xu, L H R; Adams-Huet, B; Poindexter, J R; Maalouf, N M

    2016-05-01

    In a retrospective analysis of 208 osteoporotic patients followed during a bisphosphonate holiday, lower body weight and risedronate use were associated with a more rapid decline in bone mineral density during the bisphosphonate holiday, while bone mineral density (BMD) trends were similar in patients who sustained vs. did not sustain a fracture. A drug holiday has been suggested for some bisphosphonate-treated patients with osteoporosis to minimize potential side effects from prolonged use. However, there is limited information on the evolution of BMD during a bisphosphonate holiday. Our study analyzed the longitudinal course of BMD following bisphosphonate discontinuation and assessed its determinants. Retrospective single-center cohort study of osteoporosis patients treated with alendronate or risedronate for at least 2 years and then discontinued their bisphosphonate for a drug holiday. Patients were stratified by bisphosphonate type and by fracture occurrence during drug holiday. A total of 208 patients were included in this analysis (87.5 % female). At the time of bisphosphonate cessation, mean ± SD age was 66.9 ± 8.9 years and BMI 24.5 ± 4.4 kg/m(2). Duration of bisphosphonate treatment was 5.2 ± 2.3 years, and follow-up during holiday was 3.3 ± 1.7 years. During the first 2 years of the holiday, BMD remained stable at the lumbar spine and femoral neck, but declined significantly at the total hip. BMD declined significantly at all sites thereafter. Significant predictors of BMD decline during bisphosphonate holiday included lower BMI at the start of the holiday and change in body weight during the holiday. BMD decline was more pronounced in former risedronate compared to former alendronate users. BMD trends were similar in patients who sustained vs. did not sustain a fracture during the holiday. BMD at the total hip declines significantly within 1 year of bisphosphonate discontinuation, particularly in lean patients

  10. Osteonecrosis of the jaw: a rare and devastating side effect of bisphosphonates.

    LENUS (Irish Health Repository)

    Ryan, P

    2009-12-01

    Evidence has emerged that bisphosphonate use in cancer patients is associated with osteonecrosis of the jaw. This form of osteonecrosis has been termed bisphosphonate induced osteonecrosis of the jaw (BIONJ). BIONJ is commonly precipitated by a tooth extraction in patients treated with long term, potent, high dose intravenous bisphosphonates for the management of myeloma, breast or prostate cancer. The overall prevalence of BIONJ is about 5% in patients with these malignancies. Current evidence shows that the risk of BIONJ in non-cancerous patients, such as those with osteoporosis, is very low and appears to be comparable with that of the general population. Prescribing physicians need to encourage cancer patients to see their dentists before the initiation of bisphosphonate treatment, and regularly thereafter.

  11. Atypical femoral fractures related to bisphosphonate therapy

    Directory of Open Access Journals (Sweden)

    Tarun Pankaj Jain

    2012-01-01

    Full Text Available Bisphosphonates (BP are a commonly prescribed class of drugs for the prevention of osteoporosis-related fractures. Paradoxically, however, they have recently been linked to atypical fractures in the shaft of the femur. Since many physicians including radiologists, are not aware of this entity, the incidence is likely underreported. These fractures usually occur in the sub-trochanteric region of the femur in the setting of low-energy trauma. It starts as a fracture line involving the lateral cortex and then progresses medially to give rise to a complete fracture. The fracture line is usually transverse, and there is a medial spike associated with a complete fracture. These fractures can be bilateral. Awareness of these atypical fractures and their radiological appearance should enable their early and accurate detection and thus lead to specific treatment.

  12. Bisphosphonate adverse effects, lessons from large databases

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    is on bisphosphonates used for osteoporosis. RECENT FINDINGS: Register studies have so far not confirmed a shift from classical to nonclassical femur fractures with bisphosphonates. However, studies were either small or without X-ray adjudication. Two new studies found no increase in jaw surgery for inflammatory...

  13. Bisphosphonate adverse effects, lessons from large databases

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    To review the latest findings on bisphosphonate safety from health databases, in particular sources that can provide incidence rates for stress fractures, osteonecrosis of the jaw (ONJ), atrial fibrillation and gastrointestinal lesions including esophageal cancer. The main focus is on bisphosphon...

  14. Atypical fractures on long term bisphosphonates therapy.

    LENUS (Irish Health Repository)

    Hussein, W

    2011-01-01

    Bisphosphonates reduce fractures risk in patients with osteoporosis. A new pattern of fractures is now being noted in patients on prolonged bisphosphonate therapy. We report a case of an atypical femoral fracture with preceding pain and highlight the characteristics of these fractures.

  15. Bisphosphonate associated osteonecrosis of the jaw.

    Science.gov (United States)

    Khan, Aliya A; Sándor, George K B; Dore, Edward; Morrison, Archibald D; Alsahli, Mazen; Amin, Faizan; Peters, Edmund; Hanley, David A; Chaudry, Sultan R; Lentle, Brian; Dempster, David W; Glorieux, Francis H; Neville, Alan J; Talwar, Reena M; Clokie, Cameron M; Mardini, Majd Al; Paul, Terri; Khosla, Sundeep; Josse, Robert G; Sutherland, Susan; Lam, David K; Carmichael, Robert P; Blanas, Nick; Kendler, David; Petak, Steven; Ste-Marie, Louis Georges; Brown, Jacques; Evans, A Wayne; Rios, Lorena; Compston, Juliet E

    2009-03-01

    In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%-12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

  16. Applying orthodontic tooth extrusion in a patient treated with bisphosphonate and irradiation: a case report.

    Science.gov (United States)

    Morita, Hiromitsu; Imai, Yuko; Yoneda, Masahiro; Hirofuji, Takao

    2017-01-01

    Bisphosphonates and irradiation are useful medical treatments, but can often cause oral complications such as medication-related oral necrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) during oral surgery, including tooth extraction. Therefore, we should take all risks into consideration carefully before choosing dental treatment for patients with a medical history of such therapies. A 55-year-old woman who underwent cord blood transplantation to treat extranodal natural killer T (NK/T) cell lymphoma (nasal type IVB) had a medical history of bisphosphonate and irradiation treatments. We treated her residual tooth root by applying orthodontic extrusion to avoid extraction and successfully restored the tooth. Application of an orthodontic tooth extrusion technique for conservative treatment of a residual tooth is a useful means of avoiding MRONJ or ORN in patients who have a medical history of bisphosphonate and irradiation treatments. © 2016 Special Care Dentistry Association and Wiley Periodicals, Inc.

  17. The Pharmacological Profile of a Novel Highly Potent Bisphosphonate, OX14 (1‐Fluoro‐2‐(Imidazo‐[1,2‐α]Pyridin‐3‐yl)‐Ethyl‐Bisphosphonate)

    Science.gov (United States)

    Ebetino, Frank H; Mazur, Adam; Chantry, Andrew D; Paton‐Hough, Julia; Evans, Holly R; Lath, Darren; Tsoumpra, Maria K; Lundy, Mark W; Dobson, Roy LM; Quijano, Michael; Kwaasi, Aaron A; Dunford, James E; Duan, Xuchen; Triffitt, James T; Jeans, Gwyn; Russell, R Graham G

    2017-01-01

    ABSTRACT Bisphosphonates are widely used in the treatment of clinical disorders characterized by increased bone resorption, including osteoporosis, Paget's disease, and the skeletal complications of malignancy. The antiresorptive potency of the nitrogen‐containing bisphosphonates on bone in vivo is now recognized to depend upon two key properties, namely mineral binding affinity and inhibitory activity on farnesyl pyrophosphate synthase (FPPS), and these properties vary independently of each other in individual bisphosphonates. The better understanding of structure activity relationships among the bisphosphonates has enabled us to design a series of novel bisphosphonates with a range of mineral binding properties and antiresorptive potencies. Among these is a highly potent bisphosphonate, 1‐fluoro‐2‐(imidazo‐[1,2 alpha]pyridin‐3‐yl)‐ethyl‐bisphosphonate, also known as OX14, which is a strong inhibitor of FPPS, but has lower binding affinity for bone mineral than most of the commonly studied bisphosphonates. The aim of this work was to characterize OX14 pharmacologically in relation to several of the bisphosphonates currently used clinically. When OX14 was compared to zoledronate (ZOL), risedronate (RIS), and minodronate (MIN), it was as potent at inhibiting FPPS in vitro but had significantly lower binding affinity to hydroxyapatite (HAP) columns than ALN, ZOL, RIS, and MIN. When injected i.v. into growing Sprague Dawley rats, OX14 was excreted into the urine to a greater extent than the other bisphosphonates, indicating reduced short‐term skeletal uptake and retention. In studies in both Sprague Dawley rats and C57BL/6J mice, OX14 inhibited bone resorption, with an antiresorptive potency equivalent to or greater than the comparator bisphosphonates. In the JJN3‐NSG murine model of myeloma‐induced bone disease, OX14 significantly prevented the formation of osteolytic lesions (p < 0.05). In summary, OX14 is a new, highly potent

  18. Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

    Directory of Open Access Journals (Sweden)

    Schlegel Karl A

    2010-10-01

    Full Text Available Abstract Background Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL; however, osteonecrosis of the jaw (ONJ is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP-related and denosumab (anti-RANKL antibody-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL in ONJ-altered and healthy periodontal tissue. Methods Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment. Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Results Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p Conclusions These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to

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

    Science.gov (United States)

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

    2013-01-01

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

  20. Repurposing of bisphosphonates for the prevention and therapy of nonsmall cell lung and breast cancer.

    Science.gov (United States)

    Stachnik, Agnes; Yuen, Tony; Iqbal, Jameel; Sgobba, Miriam; Gupta, Yogesh; Lu, Ping; Colaianni, Graziana; Ji, Yaoting; Zhu, Ling-Ling; Kim, Se-Min; Li, Jianhua; Liu, Peng; Izadmehr, Sudeh; Sangodkar, Jaya; Scherer, Thomas; Mujtaba, Shiraz; Galsky, Matthew; Gomez, Jorge; Epstein, Solomon; Buettner, Christoph; Bian, Zhuan; Zallone, Alberta; Aggarwal, Aneel K; Haider, Shozeb; New, Maria I; Sun, Li; Narla, Goutham; Zaidi, Mone

    2014-12-16

    A variety of human cancers, including nonsmall cell lung (NSCLC), breast, and colon cancers, are driven by the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. Having shown that bisphosphonates, a class of drugs used widely for the therapy of osteoporosis and metastatic bone disease, reduce cancer cell viability by targeting HER1, we explored their potential utility in the prevention and therapy of HER-driven cancers. We show that bisphosphonates inhibit colony formation by HER1(ΔE746-A750)-driven HCC827 NSCLCs and HER1(wt)-expressing MB231 triple negative breast cancers, but not by HER(low)-SW620 colon cancers. In parallel, oral gavage with bisphosphonates of mice xenografted with HCC827 or MB231 cells led to a significant reduction in tumor volume in both treatment and prevention protocols. This result was not seen with mice harboring HER(low) SW620 xenografts. We next explored whether bisphosphonates can serve as adjunctive therapies to tyrosine kinase inhibitors (TKIs), namely gefitinib and erlotinib, and whether the drugs can target TKI-resistant NSCLCs. In silico docking, together with molecular dynamics and anisotropic network modeling, showed that bisphosphonates bind to TKIs within the HER1 kinase domain. As predicted from this combinatorial binding, bisphosphonates enhanced the effects of TKIs in reducing cell viability and driving tumor regression in mice. Impressively, the drugs also overcame erlotinib resistance acquired through the gatekeeper mutation T790M, thus offering an option for TKI-resistant NSCLCs. We suggest that bisphosphonates can potentially be repurposed for the prevention and adjunctive therapy of HER1-driven cancers.

  1. Positive effects of bisphosphonates on bone and muscle in a mouse model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Yoon, Sung-Hee; Sugamori, Kim S; Grynpas, Marc D; Mitchell, Jane

    2016-01-01

    Patients with Duchenne muscular dystrophy are at increased risk of decreased bone mineral density and bone fracture as a result of inactivity. To determine if antiresorptive bisphosphonates could improve bone quality and their effects on muscle we studied the Mdx mouse, treated with pamidronate during peak bone growth at 5 and 6 weeks of age, and examined the outcome at 13 weeks of age. Pamidronate increased cortical bone architecture and strength in femurs with increased resistance to fracture. While overall long bone growth was not affected by pamidronate, there was significant inhibition of remodeling in metaphyseal trabecular bone with evidence of residual calcified cartilage. Pamidronate treatment had positive effects on skeletal muscle in the Mdx mice with decreased serum and muscle creatine kinase and evidence of improved muscle histology and grip strength. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Benign meningiomas: primary treatment selection affects survival

    International Nuclear Information System (INIS)

    Condra, Kellie S.; Buatti, John M.; Mendenhall, William M.; Friedman, William A.; Marcus, Robert B.; Rhoton, Albert L.

    1997-01-01

    Purpose: To examine the effect of primary treatment selection on outcomes for benign intracranial meningiomas at the University of Florida. Methods and Materials: For 262 patients, the impact of age, Karnofsky performance status, pathologic features, tumor size, tumor location, and treatment modality on local control and cause-specific survival was analyzed (minimum potential follow-up, 2 years; median follow-up, 8.2 years). Extent of surgery was classified by Simpson grade. Treatment groups: surgery alone (n = 229), surgery and postoperative radiotherapy (RT) (n = 21), RT alone (n = 7), radiosurgery alone (n = 5). Survival analysis: Kaplan-Meier method with univariate and multivariate analysis. Results: At 15 years, local control was 76% after total excision (TE) and 87% after subtotal excision plus RT (SE+RT), both significantly better (p = 0.0001) than after SE alone (30%). Cause-specific survival at 15 years was reduced after treatment with SE alone (51%), compared with TE (88%) or SE+RT (86%) (p = 0.0003). Recurrence after primary treatment portended decreased survival, independent of initial treatment group or salvage treatment selection (p = 0.001). Atypical pathologic features predicted reduced 15-year local control (54 vs. 71%) and cause-specific survival rates (57 vs. 86%). Multivariate analysis for cause-specific survival revealed treatment group (SE vs. others; p = 0.0001), pathologic features (atypical vs. typical; p = 0.0056), and Karnofsky performance status (≥80 vs. <80; p = 0.0153) as significant variables. Conclusion: Benign meningiomas are well managed by TE or SE+RT. SE alone is inadequate therapy and adversely affects cause-specific survival. Atypical pathologic features predict a poorer outcome, suggesting possible benefit from more aggressive treatment. Because local recurrence portends lower survival rates, primary treatment choice is important

  3. Subtrochanteric stress fractures in patients on oral bisphosphonate therapy: an emerging problem.

    LENUS (Irish Health Repository)

    Murphy, Colin G

    2012-01-31

    The emergence of a new variant of subtrochanteric stress fractures of the femur, affecting patients on oral bisphosphonate therapy, has only recently been described. This fracture is often preceded by pain and distinctive radiographic changes (lateral cortical thickening), and associated with a characteristic fracture pattern (transverse fracture line and medial cortical spike). A retrospective review (2007-2009) was carried out for patients who were taking oral bisphosphonates and who sustained a subtrochanteric fracture after a low velocity injury. Eleven fractures were found in 10 patients matching the inclusion criteria outlined. All were females, and taking bisphosphonates for a mean of 43 years. Five of the 10 patients mentioned prodromal symptoms, for an average of 9.4 months before the fracture. Although all fractures were deemed low velocity, 5 of 11 were even atraumatic. Two patients had previously sustained contralateral subtrochanteric fractures. Plain radiographs of two patients showed lateral cortical thickening on the contralateral unfractured femur; the bisphosphonate therapy was stopped and close surveillance was started. Patients taking oral bisphosphonates may be at risk of a new variant of stress fracture of the proximal femur. Awareness of the symptoms is the key to ensure that appropriate investigations are undertaken.

  4. 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

  5. Bisphosphonate-associated osteonecrosis of the jaws

    Directory of Open Access Journals (Sweden)

    Pankaj Agarwal

    2012-01-01

    Full Text Available Bisphosphonates constitute a group of drugs capable of modulating bone turnover and reduce its remodeling when an excessive resorption occurs. This is why they are indicated in a large group of bone diseases like postmenopausal osteoporosis or osteolysis associated with breast cancer or multiple myeloma. Over the last few years and due to their extensive use, many cases of complications associated with their use have been published. Among the most important possible adverse effects are the oral ones, with the appearance of ulcerations and, especially, osteonecrosis of the jaws associated with this therapy. In this paper, we have analyzed the general characteristics of these drugs and their mechanisms of action as well as the described adverse effects, especially oral and maxillofacial, have been made special reference, regarding the prevention of osteonecrosis of the jaws, heightened by cases described in the medical and odontological literature. The preventive protocol backs up the fundamental role of the odontologist in the effective prevention of this process before, during and after the treatment.

  6. Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features.

    Science.gov (United States)

    Wehrhan, Falk; Hyckel, Peter; Ries, Jutta; Stockmann, Phillip; Nkenke, Emeka; Schlegel, Karl A; Neukam, Friedrich W; Amann, Kerstin

    2010-10-13

    Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p Msx-1 (p Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue.

  7. Differential response of idiopathic sporadic tumoral calcinosis to bisphosphonates

    Directory of Open Access Journals (Sweden)

    Karthik Balachandran

    2014-01-01

    Full Text Available Context: Tumoral calcinosis is a disorder of phosphate metabolism characterized by ectopic calcification around major joints. Surgery is the current treatment of choice, but a suboptimal choice in recurrent and multicentric lesions. Aims: To evaluate the efficacy of bisphosphonates for the management of tumoral calcinosis on optimized medical treatment. Settings and Design: The study was done in the endocrine department of a tertiary care hospital in South India. We prospectively studied two patients with recurrent tumoral calcinosis who had failed therapy with phosphate lowering measures. Materials and Methods: After informed consent, we treated both patients with standard age adjusted doses of bisphosphonates for 18 months. The response was assessed by X ray and whole body 99mTc-methylene diphosphonate bone scan at the beginning of therapy and at the end of 1 year. We also estimated serum phosphate levels and urinary phosphate to document serial changes. Results: Two patients (aged 19 and 5 years with recurrent idiopathic hyperphosphatemic tumoral calcinosis, following surgery were studied. Both patients had failed therapy with conventional medical management − low phosphate diet and phosphate binders. They had restriction of joint mobility. Both were given standard doses of oral alendronate and parenteral pamidronate respectively for more than a year, along with phosphate lowering measures. At the end of 1 year, one of the patients had more than 95% and 90% reduction in the size of the lesions in right and left shoulder joints respectively with total improvement in range of motion. In contrast, the other patient (5-year-old had shown no improvement, despite continuing to maintain normophosphatemia following treatment. Conclusions: Bisphosphonate therapy in tumoral calcinosis is associated with lesion resolution and may be used as a viable alternative to surgery, especially in cases with multicentric recurrence or treatment failure to other

  8. New 68Ga-PhenA bisphosphonates as potential bone imaging agents

    International Nuclear Information System (INIS)

    Wu, Zehui; Zha, Zhihao; Choi, Seok Rye; Plössl, Karl; Zhu, Lin; Kung, Hank F.

    2016-01-01

    Introduction: In vivo positron emission tomography (PET) imaging of the bone using [ 68 Ga]bisphosphonates may be a valuable tool for cancer diagnosis and monitoring therapeutic treatment. We have developed new [ 68 Ga]bisphosphonates based on the chelating group, AAZTA (6-[bis(hydroxycarbonyl-methyl)amino]-1,4-bis(hydroxycarbonyl methyl)-6-methylperhydro-1,4-diazepine). Method: Phenoxy derivative of AAZTA (2,2′-(6-(bis(carboxymethyl)amino)-6-((4-(2-carboxyethyl)phenoxy) methyl)-1,4-diazepane-1,4-diyl)diacetic acid), PhenA, 2, containing a bisphosphonate group (PhenA-BPAMD, 3, and PhenA-HBP, 4) was prepared. Labeling of these chelating agents with 68 Ga was evaluated. Results: The ligands reacted rapidly in a sodium acetate buffer with [ 68 Ga]GaCl 3 eluted from a commercially available 68 Ge/ 68 Ga generator (pH 4, > 95% labeling at room temperature in 5 min) to form [ 68 Ga]PhenA-BPAMD, 3, and [ 68 Ga]PhenA-HBP, 4. The improved labeling condition negates the need for further purification. The 68 Ga bisphosphonate biodistribution and autoradiography of bone sections in normal mice after an iv injection showed excellent bone uptake. Conclusion: New 68 Ga labeled bisphosphonates may be useful as in vivo bone imaging agents in conjunction with positron emission tomography (PET).

  9. Opsismodysplasia: Phosphate wasting osteodystrophy responds to bisphosphonate therapy

    Directory of Open Access Journals (Sweden)

    Ansab eKhwaja

    2015-06-01

    Full Text Available We present two siblings affected with opsismodysplasia, a rare skeletal dysplasia caused by mutations in the INPPL1 gene. The skeletal findings include short stature with postnatal onset micromelia, marked platyspondyly, squared metacarpals, delayed skeletal ossification, metaphyseal cupping and postnatal micromelia. Respiratory compromise, delayed ambulation, and progressive lower extremity deformities are described. The severity of findings is variable. Renal phosphate wasting is associated with severe bone demineralization and a more severe phenotype. This report represents the first described cases of opsismodysplasia treated with intravenous bisphosphonate (pamidronate. Surgical management for lower extremity deformities associated with OPS is also reviewed.

  10. Bisphosphonates and oral pathology II. Osteonecrosis of the jaws: review of the literature before 2005.

    Science.gov (United States)

    Estefanía Fresco, Ruth; Ponte Fernández, Ruth; Aguirre Urizar, José Manuel

    2006-11-01

    Bisphosphonates are bone-turnover modulating drugs which are used in the management of a number of bone diseases ranging from osteoporosis to neoplasic pathology-associated osteolysis. In the last years a number of cases of osteonecrosis of the jaws associated with these drugs have been reported. In this review we analyze the cases published in the literature indexed from 2003 to December 2005. During this period 246 cases were reported, being more frequently associated with women in the sixth decade of life. More frequently associated bisphosphonates were the nitrogenated bisphosphonates (pamidronate, zolendronic acid) and the most common oral antecedent was a dental extraction. Nevertheless more than 25% of the cases were spontaneous. The most frequent site was the mandible and most of the cases presented clinical evidence of bone exposure and pain. Different treatments have been proposed with different antibiotic therapies with or without surgery, showing in general terms an uncertain prognosis with low healing rates.

  11. Oral bisphosphonate use and total knee/hip implant survival

    DEFF Research Database (Denmark)

    Prieto-Alhambra, Daniel; Lalmohamed, Arief; Abrahamsen, Bo

    2014-01-01

    of disease-modifying antirheumatic drugs as well as patients with rheumatoid arthritis, Paget's disease, or hip fracture. Participants were classified as bisphosphonate users if they had been receiving treatment for ≥6 months. A time-varying exposure was used to avoid immortal time bias. Up to 6...... was conducted within the Danish nationwide registries (5.5 million residents). Using procedure codes of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, we identified patients age ≥40 years undergoing total joint replacement in 1998-2007. We excluded users...

  12. Bisphosphonates and their clinical implications in endodontic therapy.

    Science.gov (United States)

    Moinzadeh, A-T; Shemesh, H; Neirynck, N A M; Aubert, C; Wesselink, P R

    2013-05-01

    This review gives an overview of the factors that may play a role in the development of osteonecrosis of the jaw in patients treated with bisphosphonates (BPs) and undergoing nonsurgical endodontic treatment as well as some recommendations for its prevention. BPs are a widely prescribed group of drugs for diverse bone diseases. The occasional but devastating adverse effect of these drugs has been described as bisphosphonate-related osteonecrosis of the jaw (BRONJ). As this condition is debilitating and difficult to treat, all efforts should be made to prevent its occurence in patients at risk. The main triggering event is considered to be dental extraction. Even though nonsurgical endodontic treatment appears to be a relatively safe procedure, care remains essential. After an overview of this class of drugs, the clinical presentation, epidemiology and pathogenesis of BRONJ, as well as the possible risk factors associated with its development after nonsurgical endodontic treatment will be described. Finally, several strategies will be proposed for the prevention of BRONJ during nonsurgical endodontic treatment. © 2012 International Endodontic Journal. Published by Blackwell Publishing Ltd.

  13. Optimizing dosing frequencies for bisphosphonates in the management of postmenopausal osteoporosis: patient considerations

    Directory of Open Access Journals (Sweden)

    John Sunyecz

    2008-12-01

    Full Text Available John SunyeczMenopauseRx, Inc., Hopwood, PA, USAAbstract: Postmenopausal osteoporosis is common and underrecognized among elderly women. Osteoporotic fractures cause disability and disfigurement and threaten patients’ mobility, independence, and survival. Care for incident fractures in this age group must go beyond orthopedic repair, to assessment and treatment of the underlying bone fragility. Fracture risk can be reduced by vitamin D and calcium supplementation along with antiresorptive drug treatment. First-line osteoporosis pharmacotherapy employs nitrogen-containing bisphosphonates. The inconvenience of daily oral treatment has motivated development of weekly, monthly, and intermittent oral regimens, as well as quarterly and yearly intravenous (iv regimens. Ibandronate is the first bisphosphonate to have shown direct anti-fracture efficacy with a non-daily regimen; it was approved for once-monthly oral dosing in 2005 and for quarterly iv dosing in 2006. Intermittent oral risedronate and yearly iv zoledronic acid were approved in 2007. Newly available regimens with extended dosing intervals reduce the inconvenience of bisphosphonate therapy and provide patients with a range of options from which to select a maximally sustainable course of treatment. This review discusses the development, efficacy, safety, and tolerability of extended-interval bisphosphonate regimens and examines their potential to improve patient acceptance and long-term success of osteoporosis treatment.Keywords: ibandronate, alendronate, risedronate, zoledronic acid, adherence, persistence

  14. The influence of bisphosphonates on human osteoblast migration and integrin aVb3/tenascin C gene expression in vitro

    Directory of Open Access Journals (Sweden)

    Said Yekta Sareh

    2011-02-01

    Full Text Available Abstract Background Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ often requires surgical treatment and is accompanied with a disturbed wound healing. Therefore, the influence on adhesion and migration of human osteoblasts (hOB after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods. Methods By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated. A test group of hOB, which was stimulated by zoledronate 5 × 10-5M, and a control group of unstimulated hOB were applied. Furthermore the gene expression of integrin aVb3 and tenascin C was quantified by Real-Time rtPCR at 5data points over an experimental period of 14 days. The bisphosphonates zoledronate, ibandronate and clodronate have been compared with an unstimulated hOB control. Results After initially identical migration and adhesion characteristics, zoledronate inhibited hOB migration after 50 h of stimulation. The integrinavb3 and tenascin C gene expression was effected by bisphosphonates in a cell line dependent manner with decreased, respectively inconsistent gene expression levels over time. The non-nitrogen containing bisphosphonates clodronate led to decreased gene expression levels. Conclusion Bisphosphonates seem to inhibit hOB adhesion and migration. The integrin aVb3 and tenascin C gene expression seem to be dependent on the cell line. BONJ could be enhanced by an inhibition of osteoblast adhesion and migration. The gene expression results, however, suggest a cell line dependent effect of bisphosphonates, which could explain the interindividual differences of BONJ incidences.

  15. An open-label, prospective, observational study of the efficacy of bisphosphonate therapy for painful osteoid osteoma

    Energy Technology Data Exchange (ETDEWEB)

    Bousson, Valerie; Parlier-Cuau, Caroline; Laredo, Jean-Denis [AP-HP, Hopital Lariboisiere, Service de Radiologie Osteo-Articulaire, Paris (France); Universite Paris Diderot, Sorbonne Paris Cite, Paris (France); Leturcq, Tifenn; Ea, Hang-Korng; Orcel, Philippe [AP-HP, Hopital Lariboisiere, Service de Rhumatologie, Paris (France); Universite Paris Diderot, Sorbonne Paris Cite, Paris (France); Hauger, Olivier [CHU Pellegrin Bordeaux, Service d' Imagerie Diagnostique et Therapeutique de l' Adulte, Bordeaux (France); Mehsen-Cetre, Nadia; Schaeverbeke, Thierry [CHU Pellegrin Bordeaux, Service de Rhumatologie, Bordeaux (France); Hamze, Bassam [AP-HP, Hopital Lariboisiere, Service de Radiologie Osteo-Articulaire, Paris (France)

    2018-02-15

    To assess the efficacy of bisphosphonate therapy on bone pain in patients with osteoid osteoma (OO) (main objective), and to describe bisphosphonate-induced changes in nidus mineralisation and regional bone-marrow oedema (BMO). A prospective, observational study was conducted from 2011 to 2014. Patients with risk factors for complications of percutaneous or surgical ablation or recurrence after ablation, were offered once monthly intravenous bisphosphonate treatment until significant pain alleviation was achieved. We included 23 patients. The first two patients received pamidronate and the next 21 zoledronic acid (mean, 2.95 infusions per patient). Bisphosphonate therapy was successful in 19 patients (83%), whose mean pain visual analogue scale score decreased by 76.7%; this pain-relieving effect persisted in 17 patients (74%) with a mean follow-up time of 36 months. Computed tomography (CT) demonstrated a mean nidus density increase of 177.7% (p = 0.001). By magnetic resonance imaging (MRI), mean decreases were 38.4% for BMO surface area and 30.3% for signal intensity (p = 0.001 and p = 0.000, respectively). In 17/23 patients with painful OO managed conservatively with bisphosphonates, long-term final success was achieved. Bisphosphonates may accelerate the spontaneous healing of OO. (orig.)

  16. Association between refill compliance to oral bisphosphonate treatment, incident fractures, and health care costs--an analysis using national health databases

    DEFF Research Database (Denmark)

    Olsen, K R; Hansen, C; Abrahamsen, Bo

    2013-01-01

    major osteoporotic fractures, and the direct costs related to hospital care, primary care, and pharmaceutical treatment for these excess fractures reached almost 14 M DKK (2.5 M USD) for the study population which compares to a national annual excess cost of around 17 M DKK (3.1 M USD) using 2011...

  17. Time to onset of bisphosphonate-related osteonecrosis of the jaws

    DEFF Research Database (Denmark)

    Fung, Ppl; Bedogni, G; Bedogni, A

    2017-01-01

    OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to esti...

  18. 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)

  19. Uptake of a fluorinated bisphosphonate by cultured bones

    International Nuclear Information System (INIS)

    Rowe, D.J.; Etre, L.A.

    1988-01-01

    The uptake of bisphosphonates into bone was studied using 19-day-old fetal rat bones cultured with a new fluorinated bisphosphonate, difluoromethylidene bisphosphonate (F2MBP). F2MBP uptake was assessed by determining the weight percent of fluoride using electron probe microanalysis. By 30 min the weight percent of fluoride was significantly greater in the F2MBP-treated bones than in controls and continually increased throughout the duration of the experiment to reach a fluoride concentration 6-fold greater than controls after 120 h of incubation. When the peripheral cortical bone was analyzed separately from the interior trabecular bone in the F2MBP-treated bones, the fluoride concentration in the periphery increased until 24 h and then remained somewhat constant, while the interior, which is more actively remodeling, showed a continual increase. The uptake of F2MBP during the 1 to 6 h time intervals demonstrated no differences between vital and devitalized bone and, thus, is not cell-mediated. Because analysis of free fluoride in F2MBP media incubated with bones showed that the concentration of fluoride was less than 1% of the total amount of fluoride, the fluoride detected by the probe was most likely that of the intact molecule and not free fluoride. The rapid uptake of the F2MBP molecule was supported by assessing the effects of short-term F2MBP treatment on subsequent bone resorption, as determined by the release of 45Ca from prelabeled bones. Bones treated with F2MBP for only 5 min exhibited reductions in the percentage of 45Ca released during the remainder of the 120 h incubation period similar to that when F2MBP was continuously in the medium

  20. Subtrochanteric fractures in bisphosphonate-naive patients

    DEFF Research Database (Denmark)

    Adachi, Jonathan D; Lyles, Kenneth; Boonen, Steven

    2011-01-01

    Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained ...

  1. Safety issues with bisphosphonate therapy for osteoporosis

    DEFF Research Database (Denmark)

    Suresh, Ernest; Pazianas, Michael; Abrahamsen, Bo

    2014-01-01

    Randomized controlled trials have demonstrated the efficacy of bisphosphonates (BP) in improving BMD and reducing fracture risk. Various safety issues that were not noted in clinical trials have, however, now emerged with post-marketing surveillance and increasing clinical experience. The risk...

  2. A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures.

    Science.gov (United States)

    Davis, Sarah; Martyn-St James, Marrissa; Sanderson, Jean; Stevens, John; Goka, Edward; Rawdin, Andrew; Sadler, Susi; Wong, Ruth; Campbell, Fiona; Stevenson, Matt; Strong, Mark; Selby, Peter; Gittoes, Neil

    2016-10-01

    Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax ® and Fosamax ® Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel ® and Actonel Once a Week ® , Warner Chilcott UK Ltd), ibandronic acid (Bonviva ® , Roche Products Ltd) and zoledronic acid (Aclasta ® , Novartis Pharmaceuticals UK Ltd)] for the prevention of fragility fracture and to assess their cost-effectiveness at varying levels of fracture risk. For the clinical effectiveness review, six electronic databases and two trial registries were searched: MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science and BIOSIS Previews, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform. Searches were limited by date from 2008 until September 2014. A systematic review and network meta-analysis (NMA) of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for each bisphosphonate treatment strategy and a strategy of no treatment for a simulated cohort of patients with heterogeneous characteristics. The model was populated with effectiveness evidence from the systematic review and NMA. All other parameters were estimated from published sources. A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture ® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX ® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net benefit (INB) was

  3. Paget's disease of the bone after treatment with Denosumab

    DEFF Research Database (Denmark)

    Schwarz, Peter; Rasmussen, Anne Qvist; Kvist, Torben M

    2012-01-01

    Bone affection in Paget's disease is characterized by increased bone turnover localised at one or more sites of the skeleton. Bisphosphonates are the drugs of choice when treating the increased bone turnover in Paget's disease. However, in cases of decreased kidney function only less effective tr...... treatments that are available as bisphosphonates are contraindicated in these patients. We present a case of a male patient aged 86 years with GFR of 11 mL/min and Paget's disease successfully treated by Denosumab. The bone turnover and pain decreased upon treatment....

  4. Bisphosphonates-induced osteonecrosis of the jaw: pharmacology and clinical procedures.

    Directory of Open Access Journals (Sweden)

    Candice Belchior Duplat

    2012-01-01

    Full Text Available Osteonecrosis of the jaw is a consequent condition of a variety of local and systemic factors that compromises the bone blood flow. Bisphosphonates are a class of compounds widely used for the treatment of disorders of bone metabolism, such as bone metastasis and osteoporosis. Bisphosphonates-induced osteonecrosis of the jaw is a new complication, published for the first time at 2003, and can be defined as an unexpected necrosis development on the oral cavity in patients who received bisphosphonates and were not being treated with head and neck radiotherapy. Radiographies show radiolucent zones or sclerotic bone and, in some cases, show areas with delayed or absent bone remodeling after extraction, remain the socket cavity. The treatment can be done in accordance with the condition stage, since management of 0,12% chlorhexidine and antibiotics until laser utilization, hyperbaric oxygen, surgical debridement and resection. It is important to promote more communication between physicians and dentists to guarantee dental attention during the bisphosphonate administration, establishing oral health and preventing complications, such as osteonecrosis induced by this medication.

  5. BISPHOSPHONATES-INDUCED OSTEONECROSIS OF THE JAW: PHARMACOLOGY AND CLINICAL PROCEDURES.

    Directory of Open Access Journals (Sweden)

    Candice Belchior Duplat

    2012-08-01

    Full Text Available Osteonecrosis of the jaw is a consequent condition of a variety of local and systemic factors that compromises the bone blood flow. Bisphosphonates are a class of compounds widely used for the treatment of disorders of bone metabolism, such as bone metastasis and osteoporosis. Bisphosphonates-induced osteonecrosis of the jaw is a new complication, published for the first time at 2003, and can be defined as an unexpected necrosis development on the oral cavity in patients who received bisphosphonates and were not being treated with head and neck radiotherapy. Radiographies show radiolucent zones or sclerotic bone and, in some cases, show areas with delayed or absent bone remodeling after extraction, remain the socket cavity. The treatment can be done in accordance with the condition stage, since management of 0,12% chlorhexidine and antibiotics until laser utilization, hyperbaric oxygen, surgical debridement and resection. It is important to promote more communication between physicians and dentists to guarantee dental attention during the bisphosphonate administration, establishing oral health and preventing complications, such as osteonecrosis induced by this medication.

  6. Changes in the utilization of osteoporosis drugs after the 2010 FDA bisphosphonate drug safety communication

    Directory of Open Access Journals (Sweden)

    Bander Balkhi

    2018-02-01

    Conclusions: The 2010 FDA bisphosphonates safety communication appeared to have influenced Osteoporosis utilization in Medicaid recipients. The 2010 FDA bisphosphonates safety communication was associated with a significant reduction in the utilization of bisphosphonates in the Medicaid program.

  7. Predictors of Adherence to Oral Bisphosphonate Therapy: A Register-based National Open Cohort Study

    DEFF Research Database (Denmark)

    Hansen, Carrinna; Pedersen, B D; Konradsen, Hanne

    Abstract: Aim: To assess adherence to oral bisphosphonates and determine what predicts early cessation of treatment as opposed to low refill compliance. We hypothesized that patients who stopped treatment very early would differ in demographics and comorbidity from other patients with poor...... with increasing age and in patients taking proton pump inhibitors. These findings suggest that other factors — such as patient understanding, education level and socioeconomics may be more important determinants of adherence to osteoporosis treatment....

  8. Discovery, clinical development, and therapeutic uses of bisphosphonates.

    Science.gov (United States)

    Licata, Angelo A

    2005-04-01

    To review the literature concerning the history, development, and therapeutic uses of bisphosphonates. English-language articles were identified through a search of MEDLINE (through December 2004) using the key word bisphosphonate. Reference lists of pivotal studies, reviews, and full prescribing information for the approved agents were also examined. Selected studies included those that discussed the discovery and initial applications of bisphosphonates, as well as their historical development, pharmacokinetic and pharmacodynamic properties, and current therapeutic uses. Bisphosphonates structurally resemble pyrophosphates (naturally occurring polyphosphates) and have demonstrated similar physicochemical effects to pyrophosphates. In addition, bisphosphonates reduce bone turnover and resist hydrolysis when administered orally. The information gained from initial work with etidronate generated a considerable scientific effort to design new and more effective bisphosphonates. The PCP moiety in the general bisphosphonate structure is essential for binding to hydroxyapatite and allows for a number of chemical variations by changing the 2 lateral side chains (designated R(1) and R(2)). The R(1) side chain determines binding affinity to hydroxyapatite, and the R(2) side chain determines antiresorptive potency. Accordingly, each bisphosphonate has its own characteristic profile of activity. The bisphosphonates reduce bone turnover, increase bone mass, and decrease fracture risk and therefore have a significant place in the management of skeletal disorders including osteoporosis, Paget's disease, bone metastases, osteogenesis imperfecta, and heterotopic ossification.

  9. Bifunctional Bisphosphonates for Delivering Biomolecules to Bone

    Science.gov (United States)

    2012-01-13

    formation could be analyzed after a few weeks. Scanning electron microscopy (SEM), FT-IR, X- ray Diffraction (XRD), and high-resolution X- ray computed...Bisphosphonates: Mode of action and pharmacology, Pediatrics 119 Suppl 2, S150-162. 36. Roelofs, A. J., Thompson, K., Gordon, S., and Rogers, M. J...E., Mahmood, A., Jones, A. G., Cantley, L. C., and Frangioni, J. V. (2001) In vivo near- infrared fluorescence imaging of osteoblastic activity

  10. Malignancy associated hypercalcaemia-responsiveness to IV bisphosphonates and prognosis in a palliative population.

    Science.gov (United States)

    Mallik, Shreyashee; Mallik, Girijasankar; Macabulos, Shireen Teves; Dorigo, Andrew

    2016-04-01

    Hypercalcaemia is a potentially fatal paraneoplastic complication of malignancy. It primarily manifests during the advanced phase of cancer, with the life expectancy of patients ranging from weeks to months. The mainstay of treatment is with bisphosphonates, but these are not frequently used in a palliative population due to potential conflict with goals of care. The goals of this study was to determine the reversibility of hypercalcaemia amongst patients whose underlying malignancy is not being treated and assess whether correction results in improvement in symptoms attributable to hypercalcaemia, while identifying risk factors that can predict responsiveness. We conducted a retrospective cohort study of 63 patients aged >18 years who were admitted to the St Joseph's Palliative Care Unit, Australia between 2007 and 2013, having evidence of malignancy-associated hypercalcaemia which was treated with bisphosphonates. We assessed the response to bisphosphonates based on improvement of symptoms attributable to hypercalcaemia, as well as a reduction in serum calcium. We used the Kaplan-Meier survival method and parametric survival analysis to estimate the effect of the independent variables on time till death. Thirty-six of sixty three patients achieved normocalcaemia following treatment with an intravenous bisphosphonate. Complete response was influenced by the number of instances of hypercalcaemia in the past and patient factors, such as age and albumin levels. We found that a reduction in calcium level was associated with a significantly prolonged survival, as well as symptomatic improvement, irrespective of whether normocalcaemia was achieved. Our study suggests that bisphosphonates can be recommended as a palliative measure for selected patients to improve symptoms and prolong survival.

  11. Does CPAP treatment affect the voice?

    Science.gov (United States)

    Saylam, Güleser; Şahin, Mustafa; Demiral, Dilek; Bayır, Ömer; Yüceege, Melike Bağnu; Çadallı Tatar, Emel; Korkmaz, Mehmet Hakan

    2016-12-20

    The aim of this study was to investigate alterations in voice parameters among patients using continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea syndrome. Patients with an indication for CPAP treatment without any voice problems and with normal laryngeal findings were included and voice parameters were evaluated before and 1 and 6 months after CPAP. Videolaryngostroboscopic findings, a self-rated scale (Voice Handicap Index-10, VHI-10), perceptual voice quality assessment (GRBAS: grade, roughness, breathiness, asthenia, strain), and acoustic parameters were compared. Data from 70 subjects (48 men and 22 women) with a mean age of 44.2 ± 6.0 years were evaluated. When compared with the pre-CPAP treatment period, there was a significant increase in the VHI-10 score after 1 month of treatment and in VHI- 10 and total GRBAS scores, jitter percent (P = 0.01), shimmer percent, noise-to-harmonic ratio, and voice turbulence index after 6 months of treatment. Vague negative effects on voice parameters after the first month of CPAP treatment became more evident after 6 months. We demonstrated nonsevere alterations in the voice quality of patients under CPAP treatment. Given that CPAP is a long-term treatment it is important to keep these alterations in mind.

  12. Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw.

    Science.gov (United States)

    Khan, Aliya A; Sándor, George K B; Dore, Edward; Morrison, Archibald D; Alsahli, Mazen; Amin, Faizan; Peters, Edmund; Hanley, David A; Chaudry, Sultan R; Dempster, David W; Glorieux, Francis H; Neville, Alan J; Talwar, Reena M; Clokie, Cameron M; Al Mardini, Majd; Paul, Terri; Khosla, Sundeep; Josse, Robert G; Sutherland, Susan; Lam, David K; Carmichael, Robert P; Blanas, Nick; Kendler, David; Petak, Steven; St-Marie, Louis Georges; Brown, Jacques; Evans, A Wayne; Rios, Lorena; Compston, Juliet E

    2008-07-01

    Following publication of the first reports of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates in 2003, a call for national multidisciplinary guidelines based upon a systematic review of the current evidence was made by the Canadian Association of Oral and Maxillofacial Surgeons (CAOMS) in association with national and international societies concerned with ONJ. The purpose of the guidelines is to provide recommendations regarding diagnosis, identification of at-risk patients, and prevention and management strategies, based on current evidence and consensus. These guidelines were developed for medical and dental practitioners as well as for oral pathologists and related specialists. The multidisciplinary task force established by the CAOMS reviewed all relevant areas of research relating to ONJ associated with bisphosphonate use and completed a systematic review of current literature. These evidence-based guidelines were developed utilizing a structured development methodology. A modified Delphi consensus process enabled consensus among the multidisciplinary task force members. These guidelines have since been reviewed by external experts and endorsed by national and international medical, dental, oral surgery, and oral pathology societies. RECOMMENDATIONS regarding diagnosis, prevention, and management of ONJ were made following analysis of all current data pertaining to this condition. ONJ has many etiologic factors including head and neck irradiation, trauma, periodontal disease, local malignancy, chemotherapy, and glucocorticoid therapy. High-dose intravenous bisphosphonates have been identified as a risk factor for ONJ in the oncology patient population. Low-dose bisphosphonate use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ. Prevention, staging, and treatment recommendations are based upon collective expert opinion and current data, which has been limited to case

  13. Interest of bone scintigraphy in the care of maxillary osteo-necroses induced by bis-phosphonates

    International Nuclear Information System (INIS)

    Agossa, Kevimy

    2012-01-01

    First cases of bis-phosphonates related osteonecrosis of jaws (BRONJ) have been described in 2003. Since then, this subject is one of the central concerns of several scientific communities, well beyond the oral sphere. The prevalence of BRONJ is evolving. Their etiology is not well established and the results of the treatments are inconstant. So many points that make the care to patients under bis-phosphonates really complex. Early diagnosis is essential in treatment outcome. So nuclear imaging including scintigraphy with technetium 99m seems to be helpful. It may allow detection before the onset of symptoms, facilitate localization of necrosis and it may be useful for the monitoring of such lesions after surgery. These are new applications for oncologist and dentist, in order to improve the management of patients treated by bis-phosphonates. (author) [fr

  14. Bisphosphonates for the prevention of fractures in osteogenesis imperfecta: meta-analysis of placebo-controlled trials.

    Science.gov (United States)

    Hald, Jannie D; Evangelou, Evangelos; Langdahl, Bente L; Ralston, Stuart H

    2015-05-01

    Bisphosphonates are widely used off-label in the treatment of patients with osteogenesis imperfecta (OI) with the intention of reducing the risk of fracture. Although there is strong evidence that bisphosphonates increase bone mineral density in osteogenesis imperfecta, the effects on fracture occurrence have been inconsistent. The aim of this study was to gain a better insight into the effects of bisphosphonate therapy on fracture risk in patients with osteogenesis imperfecta by conducting a meta-analysis of randomized controlled trials in which fractures were a reported endpoint. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in which the effects of bisphosphonates on fracture risk in osteogenesis imperfecta were compared with placebo and conducted a meta-analysis of these studies using standard methods. Heterogeneity was assessed using the I2 statistic. Six eligible studies were identified involving 424 subjects with 751 patient-years of follow-up. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (Relative Risk [RR] = 0.83 [95% confidence interval 0.69-1.01], p = 0.06) with no heterogeneity between studies (I2  = 0). The fracture rate was reduced by bisphosphonate treatment when all studies were considered (RR = 0.71 [0.52-0.96], p = 0.02), but with considerable heterogeneity (I2  = 36%) explained by one study where a small number of patients in the placebo group experienced a large number of fractures. When this study was excluded, the effects of bisphosphonates on fracture rate was not significant (RR = 0.79 [0.61-1.02], p = 0.07, I2  = 0%). We conclude that the effects of bisphosphonates on fracture prevention in osteogenesis imperfecta are inconclusive. Adequately powered trials with a fracture endpoint are needed to further investigate the risks and benefits of bisphosphonates in this condition. © 2014 American Society for

  15. Off-trial evaluation of bisphosphonates in patients with metastatic breast cancer

    International Nuclear Information System (INIS)

    Liauw, Winston; Segelov, Eva; Lih, Anna; Dunleavy, Ms Ruth; Links, Matthew; Ward, Robyn

    2005-01-01

    Bisphosphonate therapy has been readily accepted as standard of care for individuals with bone metastases from breast cancer. In this study we determined whether the proportion of patients experiencing a skeletal related event (SRE) in a clinical practice population was similar to that observed in phase III randomized controlled studies. A retrospective chart review was conducted of 110 patients receiving intravenous bisphosphonates for advanced breast cancer. The proportion of patients experiencing at least one SRE after 12 months of therapy was determined. SRE included vertebral or non-vertebral fracture, cord compression, surgery and/or radiotherapy to bone. The proportion of patients who had an SRE was 30% (28 individuals) and the median time to first event was greater than 350 days. Non-vertebral events and radiotherapy were the most frequent type of SRE, while cord compression and hypercalcaemia were rare (1%). Most patients in the study had bone-only disease (58.2%) and most had multiple bone lesions. In the first 12 months the mean duration of exposure to intravenous bisphosphonates was 261 days and most patients remained on treatment until just before death (median 27 days). This study suggests that the rate of clinically relevant SREs is substantially lower than the event rate observed in phase III clinical trials. We attribute this lower rate to observational bias. In the clinical trial setting it is possible that over-detection of skeletal events occurs due to the utilisation of regular skeletal survey or radionucleotide bone scan, whereas these procedures are not routine in clinical practice. Phase IV observational studies need to be conducted to determine the true benefits of bisphosphonate therapy in order to implement rationale use of bisphosphonates

  16. Bisphosphonates and Bone Fractures in Long-term Kidney Transplant Recipients

    Science.gov (United States)

    Conley, Emily; Muth, Brenda; Samaniego, Millie; Lotfi, Mary; Voss, Barbara; Armbrust, Mike; Pirsch, John; Djamali, Arjang

    2013-01-01

    Background There is little information on the role of bisphosphonates and bone mineral density (BMD) measurements for the follow-up and management of bone loss and fractures in long-term kidney transplant recipients. Methods To address this question, we retrospectively studied 554 patients who had two BMD measurements after the first year posttransplant and compared outcomes in patients treated, or not with bisphosphonates between the two BMD assessments. Kaplan-Meier survival and stepwise Cox regression analyses were performed to examine fracture-free survival rates and the risk-factors associated with fractures. Results The average time (±SE) between transplant and the first BMD was 1.2±0.05 years. The time interval between the two BMD measurements was 2.5±0.05 years. There were 239 and 315 patients in the no-bisphosphonate and bisphosphonate groups, respectively. Treatment was associated with significant preservation of bone loss at the femoral neck (HR 1.56, 95% CI 1.21-2.06, P=0.0007). However, there was no association between bone loss at the femoral neck and fractures regardless of bisphosphonate therapy. Stepwise Cox regression analyses showed that type-1 diabetes, baseline femoral neck T-score, interleukin-2 receptor blockade, and proteinuria (HR 2.02, 0.69, 0.4, 1.23 respectively, Pbone loss in long-term kidney transplant recipients. However, these data suggest a limited role for the initiation of therapy after the first posttransplant year to prevent fractures. PMID:18645484

  17. Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo.

    Science.gov (United States)

    Tower, R J; Campbell, G M; Müller, M; Glüer, C C; Tiwari, S

    2015-05-01

    The turnover of bone is a tightly regulated process between bone formation and resorption to ensure skeletal homeostasis. This process differs between bone types, with trabecular bone often associated with higher turnover than cortical bone. Analyses of bone by micro-computed tomography (micro-CT) reveal changes in structure and mineral content, but are limited in the study of metabolic activity at a single time point, while analyses of serum markers can reveal changes in bone metabolism, but cannot delineate the origin of any aberrant findings. To obtain a site-specific assessment of bone metabolic status, bisphosphonate binding kinetics were utilized. Using a fluorescently-labeled bisphosphonate, we show that early binding kinetics monitored in vivo using fluorescent molecular tomography (FMT) can monitor changes in bone metabolism in response to bone loss, stimulated by ovariectomy (OVX), or bone gain, resulting from treatment with the anabolic bone agent parathyroid hormone (PTH), and is capable of distinguishing different, metabolically distinct skeletal sites. Using time-lapse micro-CT, longitudinal bone turnover was quantified. The spine showed a significantly greater percent resorbing volume and surface in response to OVX, while mice treated with PTH showed significantly greater resorbing volume per bone surface in the spine and significantly greater forming surfaces in the knee. Correlation studies between binding kinetics and micro-CT suggest that forming surfaces, as assessed by time-lapse micro-CT, are preferentially reflected in the rate constant values while forming and resorbing bone volumes primarily affect plateau values. Additionally, we developed a blood pool correction method which now allows for quantitative multi-compartment analyses to be conducted using FMT. These results further expand our understanding of bisphosphonate binding and the use of bisphosphonate binding kinetics as a tool to monitor site-specific changes in bone metabolism in

  18. Radiographic features of bisphosphonate therapy in pediatric patients

    Energy Technology Data Exchange (ETDEWEB)

    Grissom, L.E.; Theodore Harcke, H. [Dept. of Medical Imaging, Alfred I. duPont Hospital for Children, Nemours Children' s Clinic, Wilmington, DE (United States)

    2003-04-01

    Background: Pediatric patients are being treated with bisphosphonates for low bone mineral density. Skeletal radiographic findings have been described with bisphosphonates given orally and intravenously. Objective: To determine and describe the radiographic findings of cyclic intravenous bisphosphonate therapy in the growing skeleton. Materials and methods: Retrospective review of radiographs of 32 patients with osteogenesis imperfecta or cerebral palsy treated with intravenous bisphosphonates on a quarterly schedule. Results: Principal observations were metaphyseal bands and increased bone mineral density. The bands varied in spacing according to the age of the patient, rate of growth, and the location of the metaphysis. Fractures continued to be seen in patients with osteogenesis imperfecta. Conclusion: Cyclic bisphosphonate therapy results in distinctive radiographic findings in the growing skeleton. (orig.)

  19. Radiographic features of bisphosphonate therapy in pediatric patients

    International Nuclear Information System (INIS)

    Grissom, L.E.; Theodore Harcke, H.

    2003-01-01

    Background: Pediatric patients are being treated with bisphosphonates for low bone mineral density. Skeletal radiographic findings have been described with bisphosphonates given orally and intravenously. Objective: To determine and describe the radiographic findings of cyclic intravenous bisphosphonate therapy in the growing skeleton. Materials and methods: Retrospective review of radiographs of 32 patients with osteogenesis imperfecta or cerebral palsy treated with intravenous bisphosphonates on a quarterly schedule. Results: Principal observations were metaphyseal bands and increased bone mineral density. The bands varied in spacing according to the age of the patient, rate of growth, and the location of the metaphysis. Fractures continued to be seen in patients with osteogenesis imperfecta. Conclusion: Cyclic bisphosphonate therapy results in distinctive radiographic findings in the growing skeleton. (orig.)

  20. Future of bisphosphonates and denosumab for men with advanced prostate cancer

    International Nuclear Information System (INIS)

    Iranikhah, Maryam; Stricker, Steve; Freeman, Maisha Kelly

    2014-01-01

    Prostate cancer is the most common cancer occurring in American men of all races. It is also the second leading cause of cancer death among men in the USA. Bone metastasis is a frequent occurrence in men with advanced prostate cancer, with skeletal-related events being a common complication and having negative consequences, leading to severe pain, increased health care costs, increased risk of death, and decreased quality of life for patients. Bone loss can also result from antiandrogen therapy, which can further contribute to skeletal-related events. Treatment with antiresorptive agents bisphosphonates, and the newly approved denosumab, a receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitor, has been shown to reduce the risk of skeletal-related complications and prevent treatment-induced bone loss in patients with advanced prostate cancer. This review discusses the role of antiresorptive agents bisphosphonates and RANK-L inhibitor in the current treatment of advanced prostate cancer by examining the primary literature and also focuses on the likely role of the bisphosphonates in the treatment of advanced prostate cancer in the future

  1. Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study.

    Science.gov (United States)

    Herrera, L; Leal, I; Lapi, F; Schuemie, M; Arcoraci, V; Cipriani, F; Sessa, E; Vaccheri, A; Piccinni, C; Staniscia, T; Vestri, A; Di Bari, M; Corrao, G; Zambon, A; Gregori, D; Carle, F; Sturkenboom, M; Mazzaglia, G; Trifiro, G

    2015-05-01

    Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year. Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure. We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95% confidence intervals (CI). The BP exposure was classified into current (reference point. A subgroup analysis by individual BP was then carried out. In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95% CI, 1.59-2.43). In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.

  2. Adherence With Bisphosphonates and Long-Term Risk of Hip Fractures: A Nested Case-Control Study Using Real-World Data.

    Science.gov (United States)

    Shalev, Varda; Sharman Moser, Sarah; Goldshtein, Inbal; Yu, Jingbo; Weil, Clara; Ish-Shalom, Sophia; Rouach, Vanessa; Chodick, Gabriel

    2017-09-01

    Hip fracture is a major complication of osteoporosis. Bisphosphonate medication is the mainstay of treatment for osteoporosis. However, concerns have been raised regarding the effectiveness of bisphosphonates in reducing hip fracture risk after long-term use, particularly among patients with suboptimal adherence. To examine the association between adherence with bisphosphonate therapy and long-term risk of hip fracture. Included in the present nested case-control study were osteoporotic women (n = 14 357) who initiated bisphosphonate therapy in 2000-2010 and were retrospectively followed for incident hip fracture through November 2014. Within this cohort, each case of primary hip fractures was individually matched to 3 controls without a primary hip fracture. Proportion of follow-up days covered (PDC) with bisphosphonates was calculated from bisphosphonate purchases. Adherence was categorized into the following groups: purchase of 1 or 2 months' supply (reference group), at least 3 months' supply to PDC ≤20%, PDC >20% to ≤80%, PDC >80% to ≤100%. Included in the analysis were 426 case-control groups with a mean age (SD) of 73.7 years (7.9). Compared with the reference group, PDC of 80% to 100% with bisphosphonates was associated with a significant reduction in hip fracture risk for patients with 8 to 15 years of follow-up (OR = 0.39; 95% CI = 0.18-0.87). Among patients with a follow-up of up to 3 years, OR was 0.58 (95% CI = 0.31-1.06). Adherence with bisphosphonates among osteoporotic patients is associated with lower risk of hip fracture, with no indication of diminished effectiveness with long-term use.

  3. The effect of bisphosphonates on bone mineral density in patients with ankylosing spondylitis in daily clinical practice

    NARCIS (Netherlands)

    Arends, S.; Veneberg, J.G.; Wink, F.R.; Bos, R.; Brouwer, E.; Van Der Veer, E.; Bootsma, H.; Van Roon, E.N.; Maas, F.; Spoorenberg, A.

    2016-01-01

    Background: Ankylosing spondylitis (AS) is not only characterized by excessive bone formation, but also by excessive bone loss which may lead to low bone mineral density (BMD). So far, little is known about the effect of treatment with bisphosphonates on BMD in patients with AS. Objectives: To

  4. International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates

    DEFF Research Database (Denmark)

    Diez-Perez, Adolfo; Naylor, K E; Abrahamsen, B

    2017-01-01

    Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug....

  5. Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite.

    Science.gov (United States)

    Kos, Marcin; Junka, Adam; Smutnicka, Danuta; Szymczyk, Patrycja; Gluza, Karolina; Bartoszewicz, Marzenna

    2015-07-01

    Because of the suspicion that bisphosphonates enhance bacterial colonization, this study evaluated adhesion and biofilm formation by Streptococcus mutans 25175, Staphylococcus aureus 6538, and Pseudomonas aeruginosa 14454 reference strains on hydroxyapatite coated with clodronate, pamidronate, or zoledronate. Bacterial strains were cultured on bisphosphonate-coated and noncoated hydroxyapatite discs. After incubation, nonadhered bacteria were removed by centrifugation. Biofilm formation was confirmed by scanning electron microscopy. Bacterial colonization was estimated using quantitative cultures compared by means with Kruskal-Wallis and post-hoc Student-Newman-Keuls tests. Modeling of the interactions between bisphosphonates and hydroxyapatite was performed using the Density Functional Theory method. Bacterial colonization of the hydroxyapatite discs was significantly higher for all tested strains in the presence of bisphosphonates vs. Adherence in the presence of pamidronate was higher than with other bisphosphonates. Density Functional Theory analysis showed that the protonated amine group of pamidronate, which are not present in clodronate or zoledronate, forms two additional hydrogen bonds with hydroxyapatite. Moreover, the reactive cationic amino group of pamidronate may attract bacteria by direct electrostatic interaction. Increased bacterial adhesion and biofilm formation can promote osteomyelitis, cause failure of dental implants or bisphosphonate-coated joint prostheses, and complicate bone surgery in patients on bisphosphonates. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  6. Risk factors of osteonecrosis of the jaw after tooth extraction in osteoporotic patients on oral bisphosphonates

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Ho Gui; Hwang, Jae Joon; Lee, Jeong Hee; Kim, Young Hyun; Na, Ji Yeon; Han, Sang Sun [Dept. of Oral and Maxillofacial Radiology, Yonsei University, College of Dentistry, Seoul (Korea, Republic of)

    2017-03-15

    The aim of this study was to investigate the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after tooth extraction in patients with osteoporosis on oral bisphosphonates in Korea and to evaluate local factors affecting the development of BRONJ. The clinical records of 320 patients who underwent dental extraction while receiving oral bisphosphonates were reviewed. All patients had a healing period of more than 6 months following the extractions. Each patient's clinical record was used to assess the incidence of BRONJ; if BRONJ occurred, a further radiographic investigation was carried out to obtain a more definitive diagnosis. Various local factors including age, gender, extraction site, drug type, duration of administration, and C-terminal telopeptide (CTx) level were retrieved from the patients' clinical records for evaluating their effect on the incidence of BRONJ. Among the 320 osteoporotic patients who underwent tooth extraction, 11 developed BRONJ, reflecting an incidence rate of 3.44%. Out of the local factors that may affect the incidence of BRONJ, gender, drug type, and CTx level showed no statistically significant effects, while statistically significant associations were found for age, extraction site, and duration of administration. The incidence of BRONJ increased with age, was greater in the mandible than the maxilla, and was associated with a duration of administration of more than 3 years. Tooth extraction in patients on oral bisphosphonates requires careful consideration of their age, the extraction site, and the duration of administration, and close postoperative follow-up should be carried out to facilitate effective early management.

  7. Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management

    Directory of Open Access Journals (Sweden)

    Luca Dalle Carbonare

    2010-08-01

    Full Text Available Luca Dalle Carbonare, Mirko Zanatta, Adriano Gasparetto, Maria Teresa ValentiClinic of Internal Medicine D, Department of Medicine, University of Verona, ItalyAbstract: Bisphosphonates (BPs are widely used in the treatment of postmenopausal ­osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively. The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis, and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.Keywords: bisphosphonates, osteoporosis, safety, tolerability, zoledronic acid

  8. Beneficial Effects of Concentrated Growth Factors and Resveratrol on Human Osteoblasts In Vitro Treated with Bisphosphonates

    Directory of Open Access Journals (Sweden)

    Elisa Borsani

    2018-01-01

    Full Text Available Bisphosphonates are primary pharmacological agents against osteoclast-mediated bone loss and widely used in the clinical practice for prevention and treatment of a variety of skeletal conditions, such as low bone density and osteogenesis imperfecta, and pathologies, such as osteoporosis, malignancies metastatic to bone, Paget disease of bone, multiple myeloma, and hypercalcemia of malignancy. However, long-term bisphosphonate treatment is associated with pathologic conditions including osteonecrosis of the jaw, named BRONJ, which impaired bone regeneration process. Clinical management of BRONJ is controversy and one recent approach is the use of platelet concentrates, such as Concentrated Growth Factors, alone or together with biomaterials or antioxidants molecules, such as resveratrol. The aim of the present study was to investigate the in vitro effects of Concentrated Growth Factors and/or resveratrol on the proliferation and differentiation of human osteoblasts, treated or not with bisphosphonates. Human osteoblasts were stimulated for 3 days in complete medium and for 21 days in mineralization medium. At the end of the experimental period, the in vitro effect on osteoblast proliferation and differentiation was evaluated using different techniques such as MTT, ELISA for the quantification/detection of osteoprotegerin and bone morphogenetic protein-2, immunohistochemistry for sirtuin 1 and collagen type I, and the Alizarin Red S staining for the rate of mineralization. Results obtained showed that Concentrated Growth Factors and/or resveratrol significantly increased osteoblast proliferation and differentiation and that the cotreatment with Concentrated Growth Factors and resveratrol had a protective role on osteoblasts treated with bisphosphonates. In conclusion, these data suggest that this approach could be promised in the clinical management of BRONJ.

  9. Psychosocial predictors of affect in adult patients undergoing orthodontic treatment.

    Science.gov (United States)

    Peñacoba, Cecilia; González, M José; Santos, Noelia; Romero, Martín

    2014-02-01

    In this paper we propose to study the role of psychosocial variables in affect in adult patients undergoing orthodontic treatment, considering that affect is a key variable in treatment adherence. Seventy-four patients (average age 33,24 ± 10,56) with metal multibracket-fixed orthodontic treatment were included. Patients were assessed twice. The first stage, at the beginning of treatment, included assessment of dental impact (Psychosocial Impact of Dental Aesthetics Questionnaire), trait anxiety (State-Trait Anxiety Inventory), self-esteem (Rosenberg's self-esteem scale), and self-efficacy (General Self-efficacy Scale). In the second stage, 6 months later, positive and negative affect towards treatment was assessed using the Positive and Negative Affect Scale. Dental social impact differentiates between patients with high and low negative affect, while self-efficacy differentiates between patients with high and low positive affect. Trait anxiety and self-esteem differentiate between both types of affect (positive and negative). Trait anxiety and self-esteem (when trait anxiety weight is controlled) are significant predictor variables of affective balance. These results have important practical implications, because it seems essential to adopt a bio-psychosocial model incorporating assessment methods focusing on day-to-day changes in mood and well-being.

  10. Psychosocial predictors of treatment outcome for trauma-affected refugees

    DEFF Research Database (Denmark)

    Sonne, Charlotte Kærgaard; Mortensen, Erik Lykke; Carlsson, Jessica

    2016-01-01

    outcome. Objective The objective of the study was to examine possible psychosocial predictors of treatment outcome for trauma-affected refugees. Method The participants were 195 adult refugees with posttraumatic stress disorder (PTSD) who were enrolled in a 6- to 7-month treatment programme...

  11. Osteoporosis treatment

    DEFF Research Database (Denmark)

    Pazianas, Michael; Abrahamsen, Bo

    2016-01-01

    The findings of the Women's Health Initiative study in 2002 marginalized the use of hormone replacement therapy and established bisphosphonates as the first line of treatment for osteoporosis. Denosumab could be used in selected patients. Although bisphosphonates only maintain the structure of bone...... to their benefits/harm ratio. Treatment of osteoporosis is a long process, and many patients will require treatment with more than one type of drug over their lifetime....

  12. Effect of bisphosphonates on macrophagic THP-1 cell survival in bisphosphonate-related osteonecrosis of the jaw (BRONJ).

    Science.gov (United States)

    Hoefert, Sebastian; Sade Hoefert, Claudia; Munz, Adelheid; Schmitz, Inge; Grimm, Martin; Yuan, Anna; Northoff, Hinnak; Reinert, Siegmar; Alexander, Dorothea

    2016-03-01

    Immune deficiency and bacterial infection have been suggested to play a role in the pathophysiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Zoledronate was previously found to promote THP-1 cell death. To examine this hypothesis with all commonly prescribed bisphosphonates, we tested the effect of (nitrogen-containing) ibandronate, risedronate, alendronate, pamidronate, and (non-nitrogen-containing) clodronate on macrophagic THP-1 cells. Activated THP-1 cells were exposed to .5 to 50 μM of nitrogen-containing bisphosphonates and .5 to 500 μM of clodronate. Cell adherence and survival were assessed in vitro using the xCELLigence real-time monitoring system. Results were confirmed histologically and verified with Live/Dead staining. All bisphosphonates inhibited THP-1 cell adherence and survival dose and time dependently, significant for zoledronate, alendronate, pamidronate, and clodronate in high concentrations (50 μM and 500 μM; P THP-1 cell survival compared with controls (P THP-1 cells exhibited no cytomorphologic changes at all concentrations. Commonly prescribed bisphosphonates inhibit the survival of macrophagic THP-1 cells dose-dependently without altering morphology. This may suggest a local immune dysfunction reflective of individual bisphosphonate potency leading to the pathogenesis of BRONJ. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Bisphosphonate: Brief Review of Its Development for Usage in Dentistry

    Directory of Open Access Journals (Sweden)

    Tita Ratya Utari

    2013-05-01

    Full Text Available Bisphosphonate (BP is a class of drug that prevent the loss of bone mass. It inhibits the resorption of bone by encouraging osteoclast to undergo apoptosis. Considering that oral diseases and dental procedures may lead to teeth instability whereas alveolar bone is the main tooth supporting tissue, forceful indication of this drug is for preventing and minimizing bone resorption following oral surgery and relapse movement in orthodontic treatment. Clinical use of BP in dentistry is limited by risk of osteonecrosis of the jaw (ONJ and of its systemic effects such as an increase of the bone mineral density in another bone area. Topical application with local effect would seem the choice of administration route for usage in dentistry. Until recently, no clinical usage of topical BP has been studied, however some experimental laboratory studies proved that this drug would be beneficial in a wide scope of dental treatments.DOI: 10.14693/jdi.v18i1.154

  14. Intravenous pamidronate in combination with calcium and vitamin D: highly effective in the treatment of low bone mineral density in inflammatory bowel disease

    NARCIS (Netherlands)

    Stokkers, Pieter C. F.; Deley, Maartje; van der Spek, Mirjam; Verberne, Hein J.; van Deventer, Sander J. H.; Hommes, Daniel W.

    2006-01-01

    OBJECTIVE: Decreased bone mineral density (BMD) is common in inflammatory bowel disease (IBD) and an increased risk of fractures has been reported. Guidelines state bisphosphonate treatment for IBD patients with decreased BMD, but orally available bisphosphonates have been associated with

  15. A laboratory assessment of various treatment conditions affecting ...

    African Journals Online (AJOL)

    conditions affecting the ammoniation of wheat straw by urea. 1. The effect of temperature, moisture level ... levels of 250 and 375 g/kg wheat straw and treatment periods of 0;. 1; 2; 4; 6 and 8 weeks. Dependent variables .... chloride solution containing 5 mg phenyl mercury acetate per litre. In vitro organic matter digestibility ...

  16. Factors affecting compliance to treatment among children with ...

    African Journals Online (AJOL)

    BACKGROUND:This study aimed to determine the factors affecting compliance to treatment among children with epilepsy in Enugu,Nigeria. METHODS: Children with diagnosis of epilepsy were consecutively recruited.Their 6 months retrospective and 1 month prospective data were collected;and analyzed using SPSS ...

  17. Single-tooth replacement: factors affecting different prosthetic treatment modalities

    Directory of Open Access Journals (Sweden)

    Al-Quran Firas A

    2011-12-01

    Full Text Available Abstract Background The choice between several treatment options for replacing a single missing tooth is influenced by clinical, dentist- and patient-immanent factors. This study aimed to determine the patient factors that would affect the treatment decision to replace a single missing tooth and to assess the satisfaction with several options. Method 200 volunteers involved (121 females and 79 males divided into four groups, Group A: consisted of patients with conventional fixed partial dentures or patients with resin bonded fixed partial dentures. Group B: consisted of patients who received removable partial dentures while Group C: consisted of patients who received a single implant supported crown, and a control group D: consisted of patients who received no treatment. Data were collected using a questionnaire. Results The highest percentage of males within groups (58% was within the removable prostheses category. The majority of the subjects in the study reported that the main reason for replacing a missing tooth was for esthetic and function. Most important factor affecting the choice between treatment modalities was damaging the neighboring teeth. Pain, post operative sensitivity and dental phobia were important factors in choosing the prosthesis type and affected the control group patients not to have any treatment. The highest satisfaction percentage among groups studied was recorded for dental implants then FPD groups, while the least percentage were in both the control and RPD groups, for all aspects of function, esthetic and speech efficiency. Conclusions The final choice between FPD, RPD and implant depended on several factors which affected the decision making; among these is cost and patients' awareness of the different treatment options.

  18. Psychosocial predictors of treatment outcome for trauma-affected refugees

    Directory of Open Access Journals (Sweden)

    Charlotte Sonne

    2016-05-01

    Full Text Available Background: The effects of treatment in trials with trauma-affected refugees vary considerably not only between studies but also between patients within a single study. However, we know little about why some patients benefit more from treatment, as few studies have analysed predictors of treatment outcome. Objective: The objective of the study was to examine possible psychosocial predictors of treatment outcome for trauma-affected refugees. Method: The participants were 195 adult refugees with posttraumatic stress disorder (PTSD who were enrolled in a 6- to 7-month treatment programme at the Competence Centre for Transcultural Psychiatry (CTP, Denmark. The CTP Predictor Index used in the study included 15 different possible outcome predictors concerning the patients’ past, chronicity of mental health problems, pain, treatment motivation, prerequisites for engaging in psychotherapy, and social situation. The primary outcome measure was PTSD symptoms measured on the Harvard Trauma Questionnaire (HTQ. Other outcome measures included the Hopkins Symptom Check List-25, the WHO-5 Well-being Index, Sheehan Disability Scale, Hamilton Depression and Anxiety Scales, the somatisation scale of the Symptoms Checklist-90, Global Assessment of Functioning scales, and pain rated on visual analogue scales. The relations between treatment outcomes and the total score as well as subscores of the CTP Predictor Index were analysed. Results: Overall, the total score of the CTP Predictor Index was significantly correlated to pre- to post treatment score changes on the majority of the ratings mentioned above. While employment status was the only single item significantly correlated to HTQ-score changes, a number of single items from the CTP Predictor Index correlated significantly with changes in depression and anxiety symptoms, but the size of the correlation coefficients were modest. Conclusions: The total score of the CTP Predictor Index correlated significantly

  19. Atrial fibrillation in fracture patients treated with oral bisphosphonates

    DEFF Research Database (Denmark)

    Abrahamsen, B; Eiken, P; Brixen, K

    2009-01-01

    OBJECTIVES: To determine if patients receiving oral bisphosphonates are at excess risk of atrial fibrillation (AF), stroke and myocardial infarction. DESIGN: Register-based restricted cohort study. SETTING: National Hospital Discharge Register and National Prescriptions Database (1995-2005). SUBJ......OBJECTIVES: To determine if patients receiving oral bisphosphonates are at excess risk of atrial fibrillation (AF), stroke and myocardial infarction. DESIGN: Register-based restricted cohort study. SETTING: National Hospital Discharge Register and National Prescriptions Database (1995...... to adherence. There was no increased risk of ischaemic stroke and an increased risk of myocardial infarction was not significant after adjustment for comorbidity. CONCLUSIONS: The increased occurrence of AF in fracture patients who are users of oral bisphosphonates should be attributed to targeting...

  20. Management strategy for symptomatic bisphosphonate-associated incomplete atypical femoral fractures.

    Science.gov (United States)

    Saleh, Anas; Hegde, Vishal V; Potty, Anish G; Schneider, Robert; Cornell, Charles N; Lane, Joseph M

    2012-07-01

    Long-term bisphosphonate use has often been associated with atypical femoral fractures. These fractures evolve from incomplete femoral fractures. A previous study demonstrated that the presence of a radiolucent line in an incomplete fracture can indicate a high risk of progression to complete fracture. The aim of this study is to present a management strategy for symptomatic bisphosphonate-associated incomplete atypical femoral fractures. Specific study questions include the following: (1) Is there a difference in the prognosis of these fractures based on the presence or absence of a radiolucent fracture line? (2) Can treatment with teriparatide assist in clinical/radiographic healing of these incomplete fractures? (3) Is there a characteristic biochemical profile in these patients? We retrospectively examined all femur radiographs ordered by the metabolic bone disease service at our hospital between July 1, 2006 and July 1, 2011 and identified 10 patients with a total of 14 incomplete fractures. Nine patients received bisphosphonates for a mean duration of 10 ± 5 years (range, 4-17). The mean follow-up since the time of diagnosis was 20 ± 11 months (range, 6-36 months). Five fractures did not have a radiolucent fracture line and were treated conservatively with partial weight-bearing restrictions and pharmacologic therapy. All five of these fractures healed with conservative management. Nine fractures had a radiolucent fracture line, and only two of these were treated successfully with conservative management including teriparatide. Six of the eight patients with a radiolucent line elected for surgical prophylaxis after 3 months of conservative management, whereas one patient underwent surgical prophylaxis without a trial of conservative management. Regarding the biochemical profiles, bone turnover markers for our patient cohort were in the lower quartile. Fractures without a radiolucent line appear to respond to conservative management and not

  1. Osteonecrosis de los maxilares asociada al empleo de bifosfonatos Bisphosphonate-associated osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    J.L. del Castillo Pardo de Vera

    2007-10-01

    for patients to be informed of the risk of this complication, so that they have the oppor-tunity to assess the need for dental treatment before starting therapy. Preventive measures must be taken before, during, and after treatment with bisphosphonates. Surgical treatment should be reserved for those patients who are symptomatic. Further investigation is needed to completely elucidate this complication.

  2. Is Bisphosphonate-Related Osteonecrosis of the Jaw an Infection? A Histological and Microbiological Ten-Year Summary

    Directory of Open Access Journals (Sweden)

    A. M. Hinson

    2014-01-01

    Full Text Available The role of infection in the etiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ is poorly understood. Large-scale epidemiological descriptions of the histology and microbiology of BRONJ are not found in the literature. Herein, we present a systematic review of BRONJ histology and microbiology (including demographics, immunocompromised associations, clinical signs and symptoms, disease severity, antibiotic and surgical treatments, and recovery status validating that infection should still be considered a prime component in the multifactorial disease.

  3. Bone targeting compounds for radiotherapy and imaging: *Me(III)-DOTA conjugates of bisphosphonic acid, pamidronic acid and zoledronic acid.

    Science.gov (United States)

    Meckel, M; Bergmann, R; Miederer, M; Roesch, F

    2017-01-01

    Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with macrocyclic chelators open new possibilities in bone targeted radionuclide imaging and therapy. Subsequent to positron emission tomography (PET) examinations utilizing 68 Ga-labelled analogues, endoradiotheraphy with 177 Lu-labelled macrocyclic bisphosphonates may have a great potential in the treatment of painful skeletal metastases. Based on the established pharmaceuticals pamidronate and zoledronate two new DOTA-α-OH-bisphosphonates, DOTA PAM and DOTA ZOL (MM1.MZ) were successfully synthesized. The ligands were labelled with the positron emitting nuclide 68 Ga and the β - emitting nuclide 177 Lu and compared in in vitro studies and in ex vivo biodistribution studies together with small animal PET and single photon emission computed tomography (SPECT) studies against [ 18 F]NaF and a known DOTA-α-H-bisphosphonate conjugate (BPAPD) in healthy Wistar rats. The new DOTA-bisphosphonates can be labelled in high yield of 80 to 95 % in 15 min with post-processed 68 Ga and >98 % with 177 Lu. The tracers showed very low uptake in soft tissue, a fast renal clearance and a high accumulation on bone. The best compound was [ 68 Ga]DOTA ZOL (SUV Femur  = 5.4 ± 0.6) followed by [ 18 F]NaF (SUV Femur  = 4.8 ± 0.2), [ 68 Ga]DOTA PAM (SUV Femur  = 4.5 ± 0.2) and [ 68 Ga]BPAPD (SUV Femur  = 3.2 ± 0.3). [ 177 Lu]DOTA ZOL showed a similar distribution as the diagnostic 68 Ga complex. The 68 Ga labelled compounds showed a promising pharmacokinetics, with similar uptake profile and distribution kinetics. Bone accumulation was highest for [ 68 Ga]DOTA ZOL , which makes this compound probably an interesting bone targeting agent for a therapeutic approach with 177 Lu. The therapeutic compound [ 177 Lu]DOTA ZOL showed a high target-to-background ratio. SPECT experiments showed concordance

  4. Dextromethorphan/quinidine for the treatment of pseudobulbar affect.

    Science.gov (United States)

    Patatanian, Edna; Casselman, Jessica

    2014-04-01

    To evaluate the role of dextromethorphan/quinidine (DM/Q; Nuedexta™) in the treatment of pseudobulbar affect (PBA). A literature search of MEDLINE/PubMed (January 1966-June 2013) was conducted using search terms pseudobulbar affect, pathological laughing and/or crying, emotional lability, dextromethorphan, and quinidine. English language clinical trials and case reports evaluating the safety and efficacy of DM/Q in PBA were included for review. Bibliographies of all relevant articles were reviewed for additional citations. PBA, a poorly understood disorder, is characterized by involuntary crying and/or laughing. In the past, antidepressants and antiepileptics have been used off-label with mixed results. Four clinical trials have evaluated the use of DM/Q for the treatment of PBA. Although the therapeutic outcomes with DM/Q have been positive, interpretation of the published evidence is limited by small sample size and short treatment duration. Based on the data available, DM/Q may be a viable, short-term treatment alternative for PBA. Long-term safety and efficacy data are lacking.

  5. Do bisphosphonates inhibit direct fracture healing?: A laboratory investigation using an animal model.

    Science.gov (United States)

    Savaridas, T; Wallace, R J; Salter, D M; Simpson, A H R W

    2013-09-01

    Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague-Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm(-2) (sd 7.63) vs 24.65 Nmm(-2) (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007). Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

  6. Radiographic findings of bisphosphonate-related osteonecrosis of ...

    African Journals Online (AJOL)

    Objective: The aim of this study is to assess radiographic findings of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and to evaluate the efficiency of cone-beam computed tomography (CBCT) and panoramic radiography (PR) by comparing with each other. Materials and Methods: The data of 46 patients treated ...

  7. Bisphosphonates in osteoporosis: Where do we stand in 2009? | de ...

    African Journals Online (AJOL)

    Gastrointestinal side-effects are common, but can often be avoided by taking medication in the prescribed fashion. The acute phase response to intravenous administration can be prevented by co-administration of oral paracetamol or ibuprofen. Bisphosphonates can cause bone pain. The Food and Drug Administration ...

  8. Cost-effectiveness of combined oral bisphosphonate therapy and falls prevention exercise for fracture prevention in the USA.

    Science.gov (United States)

    Mori, T; Crandall, C J; Ganz, D A

    2017-02-01

    We developed a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women without prior major osteoporotic fractures over a lifetime horizon. At ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a conventionally accepted threshold compared with bisphosphonates alone. The purpose of this study was to examine the cost-effectiveness of the combined strategy of oral bisphosphonate therapy for 5 years and falls prevention exercise for 1 year compared with either strategy in isolation. We calculated incremental cost-effectiveness ratios [ICERs] (2014 US dollars per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women with different starting ages (65, 70, 75, and 80) without prior history of hip, vertebral, or wrist fractures over a lifetime horizon from the societal perspective. At ages 65, 70, 75, and 80, the combined strategy had ICERs of $202,020, $118,460, $46,870, and $17,640 per QALY, respectively, compared with oral bisphosphonate therapy alone. The combined strategy provided better health at lower cost than falls prevention exercise alone at ages 70, 75, and 80. In deterministic sensitivity analyses, results were particularly sensitive to the change in the opportunity cost of participants' time spent exercising. In probabilistic sensitivity analyses, the probabilities of the combined strategy being cost-effective compared with the next best alternative increased with age, ranging from 35 % at age 65 to 48 % at age 80 at a willingness-to-pay of $100,000 per QALY. Among community-dwelling US white women ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a willingness-to-pay of $100,000 per QALY, compared with oral bisphosphonate therapy only. This analysis will help clinicians and policymakers make better decisions about treatment

  9. What Animal Models Have Taught Us About the Safety and Efficacy of Bisphosphonates in Chronic Kidney Disease.

    Science.gov (United States)

    Allen, Matthew R; Aref, Mohammad W

    2017-06-01

    Bisphosphonates (BPs) have long been the gold-standard anti-remodeling treatment for numerous metabolic bone diseases. Since these drugs are excreted unmetabolized through the kidney, they are not recommended for individuals with compromised kidney function due to concerns of kidney and bone toxicity. The goal of this paper is to summarize the preclinical BP work in models of kidney disease with particular focus on the bone, kidney, and vasculature. Summative data exists showing positive effects on bone and vascular calcifications with minimal evidence for bone or kidney toxicity in animal models. Preclinical data suggest it may be worthwhile to take a step back and reconsider the use of bisphosphonates to lessen skeletal/vascular complications associated with compromised kidney function.

  10. Vitamin D insufficiency reduces the protective effect of bisphosphonate on ovariectomy-induced bone loss in rats.

    Science.gov (United States)

    Mastaglia, Silvina R; Pellegrini, Gretel G; Mandalunis, Patricia M; Gonzales Chaves, Macarena M; Friedman, Silvia M; Zeni, Susana N

    2006-10-01

    The present study was carried out to obtain an experimental model of vitamin D (vit D) insufficiency and established osteopenia (experiment 1) to then investigate whether vit D status, i.e. normal or insufficient, interferes with bone mass recovery resulting from bisphosphonate therapy (experiment 2). Rats (n = 40) underwent OVX (n = 32) or a sham operation (n = 8). The first 15 days post-surgery, all groups were kept under fluorescent tube lighting and fed a diet containing 200 IU% vit D (+D). They were then assigned during an additional 45 days to receive either +D or a diet lacking vit D (-D) and kept under 12 h light/dark cycles using fluorescent or red lighting. Serum 25HOD was significantly lower in -D rats (P < 0.0001). The type of lighting did not induce differences in 25OHD, calcium (sCa), phosphorus (sP), bone alkaline phosphatase (b-AL), CTX, bone density or histology. No osteoid was observed in undecalcified bone sections. Experiment 2 (105 days): rats were fed either +D or -D according to experiment 1 and were treated with either placebo or 16 mug olpadronate (OPD)/100 g rat/week during the last 45 days. Whereas 25HOD was significantly lower (P < 0.0001) in -D/OPD than in +D/OPD rats, no significant differences in sCa, sP, b-AL or CTX were observed. OPD prevented the loss of lumbar spine (LS) and proximal tibia (PT) BMD and the decrease in bone volume (BV/TV) (P < 0.05) and in the number of trabeculae observed in untreated rats. However, +D/OPD animals presented significantly higher values of LS BMD, PT BMD and BV/TV than -D/OPD rats (P < 0.05). No osteoid was observed in undecalcified sections of bone. In summary, this is the first experimental study to provide evidence that differences in vit D status may affect the anticatabolic response to bisphosphonate treatment. However, the molecular mechanism through which vit D insufficiency reduces the effect of the aminobisphosphonate remains to be defined.

  11. Vicarious experience affects patients' treatment preferences for depression.

    Directory of Open Access Journals (Sweden)

    Seth A Berkowitz

    Full Text Available Depression is common in primary care but often under-treated. Personal experiences with depression can affect adherence to therapy, but the effect of vicarious experience is unstudied. We sought to evaluate the association between a patient's vicarious experiences with depression (those of friends or family and treatment preferences for depressive symptoms.We sampled 1054 English and/or Spanish speaking adult subjects from July through December 2008, randomly selected from the 2008 California Behavioral Risk Factor Survey System, regarding depressive symptoms and treatment preferences. We then constructed a unidimensional scale using item analysis that reflects attitudes about antidepressant pharmacotherapy. This became the dependent variable in linear regression analyses to examine the association between vicarious experiences and treatment preferences for depressive symptoms.Our sample was 68% female, 91% white, and 13% Hispanic. Age ranged from 18-94 years. Mean PHQ-9 score was 4.3; 14.5% of respondents had a PHQ-9 score >9.0, consistent with active depressive symptoms. Analyses controlling for current depression symptoms and socio-demographic factors found that in patients both with (coefficient 1.08, p = 0.03 and without (coefficient 0.77, p = 0.03 a personal history of depression, having a vicarious experience (family and friend, respectively with depression is associated with a more favorable attitude towards antidepressant medications.Patients with vicarious experiences of depression express more acceptance of pharmacotherapy. Conversely, patients lacking vicarious experiences of depression have more negative attitudes towards antidepressants. When discussing treatment with patients, clinicians should inquire about vicarious experiences of depression. This information may identify patients at greater risk for non-adherence and lead to more tailored patient-specific education about treatment.

  12. Bisphosphonate-induced zebra lines in fibrous dysplasia of bone: histo-radiographic correlation in a case of McCune-Albright syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Corsi, Alessandro; Riminucci, Mara [Sapienza University, Department of Molecular Medicine, Rome (Italy); Ippolito, Ernesto [University of Rome Tor Vergata, Department of Orthopaedic Surgery, Rome (Italy); Robey, Pamela G. [Skeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (United States); Boyde, Alan [Queen Mary University of London, Dental Physical Sciences, London (United Kingdom)

    2017-10-15

    Bisphosphonates (BPs) are currently used in the treatment of diverse bone diseases including fibrous dysplasia of bone (FD). In pediatric patients, a radiographic consequence of cyclical administration of BPs is the development of apo-, epi-, and meta-physeal sclerotic bands, otherwise known as zebra lines, which result from the temporary inhibition of osteoclastic activity at the time of drug treatment. We report here on a child with McCune-Albright syndrome (FD in addition to hyperfunctioning endocrinopathies and skin hyperpigmentation) treated with cyclical intravenous infusions of pamidronate in which conventional radiography, contact microradiography, histology, and backscattered electron image analysis demonstrated that zebra lines formed only where bone was normal, were arrested at the boundary between FD-unaffected and FD-affected bone where bone is sclerotic, and were absent within the undermineralized FD bone. Moreover, in spite of the treatment, the FD lesions continued to expand. This case report is unique because no previously published studies correlated the radiographic and the histologic features of BP-induced zebra lines in the metaphysis of an FD-affected long bone of the limbs. (orig.)

  13. Bisphosphonate-induced zebra lines in fibrous dysplasia of bone: histo-radiographic correlation in a case of McCune-Albright syndrome

    International Nuclear Information System (INIS)

    Corsi, Alessandro; Riminucci, Mara; Ippolito, Ernesto; Robey, Pamela G.; Boyde, Alan

    2017-01-01

    Bisphosphonates (BPs) are currently used in the treatment of diverse bone diseases including fibrous dysplasia of bone (FD). In pediatric patients, a radiographic consequence of cyclical administration of BPs is the development of apo-, epi-, and meta-physeal sclerotic bands, otherwise known as zebra lines, which result from the temporary inhibition of osteoclastic activity at the time of drug treatment. We report here on a child with McCune-Albright syndrome (FD in addition to hyperfunctioning endocrinopathies and skin hyperpigmentation) treated with cyclical intravenous infusions of pamidronate in which conventional radiography, contact microradiography, histology, and backscattered electron image analysis demonstrated that zebra lines formed only where bone was normal, were arrested at the boundary between FD-unaffected and FD-affected bone where bone is sclerotic, and were absent within the undermineralized FD bone. Moreover, in spite of the treatment, the FD lesions continued to expand. This case report is unique because no previously published studies correlated the radiographic and the histologic features of BP-induced zebra lines in the metaphysis of an FD-affected long bone of the limbs. (orig.)

  14. Effect of Bisphosphonates on the Levels of Rankl and Opg in Gingival Crevicular Fluid of Patients With Periodontal Disease and Post-menopausal Osteoporosis.

    Science.gov (United States)

    Verde, María E; Bermejo, Daniela; Gruppi, Adriana; Grenón, Miriam

    2015-12-01

    The Receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/Osteoprotegerine (OPG) system has been proposed as essential for osteoclast biology and identified as key part in regulating the physiology and pathology of the skeletal system. The study of the RANKL/RANK/OPG system has increased the understanding of the mechanisms involved in the bone remodeling process, especially in postmenopausal osteoporosis and periodontal disease. Bisphosphonates have become the mainstay of the treatment and prevention of post-menopausal osteoporosis. They inhibit the formation and dissolution of calcium phosphate crystals in bone and also osteoclasts, thus reducing bone turnover.Current investigations relate osteoporosis with the appearance and progression of periodontal disease. Although the etiology of both is different, the bone loss present in both shares several characteristics. Thus, therapy used for osteoporosis can be considered of value in the treatment of periodontal disease. The aim of this study was to evaluate the levels of RANKL, OPG and their relationship in gingival crevicular fluid (GCF) in patients with periodontal disease and postmenopausal osteoporosis/ osteopenia in relation to consumption of bisphosphonates. We studied 66 periodontal active sites obtained from 17 post- menopausal women patients aged between 45-70 years old with osteoporosis/osteopenia and periodontal disease. GCF samples were collected using sterile filter paper strips. To determine the concentration of RANKL and OPG, a commercial ELISA assay was used. The values of RANKL, OPG and their ratio (RANKL/ OPG) were compared with Mann-Whitney U Test. The values of RANKL, OPG and their ratio obtained in patients with osteoporosis/osteopenia and periodontal disease with or without bisphosphonates treatment showed no differences. Bisphosphonates do not alter the concentration of RANKL and OPG and their ratio in the GCF of patients with osteoporosis/ osteopenia and periodontal disease

  15. Inflammatory eye reactions in patients treated with bisphosphonates and other osteoporosis medications - cohort analysis using a national prescription database

    DEFF Research Database (Denmark)

    Pazianas, Michael; Clark, Emma M; Eiken, Pia Agnete

    2013-01-01

    Ocular inflammatory reactions have been described in patients on bisphosphonate treatment. We estimated the incidence rate of ocular inflammation at 3 and 12 months in patients treated for osteoporosis using a register based cohort linked to prescription data (hospitals and private practice.......4%) of patients on osteoporosis therapy filled one or more prescriptions for TES. TES treatment rates (per 1000 patient years) in the first year of osteoporosis treatment were 44 (95% confidence interval (CI) 42-46) for alendronate, 40 (95% CI 38-43) for etidronate, 45 (95% CI 35-57) for risedronate, 32 (95% CI...

  16. An overview of seasonal affective disorder and its treatment options.

    Science.gov (United States)

    Howland, Robert H

    2009-12-01

    Seasonal affective disorder (SAD) is defined as a history of major depressive episodes that recur regularly at a particular time of year. Depending on the diagnostic instruments and criteria available, the reported prevalence (1%-10%) varies. Neurotransmitter abnormalities have been implicated in the pathophysiology, but they do not necessarily explain the seasonal pattern or the known chronobiological abnormalities in SAD compared with nonseasonal depression. Circadian rhythm abnormalies have been hypothesized to account for these aspects of SAD, and they provide a rationale for the therapeutic use of light therapy. Family history, twin, and molecular genetics studies suggest that hereditary factors are also involved. Light therapy and antidepressant medication are effective treatment options, with limited evidence for the efficacy of psychotherapy. Some studies demonstrate that narrow-band short wavelength "blue" light, naturalistic dawn simulation, and high-density negative air ionization are effective. Patients should be informed of the benefits of diet and exercise. Light therapy should be clinically monitored in the same manner, as it is done for other antidepressant treatments.

  17. Dental complications and management of patients on bisphosphonate therapy: A review article

    OpenAIRE

    Kalra, Sandeep; Jain, Veena

    2012-01-01

    Bisphosphonates are group of drugs that inhibit bone resorption and are used to treat a range of pathologies including Paget's disease, osteoporosis, multiple myeloma and metastasis associated with breast or prostate cancer. The most common complication in patients on bisphosphonate therapy is osteonecrosis of jaw (ONJ) which can occur after any surgical dental procedure and the risk for the development of osteonecrosis of jaw is higher in patients receiving intravenous bisphosphonate therapy...

  18. Resective surgical approach shows a high performance in the management of advanced cases of bisphosphonate-related osteonecrosis of the jaws: a retrospective survey of 347 cases.

    Science.gov (United States)

    Graziani, Filippo; Vescovi, Paolo; Campisi, Giuseppina; Favia, Gianfranco; Gabriele, Mario; Gaeta, Giovanni Maria; Gennai, Stefano; Goia, Franco; Miccoli, Mario; Peluso, Franco; Scoletta, Matteo; Solazzo, Luigi; Colella, Giuseppe

    2012-11-01

    The aim of this study was to evaluate the results of the surgical treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a large cohort. A retrospective cohort multicenter study was designed. Patients were enrolled if they were diagnosed with BRONJ and received operative treatment. Data on demographic, health status, perioperative, and surgical factors were collected retrospectively. The primary outcome variable was a change in BRONJ staging (improvement, worsening, or no change). Interventions were grouped by local debridement and resective surgery. Data were collected for other variables as cofactors. Univariate analysis and logistic regressions were then performed. Of the 347 BRONJ-affected subjects, 59% showed improvement, 30% showed no change, and 11% showed worsening. Improvement was observed in 49% of cases treated with local debridement and 68% of cases treated with resective surgery. Multivariate analysis indicated that maxillary location, resective surgery, and no additional corticosteroid treatment were associated with a positive outcome. Surgical treatment of BRONJ appeared to be more effective when resective procedures were performed. Nonetheless, other factors, such as the absence of symptoms and the types of drug administration, should be taken into account before clinical decisions are made. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Malignant pilomatricoma in a dog with local and distant metastases treated with chemotherapy and bisphosphonates

    Directory of Open Access Journals (Sweden)

    Elisabetta Treggiari

    2017-07-01

    Full Text Available A ten-year-old male neutered cross breed dog presented for evaluation of a mass associated with the left scapular bone, identified as a carcinoma. The dog had a malignant pilomatricoma removed from the left lateral thigh 6 months earlier. Histopathology review of the cutaneous and scapular mass identified the same tumour type, confirming metastatic disease; additional metastases to the inguinal lymph node, liver and lungs were identified. Chemotherapy resulted in partial responses/stable disease of very short duration. Bisphosphonates were administered due to lack of a measurable response and worsening of the associated lameness. The patient ultimately developed a symptomatic vertebral metastasis and was euthanased. The dog survived 255 days since medical treatment was started and 455 days since surgical removal of the primary tumour. This case report suggests that medical treatment with the addition of analgesia may be able to palliate clinical signs and possibly extend survival in dogs with metastatic epithelial cancer.

  20. Bisphosphonates as potential adjuvants for patients with cancers of the digestive system.

    Science.gov (United States)

    Ang, Celina; Doyle, Erin; Branch, Andrea

    2016-01-21

    Best known for their anti-resorptive activity in bone, bisphosphonates (BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor (HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.

  1. Seed treatments affect functional and antinutritional properties of amaranth flours

    NARCIS (Netherlands)

    Gamel, T.H.; Linssen, J.P.H.; Mesallam, A.S.; Damir, A.A.; Shekib, L.A.

    2006-01-01

    The effects of seed treatments, including cooking, popping germination and flour air classification, on the functional properties and antinutritional factors of Amaranthus caudatus and Amaranthus cruentus seeds were studied. Thermal treatments increased the water absorption with a maximum value of

  2. Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study.

    Science.gov (United States)

    Wright, N C; Foster, P J; Mudano, A S; Melnick, J A; Lewiecki, M E; Shergy, W J; Curtis, J R; Cutter, G R; Danila, M I; Kilgore, M L; Lewis, E C; Morgan, S L; Redden, D T; Warriner, A H; Saag, K G

    2017-08-01

    The Effectiveness of Discontinuing Bisphosphonates (EDGE) study is a planned pragmatic clinical trial to guide "drug holiday" clinical decision making. This pilot study assessed work flow and feasibility of such a study. While participant recruitment and treatment adherence were suboptimal, administrative procedures were generally feasible and minimally disrupted clinic flow. The comparative effectiveness of continuing or discontinuing long-term alendronate (ALN) on fractures is unknown. A large pragmatic ALN discontinuation study has potential to answer this question. We conducted a 6-month pilot study of the planned the EDGE study among current long-term ALN users (women aged ≥65 with ≥3 years of ALN use) to determine study work flow and feasibility including evaluating the administrative aspects of trial conduct (e.g., time to contract, institutional review board (IRB) approval), assessing rates of site and participant recruitment, and evaluating post-randomization outcomes, including adherence, bisphosphonate-associated adverse events, and participant and site satisfaction. We assessed outcomes 1 and 6 months after randomization. Nine sites participated, including seven community-based medical practices and two academic medical centers. On average (SD), contract execution took 3.4 (2.3) months and IRB approval took 13.9 (4.1) days. Sites recruited 27 participants (13 to continue ALN and 14 to discontinue ALN). Over follow-up, 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported. Sites reported no issues regarding work flow, and participants were highly satisfied with the study. Administrative procedures of the EDGE study were generally feasible, with minimal disruption to clinic flow. In this convenience sample, participant recruitment was suboptimal across most practice sites. Accounting for low treatment arm adherence, a

  3. Osteomalacia: the missing link in the pathogenesis of bisphosphonate-related osteonecrosis of the jaws?

    Science.gov (United States)

    Bedogni, Alberto; Saia, Giorgia; Bettini, Giordana; Tronchet, Anita; Totola, Andrea; Bedogni, Giorgio; Tregnago, Paolo; Valenti, Maria Teresa; Bertoldo, Francesco; Ferronato, Giuseppe; Nocini, Pier Francesco; Blandamura, Stella; Dalle Carbonare, Luca

    2012-01-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-documented adverse event from treatment with nitrogen-containing bisphosphonates (NBPs). During a preliminary histomorphometric study aimed at assessing the rate of bone remodeling in the jaws of patients with surgically resected BRONJ, we found a defect of bone mineralization (unpublished data). We hypothesized that osteomalacia could be a risk factor for BRONJ in patients taking NBPs. Therefore, we looked for static and dynamic histomorphometric evidence of osteomalacia in biopsies from subjects with and without BRONJ. This case-control study used histomorphometric analysis of bone specimens of patients using NBPs (22 patients with BRONJ and 21 patients without BRONJ) who required oral surgical interventions for the treatment/prevention of osteonecrosis. Patients were given tetracycline hydrochloride according to a standardized protocol before taking bone biopsies from their jaws. Biopsies with evidence of osteomyelitis or necrosis at histology were excluded from the study. Osteomalacia was defined as a mineralization lag time >100 days, a corrected mean osteoid thickness >12.5 mm, and an osteoid volume >10%. In all, 77% of patients with BRONJ were osteomalacic compared with 5% of patients without BRONJ, according to histomorphometry. Because osteomalacia was found almost exclusively in NBP users with BRONJ, this is likely to be a generalized process in which the use of NBPs further deteriorates mechanisms of bone repair. Osteomalacia represents a new and previously unreported risk factor for disease development. This finding may contribute to a better understanding of the pathogenesis of this disease and help with the development of strategies to increase the safety of NBP administration.

  4. Pharmacoeconomics of bisphosphonates for skeletal-related event prevention in metastatic non-breast solid tumours.

    Science.gov (United States)

    Carter, John A; Joshi, Avani D; Kaura, Satyin; Botteman, Marc F

    2012-05-01

    Bisphosphonates reduce the risk of skeletal-related events (SREs; i.e. spinal cord compression, pathological fracture, radiation or surgery to the bone, and hypercalcaemia) in patients with metastatic cancer. A number of analyses have been conducted to assess the cost effectiveness of bisphosphonates in patients with bone metastases secondary to breast cancer, but few in other solid tumours. This is a review of cost-effectiveness analyses in patients with non-breast solid tumours and bone metastases. A literature search was conducted to identify cost-effectiveness analyses reporting the cost per QALY gained of bisphosphonates in patients with metastatic bone disease secondary to non-breast solid tumours. Four analyses met inclusion criteria. These included two in prostate cancer (one of which used a global perspective but expressed results in $US, and the other reported from a multiple country perspective: France, Germany, Portugal and the Netherlands). The remaining analyses were in lung cancer (in the UK, France, Germany, Portugal and the Netherlands), and renal cell carcinoma (in the UK, France and Germany). In each analysis, the cost effectiveness of zoledronic acid versus placebo was analysed. Zoledronic acid was found to be cost effective in all European countries across all three indications but not in the sole global prostate cancer analysis. Across countries and indications, assumptions regarding patient survival, drug cost and baseline utility (i.e. patient utility with metastatic disease but without an SRE) were the most robust drivers of modelled estimates. Assumptions of SRE-related costs were most often the second strongest cost driver. Further review indicated that particular attention should be paid to the inclusion or exclusion of nonsignificant survival benefits, whether health state utilities were elicited from community or patient samples or author assumptions, delineation between symptomatic and asymptomatic SREs, and the methods with which SRE

  5. Osteonecrose maxilar em pacientes portadores de doenças neoplásicas sob uso de bisfosfonatos Jaw osteonecrosis in patients with neoplastic diseases taking bisphosphonates

    Directory of Open Access Journals (Sweden)

    Paulo S. S. Santos

    2008-12-01

    Full Text Available A osteonecrose induzida por bisfosfonatos é uma complicação que pode ocorrer em pacientes acometidos por doença osteolítica tais como mieloma múltiplo, portadores de metástases tumorais em tecido ósseo, osteoporose e que fizeram uso de droga do grupo dos bisfosfonatos. A despeito dos benefícios do uso destes fármacos, a osteonecrose maxilar é uma importante complicação. Seu mecanismo de ação reduz a reabsorção óssea, o estímulo à atividade osteoblástica, a inibição do recrutamento e promoção da apoptose de osteoclastos. Até o presente momento, não há na literatura um protocolo de tratamento para a osteonecrose por bisfosfonatos. No presente trabalho, os autores fazem uma revisão da literatura e descrevem dois casos clínicos em pacientes do sexo feminino, com diferentes doenças, mieloma múltiplo e metástases ósseas por carcinoma de mama, acometidas por osteonecrose em mandíbula induzida por bisfosfonatos.The use of bisphosphonates among patients affected by osteolytic diseases, such as multiple myeloma, metastatic bone lesions and osteoporosis has been associated with the risk of osteonecrosis of the jaws. Bisphosphonates are found in areas of the bone that are undergoing inflammation or resorption. They are phagocytosed and internalized by osteoclasts. Once in the bone, these bisphosphonates cause apoptosis or cell death of the osteoclasts and as a result they may inhibit osteoclast-mediated bone resorption. Bisphosphonates seem to affect osteoclasts when it comes to both numbers and function. Although bisphosphonates are potent and valuable inhibitors of osteoclastic bone lesions, several unanswered questions exist regarding the risk of developing osteonecrosis and the management of this complication. This study reports two clinical cases of osteonecrosis of the jaws associated with the use of bisphosphonates. According to the findings, the two patients (women with different neoplasms: multiple myeloma and

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

    Science.gov (United States)

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

    2016-07-01

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

  7. Acrylic injectable and self-curing formulations for the local release of bisphosphonates in bone tissue.

    Science.gov (United States)

    Rodríguez-Lorenzo, L M; Fernández, M; Parra, J; Vázquez, B; López-Bravo, A; Román, J San

    2007-11-01

    Two bisphosphonates (BPs), namely 1-hydroxy-2-[4-aminophenyl]ethane-1,1-diphosphonic acid (APBP) and 1-hydroxy-2-[3-indolyl]ethane-1,1-diphosphonic acid (IBP), have been synthesized and incorporated to acrylic injectable and self-curing formulations. Alendronic acid monosodium trihydrated salt (ALN) containing cement was formulated as control. These systems have potential applications in low density hard tissues affected by ailments characterized by a high osteoclastic resorption, i.e. osteoporosis and osteolysis. Values of curing parameters of APBP and IBP were acceptable to obtain pastes with enough fluency to be injected through a biopsy needle into the bone cavity. Working times ranged between 8 and 15 min and maximum temperature was around 50 degrees C. Cured systems stored for a month in synthetic body fluid had compressive strengths between 90 and 96 MPa and modulus between 1.2 and 1.3 GPa, which suggest mechanical stabilization after setting and in the short time. BPs were released in PBS at an initial rate depending on the corresponding chemical structure in the order ALN > APBP > IBP to give final concentrations in PBS of 2.21, 0.44, and 0.19 mol/mL for ALN, APBP, and IBP, respectively. Cytotoxicities of bisphosphonates were evaluated, IC(50) values being in the order APBP > ALN > IBP. Absence of cytotoxicity coming from leachables of the cured systems was observed in all cases independently of the BP. An improved cell growth and proliferation for the systems loaded with APBP and IBP compared with that loaded with ALN was observed, as assessed by measuring cell adhesion and proliferation, and total DNA content.

  8. United Kingdom nationwide study of avascular necrosis of the jaws including bisphosphonate-related necrosis.

    Science.gov (United States)

    Rogers, S N; Palmer, N O A; Lowe, D; Randall, C

    2015-02-01

    We aimed to record all new patients who presented to departments of oral surgery, oral medicine, and oral and maxillofacial surgery, and to dental hospitals in the UK, with avascular necrosis of the jaws including bisphosphonate-related necrosis (BRONJ) over a 2-year period (1 June 2009-31 May 2011). They were eligible irrespective of age, cause, or coexisting conditions. Data on incidence, clinical characteristics, risk factors, and coexisting conditions were collected. A total of 383 cases were registered: 369 were described as BRONJ, 5 as avascular necrosis, and 9 were unknown. Bisphosphonates had been given orally in 207 (56%), intravenously in 125 (34%), both orally and intravenously in 27 (7%), and was unknown in 9 (2%); one had been given denosumab. The main risk factor was dental extraction, and the mandible was commonly affected. The median duration of administration until onset of BRONJ was 3 years in those treated intravenously and 4 years in those treated orally. Levels of engagement with the study varied between regions, and extrapolation from the 2 most involved (Merseyside and Northern Ireland) found around 8.2-12.8 cases/million/year, which is 508-793 patients/year across the UK. To our knowledge this is one of the first studies to estimate national rates of BRONJ. It confirms that the risk and incidence are low. With changes in trends for antiresorptive bone medication, and increasing numbers of elderly people, it would be useful to repeat the registration in the future. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  9. Influence of bone affinity on the skeletal distribution of fluorescently labeled bisphosphonates in vivo.

    Science.gov (United States)

    Roelofs, Anke J; Stewart, Charlotte A; Sun, Shuting; Błażewska, Katarzyna M; Kashemirov, Boris A; McKenna, Charles E; Russell, R Graham G; Rogers, Michael J; Lundy, Mark W; Ebetino, Frank H; Coxon, Fraser P

    2012-04-01

    Bisphosphonates are widely used antiresorptive drugs that bind to calcium. It has become evident that these drugs have differing affinities for bone mineral; however, it is unclear whether such differences affect their distribution on mineral surfaces. In this study, fluorescent conjugates of risedronate, and its lower-affinity analogues deoxy-risedronate and 3-PEHPC, were used to compare the localization of compounds with differing mineral affinities in vivo. Binding to dentine in vitro confirmed differences in mineral binding between compounds, which was influenced predominantly by the characteristics of the parent compound but also by the choice of fluorescent tag. In growing rats, all compounds preferentially bound to forming endocortical as opposed to resorbing periosteal surfaces in cortical bone, 1 day after administration. At resorbing surfaces, lower-affinity compounds showed preferential binding to resorption lacunae, whereas the highest-affinity compound showed more uniform labeling. At forming surfaces, penetration into the mineralizing osteoid was found to inversely correlate with mineral affinity. These differences in distribution at resorbing and forming surfaces were not observed at quiescent surfaces. Lower-affinity compounds also showed a relatively higher degree of labeling of osteocyte lacunar walls and labeled lacunae deeper within cortical bone, indicating increased penetration of the osteocyte canalicular network. Similar differences in mineralizing surface and osteocyte network penetration between high- and low-affinity compounds were evident 7 days after administration, with fluorescent conjugates at forming surfaces buried under a new layer of bone. Fluorescent compounds were incorporated into these areas of newly formed bone, indicating that "recycling" had occurred, albeit at very low levels. Taken together, these findings indicate that the bone mineral affinity of bisphosphonates is likely to influence their distribution within the

  10. Treatment of sleep disturbances in trauma-affected refugees

    DEFF Research Database (Denmark)

    Sandahl, Hinuga; Jennum, Poul; Baandrup, Lone

    2017-01-01

    Background: Sleep disturbances are often referred to as a hallmark and as core symptoms of post-traumatic stress disorder (PTSD). Untreated sleep disturbances can contribute to the maintenance and exacerbation of PTSD symptoms, which may diminish treatment response and constitute a risk factor...... for poor treatment outcome. Controlled trials on treatment of sleep disturbances in refugees suffering from PTSD are scarce. The present study aims to examine sleep-enhancing treatment in refugees with PTSD. We aim to assess if add-on treatment with mianserin and/or Imagery Rehearsal Therapy (IRT......) to treatment as usual (TAU) for PTSD improves sleep disturbances. We will study the relation between sleep disturbances, PTSD symptoms, psychosocial functioning and quality of life. Methods: The study is a randomised controlled superiority trial with a 2 × 2 factorial design. The study will include 230 trauma...

  11. Effect of 3-keto-1,5-bisphosphonates on obese-liver's rats.

    Science.gov (United States)

    Lahbib, Karima; Touil, Soufiane

    2016-10-01

    Obesity is associated with an oxidative stress status, which is defined by an excess of reactive oxygen species (ROS) vs. the antioxidant defense system. We report in this present work, the link between fat deposition and oxidative stress markers using a High Fat Diet-(HFD) induced rat obesity and liver-oxidative stress. We further determined the impact of chronic administration of 3-keto-1, 5-BPs 1 (a & b) (40μg/kg/8 weeks/i.p.) on liver's level. In fact, exposure of rats to HFD during 16 weeks induced body and liver weight gain and metabolic disruption with an increase on liver Alanine amino transférase (ALAT) and Aspartate aminotransférase (ASAT) concentration. HFD increased liver calcium level as well as free iron, whereas, it provoked a decrease on liver lipase activity. HFD also induced liver-oxidative stress status vocalized by an increase in reactive oxygen species (ROS) as superoxide radical (O 2 ), hydroxyl radical (OH) and Hydrogen peroxide (H 2 O 2 ). Consequently, different deleterious damages as an increase on Malon Dialdehyde MDA, Carbonyl protein PC levels with a decrease in non-protein sulfhydryls NPSH concentrations, have been detected. Interestingly, our results demonstrate a decrease in antioxidant enzymes activities such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx) and peroxidases (POD). Importantly, 3-keto-1,5-bisphosphonates treatment corrected the majority of the deleterious effects caused by HFD, but it failed to correct some liver's disruptions as mineral profile, oxidative damages (PC and NPSH levels) as well as SOD and lipase activities. Our investigation point that 3-keto-1,5-bisphosphonates could be considered as safe antioxidant agents on the hepatic level that should also find other potential biological applications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. The bisphosphonate zoledronic acid effectively targets lung cancer cells by inhibition of protein prenylation

    International Nuclear Information System (INIS)

    Xie, Fan; Li, Pengcheng; Gong, Jianhua; Zhang, Jiahong; Ma, Jingping

    2015-01-01

    Aberrant activation of oncoproteins such as members of the Ras family is common in human lung cancers. The proper function of Ras largely depends on a post-translational modification termed prenylation. Bisphosphonates have been shown to inhibit prenylation in cancer cells. In this study, we show that zoledronic acid, a third generation bisphosphonate, is effective in targeting lung cancer cells. This is achieved by the induction of apoptosis and inhibition of proliferation, through suppressing the activation of downstream Ras and EGFR signalling by zoledronic acid. The combination of zoledronic acid and paclitaxel or cisplatin (commonly used chemotherapeutic drugs for lung cancer) augmented the activity of either drug alone in in vitro lung cancer cellular system and in vivo lung xenograft mouse model. Importantly, zoledronic acid inhibits protein prenylation as shown by the increased levels of unprenylated Ras and Rap1A. In addition, the effects of zoledronic acid were reversed in the presence of geranylgeraniol and farnesol, further confirming that mechanism of zoledroinc acid's action in lung cancer cells is through prenylation inhibition. Since zoledronic acid is already available for clinic use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of lung cancer. - Highlights: • Zoledronic acid (ZA) is effectively against lung cancer cells in vitro and in vivo. • ZA acts on lung cancer cells through inhibition of protein prenylation. • ZA suppresses global downstream phosphorylation of Ras signalling. • ZA enhances the effects of chemotherapeutic drugs in lung cancer cells.

  13. The bisphosphonate zoledronic acid effectively targets lung cancer cells by inhibition of protein prenylation

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Fan [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China); Li, Pengcheng [Department of Oncology, Wuhan Union Hospital Affiliated to Huazhong University of Science and Technology, Wuhan (China); Gong, Jianhua; Zhang, Jiahong [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China); Ma, Jingping, E-mail: mjpjzhospital@hotmail.com [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China)

    2015-11-27

    Aberrant activation of oncoproteins such as members of the Ras family is common in human lung cancers. The proper function of Ras largely depends on a post-translational modification termed prenylation. Bisphosphonates have been shown to inhibit prenylation in cancer cells. In this study, we show that zoledronic acid, a third generation bisphosphonate, is effective in targeting lung cancer cells. This is achieved by the induction of apoptosis and inhibition of proliferation, through suppressing the activation of downstream Ras and EGFR signalling by zoledronic acid. The combination of zoledronic acid and paclitaxel or cisplatin (commonly used chemotherapeutic drugs for lung cancer) augmented the activity of either drug alone in in vitro lung cancer cellular system and in vivo lung xenograft mouse model. Importantly, zoledronic acid inhibits protein prenylation as shown by the increased levels of unprenylated Ras and Rap1A. In addition, the effects of zoledronic acid were reversed in the presence of geranylgeraniol and farnesol, further confirming that mechanism of zoledroinc acid's action in lung cancer cells is through prenylation inhibition. Since zoledronic acid is already available for clinic use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of lung cancer. - Highlights: • Zoledronic acid (ZA) is effectively against lung cancer cells in vitro and in vivo. • ZA acts on lung cancer cells through inhibition of protein prenylation. • ZA suppresses global downstream phosphorylation of Ras signalling. • ZA enhances the effects of chemotherapeutic drugs in lung cancer cells.

  14. Antioxidant effect of bisphosphonates and simvastatin on chondrocyte lipid peroxidation

    International Nuclear Information System (INIS)

    Dombrecht, E.J.; De Tollenaere, C.B.; Aerts, K.; Cos, P.; Schuerwegh, A.J.; Bridts, C.H.; Van Offel, J.F.; Ebo, D.G.; Stevens, W.J.; De Clerck, L.S.

    2006-01-01

    The objective of this study was to evaluate the effect of bisphosphonates (BPs) and simvastatin on chondrocyte lipid peroxidation. For this purpose, a flow cytometrical method using C11-BODIPY 581/591 was developed to detect hydroperoxide-induced lipid peroxidation in chondrocytes. Tertiary butylhydroperoxide (t-BHP) induced a time and concentration dependent increase in chondrocyte lipid peroxidation. Addition of a Fe 2+ /EDTA complex to t-BHP or hydrogen peroxide (H 2 O 2 ) clearly enhanced lipid peroxidation. The lipophilic simvastatin demonstrated a small inhibition in the chondrocyte lipid peroxidation. None of three tested BPs (clodronate, pamidronate, and risedronate) had an effect on chondrocyte lipid peroxidation induced by t-BHP. However, when Fe 2+ /EDTA complex was added to t-BHP or H 2 O 2 , BPs inhibited the lipid peroxidation process varying from 25% to 58%. This study demonstrates that BPs have antioxidant properties as iron chelators, thereby inhibiting the chondrocyte lipid peroxidation. These findings add evidence to the therapeutic potential of bisphosphonates and statins in rheumatoid arthritis

  15. Does Treatment Duration Affect Outcome After Radiotherapy for Prostate Cancer?

    International Nuclear Information System (INIS)

    D'Ambrosio, David J.; Li Tianyu; Horwitz, Eric M.; Chen, David Y.T.; Pollack, Alan; Buyyounouski, Mark K.

    2008-01-01

    Purpose: The protraction of external beam radiotherapy (RT) time is detrimental in several disease sites. In prostate cancer, the overall treatment time can be considerable, as can the potential for treatment breaks. We evaluated the effect of elapsed treatment time on outcome after RT for prostate cancer. Methods and Materials: Between April 1989 and November 2004, 1,796 men with prostate cancer were treated with RT alone. The nontreatment day ratio (NTDR) was defined as the number of nontreatment days divided by the total elapsed days of RT. This ratio was used to account for the relationship between treatment duration and total RT dose. Men were stratified into low risk (n = 789), intermediate risk (n = 798), and high risk (n = 209) using a single-factor model. Results: The 10-year freedom from biochemical failure (FFBF) rate was 68% for a NTDR <33% vs. 58% for NTDR ≥33% (p = 0.02; BF was defined as a prostate-specific antigen nadir + 2 ng/mL). In the low-risk group, the 10-year FFBF rate was 82% for NTDR <33% vs. 57% for NTDR ≥33% (p = 0.0019). The NTDR was independently predictive for FFBF (p = 0.03), in addition to T stage (p = 0.005) and initial prostate-specific antigen level (p < 0.0001) on multivariate analysis, including Gleason score and radiation dose. The NTDR was not a significant predictor of FFBF when examined in the intermediate-risk group, high-risk group, or all risk groups combined. Conclusions: A proportionally longer treatment duration was identified as an adverse factor in low-risk patients. Treatment breaks resulting in a NTDR of ≥33% (e.g., four or more breaks during a 40-fraction treatment, 5 d/wk) should be avoided

  16. Bisphosphonate drug holidays in postmenopausal osteoporosis: effect on clinical fracture risk.

    Science.gov (United States)

    Mignot, M A; Taisne, N; Legroux, I; Cortet, B; Paccou, J

    2017-12-01

    A cohort of 183 postmenopausal women, who had either discontinued or continued bisphosphonates (BPs) after first-line therapy, was used to investigate the relationships between "drug holiday" and clinical fracture. The risk of new clinical fractures was found to be 40% higher in women who had taken a BP "drug holiday." BPs are the most widely used treatment for postmenopausal osteoporosis. The optimal treatment duration, however, remains unclear. The purpose of this study was to evaluate the fracture risk in postmenopausal women with osteoporosis after discontinuing BP treatment (BP "drug holiday"). A retrospective analysis was performed at Lille University Hospital (LUH) on postmenopausal women with osteoporosis who had taken a "drug holiday" or continued treatment after first-line BP therapy (3 to 5 years). The occurrence of new clinical fractures during follow-up was also explored. Cox proportional hazards models were used to investigate the relationships between BP "drug holiday" and the occurrence of clinical fractures, while controlling for confounding factors. Survival without new clinical fractures was analyzed using Kaplan-Meier curves and log-rank tests. One hundred eighty-three women (mean age: 61.8 years; SD: 8.7) who had previously undergone BP treatment for 3 to 5 years were enrolled in our study. The patients had received alendronate (n = 81), risedronate (n = 73), zoledronic acid (n = 20), and ibandronate (n = 9). In 166 patients ("drug holiday" group: n = 31; continuous-treatment group: n = 135), follow-up ranged from 6 to 36 months (mean duration: 31.8 months; SD: 8.2). The incidences of new clinical fractures during follow-up were 16.1% (5/31) and 11.9% (16/135). After full adjustment, the hazard ratio of new clinical fractures among "drug holiday" patients was 1.40 (95% CI: 1.12-1.60; p = 0.0095). After first-line BP therapy in postmenopausal women with osteoporosis, the risk of new clinical fractures was 40% higher in

  17. Persistence with weekly and monthly bisphosphonates among postmenopausal women: analysis of a US pharmacy claims administrative database

    Directory of Open Access Journals (Sweden)

    Fan T

    2013-11-01

    follow-up was significantly higher for AOW (0.55 compared with ROW (0.52 and IOM (0.51, P < 0.05. By Kaplan–Meier analysis, the time for 50% of patients to discontinue therapy was also significantly longer with AOW (109 days compared with ROW (95 days, P < 0.05 or IOM (58 days, P < 0.05. Conclusion: In a real-world clinical setting, although persistence with all treatments was suboptimal, patients receiving prescriptions for once-weekly alendronate were more likely to be persistent than those receiving prescriptions for once-weekly risedronate or once-monthly ibandronate. Keywords: adherence, alendronate, bisphosphonates, ibandronate, osteoporosis, risedronate

  18. Palliative or curative treatment intent affects communication in radiation therapy consultations.

    NARCIS (Netherlands)

    Timmermans, L.; Maazen, R.W.M. van der; Leer, J.W.H.; Kraaimaat, F.W.

    2006-01-01

    OBJECTIVE: To assess whether communication in radiotherapy consultations is affected by palliative or curative treatment intent. SUBJECTS AND METHODS: The study involved 160 patients and 8 radiation oncologists. Eighty patients visited the radiation oncologist (RO) for palliative treatment and 80

  19. Causal explanations affect judgments of the need for psychological treatment

    Directory of Open Access Journals (Sweden)

    Nancy S. Kim

    2009-02-01

    Full Text Available Knowing what event precipitated a client's abnormal behaviors makes the client appear more normal than if the event is not known (Meehl, 1973. Does such knowledge also influence judgments of the need for psychological treatment, and if so, does it matter whether the precipitating event was inside or outside the client's control? We presented undergraduates with cases of hypothetical clients exhibiting abnormal behaviors and manipulated whether they were also told of a precipitating event explaining those behaviors. Knowing the precipitant significantly reduced perceptions of clients' need for treatment, but only when the precipitating event was outside the client's control. These findings call into question the notion that it need always be beneficial for an outside reasoner to uncover the root cause of a client's psychological problems, particularly when the root cause is still unknown to the client. The rationality of the effect and additional implications for decision-making are discussed.

  20. Obesity does not affect treatment outcomes with proton pump inhibitors.

    Science.gov (United States)

    Sharma, Prateek; Vakil, Nimish; Monyak, John T; Silberg, Debra G

    2013-09-01

    Obesity is associated with increased risk of gastroesophageal reflux disease (GERD). To evaluate the effect of obesity on symptom resolution in patients with nonerosive reflux disease (NERD) and healing rates in patients with erosive esophagitis (EE). Two post hoc analyses were performed. Analyses included pooled data from randomized, double-blind, multicenter studies of proton pump inhibitors (PPIs) in GERD patients. Analysis 1 included 704 patients with NERD receiving esomeprazole 20 mg, esomeprazole 40 mg, or placebo. Analysis 2 included 11,027 patients with EE receiving esomeprazole 40 mg, omeprazole 20 mg, or lansoprazole 30 mg. For NERD patients, no significant association between baseline heartburn severity and body mass index (BMI) was observed. In EE patients, overweight (BMI 25 to <35 kg/m) and obese (BMI ≥35 kg/m) patients had significantly higher rates of Los Angeles (LA) grade C or D EE than patients with BMI <25 kg/m (P<0.0001). Percentages of PPI-treated patients who achieved heartburn resolution or EE healing within a given LA grade were similar across BMI categories. Heartburn resolution was significantly associated with treatment (esomeprazole vs. placebo), increasing age, and for men versus women (all P≤0.0284). EE healing was significantly associated with PPI treatment (esomeprazole and lansoprazole vs. omeprazole), increasing age, race, presence of a hiatal hernia, and lower LA grade at baseline (all P≤0.0183). In patients with GERD, high BMI was associated with more severe EE at baseline. However, during PPI treatment, BMI is not a significant independent predictor of heartburn resolution or EE healing.

  1. Psychosocial predictors of treatment outcome for trauma-affected refugees

    DEFF Research Database (Denmark)

    Sonne, Charlotte; Carlsson, Jessica; Bech, Per

    2016-01-01

    situation. The primary outcome measure was PTSD symptoms measured on the Harvard Trauma Questionnaire (HTQ). Other outcome measures included the Hopkins Symptom Check List-25, the WHO-5 Well-being Index, Sheehan Disability Scale, Hamilton Depression and Anxiety Scales, the somatisation scale of the Symptoms...... Checklist-90, Global Assessment of Functioning scales, and pain rated on visual analogue scales. The relations between treatment outcomes and the total score as well as subscores of the CTP Predictor Index were analysed. Results Overall, the total score of the CTP Predictor Index was significantly...

  2. Psychosocial predictors of treatment outcome for trauma-affected refugees

    DEFF Research Database (Denmark)

    Sonne, Charlotte; Carlsson, Jessica; Bech, Per

    2016-01-01

    at the Competence Centre for Transcultural Psychiatry (CTP), Denmark. The CTP Predictor Index used in the study included 15 different possible outcome predictors concerning the patients' past, chronicity of mental health problems, pain, treatment motivation, prerequisites for engaging in psychotherapy, and social...... situation. The primary outcome measure was PTSD symptoms measured on the Harvard Trauma Questionnaire (HTQ). Other outcome measures included the Hopkins Symptom Check List-25, the WHO-5 Well-being Index, Sheehan Disability Scale, Hamilton Depression and Anxiety Scales, the somatisation scale of the Symptoms...

  3. Bisphosphonates Inhibit Pain, Bone Loss, and Inflammation in a Rat Tibia Fracture Model of Complex Regional Pain Syndrome.

    Science.gov (United States)

    Wang, Liping; Guo, Tian-Zhi; Hou, Saiyun; Wei, Tzuping; Li, Wen-Wu; Shi, Xiaoyou; Clark, J David; Kingery, Wade S

    2016-10-01

    . Alendronate (60 μg/kg/d subcutaneously [s.c.]) or zoledronate (3 mg/kg/d orally) treatment for 28 days, started at the time of fracture, completely inhibited the development of hindpaw allodynia and reduced hindpaw unweighting by 44% ± 13% and 58% ± 5%, respectively. Orally administered zoledronate (3 mg/kg/d for 21 days) treatment also completely reversed established allodynia and unweighting when started at 4 weeks postfracture. Histomorphometric and microcomputed tomography analysis demonstrated that both the 3 and 60 μg/kg/d alendronate treatments reversed trabecular bone loss (an 88% ± 25% and 188% ± 39% increase in the ipsilateral distal femur BV/TV, respectively) and blocked the increase in osteoclast numbers and erosion surface observed in bilateral distal femurs and in L5 vertebra of the fracture rats. Alendronate treatment inhibited fracture-induced increases in hindpaw inflammatory mediators, reducing postfracture levels of tumor necrosis factor by 43% ± 9%, IL-1 by 60% ± 9%, IL-6 by 56% ± 14%, and NGF by 37% ± 14%, but had no effect on increased spinal cord Fos expression, or skin and sciatic nerve immunocomplex deposition. Collectively, these results indicate that bisphosphonate therapy inhibits pain, osteoclast activation, trabecular bone loss, and cutaneous inflammation in the rat fracture model of CRPS, data supporting the hypothesis that bisphosphonate therapy can provide effective multimodal treatment for CRPS.

  4. Current options for the treatment of Paget’s disease of the bone

    Directory of Open Access Journals (Sweden)

    Daniela Merlotti

    2009-07-01

    Full Text Available Daniela Merlotti, Luigi Gennari, Giuseppe Martini, Ranuccio NutiDepartment of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, ItalyAbstract: Paget’s disease of bone (PDB is a chronic bone remodeling disorder characterized by increased osteoclast-mediated bone resorption, with subsequent compensatory increases in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This disease is most often asymptomatic but can be associated with bone pain or deformity, fractures, secondary arthritis, neurological complications, deafness, contributing to substantial morbidity and reduced quality of life. Neoplastic degeneration of pagetic bone is a relatively rare event, occurring with an incidence of less than 1%, but has a grave prognosis. Specific therapy for PDB is aimed at decreasing the abnormal bone turnover and bisphosphonates are currently considered the treatment of choice. These treatments are associated with a reduction in plasma alkaline phosphatase (ALP activity and an improvement in radiological and scintigraphic appearance and with a reduction in bone pain and bone deformity, Recently, the availability of newer, more potent nitrogen-containing bisphosphonates has improved treatment outcomes, allowing a more effective and convenient management of this debilitating disorder.Keywords: Paget’s disease of bone, bisphosphonates, aminobisphosphonates, bone remodeling

  5. he role of the affective temperament in the treatment adherence in ...

    African Journals Online (AJOL)

    Introduction: adherence to psychotropic medications is affected by factors related to the treatment, to the physician, to the environment and to the patient himself. The purpose of the present study was to investigate the influence of affective temperaments on treatment adherence. Methods: thirty six stabilized outpatients were ...

  6. Efficacy and safety of bisphosphonates in management of low bone density in inflammatory bowel disease

    Science.gov (United States)

    Yao, Liwei; Wang, Haiqing; Dong, Wenwei; Liu, Zhenxin; Mao, Haijiao

    2017-01-01

    Abstract This study aims to determine whether bisphosphonates are safe, as well as effective against bone mineral loss in inflammatory bowel disease (IBD). A computerized search of electronic databases from 1966 to 2016 was performed. Randomized controlled trials (RCTs) were included in this review to evaluate the role of bisphosphonates in the management of osteoporosis in IBD patients. A revised 7-point Jadad scale was used to evaluate the quality of each study. Overall, 13 RCTs and 923 patients met the inclusion criteria of this meta-analysis. The result showed that bisphosphonates decreased bone mass density (BMD) loss at the lumbar spine (P = 0.0002), reduced the risk of new fractures (P = 0.01), and retained the similar adverse events (P = 0.86). Bisphosphonates may provide protection and safety against bone mineral loss in IBD patients. PMID:28099343

  7. Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss: SMO-021

    Data.gov (United States)

    National Aeronautics and Space Administration — The original intent of this study was to test 10 long-duration crewmembers taking one of two bisphosphonate regimens: either 70 mg per week alendronate or a single...

  8. Pesticides from wastewater treatment plant effluents affect invertebrate communities.

    Science.gov (United States)

    Münze, Ronald; Hannemann, Christin; Orlinskiy, Polina; Gunold, Roman; Paschke, Albrecht; Foit, Kaarina; Becker, Jeremias; Kaske, Oliver; Paulsson, Elin; Peterson, Märit; Jernstedt, Henrik; Kreuger, Jenny; Schüürmann, Gerrit; Liess, Matthias

    2017-12-01

    We quantified pesticide contamination and its ecological impact up- and downstream of seven wastewater treatment plants (WWTPs) in rural and suburban areas of central Germany. During two sampling campaigns, time-weighted average pesticide concentrations (c TWA ) were obtained using Chemcatcher® passive samplers; pesticide peak concentrations were quantified with event-driven samplers. At downstream sites, receiving waters were additionally grab sampled for five selected pharmaceuticals. Ecological effects on macroinvertebrate structure and ecosystem function were assessed using the biological indicator system SPEAR pesticides (SPEcies At Risk) and leaf litter breakdown rates, respectively. WWTP effluents substantially increased insecticide and fungicide concentrations in receiving waters; in many cases, treated wastewater was the exclusive source for the neonicotinoid insecticides acetamiprid and imidacloprid in the investigated streams. During the ten weeks of the investigation, five out of the seven WWTPs increased in-stream pesticide toxicity by a factor of three. As a consequence, at downstream sites, SPEAR values and leaf litter degradation rates were reduced by 40% and 53%, respectively. The reduced leaf litter breakdown was related to changes in the macroinvertebrate communities described by SPEAR pesticides and not to altered microbial activity. Neonicotinoids showed the highest ecological relevance for the composition of invertebrate communities, occasionally exceeding the Regulatory Acceptable Concentrations (RACs). In general, considerable ecological effects of insecticides were observed above and below regulatory thresholds. Fungicides, herbicides and pharmaceuticals contributed only marginally to acute toxicity. We conclude that pesticide retention of WWTPs needs to be improved. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The Efficacy of Bisphosphonates in Preventing Aromatase Inhibitor Induced Bone Loss for Postmenopausal Women with Early Breast Cancer: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Pooleriveetil Padikkal Anagha

    2014-01-01

    Full Text Available Objectives. We aim to determine the efficacy of bisphosphonates in preventing aromatase inhibitor induced bone loss (AIBL in postmenopausal women with early breast cancer. The secondary objective was to determine the safety of bisphosphonates. Materials and Methods. We searched electronic databases in a time period of 1995 January to 2013 June. Random effects meta-analytical models were used; between study heterogeneity and publication bias was assessed. Results. A total of six eligible studies reported the BMD T score of LS at 12 months and from that 3 trials of Zoledronic acid compared the change in BMD in immediate ZOL versus delayed ZOL done with subgroups like patients with normal BMD at baseline (OR = 5.402, 95% CI = 1.329–21.959, P value = 0.018 and osteopenic BMD at baseline (OR = 4.008, 95% CI = 2.249–7.143, P value = 0.0002. Both had a significant decrease in BMD that favoured the delayed ZOL; 3 trials of risedronate and ibandronate also had a significant decrease in BMD in AIs alone group. Immediate ZOL versus delayed ZOL also showed increased risk of getting an ADR in immediate group. Conclusion. Third generation bisphosphonates has an effect on BMD of patients who are on treatment of AIs in breast cancer. Furthermore, the patients treated with immediate ZOL had a significantly high risk of musculoskeletal ADR’s than patients with delayed ZOL.

  10. 3-Keto-1,5-bisphosphonates Alleviate Serum-Oxidative Stress in the High-fat Diet Induced Obesity in Rats.

    Science.gov (United States)

    Lahbib, Karima; Aouani, Iyadh; Cavalier, Jean-François; Touil, Soufiane

    2015-09-01

    Obesity has become a leading global health problem owing to its strong association with a high incidence of oxidative stress. Many epidemiologic studies showed that an antioxidant supplementation decreases the state of oxidative stress. In the present work, a HFD-induced rat obesity and oxidative stress were used to investigate the link between fat deposition and serum-oxidative stress markers. We also studied the effect of a chronic administration of 3-keto-1,5-bisphosphonates 1 (a & b) (40 μg/kg/8 weeks/i.p.). Exposure of rats to HFD during 16 weeks induced fat deposition, weight gain and metabolic disruption characterized by an increase in cholesterol, triglyceride and glycemia levels, and a decrease in ionizable calcium and free iron concentrations. HFD also induced serum-oxidative stress status vocalized by an increase in ROS (H2 O2 ), MDA and PC levels, with a decrease in antioxidant enzyme activity (CAT, GPx, SOD). Importantly, 3-keto-1,5-bisphosphonates corrected all the deleterious effects of HFD treatment in vivo, but it failed to inhibit lipases in vitro and in vivo. These studies suggest that 3-keto-1,5-bisphosphonates 1 could be considered as safe antioxidant agents that should also find other potential biological applications. © 2014 John Wiley & Sons A/S.

  11. Affect

    NARCIS (Netherlands)

    Cetinic, M.; Diamanti, J.; Szeman, I.; Blacker, S.; Sully, J.

    2017-01-01

    This chapter historicizes four divergent but historically contemporaneous genres of affect theory – romantic, realist, speculative, and materialist. While critics credited with the turn to affect in the 1990s wrote largely in the wake of poststructuralism from the perspective of gender and queer

  12. A case of early detection of bisphosphonate-related osteonecrosis of the jaw

    OpenAIRE

    Mori, Miyu; Koide, Tetsuro; Matsui, Yuriyo; Matsuda, Toru

    2015-01-01

    Osteonecrosis of the jaws is an adverse reaction associated with the use of bisphosphonates. Although the diagnosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is based on symptomatology, it is often detected late because the patients become symptomatic only after osteonecrosis is well established. We describe a case of early oral BRONJ detected by magnetic resonance imaging (MRI) accidentally. Head MRI revealed low signal of T1-weight images in left mandibula. Patient had been...

  13. Predictors of affect following treatment decision-making for prostate cancer: conversations, cognitive processing, and coping.

    Science.gov (United States)

    Christie, Kysa M; Meyerowitz, Beth E; Giedzinska-Simons, Antoinette; Gross, Mitchell; Agus, David B

    2009-05-01

    Research suggests that cancer patients who are more involved in treatment decision-making (TDM) report better quality of life following treatment. This study examines the association and possible mechanisms between prostate cancer patient's discussions about TDM and affect following treatment. We predicted that the length of time patients spent discussing treatment options with social networks and physicians prior to treatment would predict emotional adjustment after treatment. We further predicted that cognitive processing, coping, and patient understanding of treatment options would mediate this association. Fifty-seven patients completed questionnaires prior to treatment and at 1 and 6 months following treatment completion. Findings from the present study suggest that discussing treatment options with others, prior to beginning treatment for prostate cancer, significantly contributed to improvements in affect 1 and 6 months following treatment. Residualized regression analyses indicated that discussing treatment options with patient's social networks predicted a decrease in negative affect 1 and 6 months following treatment, while discussions with physicians predicted an increase in positive affect 1 month following treatment. Patients who spent more time discussing treatment options with family and friends also reported greater pre-treatment social support and emotional expression. Mediation analyses indicated that these coping strategies facilitated cognitive processing (as measured by a decrease in intrusive thoughts) and that cognitive processing predicted improvement in affect. Greater time spent talking with family and friends about treatment options may provide opportunities for patients to cope with their cancer diagnosis and facilitate cognitive processing, which may improve patient distress over time. Copyright (c) 2008 John Wiley & Sons Ltd.

  14. Characteristics of psychiatric patients for whom financial considerations affect optimal treatment provision.

    Science.gov (United States)

    West, Joyce C; Pingitore, David; Zarin, Deborah A

    2002-12-01

    This study assessed characteristics of psychiatric patients for whom financial considerations affected the provision of "optimal" treatment. Psychiatrists reported that for 33.8 percent of 1,228 patients from a national sample, financial considerations such as managed care limitations, the patient's personal finances, and limitations inherent in the public care system adversely affected the provision of optimal treatment. Patients were more likely to have their treatment adversely affected by financial considerations if they were more severely ill, had more than one behavioral health disorder or a psychosocial problem, or were receiving treatment under managed care arrangements. Patients for whom financial considerations affect the provision of optimal treatment represent a population for whom access to treatment may be particularly important.

  15. Viewpoints of dentists on the use of bisphosphonates in rheumatology patients.

    Science.gov (United States)

    Daron, Coline; Deschaumes, Christophe; Soubrier, Martin; Mathieu, Sylvain

    2018-02-15

    Alhough typically prescribed in oncology, bisphosphonates (BPs) are also employed in rheumatology, particularly for the treatment of osteoporosis, sometimes resulting in complications, such as osteonecrosis of the jaw. Because of different opinions between rheumatologists and dentists on BP use, this study aimed to assess the views of dentists regarding administration of BPs in rheumatology. A questionnaire was sent to 880 dentists from the Auvergne region of France to determine their views on BP treatment. We obtained 382 (43.4%) responses and analysed 376 (58.7% men). In total, 156 (41.5%) of the responders analysed had attended an in-service training course (ISTC) on the topic. A total of 237 (63.0%) systematically inquired as to whether their patients were undergoing BP treatment; this proportion was higher among those who had been practicing for fewer than 10 years (P ISTC (62.6% vs. 50.7%; P < 0.03). Dentists feel ill at ease providing dental surgery to patients receiving BPs. Closer collaboration and better information-sharing between rheumatologists and dentists is necessary to facilitate the administration of BPs in rheumatology. © 2018 FDI World Dental Federation.

  16. Atypical Femur Fractures in Patients Treated with Bisphosphonates: Identification, Management, and Prevention

    Directory of Open Access Journals (Sweden)

    Judith Sarah Bubbear

    2016-10-01

    Full Text Available Osteoporosis is a common condition with significant health care costs. First-line therapy is with bisphosphonates, which have proven anti-fracture efficacy. Around 10 years after the introduction of bisphosphonates reports began to be published of atypical femoral fractures (AFFs that may be associated with this therapy. These fractures are associated with significant morbidity although lower mortality than the more common osteoporotic neck-of-femur fractures. A case definition has been described to allow identification of this class of fracture. Further work has established a high relative risk of AFFs in patients treated with bisphosphonates, but a low absolute risk in comparison to that of osteoporotic fractures. Proposed pathological mechanisms include low bone turnover states leading to stress/insufficiency fractures. Clinicians should be aware of the risk of AFFs and in particular the high rate of prodromal thigh/groin pain that warrants investigation in a patient receiving a bisphosphonate. If an incomplete fracture is diagnosed then bisphosphonate therapy needs to be stopped and prophylactic surgery may be considered. Due to these rare side effects patients on bisphosphonates require regular review, and this is particularly advised after 5 years of oral or 3 years of intravenous therapy.

  17. Long-term radiographic follow-up of bisphosphonate-associated atypical femur fractures

    Energy Technology Data Exchange (ETDEWEB)

    Favinger, Jennifer L. [University of Washington, Department of Radiology, 1959 N.E. Pacific Street, Box 357115, Seattle, WA (United States); Hippe, Daniel [University of Washington, Department of Radiology, Seattle, WA (United States); Ha, Alice S. [University of Washington, Department of Radiology, 4245 Roosevelt Way NE, Box 354755, Seattle, WA (United States)

    2016-05-15

    To evaluate the appearance of bisphosphonate-related femur insufficiency fractures on long-term follow-up radiographic studies and to describe the rate of fracture line obscuration and cortical beak healing over time. In this retrospective study, bisphosphonate-related femur fracture radiographs were reviewed by two radiologists for the presence of a fracture line, callus, and the characteristic cortical beak. Kaplan-Meier curves were used to analyze the time to first indication of healing. Femurs were also subdivided into those who underwent early versus late surgical fixation and those who underwent early versus late discontinuation of bisphosphonate. Clinical data including pain level and medication history were collected. Forty-seven femurs with a bisphosphonate-related femur fracture were identified in 28 women. Eighty-five percent took a bisphosphonate for greater than 5 years and 59 % for greater than 10 years. The median time to beak healing was 265 weeks and the median time to fracture line healing was 56 weeks in the 31 femurs with a baseline fracture. No statistically significant difference was identified between surgical fixation and conservative management. Bisphosphonate-related fractures demonstrate notably prolonged healing time on long-term follow-up. (orig.)

  18. Major new developments affecting treatment and prognosis in hypertension.

    Science.gov (United States)

    Gubner, R S

    1990-01-01

    Joint studies of the ALIMDA and Society of Actuaries, notably those of 1935, 1959 and 1979, established that there is a progressive rise in cardiovascular mortality with successive increments in blood pressure. This has provided the basis of underwriting. The converse is not true, or at least has not been true until very recently. Drugs that effectively reduce blood pressure have been available for several decades, but reduction and maintenance of blood pressure is still accomplished in only a minority of hypertensives. Long-term trials employing a combination of drugs, i.e., diuretics, vasodilators and reserpine and subsequently beta-blockers, almost without fail have not shown that treatment with these agents significantly reduces heart disease mortality and sudden death. This has been attributed, perhaps without basis, to an unfavorable countering effect of increased lipid levels, aggravating this risk factor, and other undesirable metabolic effect of diuretics, such as hypokalemia and depletion of body magnesium, increasing the propensity to ventricular arrhythmias, hyperglycemia, worsening diabetes, and hyperuricemia. A survey of 674 persons with hypertension seen personally during the period 1985-89, who were under the care of approximately that many physicians, reveals striking changes in drug prescription and use during this brief period that portend a major change in the outlook of hypertension. Two classes of drugs have increased rapidly in popularity: these are the angiotensin-converting enzyme inhibitors (ACE inhibitors) and the calcium blockers. Both classes of drugs effectively lower blood pressure and have minimal side effects with good compliance. They act not only to reduce peripheral vascular resistance, but also locally in the heart muscle to directly cause left ventricular hypertrophy to regress, an effect of great consequence. The drugs used in former trials such as the vasodilators and diuretics have no effect on left ventricular hypertrophy

  19. Pamidronate treatment for osteogenesis imperfecta in black South Africans.

    Science.gov (United States)

    Henderson, B D; Isaac, N; Mabele, O; Khiba, S; Nkayi, A; Mokoena, T

    2016-05-25

    Osteogenesis imperfecta is a heritable disorder of bone connective tissue. Type III has a high incidence in the black pop-ulation of South Africa. Affected people experience numerous fractures, bone pain and progressive disability. Until the introduction of bisphosphonates to reduce fracture incidence, treatment revolved around orthopaedic and supportive care. Objective. To assess the subjective attitude of patients towards pamidronate treatment. Thirty black patients with osteogenesis imperfecta type III treated at Universitas Hospital were approached and 26 were included in this study. Patients or their parents were interviewed using a standardised researcher-administered questionnaire, either in person or by telephone. Most patients reported a reduction in symptoms, a feeling of increased wellbeing, increased strength and rated the pamidronate treatment highly. The intravenous route of administration and the side-effects experienced were bearable. Overall all patients would recommend this treatment to other affected persons. This is first study to look at bisphosphonate treatment for osteogenesis imperfecta type III in black South Africans. The treatment is well tolerated and highly rated by the patients. Reported improvements and side-effects are similar to those reported in other populations. Using this form of treatment in this population is supported by these findings.

  20. Complexes of DOTA-bisphosphonate conjugates: probes for determination of adsorption capacity and affinity constants of hydroxyapatite.

    Science.gov (United States)

    Vitha, Tomas; Kubícek, Vojtech; Hermann, Petr; Kolar, Zvonimir I; Wolterbeek, Hubert Th; Peters, Joop A; Lukes, Ivan

    2008-03-04

    The adsorption on hydroxyapatite of three conjugates of a bisphosphonate and a macrocycle having C1, C2, and C3 spacers and their terbium complexes was studied by the radiotracer method using 160Tb as the label. The radiotracer-containing complex of the conjugate with the C3 spacer was used as a probe for the determination of the adsorption parameters of other bisphosphonates that lack a DOTA unit. A physicochemical model describing the competitive adsorption was successfully applied in the fitting of the obtained data. The maximum adsorption capacity of bisphosphonates containing bulky substituents is determined mainly by their size. For bisphosphonates having no DOTA moiety, the maximum adsorption capacity is determined by the electrostatic repulsion between negatively charged bisphosphonate groups. Compounds with a hydroxy or amino group attached to the alpha-carbon atom show higher affinities. Macrocyclic compounds containing a short spacer between the different bisphosphonic acid groups and the macrocyclic unit exhibit high affinities, indicating a synergic effect of the bisphosphonic and the macrocyclic groups during adsorption. The competition method described uses a well-characterized complex and allows a simple evaluation of the adsorption behavior of bisphosphonates. The application of the macrocycle-bisphosphonate conjugates allows easy radiolabeling via complexation of a suitable metal isotope.

  1. The “CROMa” Project: A Care Pathway for Clinical Management of Patients with Bisphosphonate Exposure

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    Mauro Capocci

    2014-01-01

    Full Text Available Aim. To describe 7 years of activity of “CROMa” (Coordination of Research on Osteonecrosis of the Jaws project of “Sapienza” University of Rome. Materials and Methods. A preventive and therapeutic care pathway was created for patients with bisphosphonates (BPs exposure. Demographic, social, behavioural, pharmacological, and clinical variables were registered in a dedicated database. Results. In the project, 502 patients, 403 females and 99 males, were observed. Bone pathologies were 79% osteometabolic diseases (OMD and 21% metastatic cancer (CA. Females were 90% in OMD group and 41% in CA. BP administration was 54% oral, 31% IV, and 11% IM; 89% of BPs were amino-BP and 11% non-amino-BP. Consistently with bone pathology (OMD/CA, alendronate appears to be prevalent for OMD (40% relative, while zoledronate was indicated in 92% of CA patients. Out of 502 cases collected, 28 BRONJ were detected: 17 of them were related to IV BP treatment. Preventive oral assessment was required for 50% of CA patients and by 4% of OMD patients. Conclusions. The proposed care pathway protocols for BP exposed patients appeared to be useful to meet treatment and preventive needs, in both oncological and osteometabolic diseases patients. Patients’ and physicians’ prevention awareness can be the starting point of a multilevel prevention system.

  2. Comparison of factors affecting orthodontic treatment motivation of Taiwanese and Thai patients in two hospitals

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    Wariya Laothong

    2017-12-01

    Full Text Available Background/purpose: Many factors, including economic, psychosocial statuses and ethnicity, affect patients' decision to seek orthodontic treatment. The present study compared orthodontic patients' motivation, attitude and the factors affecting this motivation in Taiwanese and Thai patients. We investigated the association between the aforementioned variables and patient characteristics. Materials and methods: We enrolled 250 Thai and 250 Taiwanese patients (age ≥ 20 years from Sunprasitthiprasong and Taipei Medical University Hospitals, respectively, by using self-administered questionnaires. Demographic characteristics were analyzed using Pearson's chi-square test, patients' motivation, attitude and the factors affecting this motivation were analyzed using the sample t-test. The association among the variables was investigated by multiple regression analysis. Results: In both hospitals, the main motivation for seeking orthodontic treatment was esthetic concerns; the patients believed that treatment could make them more beautiful. Taiwanese and Thai patients rejected treatment because of high treatment costs and long treatment periods, respectively. A significant association was observed between household income and Thai patients' motivation (p < 0.05. Sex was significantly associated with Thai patients' attitude (p < 0.05. Age, sex, active treatment duration, and marital status were associated with Taiwanese attitude toward treatment (p < 0.05. In addition, age, household income, and information resources were significantly associated with the factors affecting Taiwanese patients' motivation (p < 0.05. Conclusion: Ethnicity influenced patients' motivation. Economic status was the main factor affecting Thai patients, whereas many factors affected Taiwanese patients' decision to seek orthodontic treatment. However, esthetic concerns were a crucial motivation for both groups. Keywords: factors affecting

  3. Calixarene methylene bisphosphonic acids as promising effectors of biochemical processes

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    S. V. Komisarenko

    2013-12-01

    Full Text Available This interdisciplinary study, performed with participation of research workers of Palladin Institute of Biochemistry and Institute of Organic Chemist­ry of NAS of Ukraine, is devoted to analysis of biochemical effects of some calixarene methylene bisphosphonic acids (cyclic phenol oligomers on two well-known biological phenomenons – Mg2+-dependent ATP hydrolysis (myosin subfragment-1 of myometrium smooth muscle was used as an example and fibrin polymerization. Calix[4]arene С-97 (calix[4]arene methylene bisphosphonic acids is a macrocyclic substance, which contains intramolecular highly ordered lipophilic cavity formed by four aromatic rings, one of which is functionalized at the upper rim with methylene bisphosphonic group. At concentration of 100 µM, this substance was shown to effectively inhibit ATPase activity of pig myometrium myosin subfragment-1 (inhibition coefficient І0.5 = 83 ± 7 µM. At the same time, this calix[4]arene causes significant (vs. control increase of myosin subfragment-1 hydrodynamic diameter, which may indicate formation of an intermolecular complex between calixa­rene and myosin head. Computer simulation methods (docking and molecular dynamics with addition of grid technologies enabled to elucidate the grounds of intermolecular interactions between calix[4]arene С-97 and myometrium myosin subfragment-1, that involve hydrophobic, electrostatic and π-π-stacking interactions, some of which are close to the ATPase active centre. In view of the ability of calixarenes to penetrate into the cell and their low toxicity, the results obtained may be used as a basis for further development of a new generation of supramolecular effectors (starting from the above mentioned substances, in particular calix[4]arene С-97 for regulation of smooth muscle contractile activity at the level of ATP dependent actin-myosin interaction. Calix[4]arenes bearing two or four methylenebisphosphonic acid groups at the macrocyclic upper

  4. Factors affecting ionizing radiation phytosanitary treatments, and implications for research and generic treatments

    Science.gov (United States)

    Phytosanitary irradiation (PI) treatments are promising measures to overcome quarantine barriers to trade and are currently used in several countries. Although PI has advantages compared with other treatments, one disadvantage bedevils research approval/application: organisms may remain alive afte...

  5. Bisphosphonates, atherosclerosis and vascular calcification: update and systematic review of clinical studies

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    Caffarelli C

    2017-10-01

    Full Text Available Carla Caffarelli,1 Andrea Montagnani,2 Ranuccio Nuti,1 Stefano Gonnelli1 1Department of Medicine, Surgery and Neuroscience, University of Siena, Italy; 2Division of Internal Medicine, General Hospital Misericordia, Grosseto, Italy Background: Epidemiologic and clinical data have suggested the existence of a biologic linkage between the bone system and the vascular system. Bisphosphonates (BPs are effective inhibitors of bone resorption and are currently considered the drugs of choice for the prevention and treatment of osteoporosis and related fractures. Data from several publications have suggested that BPs may also be effective in reducing the atherosclerotic process and vascular calcification, but the results of these studies are contrasting. This review aimed to allow a better understanding of the relationships between BPs and atherosclerosis in humans.Materials and methods: Electronic databases of Pubmed-Medline, Cochrane Library and SCOPUS from inception to June 30, 2016 were searched. The full texts of the articles potentially eligible were carefully assessed and reviewed. Finally, 20 studies were found to be eligible and were included in the systematic review. All included studies were published between 2000 and 2014.Results: In several studies, etidronate limited the progression of aortic and coronary calcification in hemodialysis patients, whereas the nitrogen-containing-BPs given orally did not significantly reduce vascular calcifications in patients with chronic kidney disease, kidney trasplant or in those with osteoporosis. Nitrogen-containing-BPs present favorable effects both on vessel wall thickness and on arterial elasticity due to both a reduction in serum lipids and the interaction of BPs with the bone tissue, with the consequent release of bone turnover markers and cytokines into the bloodstream.Conclusion: To sum up, the BPs seem to have the potential of influencing atherosclerosis and calcium homeostasis at the level of

  6. Bilateral Incomplete Atypical Femoral Fracture due to Long-Term Bisphosphonate Use: A Case Report

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    Sibel Başaran

    2017-08-01

    Full Text Available Although the overall safety profile of bisphosphonates (BP is favorable, adverse effects associated with long-term use have came up during recent years. In this report, a case of bilateral incomplete atypical femoral fracture (AFF due to prolonged BP use was presented. A 69-year-old patient, who has been in surgical menopause for 20 years and was started on BP following vertebral fracture almost 10 years ago, was admitted with thigh pain, which was increased two weeks ago. On physical examination, she had antalgic gait, increased thoracic kyphosis and tenderness to percussion over the thoracolumbar region. Lateral cortical thickness in the subtrochanteric region of both femurs and cortical radiolucency on the left femur were observed on plain radiography. Loss of height in L3 and L4 vertebrae was detected on vertebral radiography. Serum 25-hydroxy vitamin D [25(OHD], parathyroid hormone, alkaline phosphatase and calcium levels, along with osteoporosis markers were all within the normal ranges. As the patient was diagnosed with AFF, BP therapy was terminated and vitamin D-calcium supplementation was continued. Since she did not have severe pain, conservative management (limited weight bearing, using a walking stick was recommended for 3 months. Teriparatide therapy was started and she was discharged with recommendations. AFF, which is a rare disorder, should be kept in mind in patients on long-term BP treatment who are admitted with thigh pain and, necessary interventions should be tailored before the occurrence of complete fracture.

  7. The guardians' perspective on paediatric cancer treatment in Malawi and factors affecting adherence

    NARCIS (Netherlands)

    Israëls, Trijn; Chirambo, Chawanangwa; Caron, Huib; de Kraker, Jan; Molyneux, Elizabeth; Reis, Ria

    2008-01-01

    Abandonment of paediatric cancer treatment is a common problem in developing countries. Little is known about the guardians' perspective on cancer treatment in these countries, especially the factors that affect adherence. Following a pilot study enquiring into the possible causes of abandonment, a

  8. The guardians' perspective on paediatric cancer treatment in Malawi and factors affecting adherence

    NARCIS (Netherlands)

    Israels, T.; Chirambo, C.; Caron, H.; de Kraker, J.; Molyneux, E.; Reis, R.

    2008-01-01

    Background: Abandonment of paediatric cancer treatment is a common problem in developing countries. Little is known about the guardians' perspective on cancer treatment in these countries, especially the factors that affect adherence. Methods: Following a pilot study enquiring into the possible

  9. Nonverbal interpersonal attunement and extravert personality predict outcome of light treatment in seasonal affective disorder

    NARCIS (Netherlands)

    Geerts, E; Kouwert, E; Bouhuys, N; Meesters, Y; Jansen, J

    We investigated whether personality and nonverbal interpersonal processes can predict the subsequent response to light treatment in seasonal affective disorder (SAD) patients. In 60 SAD patients, Neuroticism and Extraversion were assessed prior to light treatment (4 days with 30 min of 10.000 lux).

  10. Delayed healing of lower limb fractures with bisphosphonate therapy.

    Science.gov (United States)

    Yue, B; Ng, A; Tang, H; Joseph, S; Richardson, M

    2015-07-01

    Bisphosphonate therapy (BT) is used commonly in the management of osteoporosis. A systematic review was conducted investigating delayed union of lower limb, long bone fractures in patients on BT. We specifically assessed whether BT increases the risk of delayed union or non-union in lower limb, long bone fractures. A literature search was conducted in the PubMed and Embase™ on 4 November 2014. Articles that investigated lower limb fractures, history of BT and fracture union were included in the review. A total of 9,809 papers were retrieved and 14 were deemed suitable for this review. The mean time to union in patients on BT was 8.5 months. A longer time to union was reported in a study investigating BT users versus controls (6.5 vs 4.8 months respectively). The mean rate of delayed or non-union for BT associated atypical fractures was 20% per fracture. Specifically in one study, delayed union was more common in the cohort with more than three years of BT (67%) than in the group with less than three years of BT (26%). Surgical fixation was associated with improved outcomes compared with non-operative management. BT has been described to be associated with multiple adverse outcomes related to atypical fractures. Current evidence recommends operative management for this patient group. Further investigation is required to evaluate the exact effects of BT on lower limb fractures, in particular typical femoral fractures.

  11. Bone mineral density changes of lumbar spine and femur in osteoporotic patient treated with bisphosphonates and beta-hydroxy-beta-methylbutyrate (HMB): Case report.

    Science.gov (United States)

    Tatara, Marcin R; Krupski, Witold; Majer-Dziedzic, Barbara

    2017-10-01

    Currently available approaches to osteoporosis treatment include application of antiresorptive and anabolic agents influencing bone tissue metabolism. The aim of the study was to present bone mineral density (BMD) changes of lumbar spine in osteoporotic patient treated with bisphosphonates such as ibandronic acid and pamidronic acid, and beta-hydroxy-beta-methylbutyrate (HMB). BMD and volumetric BMD (vBMD) of lumbar spine were measured during the 6 year observation period with the use of dual-energy X-ray absorptiometry (DEXA) and quantitative computed tomography (QCT). The described case report of osteoporotic patient with family history of severe osteoporosis has shown site-dependent response of bone tissue to antiosteoporotic treatment with bisphosphonates. Twenty-five-month treatment with ibandronic acid improved proximal femur BMD with relatively poor effects on lumbar spine BMD. Over 15-month therapy with pamidronic acid was effective to improve lumbar spine BMD, while in the proximal femur the treatment was not effective. A total of 61-week long oral administration with calcium salt of HMB improved vBMD of lumbar spine in the trabecular and cortical bone compartments when monitored by QCT. Positive effects of nearly 2.5 year HMB treatment on BMD of lumbar spine and femur in the patient were also confirmed using DEXA method. The results obtained indicate that HMB may be applied for the effective treatment of osteoporosis in humans. Further studies on wider human population are recommended to evaluate mechanisms influencing bone tissue metabolism by HMB.

  12. Osteonecrosis de los maxilares asociada al uso de bifosfonatos: revisión de ocho casos Bisphosphonate-related jaw osteonecrosis: Review of eight cases

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    J. Joshi Otero

    2011-03-01

    cancer. Material and methods: A prospective study was made of patients from Hospital Virgen Macarena who presented bisphosphonate associated jaw lesions from 2006 to the present. The patient variables examined were: sex, age, bisphosphonate treatment, onset of osteonecrosis and its relation to dental treatment, treatment, and outcome. Results: Eight patients with osteonecrosis of the jaw secondary to treatment with intravenous or oral bisphosphonates for oncologic or osteoporotic pathology were treated according to their clinical and radiological findings with antibiotics and curettage and/or excision of sequestered bone, as needed. Results with a minimum follow up of 15 months are reported. Conclusions: The increased incidence of maxillary osteomyelitis in patients treated with bisphosphonates and the difficulty of treatment make it necessary to establish standard therapeutic guidelines. In the authors' experience, conservative treatment based on antibiotic therapy and/or curettage of the area under local anesthesia can adequately control and resolve the process in some patients with stage II BRJO.

  13. Differences in In Vitro Disintegration Time among Canadian Brand and Generic Bisphosphonates.

    Science.gov (United States)

    Olszynski, Wojciech P; Adachi, Jonathan D; Davison, K Shawn

    2014-01-01

    The objective of this study was to compare the disintegration times among Canadian-marketed brand (alendronate 70 mg, alendronate 70 mg plus vitamin D 5600 IU, and risedronate 35 mg) and generic (Novo-alendronate 70 mg and Apo-alendronate 70 mg) once-weekly dosed bisphosphonates. All disintegration tests were performed with a Vanderkamp Disintegration Tester. Disintegration was deemed to have occurred when no residue of the tablet, except fragments of insoluble coating or capsule shell, was visible. Eighteen to 20 samples were tested for each bisphosphonate group. The mean (±standard deviation) disintegration times were significantly (P disintegration of the generic tablets as compared to the brand bisphosphonates may have concerning safety and effectiveness implications for patients administering these therapies.

  14. 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.

  15. Antiparasitic Activity of Sulfur- and Fluorine-Containing Bisphosphonates against Trypanosomatids and Apicomplexan Parasites

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    Tamila Galaka

    2017-01-01

    Full Text Available Based on crystallographic data of the complexes 2-alkyl(aminoethyl-1,1-bisphosphonates–Trypanosoma cruzi farnesyl diphosphate synthase, some linear 1,1-bisphosphonic acids and other closely related derivatives were designed, synthesized and biologically evaluated against T. cruzi, the responsible agent of Chagas disease and against Toxoplasma gondii, the etiologic agent of toxoplasmosis and also towards the target enzymes farnesyl pyrophosphate synthase of T. cruzi (TcFPPS and T gondii (TgFPPS, respectively. The isoprenoid-containing 1,1-bisphosphonates exhibited modest antiparasitic activity, whereas the linear α-fluoro-2-alkyl(aminoethyl-1,1-bisphosphonates were unexpectedly devoid of antiparasitic activity. In spite of not presenting efficient antiparasitic activity, these data turned out to be very important to establish a structural activity relationship.

  16. Superparamagnetic Bifunctional Bisphosphonates Nanoparticles: A Potential MRI Contrast Agent for Osteoporosis Therapy and Diagnostic

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    Y. Lalatonne

    2010-01-01

    Full Text Available A bone targeting nanosystem is reported here which combined magnetic contrast agent for Magnetic Resonance Imaging (MRI and a therapeutic agent (bisphosphonates into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic γFe2O3 nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI contrast agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI T2∗ contrast agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63 show that γFe2O3@di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.

  17. Retrospective analysis of factors affecting the efficacy of surgical treatment of the scar.

    Science.gov (United States)

    Yang, Z; Shi, X; Zhang, Y; Wang, S; Lei, Z; Liu, X; Fan, D

    2014-04-01

    The scar is a major problem in the medical profession. Its timely treatment is very important for the better outcome of the scar treatment and for the improvement of the life quality of the patients. The aim of this study was retrospectively analyzed the epidemiological characteristics affecting the efficacy of the scar surgical treatment of the people in the western part of China. Total 414 scar cases were retrospectively analyzed to clarify the epidemiological characteristics and the factors affecting the scar surgical treatment efficacy. The factors included were sex, age, area distribution, treatment seasons, injury sites, injury causes, and the time from scarring to the surgical treatment. All scar cases were surgically treated with the repairing technology including skin graft, flap and soft tissue dilation. There were 206 males and 208 females with the average age 20.53±12.9 years (age range 1-68 years). The patient proportions in the age groups of 0-20, 21-40 and >40 years were 61.4% (254 cases), 29.2% (121 cases), and 9.4% (39 cases) respectively. The patient's attendance rate reached the highest during the summer and winter. Most patients were from the rural areas with an increasing tendency each year. The burn scars were the most abundant and the injury sites were mostly the head and face. Univariate analysis showed that the time from scarring to the surgical treatment and the injury sites were significantly influenced the scar surgical treatment efficacy. Logistic regression analysis demonstrated that the injured sites of the head and face significantly influenced the scar surgical treatment efficacy. With the development of economy in China, more scar patients especially younger and children visit doctors predominantely from the rural areas. Usually, they get their scars in the exposed area of their bodies (head and face) which seriously affect the patient's appearance and function. Factors influencing the scar surgical treatment efficacy has

  18. Osteonecrosis de los maxilares inducida por bifosfonatos: prevención y actitud terapéutica Bisphosphonate induced osteonecrosis of the jaws: prevention and therapeutic approach

    Directory of Open Access Journals (Sweden)

    F.J. Barrientos Lezcano

    2007-10-01

    Full Text Available Introducción. La osteonecrosis maxilar o mandibular por bifosfonatos puede convertirse en una epidemia debido a la amplia difusión de estos fármacos entre la población. Material y método. Se muestra un protocolo para la prevención y el tratamiento de esta enfermedad. Se presentan tres casos de osteonecrosis maxilar/mandibular. Resultados. Es difícil lograr una curación completa; sin embargo es posible detener la progresión de la enfermedad. Discusión. La cirugía y la suspensión de la terapia con bifosfonatos han demostrado poca utilidad. Los antibióticos y los enjuagues con clorhexidina son las únicas medidas eficaces. Conclusiones. Es imprescindible una planificación adecuada previa a la instauración del tratamiento con bifosfonatos. Ante una osteonecrosis establecida, la actitud debe ser conservadora.Introduction. Bisphosphonate-induced osteonecrosis of the jaws might reach epidemic proportions due to the widespread use of this therapy. Materials and methods. A protocol for prevention and treatment of this pathology is shown. Three clinical cases are reported. Results. It is quite difficult to reach restitutio ad integrum, but stopping the progress of the disease is possible. Discussion. Surgical treatment and cessation of bisphosphonate therapy are of no use. Only antibiotics and oral chlorhexidine have shown some benefits. Conclusions. An accurate preventive attitude is mandatory prior to undergoing bisphosphonate therapy. If osteonecrosis of the jaws is present, management should be conservative.

  19. Oral cutaneous sinus tract, vertical root fracture, and bisphosphonate-related osteonecrosis: a case report.

    Science.gov (United States)

    Wigler, Ronald; Steinbock, Nelly; Berg, Tal

    2013-08-01

    Oral cutaneous sinus tracts (OCSTs) of dental origin are often initially misdiagnosed and inappropriately treated. Accurate diagnosis is especially important in cases of bisphosphonate (BP) therapy because extraction may lead to a risk of osteonecrosis. A case report of misdiagnosis related to a tooth with a vertical root fracture in an oncologic patient treated with BPs is reported here. In 2011, a 75-year-old woman was examined at the oral medicine clinic because of pain and swelling of the left submandibular area. The patient's medical history included oral and intravenous BP therapy because she was diagnosed with metastatic breast cancer and left maxillary stage 1 antiresorptive agent-induced osteonecrosis of the jaw. The lower left odontogenic region showed no signs or symptoms, and no apical pathosis was observed on imaging. Although antibiotics were applied, clinical symptoms worsened and an OCST appeared. Intravenous antibiotic treatment was pursued. Biopsy and direct smear from fistula were not conclusive. A diagnosis of a nonexposed variant of stage 3 antiresorptive agent-induced osteonecrosis of the jaw was established. Symptoms resolved after 2 weeks of antibiotic treatment and reappeared a month later. Endodontic examination revealed that the origin of the OCST was tooth no. 18 caused by a vertical root fracture, and the tooth was extracted. The patient was scheduled for routine checkups because of the fact that osteonecrosis may occur in intravenous BP-treated patients. Early correct diagnosis can prevent unnecessary and ineffective antibiotic therapy and surgical intervention, which is not recommended in intravenous BP cases. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  20. Evolution of plasma homovanillic acid (HVA) levels during treatment in schizo-affective disorder.

    Science.gov (United States)

    Galinowski, A; Castelnau, C; Spreux-Varoquaux, O; Bourdel, M C; Olie, J P; Loo, H; Poirier, M F

    2000-11-01

    1. Plasma Homovanillic Acid (p HVA) levels were measured by HPLC (high performance liquid chromatography) in 5 schizo-affective depressed patients receiving a standardized treatment. (lithium, chlorpromazine and clomipramine) during 4 weeks. 2. Four patients were pretreated, without a washout period. 3. No significant difference was observed between patients and normal controls at baseline. Under treatment, pHVA levels increased (ppHVA levels that increase with clinical improvement, unlike schizophrenic patients whose increased pHVA concentrations decline with neuroleptic treatment.

  1. Water flow induced transport of Pseudomonas fluorescens cells through soil columns as affected by inoculant treatment

    NARCIS (Netherlands)

    Hekman, W.E.; Heijnen, C.E.; Trevors, J.T.; Elsas, van J.D.

    1994-01-01

    Water flow induced transport of Pseudomonas fluorescens cells through soil columns was measured as affected by the inoculant treatment. Bacterial cells were introduced into the topsoil of columns, either encapsulated in alginate beads of different types or mixed with bentonite clay in concentrations

  2. Study on lithium migration for electrochemical treatment of concrete affected by alkali-silica reaction

    NARCIS (Netherlands)

    Souza, L.M.S.; Copuroglu, O.; Polder, R.B.

    2014-01-01

    Alkali-silica reaction (ASR) is one of the major durability problems in concrete and affects many structures worldwide. Nevertheless, currently, there are no definite treatments to stop it once it has star ted. Lithium is known to have beneficial effects on ASR. Indeed, the use of lithium-based

  3. Barriers affecting adherence to radiation treatment and strategies to overcome those barriers.

    Science.gov (United States)

    Rangarajan, R; Jayaraman, K

    2017-01-01

    The WHO defines adherence as the extent to which a patient's behavior coincides with recommendations from a health-care provider. Nonadherence to cancer treatment has a major impact on the therapeutic outcome. To assess the prevalence of nonadherence to radiation regimen and to analyze the factors that affect adherence to cancer treatment. Patients receiving radiation treatment in our hospital were screened for adherence to appointment keeping and to the prescribed radiation regimen and patients who had unplanned treatment breaks during treatment were interviewed. Between January and July 2013, we identified 61 patients who had unplanned breaks during treatment. We analyzed the social, emotional, educational, economic, and therapeutic barriers that led to nonadherence. Of the 61 patients who had unplanned breaks during treatment, 54% were males and 46% were females. Fifty-seven percent of patients had head and neck cancers and 25% had gynecological cancers. Seventy-one percent of patients were planned for concurrent chemoradiation. The number of days of unplanned treatment breaks ranged from 3 to 27 days. Social and therapeutic barriers were found to be the most common factor that led to nonadherence in these patients. Identification of barriers that lead to nonadherence, designing strategies to overcome such barriers and effective communication becomes imperative to ensure uninterrupted treatment. Based on the above analysis, we have designed several strategies to improve adherence to treatment among our patients.

  4. [Affective bipolar disorder and ambivalence in relation to the drug treatment: analyzing the causal conditions].

    Science.gov (United States)

    Miasso, Adriana Inocenti; Cassiani, Silvia Helena De Bortoli; Pedrão, Luiz Jorge

    2011-04-01

    This study was performed with an aim to understand the conditions causing the ambivalence of the person with bipolar affective disorder (BAD) regarding following the drug treatment. A qualitative approach was used, with the Grounded Theory as the methodology framework, under the light of Symbolic Interactionism. Participants were 14 individuals with BAD who were being followed at an Outpatient Clinic for Mood Disorders of a university hospital and 14 relatives they indicated. Interviews and observation were the main forms of obtaining data. Results revealed three categories that described the referred causal conditions: experiencing the crises of the disorder; needing the drug; and living with the side effects of the drugs. It was found that there is a need to change the attitude of some health professionals from blaming the patient for interrupting the treatment to one of listening, valuing their symbolic and affective universe as well as the partnership in the treatment.

  5. EFFECTIVENESS OF NITROGEN-CONTAINING BISPHOSPHONATES IN THE REGULATION OF MINERAL METABOLISM DISTURBANCES ASSOCIATED WITH ALIMENTARY OSTEOPOROSIS IN RATS

    Directory of Open Access Journals (Sweden)

    Komisarenko S. V.

    2015-08-01

    Full Text Available The aim of the study was to investigate the effectiveness of nitrogen-containing bisphosphonates synthesized as promising substances for correction of mineral metabolism in osteoporosis. The study was carried out on a model of alimentary osteoporosis that was characterized by hypocalcaemia, hypophosphatemia, decreased 25-Hydroxyvitamin D3 content in blood serum and severe bone tissue demineralization (reduced ash content and mineral components. It was found that synthesized novel nitrogen bisphosphonates (pyrazole-containing analogues, like reference drugs — metylene bisphosphonate (disodium salt of metylene bisphosphonic acid and alendronate (4-amino-1-hidroxybutyliden bisphosphonate, inhibit with the different efficiency demineralization of the bone tissue and increase the mineral metabolism in rats with alimentary (nutritional osteoporosis that was assessed by the marker parameters of bone formation. In particular, drug administration (bisphosphonates І-12, І-40, І-42 resulted in elevation of calcium and phosphate levels and decreased the total activity of alkaline phosphatase and its isoenzymes in blood serum. The ash content and the levels of calcium and phosphorus in the ash of tibia and femur bones were shown to be markedly elevated. Bisphosphonate І-12 has shown more profound antiresorbtive activity and ability to correct mineral metabolism in alimentary osteoporosis, including such of reference drugs. It was found a significant decrease of 25-Hydroxyvitamin D3 content in the serum that is considered as a profound vitamin D3 deficiency associated with nutritional osteoporosis. As it was not compensated by bisphosphonates, we suggest that further investigations should be directed to the combined use of both: bisphosphonates as inhibitors of osteoclast activity that diminish bone resorption and vitamin D3 as a key regulator of bone remodeling process and osteosynthesis activator.

  6. Cost-effectiveness of increasing bisphosphonates adherence for osteoporosis in community pharmacies

    NARCIS (Netherlands)

    Van Boven, J.F.M.; Oosterhof, P.; Hiddink, E.G.; Stuurman-Bieze, A.G.G.; Postma, M.J.; Vegter, S.

    2011-01-01

    OBJECTIVES: Increasing real-life adherence to bisphosphonates therapy is important to achieve the clinical benefits of reducing fractures reported in randomized clinical trials (RCTs). The aim of this pharmacoeconomic analysis was to determine the cost-effectiveness of a pharmaceutical care

  7. Kinetic release studies of nitrogen-containing bisphosphonate fromgum acacia crosslinked hydrogels

    CSIR Research Space (South Africa)

    Aderibigbe, BA

    2014-11-01

    Full Text Available on the release mechanism of nitrogen-containing bisphosphonate (BP) wasstudied at pH 1.2 and 7.4. The hydrogels exhibited high swelling ratios at pH 7.4 and low swelling ratiosat pH 1.2. The release study was performed using UV–Visible spectroscopy via complex...

  8. Implant failure caused by non-union of bisphosphonate-associated subtrochanteric femur fracture.

    LENUS (Irish Health Repository)

    O'Neill, Barry James

    2014-04-03

    Bisphosphonate use has been identified as a contributory factor in atypical subtrochanteric fracture of the femur. These fractures are commonly treated with an intramedullary device. We present a case of implant failure of an intrameduallary device caused by non-union of an atypical subtrochanteric fracture.

  9. Comparison of nonexposed and exposed bisphosphonate-induced osteonecrosis of the jaws

    DEFF Research Database (Denmark)

    Schiodt, Morten; Reibel, Jesper; Oturai, Peter

    2014-01-01

    Nonexposed osteonecrosis of the jaws (NE-ONJ) does not fit into the current definition of osteonecrosis, which requires exposed bone. A modification of the classification of bisphosphonate-induced osteonecrosis of the jaws (ONJ) is proposed. This study aimed to test proposed criteria for NE...

  10. Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study

    Directory of Open Access Journals (Sweden)

    GVA Stadelmann

    2008-07-01

    Full Text Available It is a clinical challenge to obtain a sufficient orthopaedic implant fixation in weak osteoporotic bone. When the primary implant fixation is poor, micromotions occur at the bone-implant interface, activating osteoclasts, which leads to implant loosening. Bisphosphonate can be used to prevent the osteoclastic response, but when administered systemically its bioavailability is low and the time it takes for the drug to reach the periprosthetic bone may be a limiting factor. Recent data has shown that delivering bisphosphonate locally from the implant surface could be an interesting solution. Local bisphosphonate delivery increased periprosthetic bone density, which leads to a stronger implant fixation, as demonstrated in rats by the increased implant pullout force. The aim of the present study was to verify the positive effect on periprosthetic bone remodelling of local bisphosphonate delivery in an osteoporotic sheep model. Four implants coated with zoledronate and two control implants were inserted in the femoral condyle of ovariectomized sheep for 4 weeks. The bone at the implant surface was 50% higher in the zoledronate-group compared to control group. This effect was significant up to a distance of 400µm from the implant surface. The presented results are similar to what was observed in the osteoporotic rat model, which suggest that the concept of releasing zoledronate locally from the implant to increase the implant fixation is not species specific. The results of this trial study support the claim that local zoledronate could increase the fixation of an implant in weak bone.

  11. Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer.

    Science.gov (United States)

    Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

    2016-07-01

    Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

  12. Live imaging of osteoclast inhibition by bisphosphonates in a medaka osteoporosis model

    Directory of Open Access Journals (Sweden)

    Tingsheng Yu

    2016-02-01

    Full Text Available Osteoclasts are bone-resorbing cells derived from the monocyte/macrophage lineage. Excess osteoclast activity leads to reduced bone mineral density, a hallmark of diseases such as osteoporosis. Processes that regulate osteoclast activity are therefore targeted in current osteoporosis therapies. To identify and characterize drugs for treatment of bone diseases, suitable in vivo models are needed to complement cell-culture assays. We have previously reported transgenic medaka lines expressing the osteoclast-inducing factor receptor activator of nuclear factor κB ligand (Rankl under control of a heat shock-inducible promoter. Forced Rankl expression resulted in ectopic osteoclast formation, as visualized by live imaging in fluorescent reporter lines. This led to increased bone resorption and a dramatic reduction of mineralized matrix similar to the situation in humans with osteoporosis. In an attempt to establish the medaka as an in vivo model for osteoporosis drug screening, we treated Rankl-expressing larvae with etidronate and alendronate, two bisphosphonates commonly used in human osteoporosis therapy. Using live imaging, we observed an efficient, dose-dependent inhibition of osteoclast activity, which resulted in the maintenance of bone integrity despite an excess of osteoclast formation. Strikingly, we also found that bone recovery was efficiently promoted after inhibition of osteoclast activity and that osteoblast distribution was altered, suggesting effects on osteoblast-osteoclast coupling. Our data show that transgenic medaka lines are suitable in vivo models for the characterization of antiresorptive or bone-anabolic compounds by live imaging and for screening of novel osteoporosis drugs.

  13. Anticancer Activity of Polyoxometalate-Bisphosphonate Complexes: Synthesis, Characterization, In Vitro and In Vivo Results.

    Science.gov (United States)

    Boulmier, Amandine; Feng, Xinxin; Oms, Olivier; Mialane, Pierre; Rivière, Eric; Shin, Christopher J; Yao, Jiaqi; Kubo, Tadahiko; Furuta, Taisuke; Oldfield, Eric; Dolbecq, Anne

    2017-07-03

    We synthesized a series of polyoxometalate-bisphosphonate complexes containing Mo VI O 6 octahedra, zoledronate, or an N-alkyl (n-C 6 or n-C 8 ) zoledronate analogue, and in two cases, Mn as a heterometal. Mo 6 L 2 (L = Zol, ZolC 6 , ZolC 8 ) and Mo 4 L 2 Mn (L = Zol, ZolC 8 ) were characterized by using single-crystal X-ray crystallography and/or IR spectroscopy, elemental and energy dispersive X-ray analysis and 31 P NMR. We found promising activity against human nonsmall cell lung cancer (NCI-H460) cells with IC 50 values for growth inhibition of ∼5 μM per bisphosphonate ligand. The effects of bisphosphonate complexation on IC 50 decreased with increasing bisphosphonate chain length: C 0 ≈ 6.1×, C 6 ≈ 3.4×, and C 8 ≈ 1.1×. We then determined the activity of one of the most potent compounds in the series, Mo 4 Zol 2 Mn(III), against SK-ES-1 sarcoma cells in a mouse xenograft system finding a ∼5× decrease in tumor volume than found with the parent compound zoledronate at the same compound dosing (5 μg/mouse). Overall, the results are of interest since we show for the first time that heteropolyoxomolybdate-bisphosphonate hybrids kill tumor cells in vitro and significantly decrease tumor growth, in vivo, opening up new possibilities for targeting both Ras as well as epidermal growth factor receptor driven cancers.

  14. Er:YAG Laser Dental Treatment of Patients Affected by Epidermolysis Bullosa

    Directory of Open Access Journals (Sweden)

    Angela Galeotti

    2014-01-01

    Full Text Available Aim. The purpose of this study was to evaluate the efficacy of Er:YAG laser used for treating hard dental tissue in patients with epidermolysis bullosa (EB. Methods. We report two cases of EB in which an Er:YAG laser was used for conservative treatments. In the first case, the Er:YAG laser (2,940 μm, 265 mJ, 25 Hz was used to treat caries on a deciduous maxillary canine in an 8-year-old male patient affected by dystrophic EB. In the second case, we treated a 26-year-old female patient, affected by junctional EB, with generalized enamel hypoplasia, and an Er:YAG laser (2,940 μm, 265 mJ, 25 Hz was used to remove the damaged enamel on maxillary incisors. Results. The use of the Er:YAG laser, with the appropriate energy, was effective in the selective removal of carious tissue and enamel hypoplasia. During dental treatment with the Er:YAG laser, patients required only a few interruptions due to the absence of pain, vibration, and noise. Conclusions. Laser treatment of hard dental tissues is a valuable choice for patients affected by EB since it is less invasive compared to conventional treatment, resulting in improved patient compliance.

  15. Comparison of orally administered bisphosphonate drugs in reducing the risk of hip fracture in older adults: a population-based cohort study.

    Science.gov (United States)

    Cadarette, Suzanne M; Lévesque, Linda; Mamdani, Muhammad; Perreault, Sylvie; Juurlink, David N; Paterson, J Michael; Carney, Greg; Gunraj, Nadia; Hawker, Gillian A; Tadrous, Mina; Wong, Lindsay; Dormuth, Colin R

    2013-09-01

    Orally administered bisphosphonate drugs (i.e., alendronate, etidronate, risedronate) can reduce the risk of vertebral fracture. However, only alendronate and risedronate have proven efficacy in reducing the risk of hip fracture. We sought to examine the comparative effectiveness of orally administered bisphosphonate drugs in reducing hip fractures among older adults. We identified new users of orally administered bisphosphonate drugs in British Columbia and Ontario between 2001 and 2008. We used province- and sex-specific propensity score-matching strategies to maximize comparability between exposure groups. We used Cox proportional hazards models to compare time-to-hip fracture within 1 year of treatment between exposures by sex in each province. Our secondary analyses considered hip fracture rates within 2 and 3 years' follow-up. We used alendronate as the reference for all comparisons and pooled provincial estimates using random effects variance-weighted meta-analysis. We identified 321 755 patients who were eligible for inclusion in the study. We found little difference in fracture rates between men (pooled hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.74-1.14) or women (pooled HR 1.15, 95% CI 0.73-1.56) taking risedronate and those taking alendronate. We similarly identified little difference in fracture rates between women taking etidronate and those taking alendronate (pooled HR 1.00, 95% CI 0.82-1.18). However, we identified lower rates of hip fracture among men taking etidronate relative to alendronate (pooled HR 0.77, 95% CI 0.60-0.94). Results extended to 2 and 3 years' follow-up were similar. However, with 3 years' follow-up, rates of hip fracture were lower among women in British Columbia who had taken alendronate. We identified little overall difference between alendronate and risedronate in reducing the risk of hip fracture in men or women. Our finding that etidronate is associated with lower fracture risk among men is likely due to

  16. Factors affecting treatment adherence to atomoxetine in ADHD: a systematic review

    Directory of Open Access Journals (Sweden)

    Treuer T

    2016-05-01

    Full Text Available Tamás Treuer,1 Luis Méndez,2 William Montgomery,3 Shenghu Wu4 1Neuroscience Research, Eli Lilly and Company, Budapest, Hungary; 2Eli Lilly de Mexico, Mexico City, Mexico; 3Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 4Neuroscience Research, Eli Lilly Asia, Inc, Shanghai, People’s Republic of China Abstract: The purpose of this paper was to systematically review the literature related to research about the factors affecting treatment adherence and discontinuation of atomoxetine in pediatric, adolescent, and adult patients with attention-deficit/hyperactivity disorder (ADHD. Medline was systematically searched using the following prespecified terms: “ADHD”, “Adherence”, “Compliance”, “Discontinuation”, and “Atomoxetine”. We identified 31 articles that met all inclusion and exclusion criteria. The findings from this review indicate that persistence and adherence to atomoxetine treatment were generally high. Factors found to influence adherence and nonadherence to atomoxetine treatment in ADHD in this review include age, sex, the definition of response used, length of treatment, initial dose of treatment, comorbid conditions, and reimbursement. Tolerability was cited as an important reason for treatment discontinuation. More research is needed to understand those factors that can help to identify patients at risk for poor adherence and interventions that could improve treatment adherence early in the stage of this illness to secure a better long-term prognosis. Keywords: atomoxetine, treatment discontinuation, adherence, compliance, ADHD medication, relapse

  17. Relationship between drug dreams, affect, and craving during treatment for substance dependence.

    Science.gov (United States)

    Tanguay, Hélène; Zadra, Antonio; Good, Daniel; Leri, Francesco

    2015-01-01

    To explore the relationship between occurrence of drug dreams (DDs) and daytime negative affect and drug craving during the course of a 5-week treatment program for substance dependence. Using the dream journal methodology, 86 participants reported occurrence of dreams, dream content, and ratings of affect and drug craving. The relationships between the experience of DD, dream content ("active" vs "passive"), and affect and craving were analyzed using mixed model methods. The experience of DD was associated with higher levels of negative affect (P < 0.001) and craving (P < 0.001). The occurrence of DD did not decrease significantly over the 5 weeks of the study. Cocaine/crack users reported a higher occurrence of DD (P < 0.05) than the other drug groups (opiates and alcohol), and DD involving "active" drug use was associated with larger (P < 0.05) changes in negative affect. These results are consistent with the hypothesis that DD can act as drug-conditioned stimuli to elevate negative affect and craving in abstaining individuals. Although correlational, such findings support the implementation of psychological and pharmacological interventions aimed at minimizing the impact of DD on individuals in recovery from drug addiction.

  18. Chronic lithium treatment with or without haloperidol fails to affect the morphology of the rat cerebellum

    DEFF Research Database (Denmark)

    Licht, R W; Larsen, Jytte Overgaard; Smith, D

    2003-01-01

    We used unbiased stereological principles to determine whether long-term administration of lithium at human therapeutic levels, with or without haloperidol, affects the number or sizes of cerebellar Purkinje cells or the volume of histological layers in the rat cerebellum. Twenty-eight rats were...... randomly divided into three groups, receiving either no treatment, lithium, or lithium combined with haloperidol. The serum lithium levels ranged from 0.50 to 0.77 mmol/l. Haloperidol was given at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the cerebelli were...

  19. Applications of Text Messaging, and Bibliotherapy for Treatment of Patients Affected by Depressive Symptoms.

    Science.gov (United States)

    Taleban, Roya; Zamani, Ahmadreza; Moafi, Mohammad; Jiryaee, Nasrin; Khadivi, Reza

    2016-01-01

    Intensity of depressive symptoms could be exacerbated due to the paucity of appropriate treatments. We assessed the effectiveness of bibliotherapy and text messaging, which aimed at amelioration of patient's behavior and consciousness, which could lead to suicide prevention. This was a randomized clinical trial implemented in rural health centers of Isfahan district (Iran). Health centers were assigned in three trials consisting of the booklet, text messaging, and control groups. Each group consisted of 70 patients. Inclusion criteria were being affected by depressive symptom, text messaging. Out of 210 individuals, 198 patients finished this study. The intensity of depressive symptom was significantly affected through time and group factors as well as time-group interaction (F = 12.30, P text messaging group achieved neither durable nor significant success; thus, bibliotherapy could be utilized as a complementary methodology aiming depression treatment.

  20. Osteogenesis Imperfecta in Adult Twins Responded To Treatment With Pamidronate

    OpenAIRE

    Mehtap Çakır; Mine Öztürk

    2011-01-01

    Bisphosphonates are strong inhibitors of bone resorption and are used in the treatment of osteoporosis. Bisphosphonates are known to be effective in prevention of fractures, improvement of bone mineral density as well as in relieving bone pain in osteogenesis imperfecta (OI) patients. Recent studies have shown that especially intravenous pamidronate may be more effective when given in childhood and adolescence. This effect was also shown in adult OI patients in some clinical trials.22-year-ol...

  1. Mechanisms of Behavioral and Affective Treatment Outcomes in a Cognitive Behavioral Intervention for Boys.

    Science.gov (United States)

    Burke, Jeffrey D; Loeber, Rolf

    2016-01-01

    Evidence for effective treatment for behavioral problems continues to grow, yet evidence about the effective mechanisms underlying those interventions has lagged behind. The Stop Now and Plan (SNAP) program is a multicomponent intervention for boys between 6 and 11. This study tested putative treatment mechanisms using data from 252 boys in a randomized controlled trial of SNAP versus treatment as usual. SNAP includes a 3 month group treatment period followed by individualized intervention, which persisted through the 15 month study period. Measures were administered in four waves: at baseline and at 3, 9 and 15 months after baseline. A hierarchical linear modeling strategy was used. SNAP was associated with improved problem-solving skills, prosocial behavior, emotion regulation skills, and reduced parental stress. Prosocial behavior, emotion regulation skills and reduced parental stress partially mediated improvements in child aggression. Improved emotion regulation skills partially mediated treatment-related child anxious-depressed outcomes. Improvements in parenting behaviors did not differ between treatment conditions. The results suggest that independent processes may drive affective and behavioral outcomes, with some specificity regarding the mechanisms related to differing treatment outcomes.

  2. Suicide in primary affective disorders revisited: A systematic review by treatment era

    OpenAIRE

    O'Leary, D.; Paykel, E.; Todd, C.; Vardulaki, K.

    2001-01-01

    Background: We reviewed suicide rates in affective disorder and their variation with electro-convulsive therapy (ECT) and antidepressant availability. Method: Suicide rates were calculated from 75 follow-up studies, identified by systematic literature searches and analyzed for differences over time eras characterized by the availability of specific treatments. Data Sources and Study Selection: MEDLINE, EMBASE, BIOSIS Previews, and Psychological Abstracts literature searches were conducted for...

  3. A randomized controlled trial to compare the efficacy of bisphosphonates in the management of painful bone metastasis

    Directory of Open Access Journals (Sweden)

    Krishnangshu Bhanja Choudhury

    2011-01-01

    Conclusion: The use of bisphosphonates for 6 months or more results in a statistical significant improvement in bone pain, more so with zoledronic acid. Hypercalcemia, an SRE, was significantly less in the zoledronic acid arm.

  4. Efficacy and safety of bisphosphonates in management of low bone density in inflammatory bowel disease: A meta-analysis.

    Science.gov (United States)

    Yao, Liwei; Wang, Haiqing; Dong, Wenwei; Liu, Zhenxin; Mao, Haijiao

    2017-01-01

    This study aims to determine whether bisphosphonates are safe, as well as effective against bone mineral loss in inflammatory bowel disease (IBD). A computerized search of electronic databases from 1966 to 2016 was performed. Randomized controlled trials (RCTs) were included in this review to evaluate the role of bisphosphonates in the management of osteoporosis in IBD patients. A revised 7-point Jadad scale was used to evaluate the quality of each study. Overall, 13 RCTs and 923 patients met the inclusion criteria of this meta-analysis. The result showed that bisphosphonates decreased bone mass density (BMD) loss at the lumbar spine (P = 0.0002), reduced the risk of new fractures (P = 0.01), and retained the similar adverse events (P = 0.86). Bisphosphonates may provide protection and safety against bone mineral loss in IBD patients.

  5. Teriparatide versus low-dose bisphosphonates before and after surgery for adult spinal deformity in female Japanese patients with osteoporosis.

    Science.gov (United States)

    Seki, Shoji; Hirano, Norikazu; Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Suzuki, Kayo; Watanabe, Kenta; Makino, Hiroto; Kanamori, Masahiko; Kimura, Tomoatsu

    2017-08-01

    Complications of adult spinal deformity surgery are problematic in osteoporotic individuals. We compared outcomes between Japanese patients treated perioperatively with teriparatide vs. low-dose bisphosphonates. Fifty-eight osteoporotic adult Japanese female patients were enrolled and assigned to perioperative teriparatide (33 patients) and bisphosphonate (25 patients) groups in non-blinded fashion. Pre- and post-operative X-ray and computed tomography imaging were used to assess outcome, and rates were compared between the groups and according to age. Pain scores and Oswestry Disability Indices (ODI) were calculated before and 2 years after surgery. Adjacent vertebral fractures and implant failure, fusion failure, and poor pain and ODI outcomes were significantly more common in the bisphosphonates group than the teriparatide group. Perioperative administration of teriparatide is more effective than that of low-dose bisphosphonates in preventing complications and maintaining fusion rates in osteoporotic Japanese females with spinal deformities undergoing surgery.

  6. Effect of Long-Term Use of Bisphosphonates on Forearm Bone: Atypical Ulna Fractures in Elderly Woman with Osteoporosis

    Directory of Open Access Journals (Sweden)

    Yusuf Erdem

    2016-01-01

    Full Text Available Osteoporosis is a common musculoskeletal disease of the elderly population characterized by decreased bone mineral density and subsequent fractures. Bisphosphonates are a widely accepted drug therapy which act through inhibition of bone resorption and prevent fractures. However, in long-term use, atypical bisphosphonate induced fractures may occur, particularly involving the lower weight bearing extremity. Atypical ulna fracture associated with long-term bisphosphonate use is rarely reported in current literature. We present a 62-year-old woman with atypical ulna due to long-term alendronate therapy without a history of trauma or fall. Clinicians should be aware of stress fracture in a patient who has complaints of upper extremity pain and history of long-term bisphosphonate therapy.

  7. Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue

    Directory of Open Access Journals (Sweden)

    Remesar Xavier

    2007-08-01

    Full Text Available Abstract Background Short-term OE (oleoyl-estrone treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Results Gene expression in adipose tissue from female treated rats (48 hours was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL were decreased by 52%, those of Fatty Acid Synthase (FAS by 95%, those of Hormone Sensible Lipase (HSL by 32%, those of Acetyl CoA Carboxylase (ACC by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b by 45%, and those of Fatty Acid Transport Protein 1 (FATP1 and Adipocyte Fatty Acid Binding Protein (FABP4 by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFα values showed overexpression (198%. Conclusion Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism.

  8. Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue.

    Science.gov (United States)

    Salas, Anna; Noé, Véronique; Ciudad, Carlos J; Romero, M Mar; Remesar, Xavier; Esteve, Montserrat

    2007-08-28

    Short-term OE (oleoyl-estrone) treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Gene expression in adipose tissue from female treated rats (48 hours) was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL) were decreased by 52%, those of Fatty Acid Synthase (FAS) by 95%, those of Hormone Sensible Lipase (HSL) by 32%, those of Acetyl CoA Carboxylase (ACC) by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b) by 45%, and those of Fatty Acid Transport Protein 1 (FATP1) and Adipocyte Fatty Acid Binding Protein (FABP4) by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFalpha) values showed overexpression (198%). Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism.

  9. How does obesity affect fertility in men - and what are the treatment options?

    Science.gov (United States)

    Stokes, Victoria J; Anderson, Richard A; George, Jyothis T

    2015-05-01

    Adiposity is associated with reduced fertility in men. The aetiology is multifactorial, with obese men at greater risk of suffering from impaired spermatogenesis, reduced circulating testosterone levels, erectile dysfunction and poor libido. The diagnosis and treatment of reduced fertility observed in obese men therefore requires insight into the underlying pathology, which has hormonal, mechanical and psychosocial aspects. This article summarises the current epidemiological, experimental and clinical trial evidence from the perspective of a practicing clinician. The following conclusions and recommendations can be drawn: Obesity is associated with low serum testosterone concentrations, but treatment with exogenous testosterone is likely to adversely impact on fertility. It is important to discuss this with men prior to initiation of testosterone therapy. Obesity adversely affects sperm concentration and may affect sperm quality. However, whether or not weight loss will correct these factors remain to be established. Oestrogen receptor modulators (and aromatase inhibitors) are unlicensed in the treatment for male hypogonadism and/or infertility. These treatments should hence be considered experimental approach until ongoing clinical trials report their outcomes. © 2014 John Wiley & Sons Ltd.

  10. Evaluation of dental implants as a risk factor for the development of bisphosphonate-related osteonecrosis of the jaw in breast cancer patients.

    Science.gov (United States)

    Matsuo, Akira; Hamada, Hayato; Takahashi, Hidetoshi; Okamoto, Ayako; Kaise, Hiroshi; Chikazu, Daichi

    2016-09-01

    It remains unclear whether dental implants are a risk factor for the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We retrospectively evaluated the status of dental implants in patients given intravenous bisphosphonates (BPs) in a breast cancer cohort to elucidate the risk for BRONJ at the implant site. We established a BRONJ oral monitoring program for 247 breast cancer patients given intravenous BP in our institution. The 3-year cumulative incidence rate was determined. The systemic and local risk factors of 44 patients who completed comprehensive oral examinations were evaluated by logistic regression analysis. The 3-year cumulative incidence rate of the 247 patients was 0.074 % (8/247, 95 % CI 0.0081-0.014). In the 44 orally examined patients, 6 (13.6 %: 6/44) had dental implants. Of these 6 patients, 1 developed BRONJ at the implant site. There were no significant differences in the age, total BP treatment period, number of residual teeth, time of regular oral monitoring, oral hygiene level, or dental implant insertion. Although a case of ONJ was identified, dental implants which were inserted before intravenous BP administration were not a risk factor for the development of ONJ in breast cancer patients.

  11. Microscopic Evaluation of the Effect of Oral Microbiota on the Development of Bisphosphonate-Related Osteonecrosis of the Jaws in Rats

    Directory of Open Access Journals (Sweden)

    Felipe M. Silveira

    2017-01-01

    Full Text Available Objectives: Osteonecrosis of the jaws is a side effect associated with the use of bisphosphonates. Using histologic analysis, this study aimed to evaluate the influence of microbial colonies in the development of osteonecrosis in the jaws of rats subjected to nitrogenous and non-nitrogenous bisphosphonates, undergoing surgical procedures. Material and Methods: Thirty-four rats (Rattus norvegicus, Wistar strain were allocated randomly into three groups: 12 animals treated with zoledronic acid; 12 animals treated with clodronate; and 10 animals treated with saline. Sixty days after the start of treatment, the animals underwent three extractions of the upper right molars. After 120 days of drug administration, the rats were killed. Histologic analysis was performed on specimens stained with hematoxylin and eosin by the technique of manual counting points using Image-Pro Plus software on images of the right hemimaxilla. Results: Osteonecrosis was induced in the test groups. There was no statistically significant association between the presence of microbial colonies and the presence of non-vital bone (Kruskal-Wallis, P > 0.05. Conclusions: Use of zoledronic acid was associated with non-vital bone and the results suggested that the presence of microbial colonies does not lead to osteonecrosis.

  12. Incidence of bisphosphonate-related osteonecrosis of the jaw in high-risk patients undergoing surgical tooth extraction.

    Science.gov (United States)

    Bodem, Jens Philipp; Kargus, Steffen; Eckstein, Stefanie; Saure, Daniel; Engel, Michael; Hoffmann, Jürgen; Freudlsperger, Christian

    2015-05-01

    As the most suitable approach for preventing bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients undergoing surgical tooth extraction is still under discussion, the present study evaluates the incidence of BRONJ after surgical tooth extraction using a standardized surgical protocol in combination with an adjuvant perioperative treatment setting in patients who are at high-risk for developing BRONJ. High-risk patients were defined as patients who received intravenous bisphosphonate (BP) due to a malignant disease. All teeth were removed using a standardized surgical protocol. The perioperative adjuvant treatment included intravenous antibiotic prophylaxis starting at least 24 h before surgery, a gastric feeding tube and mouth rinses with chlorhexidine (0.12%) three times a day. In the follow-up period patients were examined every 4 weeks for the development of BRONJ. Minimum follow-up was 12 weeks. In 61 patients a total number of 184 teeth were removed from 102 separate extraction sites. In eight patients (13.1%) BRONJ developed during the follow-up. A higher risk for developing BRONJ was found in patients where an additional osteotomy was necessary (21.4% vs. 8.0%; p = 0.0577), especially for an osteotomy of the mandible (33.3% vs. 7.3%; p = 0.0268). Parameters including duration of intravenous antibiotic prophylaxis, the use of a gastric feeding tube and the duration of intravenous BP therapy showed no statistical impact on the development of BRONJ. Furthermore, patients currently undergoing intravenous BP therapy showed no higher risk for BRONJ compared with patients who have paused or completed their intravenous BP therapy (p = 0.4232). This study presents a protocol for surgical tooth extraction in high-risk BP patients in combination with a perioperative adjuvant treatment setting, which reduced the risk for postoperative BRONJ to a minimum. However, the risk for BRONJ increases significantly if an additional osteotomy is necessary

  13. Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones.

    Science.gov (United States)

    Prochaska, Megan; Taylor, Eric; Vaidya, Anand; Curhan, Gary

    2017-08-07

    Previous studies have demonstrated lower bone density in patients with kidney stones, but no longitudinal studies have evaluated kidney stone risk in individuals with low bone density. Small studies with short follow-up reported reduced 24-hour urine calcium excretion with bisphosphonate use. We examined history of low bone density and bisphosphonate use and the risk of incident kidney stone as well as the association with 24-hour calcium excretion. We conducted a prospective analysis of 96,092 women in the Nurses' Health Study II. We used Cox proportional hazards models to adjust for age, body mass index, thiazide use, fluid intake, supplemental calcium use, and dietary factors. We also conducted a cross-sectional analysis of 2294 participants using multivariable linear regression to compare 24-hour urinary calcium excretion between participants with and without a history of low bone density, and among 458 participants with low bone density, with and without bisphosphonate use. We identified 2564 incident stones during 1,179,860 person-years of follow-up. The multivariable adjusted relative risk for an incident kidney stone for participants with history of low bone density compared with participants without was 1.39 (95% confidence interval [95% CI], 1.20 to 1.62). Among participants with low bone density, the multivariable adjusted relative risk for an incident kidney stone for bisphosphonate users was 0.68 (95% CI, 0.48 to 0.98). In the cross-sectional analysis of 24-hour urine calcium excretion, the multivariable adjusted mean difference in 24-hour calcium was 10 mg/d (95% CI, 1 to 19) higher for participants with history of low bone density. However, among participants with history of low bone density, there was no association between bisphosphonate use and 24-hour calcium with multivariable adjusted mean difference in 24-hour calcium of -2 mg/d (95% CI, -25 to 20). Low bone density is an independent risk factor for incident kidney stone and is associated with

  14. Additive effects of nutritional supplementation, together with bisphosphonates, on bone mineral density after hip fracture: a 12-month randomized controlled study

    Directory of Open Access Journals (Sweden)

    Flodin L

    2014-07-01

    Full Text Available Lena Flodin,1,2 Maria Sääf,3 Tommy Cederholm,4 Amer N Al-Ani,2,5 Paul W Ackermann,5,6 Eva Samnegård,7 Nils Dalen,7 Margareta Hedström2,51Department of Geriatric Medicine, Karolinska University Hospital Stockholm, Sweden; 2Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden; 3Department of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital, Stockholm, Sweden; 4Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden; 5Department of Orthopedics, Karolinska University Hospital, Stockholm, Sweden; 6Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 7Department of Clinical Science, Division of Orthopedics, Karolinska Institutet, Danderyd Hospital, Stockholm, SwedenBackground: After a hip fracture, a catabolic state develops, with increased bone loss during the first year. The aim of this study was to evaluate the effects of postoperative treatment with calcium, vitamin D, and bisphosphonates (alone or together with nutritional supplementation on total hip and total body bone mineral density (BMD.Methods: Seventy-nine patients (56 women, with a mean age of 79 years (range, 61–96 years and with a recent hip fracture, who were ambulatory before fracture and without severe cognitive impairment, were included. Patients were randomized to treatment with bisphosphonates (risedronate 35 mg weekly for 12 months (B; n=28, treatment with bisphosphonates along with nutritional supplementation (40 g protein, 600 kcal daily for the first 6 months (BN; n=26, or to controls (C; n=25. All participants received calcium (1,000 mg and vitamin D3 (800 IU daily. Total hip and total body BMD were assessed with dual-energy X-ray absorptiometry at baseline, 6, and 12 months. Marker of bone resorption C-terminal telopeptide of collagen I and 25-hydroxy vitamin D were analyzed in serum

  15. The interactions among impact factors affecting 131I treatment efficacy of Graves' disease

    International Nuclear Information System (INIS)

    Wang Peng; Tan Jian; Zhang Guizhi; He Yajing; Dong Feng; Wang Renfei; Xiao Qian

    2011-01-01

    Objective: To evaluate the possible interactions among different impact factors possibly affecting the treatment efficacy of 131 I in Graves' disease (GD). Methods: Six hundred and thirty two GD patients that had been treated by 131 I, with or without antithyroid drugs (ATD), were included in this study. The impact factors were pre-defined as age (x 1 ), sex (x 2 ), mass of thyroid (x 3 ), course of disease (x 4 ), initial symptom (x 5 ), condition of disease (x 6 ), ATD treatment duration (x 7 ), effective half life time (x 8 ), maximum 131 I uptake rate (x 9 ), total dose of 131 I (x 10 ), dose of 131 I per gram of thyroid (x 11 ), TRAb (x 12 ), TSI (x 13 ), TgAb (x 14 ), and thyroid microsomal antibody(TMAb) level (x 15 ). Interactions among different impact factors were studied by t-test, χ 2 test and multi-variant logistic regression. Results: Age, mass of thyroid, ATD treatment duration, maximum 131 I uptake rate, dose of 131 I per gram of thyroid tissue and TSI level were identified as independent impact factors affecting the 131 I treatment efficacy on GD (χ 2 =6.908, t=-4.063, χ 2 =13.558, t=-2.553, t=4.528, χ 2 =9.716, all P 131 I uptake rate (likelihood χ 2 =8.176, P>0.05; F=2.928, 1.992, 2.629, 2.215, all P 131 I treatment, which might guide the prescription of 131 I dosage for GD treatment. (authors)

  16. Endoscopic Laser Treatment for Rectosigmoid Villous Adenoma: Factors Affecting the Results

    Directory of Open Access Journals (Sweden)

    JM Brunetaud

    1992-01-01

    Full Text Available Endoscopic laser treatment is now commonly used for palliation of advanced digestive cancers in nonsurgical candidates. lt has also been used for treatment of benign rectosigmoid villous adenoma. The present work reports the long term results in 387 patients with benign rectosigmoid villous adenomas revealed by biopsy. Patients included 39% who had contraindications to surgery, 19% who had a tumour recurrence after a nonlaser treatment, 41 % for whom surgical resection appeared to be too drastic for a tumour found benign on biopsy, and 1 % who refused surgery. Two types of wavelength were used: the 1.06 µm infrared light from the Nd:YAG laser and the green light from the argon laser or the Nd:YAG frequency doubled laser. In some patients, both wavelengths were used. Treatment was completed in 343 patients. Total tumour destruction was achieved in 92.8% of patients, a carcinoma was detected in 6.4% on biopsy specimens obtained during laser treatment and benign villous tissue persisted in 0.8%. During the average 30-month follow-up period of the patients with total tumour destruction , 16% had a recurrence. Treatment was well-tolerated with a complication race of 2.3% (one patient with a perforation, one with hemorrhage and seven with stenosis requiring dilation. Circumferential extension of the tumour base was the only factor affecting the duration of treatment, the rate of cancers detected during treatment and the rate of complications. Recurrence rate after initial treatment was higher in patients treated for a recurrence after a previous nonlaser treatment than in patients treated only by laser (P<0.01. It was also higher when the initial histology showed low grade dysplasia as opposed to high grade dysplasia (P<0.01 and when the tumour was located in the lower or middle rectum rather than in the upper rectum or sigmoid (P<0.01. Direct cost of laser treatments was estimated to be 28 to 40% of the surgery charges for lesions of identical size

  17. Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class.

    Directory of Open Access Journals (Sweden)

    Monica Vera-Lise Tulstrup

    Full Text Available Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, as it disrupts the intricate balance between specific bacterial groups within this ecosystem, potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group were dosed by oral gavage with either amoxicillin (AMX, cefotaxime (CTX, vancomycin (VAN, metronidazole (MTZ, or water (CON daily for 10-11 days. Bacterial composition, alpha diversity and caecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity and an increase in the relative abundance of Proteobacteria was observed for all three antibiotics. Additionally, the relative abundance of Bifidobacteriaceae was increased in the CTX group and both Lactobacillaceae and Verrucomicrobiaceae were increased in the VAN group compared to the CON group. No changes in microbiota composition or function were observed following MTZ treatment. Intestinal permeability to 4 kDa FITC-dextran decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes were found in any treatment group. A strong correlation between the level of caecal succinate, the relative abundance of Clostridiaceae 1 family in the caecum, and the level of acute phase protein haptoglobin in blood plasma was observed. In conclusion, antibiotic-induced changes in microbiota may be linked to alterations in intestinal permeability, although the specific interactions remain to be elucidated as changes in

  18. Factors Affecting Compliance to Antihypertensive Treatment among Adults in a Tertiary Care Hospital in Mumbai.

    Science.gov (United States)

    Shah, Ayushi Jayesh; Singh, Vijaykumar; Patil, Subita P; Gadkari, Mithila R; Ramchandani, Varun; Doshi, Karan Janak

    2018-01-01

    Compliance to antihypertensive therapy reduces the risk of complications. It is important to understand the factors affecting compliance in patients so that the goal of successful treatment is not jeopardized. To determine the proportion of participants' compliant to treatment and various factors associated with compliance of antihypertensive treatment. A cross-sectional study of 330 hypertensive patients on treatment attending the outpatient department of a tertiary care hospital in Mumbai. It was conducted over 8 weeks using a validated, pretested questionnaire including information on the individual's sociodemographic profile, compliance to antihypertensive therapy and lifestyle advice assessed using a 4-point Likert scale. Data were entered into MS Excel 2007 and analyzed using SPSS 20. Participants' mean age was 55.2 ± 12.6 years. 39.4% were compliant to their treatment. Common reasons for frequently skipping the dose - forgetfulness (41.2%) and discontinued the medication when feeling well (30.3%). Factors positively associated with compliance were gender and illiteracy. The proportion of noncompliance among smokers and alcoholics was statistically significant. Forgetfulness and subjective feeling of wellness were the prevalent reasons for noncompliance. Controlling habits such as smoking and alcohol may prove as key factors for compliance.

  19. Digestibility and energetic value of agricultural wastes as affected by gamma irradiation and chemical treatments

    International Nuclear Information System (INIS)

    Al-Masri, M.R.

    2002-01-01

    Experiments were carried out to study the changes in the values of in-vitro apparent organic matter digestibility (IVOMD), metabolizable energy (ME) and net energy lactation (NEL) of wheat straw, sunflower seed shell, olive cake wood, date palm seeds and peanut shell after spraying with different concentrations of hydrobromic acid (HBr) and sodium hydroxide (NaOH) (0,3,6 ml HBr and 3,6 g NaOH/25 ml water/100 g Dm) or after exposure to various doses of gamma radiation (0, 20, 40, 60 kGy). Results indicated that, except for the date palm seeds, the chemical treatments with either HBr or NaOH significantly (P<0.05) increased IVOMD, Me and NEL values for all treated samples. The experimental agricultural wastes did not respond equally to the chemical treatments investigated, i.e. they differ in the induced increases pertaining to their IVOMD, ME and NEL. The highest changes in the studied parameters due to chemical treatments were obtained when applying the 6% concentration. There was no significant effect (P<0.05) of irradiation on IVOMD, ME and NEL values for all treated samples. Moreover, the combined treatments of irradiation and hydrobromic acid or sodium hydroxide were found to have no significant affects on the IVOMD, ME and NEL values compared to the individual chemical treatments. (author)

  20. Rice grain yield as affected by subsoiling, compaction on sowing furrow and seed treatment

    Directory of Open Access Journals (Sweden)

    Veneraldo Pinheiro

    2016-05-01

    Full Text Available ABSTRACT This study aimed to determine the effects of subsoiling, compaction on sowing furrow and seed treatments with insecticides on the grain yield of upland rice cultivated under no-tillage. Two experiments were carried out, one in an area with and the other in an area without subsoiling, in which five seed treatments combined with five compaction pressures on the sowing furrow were compared in a randomized block design, in a factorial scheme, with three replicates. The seed treatments were: T0 - without treatment, T1 - imidacloprid + thiodicarb, T2 - thiamethoxam, T3 - carbofuran, and T4 - fipronil + pyraclostrobin + thiophanate methyl. The compaction pressures were: 25, 42, 126, 268 and 366 kPa. Subsoiling positively affected rice yield in the presence of higher compaction pressures on the sowing furrow. Seed treatment was effective at increasing rice grain yield only at the lowest compaction pressures. Rice yield showed quadratic response to compaction on the sowing furrow, with maximum values obtained at pressures ranging from 238.5 to 280.3 kPa.

  1. Digestibility and energetic value of some agricultural wastes as affected by gamma irradiation and chemical treatments

    International Nuclear Information System (INIS)

    Al-Masri, M.R.

    2001-08-01

    Experiments were carried out to study the changes in the values of in-vitro apparent organic matter digestibility (IVOMD), metabolizable energy (ME) and net energy lactation (NEL) of wheat straw, sunflower seed shell, olive cake wood, date palm seeds and peanut shell after spraying with different concentrations of hydrobromic acid (HBr) and sodium hydroxide (NaOH) (0,3,6 ml HBr and 3,6 g NaOH/25 ml water/100 g DM) or after exposure to various doses of gamma radiation (0, 20, 40, 60 kGy). Results indicated that, except for the date palm seeds, the chemical treatments with either HBr or NaOH significantly (P<0.05) increased IVOMD, Me and NEL values for all treated samples. The experimental agricultural wastes did not respond equally to the chemical treatments investigated, i.e. they differ in the induced increases pertaining to their IVOMD, ME and NEL. The highest changes in the studied parameters due to chemical treatments were obtained when applying the 6% concentration. There was no significant effect (P<0.05) of irradiation on IVOMD, ME and NEL values for all treated samples. Moreover, the combined treatments of irradiation and hydrobromic acid or sodium hydroxide were found to have no significant affects on the IVOMD, ME and NEL values compared to the individual chemical treatments. (author)

  2. The Range and Impact of Postmigration Stressors During Treatment of Trauma-Affected Refugees.

    Science.gov (United States)

    Bruhn, Maja; Rees, Susan; Mohsin, Mohammed; Silove, Derrick; Carlsson, Jessica

    2018-01-01

    Trauma-affected refugees commonly experience postmigration stressors, which can compound conflict-related emotional distress. Our study aimed to assess clinician-rated frequency and types of postmigration stressors deemed to be interfering with the treatment of refugees attending a service for trauma-related mental distress. A total of 116 patients completed 6 months of multidisciplinary treatment. Clinician-rated postmigration stressors were registered at each session. Outcome measures were Harvard Trauma Questionnaire and Global Assessment of Functioning, function (GAF-F) and symptom. Postmigration stressors were deemed to impact on 39.1% of treatment sessions with medical personnel. Issues related to work, finances, and family were the most frequently identified stressors. Postmigration stressors interfering with treatment were more common among male refugees, those living alone, those from Middle Eastern origin, and persons with low baseline GAF-F. Explicitly identifying and, where possible, dealing with postmigration stressors may assist in averting their interference with the treatment of distress in refugees.

  3. Factors affecting compliance to antihypertensive treatment among adults in a tertiary care hospital in Mumbai

    Directory of Open Access Journals (Sweden)

    Ayushi Jayesh Shah

    2018-01-01

    Full Text Available Background: Compliance to antihypertensive therapy reduces the risk of complications. It is important to understand the factors affecting compliance in patients so that the goal of successful treatment is not jeopardized. Objectives: To determine the proportion of participants' compliant to treatment and various factors associated with compliance of antihypertensive treatment. Settings and Design: A cross-sectional study of 330 hypertensive patients on treatment attending the outpatient department of a tertiary care hospital in Mumbai. Subjects and Methods: It was conducted over 8 weeks using a validated, pretested questionnaire including information on the individual's sociodemographic profile, compliance to antihypertensive therapy and lifestyle advice assessed using a 4-point Likert scale. Statistical Analysis: Data were entered into MS Excel 2007 and analyzed using SPSS 20. Results: Participants' mean age was 55.2 ± 12.6 years. 39.4% were compliant to their treatment. Common reasons for frequently skipping the dose – forgetfulness (41.2% and discontinued the medication when feeling well (30.3%. Factors positively associated with compliance were gender and illiteracy. The proportion of noncompliance among smokers and alcoholics was statistically significant. Conclusion: Forgetfulness and subjective feeling of wellness were the prevalent reasons for noncompliance. Controlling habits such as smoking and alcohol may prove as key factors for compliance.

  4. The guardians' perspective on paediatric cancer treatment in Malawi and factors affecting adherence.

    Science.gov (United States)

    Israëls, Trijn; Chirambo, Chawanangwa; Caron, Huib; de Kraker, Jan; Molyneux, Elizabeth; Reis, Ria

    2008-11-01

    Abandonment of paediatric cancer treatment is a common problem in developing countries. Little is known about the guardians' perspective on cancer treatment in these countries, especially the factors that affect adherence. Following a pilot study enquiring into the possible causes of abandonment, a problem analysis diagram was drawn which helped to develop the questionnaires. Semi-structured interviews (n = 83) and focus group discussions (n = 8) were held with the guardians of 25 Burkitt lymphoma patients and 7 Wilms tumour patients at different phases of therapy in Malawi. Parents in Malawi are very motivated to continue treatment if they think that it will cure their child. Financial costs are important concerns. Not all tasks at home are assumed by other household members. The diagnosis of cancer was unknown before being told about it in hospital and caused fear of recurrence and death. Guardians are reluctant to ask the health personnel questions. They worry that taking frequent blood samples will weaken their child. The side effects of the chemotherapy are seen as a proof of efficacy. It is important to appreciate the guardians' concerns when offering treatment that requires their sustained commitment. It is necessary to provide not only medical treatment, but also travel allowances and adequate nutritional support during long hospital stays to impoverished families. Information should be given proactively. (c) 2008 Wiley-Liss, Inc.

  5. Molar incisor hypomineralization (MIH: conservative treatment management to restore affected teeth

    Directory of Open Access Journals (Sweden)

    Camila Maria Bullio FRAGELLI

    2015-01-01

    Full Text Available The purpose of this study was to evaluate the 12-month clinical performance of glass ionomer restorations in teeth with MIH. First permanent molars affected by MIH (48 were restored with glass ionomer cement (GIC and evaluated at baseline, at 6 and at 12 months, by assessing tooth enamel breakdown, GIC breakdown and caries lesion associations. The data were analyzed using the chi-square test and actuarial survival analysis. The likelihood of a restored tooth remaining unchanged at the end of 12 months was 78%. No statistically significant difference was observed in the association between increased MIH severity and caries at baseline (p > 0.05 for a 6-month period, or between increased MIH severity and previous unsatisfactory treatment at baseline (p > 0.05 for both a 6- and 12-month period. A statistically significant difference was observed in the association between increased MIH severity and extension of the restoration, involving 2 or more surfaces (p < 0.05 at both periods, and between increased MIH severity and caries at baseline (p < 0.05 at a 12-month period. Because the likelihood of maintaining the tooth structures with GIC restorations is high, invasive treatment should be postponed until the child is sufficiently mature to cooperate with the treatment, mainly of teeth affected on just one face.

  6. Molar incisor hypomineralization (MIH): conservative treatment management to restore affected teeth.

    Science.gov (United States)

    Fragelli, Camila Maria Bullio; Souza, Juliana Feltrin de; Jeremias, Fabiano; Cordeiro, Rita de Cássia Loiola; Santos-Pinto, Lourdes

    2015-01-01

    The purpose of this study was to evaluate the 12-month clinical performance of glass ionomer restorations in teeth with MIH. First permanent molars affected by MIH (48) were restored with glass ionomer cement (GIC) and evaluated at baseline, at 6 and at 12 months, by assessing tooth enamel breakdown, GIC breakdown and caries lesion associations. The data were analyzed using the chi-square test and actuarial survival analysis. The likelihood of a restored tooth remaining unchanged at the end of 12 months was 78%. No statistically significant difference was observed in the association between increased MIH severity and caries at baseline (p > 0.05) for a 6-month period, or between increased MIH severity and previous unsatisfactory treatment at baseline (p > 0.05) for both a 6- and 12-month period. A statistically significant difference was observed in the association between increased MIH severity and extension of the restoration, involving 2 or more surfaces (p MIH severity and caries at baseline (p < 0.05) at a 12-month period. Because the likelihood of maintaining the tooth structures with GIC restorations is high, invasive treatment should be postponed until the child is sufficiently mature to cooperate with the treatment, mainly of teeth affected on just one face.

  7. Antibiotic treatment affects intestinal permeability and gut microbial composition in Wistar rats dependent on antibiotic class

    DEFF Research Database (Denmark)

    Tulstrup, Monica Vera-Lise; Christensen, Ellen Gerd; Carvalho, Vera

    2015-01-01

    Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, by disrupting the intricate balance between specific bacterial groups within this ecosystem...... potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (n=12 per group) were dosed by oral gavage with either amoxicillin...... (AMX), cefataxime (CTX), vancomycin (VAN), metronidazole (MTZ), or water (CON) daily for 10-11 days. Bacterial composition, alpha diversity and cecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity...

  8. Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism.

    Science.gov (United States)

    Otto, Sven; Pautke, Christoph; Opelz, Christine; Westphal, Ines; Drosse, Inga; Schwager, Joanna; Bauss, Frieder; Ehrenfeld, Michael; Schieker, Matthias

    2010-11-01

    Osteonecrosis of the jaw has been reported in patients receiving high doses of intravenous nitrogen-containing bisphosphonates (N-BPs) because of malignant disease. The exact pathomechanisms have been elusive and questions of paramount importance remain unanswered. Recent studies have indicated toxic effects of bisphosphonates on different cell types, apart from osteoclast inhibition. Multipotent stem cells play an important role in the processes of wound healing and bone regeneration, which seem to be especially impaired in the jaws of patients receiving high doses of N-BPs. Therefore, the aim of the present study was to investigate the effects of different bisphosphonate derivatives and dose levels combined with varying pH levels on the mesenchymal stem cells in vitro. The effect of 2 N-BPs (zoledronate and ibandronate) and 1 non-N-BP (clodronate) on immortalized mesenchymal stem cells was tested at different concentrations, reflecting 1, 3, and 6 months and 1, 3, 5, and 10 years of exposure to standard oncology doses of the 2 N-BPs and equimolar concentrations of clodronate at different pH values (7.4, 7.0, 6.7, and 6.3). Cell viability and activity were analyzed using a WST assay. Cell motility was investigated using scratch wound assays and visualized using time-lapse microscopy. Both types of bisphosphonates revealed remarkable differences. Zoledronate and ibandronate showed a dose- and pH-dependent cellular toxicity. Increasing concentrations of both N-BPs and an acidic milieu led to a significant decrease in cell viability and activity (P key role in the pathogenesis of osteonecrosis of the jaw in patients receiving high doses of N-BPs for malignant diseases. Also the potency of N-BPs might be different, suggesting a greater risk of osteonecrosis of the jaw with zoledronate. Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Aspects of osseous, peritoneal and renal handling of bisphosphonate during peritoneal dialysis: a methodological study

    DEFF Research Database (Denmark)

    Joffe, P; Henriksen, Jens Henrik

    1996-01-01

    .5 and 2.8 ml min-1 (not significant), respectively. The bone bisphosphonate clearance (BBC) at steady state was 26.0 ml min-1, a value which was significantly higher than that at infinity (16.5 ml min-1, p ... by their different molecular weight. The differences in the BBCs at infinity and at steady state are most probably due to late recirculation of MBP from the bone compartment. Hence, the BBC technique can be applied in the CAPD setting....

  10. Atypical metatarsal fracture in a patient on long term bisphosphonate therapy

    Directory of Open Access Journals (Sweden)

    Pavan Pradhan

    2012-01-01

    Full Text Available A 24 years old female of cushing disease had undergone adrenelectomy. She was put on alendronate and steroid. After six and a half years she developed pathological fracture subtrochanteric femur. The patient was treated with proximal femoral nailing and the fracture united. 2 years later she developed pain right foot. She was diagnosed as transverse fracture of fifth metatarsal. We report this rare case of atypical metatarsal fracture in a patient on long term bisphosphonate therapy.

  11. A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures.

    OpenAIRE

    Davis, S.; Martyn-St James, M.; Sanderson, J.; Stevens, J.; Goka, E.; Rawdin, A.; Sadler, S.; Wong, R.; Campbell, F.; Stevenson, M.; Strong, M.; Selby, P.; Gittoes, N.

    2016-01-01

    BACKGROUND: Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. OBJECTIVES: To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax(®) and Fosamax(®) Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel(®) and Actonel Once a Week(®), Warner Chilcott UK Ltd), ibandronic acid (Bonviva(®), Roche Products Ltd) and zoledronic acid (Aclasta(®), Novartis Pharmaceuticals UK Ltd)] for the p...

  12. The bisphosphonate zoledronate prevents vertebral bone loss in mature estrogen-deficient rats as assessed by micro-computed tomography

    Directory of Open Access Journals (Sweden)

    Glatt M.

    2001-01-01

    Full Text Available The effect of long-term treatment with the bisphosphonate zoledronate on vertebral bone architecture was investigated in estrogen-deficient mature rats. 4-month-old rats were ovariectomized and development of cancellous osteopenia was assessed after 1 year. The change of bone architectural parameters was determined with a microtomographic instrument of high resolution. After 1 year of estrogen-deficiency, animals lost 55% of vertebral trabecular bone in comparison to sham operated control animals. Trabecular number (Tb.N and trabecular thickness (Tb.Th were significantly reduced in ovariectomized animals, whereas trabecular separation (Tb.Sp, bone surface to volume fraction (BS/BV and trabecular bone pattern factor (TBPf were significantly increased, indicating a loss of architectural integrity throughout the vertebral body. 3 groups of animals were treated subcutaneously with zoledronate for 1 year with 0.3, 1.5 and 7.5 microgram/kg/week to inhibit osteoclastic bone degradation. Administration started immediately after ovariectomy and treatment dose-dependently prevented the architectural bone deterioration and completely suppressed the effects of estrogen deficiency at the higher doses. The results show that microtomographic determination of static morphometric parameters can be used to quantitate the effects of drugs on vertebral bone architecture in small laboratory animals and that zoledronate is highly effective in this rat model.

  13. Service providers' perception of affective influences on decision-making about treatments for chronic pain.

    Science.gov (United States)

    Brown, Cary A

    2004-01-07

    Service providers working with people who have complex health problems like chronic pain are considered at particular risk from the heavy emotional content of these interactions (frustration, guilt, hostility). For the good of service users and in the interests of healthcare workers' own health it is important for them to employ reflective practice acknowledging these issues. Service providers are inculcated to negate the affective domain of their practice despite the growing awareness that wellbeing can no longer be envisioned as a linear (cause and effect) process divorced from socio-cultural influences and attendant values and beliefs. The aim of this report is to examine to what degree service users (SU) and service providers (SP) believe their decisions about treatment importance are influenced by self-image and emotion. These results are extrapolated from a larger study based on a postal questionnaire that went to members of the Pain Society (UK Chapter of IASP) and service users belonging to chronic pain support groups in the North-West of England. The question of interest in this report asked participants to identify their level of agreement with statements about how four themes influence their decision-making about whether a treatment is important. The themes (coherence, purposiveness, self-image and affect) arise from Chapman's model of consciousness and pain. Only 20.5% of service providers rated the influence of self-image (what someone like me would think) as 3 (mostly) or 4 (completely). Service provider rating for the influence of affect (how this treatment makes me feel) were similarly low with only 19.4% of respondents selecting a rating of 3 or 4. In marked contrast, 73.3% of the service users selected self-image and 92.9% selected affect as a strong influence. Service providers felt that affect and self-image had little influence on their decision-making. However, there is growing evidence in the literature to suggest that it is not possible, nor

  14. Factors affecting visual outcomes after treatment of infectious endophthalmitis in northeastern Thailand

    Directory of Open Access Journals (Sweden)

    Yospaiboon Y

    2018-04-01

    Full Text Available Yosanan Yospaiboon, Anocha Intarapanich, Wipada Laovirojjanakul, Tanapat Ratanapakorn, Suthasinee Sinawat, Thuss Sanguansak, Chavakij Bhoomibunchoo KKU Eye Center, Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand Objective: To determine factors affecting visual outcomes after treatment of infectious endophthalmitis during 2012–2016 at a large referral eye center in northeastern Thailand. Patients and methods: Medical charts of patients with a diagnosis of infectious endophthalmitis including demographic data, types of endophthalmitis, causative organisms, methods of treatment, anatomical, and functional outcomes were retrospectively reviewed. Factors associated with improved visual outcomes were analyzed.Results: Four hundred and eleven patients (417 eyes were recruited for the study. The three most common types were post-traumatic (44.53%, post-operative (31.87%, and endogenous endophthalmitis (17.52%. Vitreous cultures revealed causative organisms in 41.25%. Most common Gram-positive organisms were coagulase-negative Staphylococcus 30% (36/120, Bacillus spp. 20% (24/120, and Streptococcus pneumoniae 18.33% (20/120. Most common Gram-negatives were Pseudomonas spp. 24.32% (9/37, Klebsiella spp. 24.32% (9/37, and Enterobacter spp. 16.21% (6/37. Methods of treatment were medical treatment (18.71% and surgical treatment (81.29%, including pars plana vitrectomy with or without silicone oil tamponade (62.59% and destructive surgery (18.71%. After treatment, visual improvement was noted in 44.6%, stable vision in 18.47%, and worse vision in 36.93%. Factors associated with improved visual outcomes were post-operative endophthalmitis (P<0.001, coagulase-negative Staphylococcus (P=0.003, and initial visual acuity before treatment of hand motion or better (P=0.017.Conclusion: Most infectious endophthalmitis patients were post-traumatic, post-operative, and endogenous. The most common method of treatment was

  15. Does cannabis use affect treatment outcome in bipolar disorder? A longitudinal analysis

    DEFF Research Database (Denmark)

    van Rossum, Inge; Boomsma, Maarten; Tenback, Diederik

    2009-01-01

    Research suggests that cannabis use affects negatively on onset and outcome of schizophrenia, but less is known about possible effects in mood disorders. Bipolar in- and outpatients (N = 3459) were enrolled in an observational study. The influence of cannabis exposure on clinical and social...... treatment outcome measures was examined over the course of 1 year, as well as the effects on these associations of third mediating variables. Over 12 months of treatment, cannabis users exhibited less compliance and higher levels of overall illness severity, mania, and psychosis compared with nonusers....... Additionally, cannabis users experienced less satisfaction with life and had a lower probability of having a relationship compared with nonusers. There was little evidence that cannabis-outcome associations were mediated by third variables. An independent impact of cannabis use on psychopathologic outcomes...

  16. Factors affecting direction and strength of patient preferences for treatment of molar teeth with nonvital pulps.

    Science.gov (United States)

    Vernazza, C R; Steele, J G; Whitworth, J M; Wildman, J R; Donaldson, C

    2015-12-01

    To elicit the factors affecting willingness to pay (WTP) values for the preferred options of participants for dealing with a molar tooth with a nonvital pulp, a common but difficult problem. A total of 503 patients were recruited from dental practices in the North East of England and interviewed. Their preferred treatment option for a molar tooth with a nonvital pulp (endodontics, extraction and various prosthetic restorative options) and WTP for this preferred option were elicited. Factors affecting preferred option and WTP were analysed using econometric modelling. Overall, 53% of the sample wished to save the tooth with a mean WTP of £373. The variance in WTP was high. Of those opting for extraction, the majority chose to leave a gap or have an implant. The preferred option was influenced by previous treatment experience. WTP was only influenced by having a low income. The high level of variance in WTP and its relatively unpredictable nature pose difficult questions for policy makers trying to ensure the delivery of an equitable service. For dentists, it is important not to make assumptions about patient preference and strength of preference when making decisions. Ideally, WTP values should be considered alongside effectiveness data, and those on costs, in policy making. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  17. Factors affecting 18 F FDOPA standardized uptake value in patients with primary brain tumors after treatment

    International Nuclear Information System (INIS)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Villani, Veronica; Carapella, Carmine; Pace, Andrea; Di Pietro, Barbara; Di Russo, Carmen; Palumbo, Barbara; Floris, Roberto; Schillaci, Orazio

    2015-01-01

    Aim: To investigate the factors affecting 18 F FDOPA uptake in patients with primary brain tumors (PBT) after treatment. Materials and methods: 97 patients with PBT (6 were grade I, 40 were grade II, 29 were grade III and 22 were grade IV) underwent 18 F FDOPA positron emission tomography/computed tomography (PET/CT) after treatment. Intervals from surgery, chemotherapy (CHT) and radiotherapy (RT) were 41.48 (± 42.27), 16.04 (± 29.08) and 28.62 (± 34.49) months respectively. Results: 18 F FDOPA uptake in the site of recurrence was not related to the interval from surgery and CHT while a significant relationship has been found with the interval from RT and tumor grade. Conclusions: The results of our study show that the interval from RT and the grade of PBT should be considered carefully when evaluating brain PET/CT scans since these factors could directly affect 18 F FDOPA uptake

  18. Zinc treatment increases the titre of 'Candidatus Liberibacter asiaticus' in huanglongbing-affected citrus plants while affecting the bacterial microbiomes

    Science.gov (United States)

    The bacterial microbiomes of citrus plants in response to ‘Candidatus Liberibacter asiaticus’ (Las)-infection and zinc treatments were deciphered by Phylochip-based metagenomics. The results indicated that 5,475 of over 50,000 known Operational Taxonomic Units (OTUs) in 52 phyla were detected in cit...

  19. Factors affecting stone-free rate and complications of percutaneous nephrolithotomy for treatment of staghorn stone.

    Science.gov (United States)

    el-Nahas, Ahmed R; Eraky, Ibrahim; Shokeir, Ahmed A; Shoma, Ahmed M; el-Assmy, Ahmed M; el-Tabey, Nasr A; Soliman, Shady; Elshal, Ahmed M; el-Kappany, Hamdy A; el-Kenawy, Mahmoud R

    2012-06-01

    To determine factors affecting the stone-free rate and complications of percutaneous nephrolithotomy (PNL) for treatment of staghorn stones. The computerized database of patients who underwent PNL for treatment of staghorn stones between January 2003 and January 2011 was reviewed. All perioperative complications were recorded and classified according to modified Clavien classification system. The stone-free rate was evaluated with low-dose noncontrast computed tomography (CT). Univariate and multivariate statistical analyses were performed to determine factors affecting stone-free and complication rates. The study included 241 patients (125 male and 116 female) with a mean age of 48.7 ±14.3 years. All patients underwent 251 PNL (10 patients had bilateral stones). The stone-free rate of PNL monotherapy was 56% (142 procedures). At 3 months, the stone-free rate increased to 73% (183 kidneys) after shock wave lithotripsy. Independent risk factors for residual stones were complete staghorn stone and presence of secondary calyceal stones (relative risks were 2.2 and 3.1, respectively). The complication rate was 27% (68 PNL). Independent risk factors for development of complications were performance of the procedure by urologists other than experienced endourologist and positive preoperative urine culture (relative risks were 2.2 and 2.1, respectively). Factors affecting the incidence of residual stones after PNL are complete staghorn stones and the presence of secondary calyceal stones. Complications are significantly high if PNL is not performed by an experienced endourologist or if preoperative urine culture is positive. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. How the detector resolution affects the clinical significance of SBRT pre-treatment quality assurance results.

    Science.gov (United States)

    Bruschi, A; Esposito, M; Pini, S; Ghirelli, A; Zatelli, G; Russo, S

    2017-12-01

    Aim of this work was to study how the detector resolution can affect the clinical significance of SBRT pre-treatment volumetric modulated arc therapy (VMAT) verification results. Three detectors (PTW OCTAVIUS 4D 729, 1500 and 100 SRS) used in five configurations with different resolution were compared: 729, 729 merged, 1500, 1500 merged and 1000 SRS. Absolute local gamma passing rates of 3D pre-treatment quality assurance (QA) were evaluated for 150 dose distributions in 30 plans. Five different kinds of error were introduced in order to establish the detection sensitivity of the three devices. Percentage dosimetric differences were evaluated between planned dosevolume histogram (DVH) and patients' predicted DVH calculated by PTW DVH 4D® software. The mean gamma passing rates and the standard deviations were 92.4% ± 3.7%, 94.6% ± 1.8%, 95.3% ± 4.2%, 97.4% ± 2.5% and 97.6% ± 1.4 respectively for 729, 729 merged, 1500, 1500 merged and 1000 SRS with 2% local dose/2mm criterion. The same trend was found on the sensitivity analysis: using a tight gamma analysis criterion (2%L/1mm) only the 1000 SRS detected every kind of error, while 729 and 1500 merged detected three and four kinds of error respectively. Regarding dose metrics extracted from DVH curves, D50% was within the tolerance level in more than 90% of cases only for the 1000 SRS. The detector resolution can significantly affect the clinical significance of SBRT pre-treatment verification results. The choice of a detector with resolution suitable to the investigated field size is of main importance to avoid getting false positive. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  1. External Resistances Applied to MFC Affect Core Microbiome and Swine Manure Treatment Efficiencies

    Science.gov (United States)

    Vilajeliu-Pons, Anna; Bañeras, Lluis; Puig, Sebastià; Molognoni, Daniele; Vilà-Rovira, Albert; Hernández-del Amo, Elena; Balaguer, Maria D.; Colprim, Jesús

    2016-01-01

    Microbial fuel cells (MFCs) can be designed to combine water treatment with concomitant electricity production. Animal manure treatment has been poorly explored using MFCs, and its implementation at full-scale primarily relies on the bacterial distribution and activity within the treatment cell. This study reports the bacterial community changes at four positions within the anode of two almost identically operated MFCs fed swine manure. Changes in the microbiome structure are described according to the MFC fluid dynamics and the application of a maximum power point tracking system (MPPT) compared to a fixed resistance system (Ref-MFC). Both external resistance and cell hydrodynamics are thought to heavily influence MFC performance. The microbiome was characterised both quantitatively (qPCR) and qualitatively (454-pyrosequencing) by targeting bacterial 16S rRNA genes. The diversity of the microbial community in the MFC biofilm was reduced and differed from the influent swine manure. The adopted electric condition (MPPT vs fixed resistance) was more relevant than the fluid dynamics in shaping the MFC microbiome. MPPT control positively affected bacterial abundance and promoted the selection of putatively exoelectrogenic bacteria in the MFC core microbiome (Sedimentibacter sp. and gammaproteobacteria). These differences in the microbiome may be responsible for the two-fold increase in power production achieved by the MPPT-MFC compared to the Ref-MFC. PMID:27701451

  2. Multiple Sclerosis-related Uveitis: Does MS Treatment Affect Uveitis Course?

    Science.gov (United States)

    Jouve, Léa; Benrabah, Rabah; Héron, Emmanuel; Bodaghi, Bahram; Le Hoang, Phuc; Touitou, Valérie

    2017-06-01

    Few data are available regarding the optimal treatment of multiple sclerosis (MS)-related uveitis. The aim of this study was to describe clinical features of MS-associated uveitis and determine how MS treatment affects the course of uveitis. Retrospective, multicenter study. Patients were divided into two groups according to the use (group 2) or not (group 1) of immunomodulatory drugs. Characteristics of uveitis and treatment were reviewed. A total of 68 eyes from 36 patients (17 in group 1 and 19 in group 2) were included. All patients were treated with topical and/or systemic steroids for uveitis. Uveitis occurred 1-17 years prior to neurologic symptoms in 78% of patients. Uveitis was more severe in group 2 (puveitis (p = 0.06). MS-related uveitis has often a favorable evolution. Patients on interferon-beta have more severe and chronic uveitis. As far as we are concerned, interferon-beta given on the sole indication of uveitis is not recommended. If steroid-sparing agent is required for intraocular inflammation, immunosuppressive drugs should be considered.

  3. Metformin Treatment Does Not Affect Testicular Size in Offspring Born to Mothers with Gestational Diabetes.

    Science.gov (United States)

    Tertti, Kristiina; Toppari, Jorma; Virtanen, Helena E; Sadov, Sergey; Rönnemaa, Tapani

    2016-01-01

    Studies in rodents suggest that metformin treatment during pregnancy may have harmful effects on testicular development in offspring. Our aim was to determine whether metformin treatment of gestational diabetes mellitus (GDM) affects testicular size in male offspring. We compared the testicular size in prepubertal boys born to mothers who participated in a randomized controlled trial (RCT) comparing metformin with insulin in the treatment of GDM. Twenty-five (42.4% of invited) and 27 (52.9% of invited) boys whose mothers had been treated with metformin or insulin, respectively, participated in the study. Testicular size was measured by a ruler, an orchidometer, and by ultrasonography at the age of 33 to 85 months. The mean age of the boys was 60 months at the time of examination, and did not differ between the metformin and insulin group (p = 0.88). There was no difference in testicular size between the boys in the two groups (p always ≥ 0.40), and there were no significant differences in height, weight, BMI, BMI z-score, or waist-to-hip ratio (WHR) between the boys in the groups. Prepubertal testicular size did not differ between offspring born to metformin-treated mothers and those born to insulin-treated mothers.

  4. Treatment of Osteomyelitis: A Case for Disruption of the Affected Adjacent Periosteum.

    Science.gov (United States)

    Hudson, John W; Daly, Austin P; Foster, Michael

    2017-10-01

    To evaluate the response of mandibular osteomyelitis treated by surgical decortication with disruption of the affected adjacent periosteum in concert with long-term targeted antibiotic therapy. The hypothesis is that, by removing the buccal cortical plate and disrupting the hypertrophically inflamed adjacent periosteum, the medullary bone will be brought in contact with bleeding tissue and circulating immunologic factors and antibiotics, which will promote definitive resolution. A retrospective review was conducted of 7 patient charts with associated radiographs from November 2010 to August 2016 treated by the first author at the University of Tennessee Medical Center (Knoxville, TN). Patients with chronic suppurative or nonsuppurative osteomyelitis of the mandible without condylar involvement or pathologic fracture were selected and treated with decortication with periosteal disruption in combination with long-term targeted antibiotic therapy. Seven patients (3 women and 4 men; mean age, 60 yr) underwent decortication with periosteal disruption of the affected area and received at least 6 weeks of targeted intravenous antibiotics. Computed tomography was performed preoperatively and a repeat study was performed after completion of antibiotics. In each case, post-treatment imaging showed definitive resolution after treatment with decortication in concert with disruption of the inflamed hypertrophic periosteum and intravenous antibiotics. Debridement of the infected cortical bone with restoration of the blood supply through disruption of the adjacent periosteum provided definitive resolution of mandibular osteomyelitis in the 7 patients treated. The hypothesis is that disruption of the affected adjacent periosteum reintroduces an immune-mediated response in concert with improved antibiotic delivery to and penetrance of the diseased mandible, aiding in definitive resolution. Decortication with periosteal disruption allows for preservation of the inferior alveolar

  5. Bisphosphonate-associated atypical sub-trochanteric femur fractures: paired bone biopsy quantitative histomorphometry before and after teriparatide administration.

    Science.gov (United States)

    Miller, Paul D; McCarthy, Edward F

    2015-04-01

    Bisphosphonate-associated atypical sub-trochanteric femur fractures (ASFF) may be seen with long-term bisphosphonate use, though these fractures are also seen in patients never exposed to bisphosphonates. One theory for the mechanism of action whereby bisphosphonates may induce these ASFF is over-suppression of bone turnover. Bisphosphonates suppress bone turnover, but in bisphosphonate clinical trials, over-suppression defined whether by maintaining the biochemical markers of bone turnover below the defined reference range or by quantitative bone histomorphometry, has not been observed. We studied 15 clinic patients referred to The Colorado Center for Bone Research (CCBR) after they had a bisphosphonate-associated ASFF and performed quantitative bone histomorphometry both before and after 12 months of teriparatide (20µg SQ/day). All patients had been on long-term alendronate (mean = 7 years, range: 6-11 years) and had already had intramedullary rods placed when first seen (6 weeks to 7 months after rod placement). Alendronate had been discontinued in all patients at the time of their first clinic visit to CCBR. All of the fractures fulfilled The American Society for Bone and Mineral Research major radiological criteria for ASFF. Three key dynamic histomorphometric features show that 7 of the 15 patients had unmeasurable bone formation, mineralizing surface, and mineral apposition, while the other 8 patients had measurable dynamic parameters; although for all 15 patients, the mean values for all 3 dynamic parameters was far below the average for the published normal population. Administration of teriparatide was associated with an increase in all 3 dynamic histomorphometric parameters. Baseline bone turnover markers did not correlate with the baseline histomorphometry. While there is heterogeneity in the bone turnover in patients with bisphosphonate ASFF, there is a large portion in this uncontrolled series that had absent bone turnover at the standard biopsy site

  6. 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.

  7. Fascioliasis and Intestinal Parasitoses Affecting Schoolchildren in Atlixco, Puebla State, Mexico: Epidemiology and Treatment with Nitazoxanide

    Science.gov (United States)

    Zumaquero-Ríos, José Lino; Sarracent-Pérez, Jorge; Rojas-García, Raúl; Rojas-Rivero, Lázara; Martínez-Tovilla, Yaneth; Valero, María Adela; Mas-Coma, Santiago

    2013-01-01

    Background The Atlixco municipality, Puebla State, at a mean altitude of 1840 m, was selected for a study of Fasciola hepatica infection in schoolchildren in Mexico. This area presents permanent water collections continuously receiving thaw water from Popocatepetl volcano (5426 m altitude) through the community supply channels, conforming an epidemiological scenario similar to those known in hyperendemic areas of Andean countries. Methodology and Findings A total of 865 6–14 year-old schoolchildren were analyzed with FasciDIG coproantigen test and Lumbreras rapid sedimentation technique, and quantitatively assessed with Kato-Katz. Fascioliasis prevalences ranged 2.94–13.33% according to localities (mean 5.78%). Intensities were however low (24–384 epg). The association between fascioliasis and the habit of eating raw vegetables was identified, including watercress and radish with pronouncedly higher relative risk than lettuce, corncob, spinach, alfalfa juice, and broccoli. Many F. hepatica-infected children were coinfected by other parasites. Entamoeba histolytica/dispar, Giardia intestinalis, Blastocystis hominis, Hymenolepis nana and Ascaris lumbricoides infection resulted in risk factors for F. hepatica infection. Nitazoxanide efficacy against fascioliasis was 94.0% and 100% after first and second treatment courses, respectively. The few children, for whom a second treatment course was needed, were concomitantly infected by moderate ascariasis burdens. Its efficacy was also very high in the treatment of E. histolytica/E. dispar, G. intestinalis, B. hominis, H. nana, A. lumbricoides, Trichuris trichiura, and Enterobius vermicularis. A second treatment course was needed for all children affected by ancylostomatids. Conclusions Fascioliasis prevalences indicate this area to be mesoendemic, with isolated hyperendemic foci. This is the first time that a human fascioliasis endemic area is described in North America. Nitazoxanide appears as an appropriate

  8. Fascioliasis and intestinal parasitoses affecting schoolchildren in Atlixco, Puebla State, Mexico: epidemiology and treatment with nitazoxanide.

    Science.gov (United States)

    Zumaquero-Ríos, José Lino; Sarracent-Pérez, Jorge; Rojas-García, Raúl; Rojas-Rivero, Lázara; Martínez-Tovilla, Yaneth; Valero, María Adela; Mas-Coma, Santiago

    2013-11-01

    The Atlixco municipality, Puebla State, at a mean altitude of 1840 m, was selected for a study of Fasciola hepatica infection in schoolchildren in Mexico. This area presents permanent water collections continuously receiving thaw water from Popocatepetl volcano (5426 m altitude) through the community supply channels, conforming an epidemiological scenario similar to those known in hyperendemic areas of Andean countries. A total of 865 6-14 year-old schoolchildren were analyzed with FasciDIG coproantigen test and Lumbreras rapid sedimentation technique, and quantitatively assessed with Kato-Katz. Fascioliasis prevalences ranged 2.94-13.33% according to localities (mean 5.78%). Intensities were however low (24-384 epg). The association between fascioliasis and the habit of eating raw vegetables was identified, including watercress and radish with pronouncedly higher relative risk than lettuce, corncob, spinach, alfalfa juice, and broccoli. Many F. hepatica-infected children were coinfected by other parasites. Entamoeba histolytica/dispar, Giardia intestinalis, Blastocystis hominis, Hymenolepis nana and Ascaris lumbricoides infection resulted in risk factors for F. hepatica infection. Nitazoxanide efficacy against fascioliasis was 94.0% and 100% after first and second treatment courses, respectively. The few children, for whom a second treatment course was needed, were concomitantly infected by moderate ascariasis burdens. Its efficacy was also very high in the treatment of E. histolytica/E. dispar, G. intestinalis, B. hominis, H. nana, A. lumbricoides, Trichuris trichiura, and Enterobius vermicularis. A second treatment course was needed for all children affected by ancylostomatids. Fascioliasis prevalences indicate this area to be mesoendemic, with isolated hyperendemic foci. This is the first time that a human fascioliasis endemic area is described in North America. Nitazoxanide appears as an appropriate alternative to triclabendazole, the present drug of choice

  9. Fascioliasis and intestinal parasitoses affecting schoolchildren in Atlixco, Puebla State, Mexico: epidemiology and treatment with nitazoxanide.

    Directory of Open Access Journals (Sweden)

    José Lino Zumaquero-Ríos

    2013-11-01

    Full Text Available The Atlixco municipality, Puebla State, at a mean altitude of 1840 m, was selected for a study of Fasciola hepatica infection in schoolchildren in Mexico. This area presents permanent water collections continuously receiving thaw water from Popocatepetl volcano (5426 m altitude through the community supply channels, conforming an epidemiological scenario similar to those known in hyperendemic areas of Andean countries.A total of 865 6-14 year-old schoolchildren were analyzed with FasciDIG coproantigen test and Lumbreras rapid sedimentation technique, and quantitatively assessed with Kato-Katz. Fascioliasis prevalences ranged 2.94-13.33% according to localities (mean 5.78%. Intensities were however low (24-384 epg. The association between fascioliasis and the habit of eating raw vegetables was identified, including watercress and radish with pronouncedly higher relative risk than lettuce, corncob, spinach, alfalfa juice, and broccoli. Many F. hepatica-infected children were coinfected by other parasites. Entamoeba histolytica/dispar, Giardia intestinalis, Blastocystis hominis, Hymenolepis nana and Ascaris lumbricoides infection resulted in risk factors for F. hepatica infection. Nitazoxanide efficacy against fascioliasis was 94.0% and 100% after first and second treatment courses, respectively. The few children, for whom a second treatment course was needed, were concomitantly infected by moderate ascariasis burdens. Its efficacy was also very high in the treatment of E. histolytica/E. dispar, G. intestinalis, B. hominis, H. nana, A. lumbricoides, Trichuris trichiura, and Enterobius vermicularis. A second treatment course was needed for all children affected by ancylostomatids.Fascioliasis prevalences indicate this area to be mesoendemic, with isolated hyperendemic foci. This is the first time that a human fascioliasis endemic area is described in North America. Nitazoxanide appears as an appropriate alternative to triclabendazole, the present

  10. Bone Loss Prevention of Bisphosphonates in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yan Hu

    2017-01-01

    Full Text Available Objective. The purpose of this study was to evaluate the effect of bisphosphonates in improving bone mineral density (BMD and decreasing the occurrence rate of fractures and adverse events in patients with inflammatory bowel disease (IBD. Methods. Randomized controlled trials (RCTs which use bisphosphonates in IBD patients were identified in PubMed, MEDLINE database, EMBASE database, Web of Knowledge, and the Cochrane Databases between 1990 and June 2016. People received bisphosphonate or placebos with a follow-up of at least one year were also considered. STATA 12.0 software was used for the meta-analysis. Results. Eleven randomized clinical trials were included in the meta-analysis. The data indicated that the percentage change in the increased BMD in the bisphosphonates groups was superior to that of the control groups at the lumbar spine and total hip. At the femoral neck, there was no significant difference between the two groups. The incidence of new fractures during follow-up showed significant reduction. The adverse event analysis revealed no significant difference between the two groups. Conclusion. Our results demonstrate that bisphosphonates therapy has an effect on bone loss in patients with IBD but show no evident efficiency at increasing the incidence of adverse events.

  11. Investigation of patient, tumour and treatment variables affecting residual motion for respiratory-gated radiotherapy

    International Nuclear Information System (INIS)

    George, R; Ramakrishnan, V; Siebers, J V; Chung, T D; Keall, P J

    2006-01-01

    Respiratory gating can reduce the apparent respiratory motion during imaging and treatment; however, residual motion within the gating window remains. Respiratory training can improve respiratory reproducibility and, therefore, the efficacy of respiratory-gated radiotherapy. This study was conducted to determine whether residual motion during respiratory gating is affected by patient, tumour or treatment characteristics. The specific aims of this study were to: (1) identify significant characteristics affecting residual motion, (2) investigate time trends of residual motion over a period of days (inter-session) and (3) investigate time trends of residual motion within the same day (intra-session). Twenty-four lung cancer patients were enrolled in an Institutional Review Board (IRB)-approved protocol. For approximately five sessions, 331 four-minute, respiratory motion traces were acquired with free breathing, audio instructions and audio-visual biofeedback for each patient. The residual motion was quantified by the standard deviation of the displacement within the gating window. The generalized linear model was used to obtain coefficients for each variable within the model and to evaluate the clinical and statistical significance. The statistical significance was determined by a p-value <0.05, while effect sizes of ≥0.1 cm (one standard deviation) were considered clinically significant. This data analysis was applied to patient, tumour and treatment variables. Inter- and intra-session variations were also investigated. The only variable that was significant for both inhale- and exhale-based gating was disease type. In addition, visual-training displacement, breathing type and Karnofsky performance status (KPS) values were significant for inhale-based gating, and dose-per-fraction was significant for exhale-based gating. Temporal respiratory variations within and between sessions were observed for individual patients. However inter- and intra-session analyses did

  12. Investigation of patient, tumour and treatment variables affecting residual motion for respiratory-gated radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    George, R [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Ramakrishnan, V [Department of Biostatistics, Virginia Commonwealth University, Richmond, VA (United States); Siebers, J V [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Chung, T D [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Keall, P J [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States)

    2006-10-21

    Respiratory gating can reduce the apparent respiratory motion during imaging and treatment; however, residual motion within the gating window remains. Respiratory training can improve respiratory reproducibility and, therefore, the efficacy of respiratory-gated radiotherapy. This study was conducted to determine whether residual motion during respiratory gating is affected by patient, tumour or treatment characteristics. The specific aims of this study were to: (1) identify significant characteristics affecting residual motion, (2) investigate time trends of residual motion over a period of days (inter-session) and (3) investigate time trends of residual motion within the same day (intra-session). Twenty-four lung cancer patients were enrolled in an Institutional Review Board (IRB)-approved protocol. For approximately five sessions, 331 four-minute, respiratory motion traces were acquired with free breathing, audio instructions and audio-visual biofeedback for each patient. The residual motion was quantified by the standard deviation of the displacement within the gating window. The generalized linear model was used to obtain coefficients for each variable within the model and to evaluate the clinical and statistical significance. The statistical significance was determined by a p-value <0.05, while effect sizes of {>=}0.1 cm (one standard deviation) were considered clinically significant. This data analysis was applied to patient, tumour and treatment variables. Inter- and intra-session variations were also investigated. The only variable that was significant for both inhale- and exhale-based gating was disease type. In addition, visual-training displacement, breathing type and Karnofsky performance status (KPS) values were significant for inhale-based gating, and dose-per-fraction was significant for exhale-based gating. Temporal respiratory variations within and between sessions were observed for individual patients. However inter- and intra-session analyses did

  13. Does outcome of neuropsychological treatment in patients with unilateral spatial neglect after stroke affect functional outcome?

    Science.gov (United States)

    Matano, A; Iosa, M; Guariglia, C; Pizzamiglio, L; Paolucci, S

    2015-12-01

    .039) effectively predict the response to neuropsychological treatment. The outcome of the whole rehabilitation resulted affected by the outcome of neuropsychological treatment in patients with USN, being a low score at Barrage test at the beginning of therapy a negative predictor of USN recovery. Patients with USN after stroke can benefit of a specific training for reducing USN also in terms of functional outcome. Further, the simple use of Barrage test could provide important prognostic information about recovery.

  14. Zinc Transport Differs in Rat Spermatogenic Cell Types and Is Affected by Treatment with Cyclophosphamide1

    Science.gov (United States)

    Downey, Anne Marie; Hales, Barbara F.; Robaire, Bernard

    2016-01-01

    Adequate zinc levels are required for proper cellular functions and for male germ cell development. Zinc transport is accomplished by two families of zinc transporters, the ZIPs and the ZnTs, that increase and decrease cytosolic zinc levels, respectively. However, very little is known about zinc transport in the testis. Furthermore, whether cytotoxic agents such as cyclophosphamide (CPA), a known male germ cell toxicant, can affect zinc transport and homeostasis is unknown. We examined zinc transporter expression and zinc transport in pachytene spermatocytes (PS) and round spermatids (RS) in a normal state and after exposure to CPA. We observed differences in the expression of members of the ZnT and ZIP families in purified populations of PS and RS. We also observed that RS accumulate more zinc over time than PS. The expression of many zinc binding genes was altered after CPA treatment. Interestingly, we found that the expression levels of ZIP5 and ZIP14 were increased in PS from animals treated daily with 6 mg/kg CPA for 4 wk but not in RS. This up-regulation led to an increase in zinc uptake in PS but not in RS from treated animals compared to controls. These data suggest that CPA treatment may alter zinc homeostasis in male germ cells leading to an increased need for zinc. Altered zinc homeostasis may disrupt proper germ cell development and contribute to infertility and effects on progeny. PMID:27281708

  15. Pharmacological treatments in asthma-affected horses: A pair-wise and network meta-analysis.

    Science.gov (United States)

    Calzetta, L; Roncada, P; di Cave, D; Bonizzi, L; Urbani, A; Pistocchini, E; Rogliani, P; Matera, M G

    2017-11-01

    Equine asthma is a disease characterised by reversible airflow obstruction, bronchial hyper-responsiveness and airway inflammation following exposure of susceptible horses to specific airborne agents. Although clinical remission can be achieved in a low-airborne dust environment, repeated exacerbations may lead to irreversible airway remodelling. The available data on the pharmacotherapy of equine asthma result from several small studies, and no head-to-head clinical trials have been conducted among the available medications. To assess the impact of the pharmacological interventions in equine asthma and compare the effect of different classes of drugs on lung function. Pair-wise and network meta-analysis. Literature searches for clinical trials on the pharmacotherapy of equine asthma were performed. The risk of publication bias was assessed by funnel plots and Egger's test. Changes in maximum transpulmonary or pleural pressure, pulmonary resistance and dynamic lung compliance vs. control were analysed via random-effects models and Bayesian networks. The results obtained from 319 equine asthma-affected horses were extracted from 32 studies. Bronchodilators, corticosteroids and chromones improved maximum transpulmonary or pleural pressure (range: -8.0 to -21.4 cmH 2 O; Ptherapies. Long-term treatments were more effective than short-term treatments. Weak publication bias was detected. This study demonstrates that long-term treatments with inhaled corticosteroids and long-acting β 2 -AR agonists may represent the first choice for treating equine asthma. Further high quality clinical trials are needed to clarify whether inhaled bronchodilators should be preferred to inhaled corticosteroids or vice versa, and to investigate the potential superiority of combination therapy in equine asthma. © 2017 EVJ Ltd.

  16. Factors Affecting Distribution of Estrogenicity in the Influents, Effluents, and Biosolids of Canadian Wastewater Treatment Plants.

    Science.gov (United States)

    Shieh, Ben H H; Louie, Alvin; Law, Francis C P

    2016-05-01

    Canadian wastewater treatment plants (WWTPs) release significant amounts of estrogenic chemicals to nearby surface waters. Environmental estrogens have been implicated as the causative agents of many developmental and reproductive problems in animals, including fish. The goals of this study were to assess the estrogenic activity in the influents, effluents, and biosolids of thirteen Canadian WWTPs using the yeast estrogen screen (YES) bioassay and to investigate whether factors, such as wastewater treatment method, sample storage, extraction efficiency, population, and summer/winter temperature had any effects on the distribution of estrogenicity in the WWTPs. Results of the study showed that estrogenicity from the influent to the effluent decreased in seven WWTPs, increased in two WWTPs, and did not change in four WWTPs during the winter. Estrogenic concentrations generally decreased in the order of biosolids > influents > effluents and ranged from 1.57 to 24.6, 1.25E-02 to 3.84E-01, and 9.46E-03 to 3.90E-01 ng estradiol equivalents/g or ml, respectively. The estrogenicity in the final effluents, but not those in the influents and biosolids, was significantly higher in the summer than the winter. Among the WWTP treatment methods, advanced, biological nutrient removal appeared to be the most effective method to remove estrogenic chemicals from wastewaters in Canada. Our studies help to identify factors or mechanisms that affect the distribution of estrogenicity in WWTPs, providing a better understanding on the discharges of estrogenic chemicals from WWTPs.

  17. Organization of medical aid and treatment of individuals affected in radiation accidents

    International Nuclear Information System (INIS)

    Mikhajlov, M.G.; Andreev, E.A.; Bliznakov, V.

    1979-01-01

    The emergency programme of the medical service for radiation accidents constitutes part of the whole emergency programme of the establishment whose production process is derectly connected with the utilization of ionizing radiation sources. The chief of the establishment health centre also heads the operative radiation accident group. When a radiation accident occurs the medical personnel, according to a previously developed plan, reports at the Health centre. The medical aid is based on the principle of step treatment and evacuation of the affected persons, according to the prescriptions. The first step of the medical evacuation is the health centre; the second - the District hospital, where a team of specialists is formed, all of them previously well trained in the recognition and treatment of radiation sickness. The third step is the specialized clinic for radiation injuries. Persons, who have received irradiation dose of up to 100 rad, or are in a shock state, or have incorporated radioactive substances, are temporarily hospitalized at the health centre. The assistance rended to them consists of: control of shock, asphyxia and bleeding, primary surgical treatment of wounds in cases of complex injuries, deactivation under dosimetric control, attempt for accelerated removal of the radioactive substances, etc. At the District hospital and the specialized clinic the therapeutic measures are conformed to the pathogenetic mechanism and severity of clinical symptoms, and their dynamics. Their aim is first of all to block the earlier radiation effects, to prevent and to treat the haemorrhagic phenomena and infectious complications, to restore the activity of the blood organs, etc. (A.B.)

  18. Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α.

    Science.gov (United States)

    Brunetti, G; Papadia, F; Tummolo, A; Fischetto, R; Nicastro, F; Piacente, L; Ventura, A; Mori, G; Oranger, A; Gigante, I; Colucci, S; Ciccarelli, M; Grano, M; Cavallo, L; Delvecchio, M; Faienza, M F

    2016-07-01

    In this study, we investigated the bone cell activity in patients with osteogenesis imperfecta (OI) treated and untreated with neridronate. We demonstrated the key role of Dickkopf-1 (DKK1), receptor activator of nuclear factor-κB ligand (RANKL), and tumor necrosis factor alpha (TNF-α) in regulating bone cell of untreated and treated OI subjects. These cytokines could represent new pharmacological targets for OI. Bisphosphonates are widely used in the treatment of children with osteogenesis imperfecta (OI) with the objective of reducing the risk of fractures. Although bisphosphonates increase bone mineral density in OI subjects, the effects on fracture incidence are conflicting. The aim of this study was to investigate the mechanisms underlying bone cell activity in subjects with mild untreated forms of OI and in a group of subjects with severe OI treated with cycles of intravenous neridronate. Sclerostin, DKK1, TNF-α, RANKL, osteoprotegerin (OPG), and bone turnover markers were quantified in serum of 18 OI patients (12 females, mean age 8.86 ± 3.90), 8 of which were receiving cyclic intravenous neridronate, and 21 sex- and age-matched controls. The effects on osteoblastogenesis and OPG expression of media conditioned by the serum of OI patients and anti-DKK1 neutralizing antibody were evaluated. Osteoclastogenesis was assessed in cultures from patients and controls. DKK1 and RANKL levels were significantly increased both in untreated and in treated OI subjects with respect to controls. The serum from patients with high DKK1 levels inhibited both osteoblast differentiation and OPG expression in vitro. High RANKL and low OPG messenger RNA (mRNA) levels were found in lymphomonocytes from patients. High amounts of TNF-α were expressed by monocytes, and an elevated percentage of circulating CD11b-CD51/CD61+ osteoclast precursors was observed in patients. Our study demonstrated the key role of DKK1, RANKL, and TNF-α in regulating bone cell activity of subjects

  19. Prediction of bioavailability of selected bisphosphonates using in silico methods towards categorization into a biopharmaceutical classification system.

    Science.gov (United States)

    Biernacka, Joanna; Betlejewska-Kielak, Katarzyna; Kłosińska-Szmurło, Ewa; Pluciński, Franciszek A; Mazurek, Aleksander P

    2013-01-01

    The physicochemical properties relevant to biological activity of selected bisphosphonates such as clodronate disodium salt, etidronate disodium salt, pamidronate disodium salt, alendronate sodium salt, ibandronate sodium salt, risedronate sodium salt and zoledronate disodium salt were determined using in silico methods. The main aim of our research was to investigate and propose molecular determinants thataffect bioavailability of above mentioned compounds. These determinants are: stabilization energy (deltaE), free energy of solvation (deltaG(solv)), electrostatic potential, dipole moment, as well as partition and distribution coefficients estimated by the log P and log D values. Presented values indicate that selected bisphosphonates a recharacterized by high solubility and low permeability. The calculated parameters describing both solubility and permeability through biological membranes seem to be a good bioavailability indicators of bisphosphonates examined and can be a useful tool to include into Biopharmaceutical Classification System (BCS) development.

  20. Bisphosphonate-related osteonecrosis of the jaw in a multiple myeloma patient: A case report with characteristic radiographic features.

    Science.gov (United States)

    Lee, Byung-Do; Park, Moo-Rim; Kwon, Kyung-Hwan

    2015-09-01

    A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature.

  1. Bisphosphonate-related osteonecrosis of the jaw in a multiple myeloma patient: A case report with characteristic radiographic features

    International Nuclear Information System (INIS)

    Lee, Byung Do; Kwon, Kyung Hwan; Park, Moo Rim

    2015-01-01

    A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature

  2. Bisphosphonate-related osteonecrosis of the jaw in a multiple myeloma patient: A case report with characteristic radiographic features

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Do; Kwon, Kyung Hwan [College of Dentistry, Wonkwang University, Iksan (Korea, Republic of); Park, Moo Rim [Dept. of Internal Medicine, School of Medicine, Wonkwang University, Iksan (Korea, Republic of)

    2015-09-15

    A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature.

  3. Symptomatic Hypocalcemia Associated with Zoledronic Acid Treatment for Osteoporosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Abdulmohsen H. Al Elq

    2013-03-01

    Full Text Available Intravenous bisphosphonates are widely used in the management of solid tumors, metastatic bone disease, metabolic bone diseases and hypercalcemia of malignancies. Recently, yearly intravenous injections of zoledronic acid, one of the potent nitrogen-containing bisphosphonates, have also been approved for the prevention and treatment of osteoporosis. Although infrequently observed, asymptomatic hypocalcemia mainly due to intravenous bisphosphonates has been documented. Here we report a female patient who exhibited profound symptomatic hypocalcemia after receiving intravenous zoledronic acid as treatment of postmenopausal osteoporosis. The patient was not assessed for calcium status prior to the intravenous bisphosphonate therapy, and she was later found to have severe vitamin D deficiency. To our knowledge, this is the first patient with symptomatic hypocalcemia to be reported after zoledronic acid was approved for the management of osteoporosis. We highlight the importance of evaluating calcium and vitamin D levels before initiating intravenous bisphosphonate treatment, particularly in the presence of widespread vitamin D deficiency and the likelihood of future increases in the prescription of intravenous bisphosphonates.

  4. Interaction between Bisphosphonates and Mineral Water: Study of Oral Risedronate Absorption in Rats.

    Science.gov (United States)

    Itoh, Akihisa; Akagi, Yuuki; Shimomura, Hitoshi; Aoyama, Takao

    2016-01-01

    Bisphosphonates are antiosteoporotic agents prescribed for patients with osteoporosis. Drug package inserts for bisphosphonate supplements indicate that their bioavailability is reduced by high levels of metal cations (Ca(2+), Mg(2+), etc.). However, standards for these cations in water used for taking risedronate have not been defined. Here, we examined the effect of calcium and magnesium in mineral waters on the bioavailability of the third-generation bisphosphonate, risedronate, following oral administration in rats. As risedronate is unchanged and eliminated renally, risedronate absorption was estimated from the amount excreted in the urine. Risedronate was dissolved in mineral water samples and administered orally at 0.35 mg/kg. Urine samples were collected for 24 h after dosing. Risedronate was extracted from urine using ion-pair solid-phase cartridges and quantified by HPLC with UV detection (262 nm). Cumulative recovery of risedronate was calculated from the amount excreted in the urine. The 24-h recovery of risedronate from evian® (0.32±0.02% [mean±standard deviation (S.D.)], n=4) and Contrex(®) (0.22±0.05%) mineral waters was significantly lower than that from tap water (0.47±0.04%, pAbsorption of risedronate in calcium chloride and magnesium chloride aqueous solutions of the same hardness (822 mg/L) was 54% (0.27±0.04%) and 12% (0.51±0.08%) lower, respectively, compared with ultrapure water; suggesting that absorption of risedronate declines as the calcium concentration of mineral waters increases. Consumption of mineral waters containing high levels of calcium (80 mg/L or above), such as evian® and Contrex(®), is therefore not recommended when taking risedronate.

  5. Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent

    International Nuclear Information System (INIS)

    Ogawa, Kazuma; Takai, Kenichiro; Kanbara, Hiroya; Kiwada, Tatsuto; Kitamura, Yoji; Shiba, Kazuhiro; Odani, Akira

    2011-01-01

    Introduction: 68 Ga is a radionuclide of great interest as a positron emitter for positron emission tomography (PET). To develop a new bone-imaging agent with radiogallium, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as a chelating site and Ga-DOTA complex-conjugated bisphosphonate, which has a high affinity for bone, was prepared and evaluated. Although we are interested in developing 68 Ga-labeled bone imaging agents for PET, in these initial studies 67 Ga was used because of its longer half-life. Methods: DOTA-conjugated bisphosphonate (DOTA-Bn-SCN-HBP) was synthesized by conjugation of 2-(4-isothiocyanatebenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate). 67 Ga-DOTA-Bn-SCN-HBP was prepared by coordination with 67 Ga, and its in vitro and in vivo evaluations were performed. Results: 67 Ga-DOTA-Bn-SCN-HBP was prepared with a radiochemical purity of over 95% without purification. 67 Ga-DOTA-Bn-SCN-HBP had great affinity for hydroxyapatite in binding assay. In biodistribution experiments, 67 Ga-DOTA-Bn-SCN-HBP accumulated in bone rapidly but was hardly observed in tissues other than bone. Pretreatment of an excess amount of alendronate inhibited the bone accumulation of 67 Ga-DOTA-Bn-SCN-HBP. Conclusions: 67 Ga-DOTA-Bn-SCN-HBP showed ideal biodistribution characteristics as a bone-imaging agent. These findings should provide useful information on the drug design of bone imaging agents for PET with 68 Ga.

  6. Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuma, E-mail: kogawa@p.kanazawa-u.ac.jp [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192 (Japan); Takai, Kenichiro; Kanbara, Hiroya; Kiwada, Tatsuto [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192 (Japan); Kitamura, Yoji; Shiba, Kazuhiro [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Odani, Akira [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192 (Japan)

    2011-07-15

    Introduction: {sup 68}Ga is a radionuclide of great interest as a positron emitter for positron emission tomography (PET). To develop a new bone-imaging agent with radiogallium, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as a chelating site and Ga-DOTA complex-conjugated bisphosphonate, which has a high affinity for bone, was prepared and evaluated. Although we are interested in developing {sup 68}Ga-labeled bone imaging agents for PET, in these initial studies {sup 67}Ga was used because of its longer half-life. Methods: DOTA-conjugated bisphosphonate (DOTA-Bn-SCN-HBP) was synthesized by conjugation of 2-(4-isothiocyanatebenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate). {sup 67}Ga-DOTA-Bn-SCN-HBP was prepared by coordination with {sup 67}Ga, and its in vitro and in vivo evaluations were performed. Results: {sup 67}Ga-DOTA-Bn-SCN-HBP was prepared with a radiochemical purity of over 95% without purification. {sup 67}Ga-DOTA-Bn-SCN-HBP had great affinity for hydroxyapatite in binding assay. In biodistribution experiments, {sup 67}Ga-DOTA-Bn-SCN-HBP accumulated in bone rapidly but was hardly observed in tissues other than bone. Pretreatment of an excess amount of alendronate inhibited the bone accumulation of {sup 67}Ga-DOTA-Bn-SCN-HBP. Conclusions: {sup 67}Ga-DOTA-Bn-SCN-HBP showed ideal biodistribution characteristics as a bone-imaging agent. These findings should provide useful information on the drug design of bone imaging agents for PET with {sup 68}Ga.

  7. Treatment of trauma-affected refugees with venlafaxine versus sertraline combined with psychotherapy - a randomised study.

    Science.gov (United States)

    Sonne, Charlotte; Carlsson, Jessica; Bech, Per; Elklit, Ask; Mortensen, Erik Lykke

    2016-11-08

    The prevalence of trauma-related psychiatric disorders is high among refugees. Despite this, little is known about the effect of pharmacological treatment for this patient group. The objective of the present study was therefore to examine differences in the effects of venlafaxine and sertraline on Post-Traumatic Stress Disorder (PTSD), depression and functional impairment in trauma-affected refugees. The study was a randomised pragmatic trial comparing venlafaxine and sertraline in combination with psychotherapy and social counselling. PTSD symptoms were measured on the Harvard Trauma Questionnaire - part IV, which was the primary outcome measure. Other outcome measures included: Hopkins Symptom Check List-25 (depression and anxiety), Social Adjustment Scale - short version (social functioning), WHO-5 Well-being Index (quality of life), Crisis Support Scale (support from social network), Sheehan Disability Scale (disability in three areas of functioning), Hamilton Depression and Anxiety scale, the somatisation items of the Symptoms Checklist-90, Global Assessment of Functioning scales and the summarised score of pain in four body areas rated on visual analogue scales. Two hundred seven adult refugee patients were included in the trial (98 in the venlafaxine and 109 in the sertraline group). Of these, 195 patients were eligible for intention-to-treat analyses. Small but significant pre-treatment to post-treatment differences were found on the Harvard Trauma Questionnaire and a number of other ratings in both groups. On the primary outcome measure, no difference was found in treatment effect between the sertraline and venlafaxine group. A significant group difference was found in favour of sertraline on the Sheehan Disability Scale. Sertraline had a slightly better outcome than venlafaxine on some of the secondary outcome measures, but not on the primary outcome measure. Furthermore, a higher percentage of dropouts was found in the venlafaxine group compared to the

  8. Bisphosphonate-Induced Osteonecrosis of the Maxilla Resembling a Persistent Endodontic Lesion.

    Science.gov (United States)

    Mosaferi, Hossein; Fazlyab, Mahta; Sharifi, Sanaz; Rahimian, Sepideh

    2016-01-01

    A 52-year-old Caucasian woman suffering from pain in the anterior maxillary region, presented to the clinic. Examination revealed a draining sinus tract in the buccal vestibule of the maxilla in the left anterior segment and expansion in the middle of palate. On conventional radiographic examination the lesion was initially assumed to be a periapical problem related to the incisors but subsequently it was diagnosed to be a bisphosphonate osteonecrosis. Acquiring a comprehensive medical history from the patients, conducting the clinical vitality tests and most importantly being familiar with the non-odontogenic lesions that can be side effects of specific medications are important requirements for reaching a correct diagnosis.

  9. Fluorescent Bisphosphonate and Carboxyphosphonate Probes: A Versatile Imaging Toolkit for Applications in Bone Biology and Biomedicine.

    Science.gov (United States)

    Sun, Shuting; Błażewska, Katarzyna M; Kadina, Anastasia P; Kashemirov, Boris A; Duan, Xuchen; Triffitt, James T; Dunford, James E; Russell, R Graham G; Ebetino, Frank H; Roelofs, Anke J; Coxon, Fraser P; Lundy, Mark W; McKenna, Charles E

    2016-02-17

    A bone imaging toolkit of 21 fluorescent probes with variable spectroscopic properties, bone mineral binding affinities, and antiprenylation activities has been created, including a novel linking strategy. The linking chemistry allows attachment of a diverse selection of dyes fluorescent in the visible to near-infrared range to any of the three clinically important heterocyclic bisphosphonate bone drugs (risedronate, zoledronate, and minodronate or their analogues). The resultant suite of conjugates offers multiple options to "mix and match" parent drug structure, fluorescence emission wavelength, relative bone affinity, and presence or absence of antiprenylation activity, for bone-related imaging applications.

  10. Smoking affects treatment outcome in patients with resected esophageal squamous cell carcinoma who received chemotherapy.

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    Yuzhen Zheng

    Full Text Available Cigarette smoking is reported to decrease survival and induce chemotherapy resistance in patients with various cancers. However, the impact of cigarette smoking on patients with esophageal squamous cell carcinoma (ESCC remains unknown.A total of 1,084 ESCC patients were retrospectively enrolled from a southern Chinese institution. Patients were divided into two groups according to their treatment modalities: the SC group (surgery with chemotherapy (n = 306 and the S group (surgery without chemotherapy (n = 778. Smoking status was quantified as smoking history (non-smoker, ex-smoker, and current smoker and cumulative smoking (0, between 0 and 20, and greater than 20 pack-years. The association between cigarette smoking and overall survival (OS was evaluated using the Kaplan-Meier method and univariate/multivariate regression analysis.Among 1,084 patients, 702 (64.8% reported a cigarette smoking history, and the 5-year OS for non-smokers and smokers was 45.8% and 37.3%, respectively. In the SC group, compared with non-smoker, the adjusted HRs of ex-smoker and current smoker were 1.540 (95% CI, 1.1-2.2 and 2.110 (95% CI, 1.4-3.1, respectively; there is a correlative trend of decreased OS with increased cigarette smoking (Ptrend = 0.001. These associations were insignificant in the S group. In subgroup analysis of the SC group, the lower OS conferred by smoking was not significantly modified by age, gender, body mass index, alcohol drinking, or chemotherapy method (chemotherapy and chemoradiotherapy.Our results suggest that smoking may affect treatment outcome in patients with resected ESCC who received chemotherapy.

  11. Which Factors Affect the Hospital Re-admission After Treatment Approaches to Urethral Strictures?

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    Reha Girgin

    2017-12-01

    Full Text Available Objective: To investigate patient- and procedure-related factors associated with hospital re-admission following urethral manipulations for the treatment of urethral strictures. Materials and Methods: Data of patients who underwent dilation or internal urethrotomy for urethral strictures between 2011 and 2016 were retrospectively analyzed. Patients who were admitted to our institute for any reason within one month after hospital discharge were evaluated. The patient- and procedure-related factors affecting the readmission rates were revealed by multiple binary logistic regression using stepwise backward elinimination. Results: The average age of 76 male patients was 61.7±14.4 years. The mean maximal flow rate at preoperative uroflowmetry was 6.01±4.3 and the median American Society of Anesthesiologists score was 2.38. The process was the first for 45 (59.2% patients, the second for 16 (21.1% patients, the third for 9 (11.8% patients, and the fourth for 6 (7.9% patients. Amplatz dilators, cold knife and Ho:YAG laser were used in 50%, 27.6% and 22.4% of patients, respectively. The mean length of hospital stay was 0.89±0.31 days, and the complication rate was 19.7% (15/76. The mean urethral catheter dwell time was 8.9±14.2 day. Overall, the procedure was successful in 61 (80.3% patients and failed (Qmax <15 mL/sec in 19.7% of the cases. Fifteen (19.7% patients were re-admitted, while 2 (2.6% patients among them were re-hospitalized for further treatment. Comorbidity and age were independent predictors of re-admission. Conclusion: We found that younger age and lower comorbidities predicted hospital re-admission following procedures for urethral strictures.

  12. Telmisartan in daily clinical practice: Factors affecting efficacy in treatment of primary arterial hypertension

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    Bergovac M

    2009-01-01

    Full Text Available Background: Telmisartan provides effective treatment of hypertension in a broad spectrum of patients. Aims: To evaluate factors affecting the efficacy of telmisartan in daily clinical practice. Setting and Design: Prospective practice-based 12-week uncontrolled cohort study. Materials and Methods: Consecutive incident/prevalent outpatients with mild to moderate essential hypertension were started on telmisartan 40 mg/day with optional up-titration to 80 mg/day in order to achieve seated systolic (SSBP and diastolic (SDBP blood pressure < 140/90 mm Hg. Intent-to-treat (ITT, N=282 and per protocol (PP, N=275 efficacy assessment was based on SSBP/SDBP reduction and delivered doses. Results: SSBP/SDBP decreased (165.2±13.1 / 98.3±6.7 mm Hg to 137.9±13.2 / 82.6±7.3 mm Hg, whilst telmisartan was up-titrated in 40.5% of patients during the study. Multivariate (practically identical ITT and PP analysis indicated poorer response in obese vs. non-obese patients: lesser SDBP reduction (by around 2.2-2.3 mm Hg, P < 0.05 with higher odds of dose up-titration (odds ratio, OR around 1.90, P < 0.05; and better response in: a patients started on telmisartan monotherapy than when added to a preexisting treatment: greater SSBP/SDBP reduction (by around 4.0 and 3.0 mm Hg, respectively, P < 0.05 with comparable odds of up-titration; b diabetics vs. non-diabetics: greater SDBP reduction (by around 3.6-3.7 mm Hg, P < 0.05 with comparable odds of up-titration; c men vs. women: slightly greater SDBP reduction (by around 1.2 mm Hg, 0.05 P < 0.1 with lower odds of up-titration (OR around 0.51, P < 0.05. Conclusion: Previous unsuccessful treatment, obesity, diabetes and gender should be considered in order to optimize the use of telmisartan for mild to moderate essential hypertension in daily clinical practice.

  13. Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect

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    Schoedel KA

    2014-06-01

    Full Text Available Kerri A Schoedel,1 Sarah A Morrow,2 Edward M Sellers3,4 1Altreos Research Partners, Inc., Toronto, 2Western University, London, 3DL Global Partners, Inc., Toronto, 4University of Toronto, Toronto, Ontario, Canada Abstract: Pseudobulbar affect (PBA is a common manifestation of brain pathology associated with many neurological diseases, including amyotrophic lateral sclerosis, Alzheimer’s disease, stroke, multiple sclerosis, Parkinson’s disease, and traumatic brain injury. PBA is defined by involuntary and uncontrollable expressed emotion that is exaggerated and inappropriate, and also incongruent with the underlying emotional state. Dextromethorphan/quinidine (DM/Q is a combination product indicated for the treatment of PBA. The quinidine component of DM/Q inhibits the cytochrome P450 2D6-mediated metabolic conversion of dextromethorphan to its active metabolite dextrorphan, thereby increasing dextromethorphan systemic bioavailability and driving the pharmacology toward that of the parent drug and away from adverse effects of the dextrorphan metabolite. Three published efficacy and safety studies support the use of DM/Q in the treatment of PBA; significant effects were seen on the primary end point, the Center for Neurologic Study-Lability Scale, as well as secondary efficacy end points and quality of life. While concentration–effect relationships appear relatively weak for efficacy parameters, concentrations of DM/Q may have an impact on safety. Some special safety concerns exist with DM/Q, primarily because of the drug interaction and QT prolongation potential of the quinidine component. However, because concentrations of dextrorphan (which is responsible for many of the parent drug’s side effects and quinidine are lower than those observed in clinical practice with these drugs administered alone, some of the perceived safety issues may not be as relevant with this low dose combination product. However, since patients with PBA have a

  14. Surgical Orthodontic Treatment of a Patient Affected by Type 1 Myotonic Dystrophy (Steinert Syndrome).

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    Cacucci, Laura; Ricci, Beatrice; Moretti, Maria; Gasparini, Giulio; Pelo, Sandro; Grippaudo, Cristina

    2017-01-01

    Myotonic dystrophy, or Steinert's disease, is the most common form of muscular dystrophy that occurs in adults. This multisystemic form involves the skeletal muscles but affects also the eye, the endocrine system, the central nervous system, and the cardiac system. The weakness of the facial muscles causes a characteristic facial appearance frequently associated with malocclusions. Young people with myotonic dystrophy, who also have severe malocclusions, have bad oral functions such as chewing, breathing, and phonation. We present a case report of a 15-year-old boy with anterior open bite, upper and lower dental crowding, bilateral crossbite, and constriction of the upper jaw with a high and narrow palate. The patient's need was to improve his quality of life. Because of the severity of skeletal malocclusion, it was necessary to schedule a combined orthodontic and surgical therapy in order to achieve the highest aesthetic and functional result. Although therapy caused an improvement in patient's quality of life, the clinical management of the case was hard. The article shows a balance between costs and benefits of a therapy that challenges the nature of the main problem of the patient, and it is useful to identify the most appropriate course of treatment for similar cases.

  15. Surgical Orthodontic Treatment of a Patient Affected by Type 1 Myotonic Dystrophy (Steinert Syndrome

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    Laura Cacucci

    2017-01-01

    Full Text Available Myotonic dystrophy, or Steinert’s disease, is the most common form of muscular dystrophy that occurs in adults. This multisystemic form involves the skeletal muscles but affects also the eye, the endocrine system, the central nervous system, and the cardiac system. The weakness of the facial muscles causes a characteristic facial appearance frequently associated with malocclusions. Young people with myotonic dystrophy, who also have severe malocclusions, have bad oral functions such as chewing, breathing, and phonation. We present a case report of a 15-year-old boy with anterior open bite, upper and lower dental crowding, bilateral crossbite, and constriction of the upper jaw with a high and narrow palate. The patient’s need was to improve his quality of life. Because of the severity of skeletal malocclusion, it was necessary to schedule a combined orthodontic and surgical therapy in order to achieve the highest aesthetic and functional result. Although therapy caused an improvement in patient’s quality of life, the clinical management of the case was hard. The article shows a balance between costs and benefits of a therapy that challenges the nature of the main problem of the patient, and it is useful to identify the most appropriate course of treatment for similar cases.

  16. Foraging at wastewater treatment works affects brown adipose tissue fatty acid profiles in banana bats

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    Kate Hill

    2016-02-01

    Full Text Available In this study we tested the hypothesis that the decrease in habitat quality at wastewater treatment works (WWTW, such as limited prey diversity and exposure to the toxic cocktail of pollutants, affect fatty acid profiles of interscapular brown adipose tissue (iBrAT in bats. Further, the antioxidant capacity of oxidative tissues such as pectoral and cardiac muscle may not be adequate to protect those tissues against reactive molecules resulting from polyunsaturated fatty acid auto-oxidation in the WWTW bats. Bats were sampled at two urban WWTW, and two unpolluted reference sites in KwaZulu-Natal, South Africa. Brown adipose tissue (BrAT mass was lower in WWTW bats than in reference site bats. We found lower levels of saturated phospholipid fatty acids and higher levels of mono- and polyunsaturated fatty acids in WWTW bats than in reference site bats, while C18 desaturation and n-6 to n-3 ratios were higher in the WWTW bats. This was not associated with high lipid peroxidation levels in pectoral and cardiac muscle. Combined, these results indicate that WWTW bats rely on iBrAT as an energy source, and opportunistic foraging on abundant, pollutant-tolerant prey may change fatty acid profiles in their tissue, with possible effects on mitochondrial functioning, torpor and energy usage.

  17. Treatment factors affecting longitudinal quality of life in new onset pediatric epilepsy.

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    Modi, Avani C; Ingerski, Lisa M; Rausch, Joseph R; Glauser, Tracy A

    2011-05-01

    Recognizing the importance of patient-reported outcomes, this longitudinal, prospective study examined: Changes in health-related quality of life (HRQOL) over seven months following antiepileptic drug (AED) initiation and the relationship of seizures, AED side-effects, and AED type to HRQOL. Parents of 124 children with newly diagnosed epilepsy completed measures of HRQOL and side-effects at each clinic visit. Treatment information was also collected. HRQOL remained stable over time; however, seizures and AED side-effects significantly affected multiple HRQOL domains. Higher seizure activity was associated with decreased Physical HRQOL. Side-effects were negatively associated with all HRQOL domains. Children taking carbamazepine who experienced higher side-effects early in therapy demonstrated declining emotional functioning compared to children experiencing no/some side-effects. AED side-effects, AED type, and seizure frequency were associated with longitudinal HRQOL in children with newly-diagnosed epilepsy. Routine assessment of AED side-effects and HRQOL may be useful for clinical decision making.

  18. Income trajectories affect treatment of dental caries from childhood to young adulthood: a birth cohort study.

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    Peres, Marco Aurelio; Liu, Pingzhou; Demarco, Flavio Fernando; Silva, Alexandre Emidio Ribeiro; Wehrmeister, Fernando Cesar; Menezes, Ana Maria; Peres, Karen Glazer

    2018-01-01

    We aimed to analyze the effects of family income trajectories on the increase in dental caries from childhood to young adulthood. Data from the 1993 Pelotas (Brazil) birth cohort study, in which dental caries was measured at ages 6, 12, and 18 years, were analyzed. Family income of 302 participants was assessed at birth, and at 4, 11, 15, and 18 years of age. Mother's education, toothbrushing frequency, dental visiting, dental caries in primary dentition, and birth weight were covariates. A latent class growth analysis was conducted to characterize trajectories of time-varying variables. The influence of income trajectories on the increase in dental caries from age 6 to age 18 was evaluated by a generalized linear mixed model. After adjustment, the increases in numbers of decayed and missing teeth (DMT) from age 6 to age 18 were associated with family income trajectory. The incident rate ratios (IRR) of DMT compared with the group of stable high incomes were 2.36 for stable low incomes, 1.71 for downward, and 1.64 for upward. The IRR of teeth being filled in stable low-income groups compared with stable high-income groups was 0.55. Family income mobility affected treatment patterns of dental caries. Differences across income trajectory groups were found in the components of dental caries indices rather than in the experience of disease.

  19. Pregnancy-associated spinal osteoporosis treated with bisphosphonates: long-term follow-up of maternal and infants outcome.

    Science.gov (United States)

    Vujasinovic-Stupar, Nada; Pejnovic, Nada; Markovic, Ljiljana; Zlatanovic, Maja

    2012-03-01

    Pregnancy-associated spinal osteoporosis (PPSO) is a rare condition characterized by severe back pain occurring near the end of the first pregnancy or shortly afterward. The aim of this report is to present a 12-year follow-up of a patient with PPSO. Also, the outcomes of patient's two pregnancies and her infants after long-term treatment with bisphosphonates are assessed. A young woman was referred to our tertiary care hospital aged 30 years, due to intense pain in thoracic and lumbar region that started during the last month of her first pregnancy and got worse after delivery. Bone mineral density (BMD) measurement, clinical, and biochemical parameters were performed. Extremely low lumbar spine BMD, L2-L4: 0.627 g/cm(2), T-score -4.8, Z-score -4.3, 52% young adult indicated severe osteoporosis. Cyclical treatment with etidronate and then pamidronate was started, and a substantial increase in the BMD and the reduction in back pain intensity were observed. An increase in BMD of 44.8% over baseline was observed after 12 years of follow-up. Her two pregnancies were uneventful, and no neonatal adverse effects were observed. Control DXA scan in her girl child aged 6.8 years revealed low BMD at the lumbar spine. As PPSO seems to be an underdiagnosed severe disease, caution is recommended if back pain occurs in the last trimester or early post-partum period. Although pre-pregnancy use of bisphosponates does not pose a substantial fetal risk, their use in women of childbearing age might best be done only when strong clinical indications exist.

  20. Inherited multicentric osteolysis: case report of three siblings treated with bisphosphonate

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    Whitewood Colin

    2010-04-01

    Full Text Available Abstract Inherited Multicentric Osteolysis (IMO is an uncommon familial condition of idiopathic pathophysiology causing bone osteolysis and dysplasia. These patients present with common rheumatologic complaints of pain, dysfunction and disability, and are often initially misdiagnosed as a chronic rheumatic disease of childhood such as juvenile idiopathic arthritis. We report a case of three siblings diagnosed with IMO. Diagnosis was made during childhood, with each sibling having different manifestations and course of disease. One had a previous history of bilateral hip dysplasia. Two had osteolysis of the foot, distal tibia and femur (lower limb bones, whilst one had osteolysis of the rib and unusual clavicular fractures. Unusually, all siblings appear to experience decreased pain sensation compared to norms. All siblings were treated with bisphosphonates and experienced a rapid improvement in pain symptoms, decreased analgesic requirements. Two had bone mineral density testing performed and both had increases post-bisphosphonate. In all three, there was subjective evidence of stabilisation of bone disease. Testing for matrix metalloproteinase-2 (MMP2 gene was negative.

  1. Bisphosphonate-associated osteonecrosis of jaw reoccurrence after methotrexate therapy: a case report.

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    Alsalleeh, Fahd; Keippel, Jeffery; Adams, Lyde; Bavitz, Bruce

    2014-09-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-known complication caused by amino-bisphosphonate therapy. We document one case of BRONJ associated with oral administration of methotrexate, a known immunosuppressive drug used to treat rheumatoid arthritis. A 66-year-old woman was referred for evaluation and endodontic surgery of recently re-treated tooth 13. Tooth 14 was extracted 3 months prior, and the extraction site had not completely healed. Her medical history revealed rheumatoid arthritis and osteoporosis. She had been taking Fosamax (alendronate) 70 mg daily. Because of adequate root canal therapy of tooth 13, endodontic surgery was performed. Five months after apicoectomy, her symptoms had not changed. Tooth 13 was extracted, and the socket healed without complications. The socket of extracted tooth 14 was also healing. At the 3-month recall visit, bone exposure and purulent discharge at the site of extracted tooth 14 were noted. The patient had recently received methotrexate. The methotrexate was discontinued, and she was given course of amoxicillin. At the 18-month follow-up, the healing progressed, and the wound was closed. A medication that suppresses the immune system such as methotrexate may complicate the management of BRONJ. Once a diagnosis of BRONJ is made, a closely monitored conservative approach is recommended. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  2. Synergistic effects of bisphosphonate and calcium phosphate nanoparticles on peri-implant bone responses in osteoporotic rats.

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    Alghamdi, Hamdan S; Bosco, Ruggero; Both, Sanne K; Iafisco, Michele; Leeuwenburgh, Sander C G; Jansen, John A; van den Beucken, Jeroen J J P

    2014-07-01

    The prevalence of osteoporosis will increase within the next decades due to the aging world population, which can affect the bone healing response to dental and orthopedic implants. Consequently, local drug targeting of peri-implant bone has been proposed as a strategy for the enhancement of bone-implant integration in osteoporotic conditions. In the present study, an established in-vivo femoral condyle implantation model in osteoporotic and healthy bone is used to analyze the osteogenic capacity of titanium implants coated with bisphosphonate (BP)-loaded calcium phosphate nanoparticles (nCaP) under compromised medical conditions. After 4 weeks of implantation, peri-implant bone volume (%BV; by μCT) and bone area (%BA; by histomorphometry) were significantly increased within a distance of 500 μm from implant surfaces functionalized with BP compared to control implants in osteoporotic and healthy conditions. Interestingly, the deposition of nCaP/BP coatings onto implant surfaces increased both peri-implant bone contact (%BIC) and volume (%BV) compared to the deposition of nCaP or BP coatings individually, in osteoporotic and healthy conditions. The results of real-time PCR revealed similar osteogenic gene expression levels to all implant surfaces at 4-weeks post-implantation. In conclusion, simultaneous targeting of bone formation (by nCaP) and bone resorption (by BP) using nCaP/BP surface coatings represents an effective strategy for synergistically improvement of bone-implant integration, especially in osteoporotic conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Activation of Src kinase by protein-tyrosine phosphatase-PEST in osteoclasts: comparative analysis of the effects of bisphosphonate and protein-tyrosine phosphatase inhibitor on Src activation in vitro.

    Science.gov (United States)

    Chellaiah, Meenakshi A; Schaller, Michael D

    2009-08-01

    PTP-PEST is involved in the regulation of sealing ring formation in osteoclasts. In this article, we have shown a regulatory role for PTP-PEST on dephosphorylation of c-Src at Y527 and phosphorylation at Y418 in the catalytic site. Activation of Src in osteoclasts by over-expression of PTP-PEST resulted in the phosphorylation of cortactin at Y421 and WASP at Y294. Also enhanced as a result, is the interaction of Src, cortactin, and Arp2 with WASP. Moreover, the number of osteoclasts displaying sealing ring and bone resorbing activity was increased in response to PTP-PEST over-expression as compared with control osteoclasts. Cells expressing constitutively active-Src (527YDeltaF) simulate the effects mediated by PTP-PEST. Treatment of osteoclasts with a bisphosphonate alendronate or a potent PTP inhibitor PAO decreased the activity and phosphorylation of Src at Y418 due to reduced dephosphorylation state at Y527. Therefore, Src-mediated phosphorylation of cortactin and WASP as well as the formation of WASP.cortactin.Arp2 complex and sealing ring were reduced in these osteoclasts. Similar effects were observed in osteoclasts treated with an Src inhibitor PP2. We have shown that bisphosphonates could modulate the function of osteoclasts by inhibiting downstream signaling mediated by PTP-PEST/Src, in addition to its effect on the inhibition of the post-translational modification of small GTP-binding proteins such as Rab, Rho, and Rac as shown by others. The promising effects of the inhibitors PP2 and PAO on osteoclast function suggest a therapeutic approach for patients with bone metastases and osteoporosis as an alternative to bisphosphonates.

  4. Long-term treatment effect of trauma-affected refugees with flexible cognitive behavioural therapy and antidepressants.

    Science.gov (United States)

    Buhmann, Caecilie Böck; Nordentoft, Merete; Ekstroem, Morten; Carlsson, Jessica; Mortensen, Erik Lykke

    2018-04-04

    Few studies exist on the long-term effect of treatment of trauma-affected refugees. The purpose of this study was to estimate the long-term treatment effects of cognitive behavioural therapy and antidepressants (sertraline and mianserin) in trauma-affected refugees. Follow-ups were conducted 6 and 18 months after a randomised controlled clinical trial. The included patients were refugees with war-related traumatic experiences, PTSD and without psychotic disorders. We found a small improvement over time in PTSD, depression and anxiety symptoms and level of functioning, but the improvement was not associated with any specific treatment. Personality change after catastrophic experiences and life events influenced the symptom level at all follow-ups while depression at completion of treatment was associated with a steeper decline in symptom load at the follow-ups. In spite of the limited decline in symptom scores and treatment effects immediately after treatment, the condition of the treated trauma-affected refugees was significantly improved 6 and 18 months after treatment although the improvement was small. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Factors Affecting Outcome in Treatment of Chronic Subdural Hematoma in ICU Patients: Impact of Anticoagulation.

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    Szczygielski, Jacek; Gund, Sina-Maria; Schwerdtfeger, Karsten; Steudel, Wolf-Ingo; Oertel, Joachim

    2016-08-01

    The use of anticoagulants and older age are the main risk factors for chronic subdural hematoma (CSDH). Because the age of the population and use of anticoagulants are increasing, a growing number of CSDH cases is expected. To address this issue, we analyzed the impact of anticoagulants on postsurgical outcome in patients in the intensive care unit (ICU). Demographic data, coagulation parameters, surgical details, radiologic appearance of hematoma, Glasgow Coma Scale (GCS) score on admission, and Glasgow Outcome Scale (GOS) score on discharge were retrieved and retrospectively analyzed in 98 patients with CSDH treated in the neurosurgical ICU using correlation coefficient tests and multivariate analysis test. Overall outcome was good (GOS score 4 and 5) in 55.1% of patients. Overall mortality was 9.1%. There was a correlation between GCS score on admission and GOS score. There was no correlation between hematoma thickness/radiologic appearance and impaired coagulation. Disturbance in thrombocyte function (usually resulting from aspirin intake) correlated with improved outcome, whereas warfarin-related coagulopathy correlated with poor recovery. Nevertheless, patients with thrombocytopathy presented with better initial GCS scores. Neither hematoma size nor recurrence rate affected the outcome. The size of CSDH was not associated with poor outcome and is not necessarily determined by the use of anticoagulants. Coagulopathy does not rule out a good outcome, but the impact of anticoagulation on treatment results in CSDH varies between the main groups of drugs (warfarin vs. antiplatelet drugs). Patients in good neurologic condition on ICU admission have better chances of recovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Efficacy of surgical techniques and factors affecting residual stone rate in the treatment of kidney stones.

    Science.gov (United States)

    Aydemir, Hüseyin; Budak, Salih; Kumsar, Şükrü; Köse, Osman; Sağlam, Hasan Salih; Adsan, Öztuğ

    2014-09-01

    In this study, we aimed to evaluate, the efficacy of surgical methods and the factors affecting the residual stone rate by scrutinizing retrospectively the patients who had undergone renal stone surgery. Records of 109 cases of kidney stones who had been surgically treated between January 2010, and July 2013 were reviewed. Patients were divided into three groups in terms of surgical treatment; open stone surgery, percutaneous nephrolithotomy (PNL) and retrograde intrarenal surgery (RIRS). Patients' history, physical examination, biochemical and radiological images and operative and postoperative data were recorded. The patients had undergone PNL (n=74; 67.9%), RIRS (n=22;20.2%), and open renal surgery (n=13; 11.9%). The mean and median ages of the patients were 46±9, 41 (21-75) and, 42 (23-67) years, respectively. The mean stone burden was 2.6±0.7 cm(2) in the PNL, 1.4±0.1 cm(2) in the RIRS, and 3.1±0.9 cm(2) in the open surgery groups. The mean operative times were 126±24 min in the PNL group, 72±12 min in the RIRS group and 82±22 min in the open surgery group. The duration of hospitalisation was 3.1±0.2 days, 1.2±0.3 days and 3.4±1.1 days respectively. While the RIRS group did not need blood transfusion, in the PNL group blood transfusions were given in the PNL (n=18), and open surgery (n=2) groups. Residual stones were detected in the PNL (n=22), open surgery (n=2), and RIRS (n=5) groups. PNL and RIRS have been seen as safe and effective methods in our self application too. However, it should not be forgotten that as a basical method, open surgery may be needed in cases of necessity.

  7. Factors affecting professional delay in diagnosis and treatment of oral cancer in Iran.

    Science.gov (United States)

    Esmaelbeigi, Farhad; Hadji, Maryam; Harirchi, Iraj; Omranipour, Ramesh; vand Rajabpour, Mojtaba; Zendehdel, Kazem

    2014-04-01

    Oral cancer is the most common malignant tumor among head and neck cancers. Delay in diagnosis affects the treatment and prognosis of oral cancer. We measured the professional delay in the diagnosis and its attributes in the Cancer Institute of Iran, the largest referral center for oral cancer patients in the country.  We interviewed oral cancer patients to measure the delay and used case-control approach to study association of various prognostic factors with professional delay and tumor stage. Out of 206 patients, 71.4% were diagnosed at the advanced stage. The median of the patient, professional and total delays were 45, 86 and 140 day, receptively. In the univariate model, prescription of medicines like analgesics (OR = 5.3, 95% CI 2.2-12.9) and history of dental procedure (OR=6.8, 95% CI 1.7-26.9) were associated with higher risk of delay compared to patient who were biopsied from the beginning. History of loose teeth increased risk of delay 4 times (OR = 4.0, 95% CI 1.6-9.8). Patients with primary education had 70% lower risk of delay compared to the illiterate patients (OR = 0.3, 95% CI 0.1-0.7) and the risk was lower among patients who had diploma (OR = 0.04, 95% CI 0-0.7) and college education (OR = 0.1, 95% CI 0-0.4). The delayed patients were diagnosed in more advanced stage compared to the patients without delay (OR = 2.1, 95% CI 1.0-4.4). Development of a national guideline for follow-up of oral lesions, training and awareness of health care professionals about oral cancer diagnosis may decrease the delay and improve the oral cancer outcome in Iran.

  8. Bioaccessibility of Pb from ammunition in game meat is affected by cooking treatment.

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    Rafael Mateo

    Full Text Available BACKGROUND: The presence of lead (Pb ammunition residues in game meat has been widely documented, yet little information exists regarding the bioaccessibility of this Pb contamination. We study how cooking treatment (recipe can affect Pb bioaccessibility in meat of animals hunted with Pb ammunition. METHODOLOGY/PRINCIPAL FINDINGS: We used an in vitro gastrointestinal simulation to study bioaccessibility. The simulation was applied to meat from red-legged partridge (Alectoris rufa hunted with Pb shot pellets and cooked using various traditional Spanish game recipes involving wine or vinegar. Total Pb concentrations in the meat were higher in samples with visible Pb ammunition by X-ray (mean±SE: 3.29±1.12 µg/g w.w. than in samples without this evidence (1.28±0.61 µg/g. The percentage of Pb that was bioaccessible within the simulated intestine phase was far higher in meat cooked with vinegar (6.75% and wine (4.51% than in uncooked meat (0.7%. Risk assessment simulations using our results transformed to bioavailability and the Integrated Exposure Uptake Biokinetic model (IEUBK; US EPA show that the use of wine instead of vinegar in cooking recipes may reduce the percentage of children that would be expected to have >10 µg/dl of Pb in blood from 2.08% to 0.26% when game meat represents 50% of the meat in diet. CONCLUSIONS/SIGNIFICANCE: Lead from ammunition in game meat is more bioaccessible after cooking, especially when using highly acidic recipes. These results are important because existing theoretical models regarding Pb uptake and subsequent risk in humans should take such factors into account.

  9. Bioaccessibility of Pb from ammunition in game meat is affected by cooking treatment.

    Science.gov (United States)

    Mateo, Rafael; Baos, Ana R; Vidal, Dolors; Camarero, Pablo R; Martinez-Haro, Monica; Taggart, Mark A

    2011-01-14

    The presence of lead (Pb) ammunition residues in game meat has been widely documented, yet little information exists regarding the bioaccessibility of this Pb contamination. We study how cooking treatment (recipe) can affect Pb bioaccessibility in meat of animals hunted with Pb ammunition. We used an in vitro gastrointestinal simulation to study bioaccessibility. The simulation was applied to meat from red-legged partridge (Alectoris rufa) hunted with Pb shot pellets and cooked using various traditional Spanish game recipes involving wine or vinegar. Total Pb concentrations in the meat were higher in samples with visible Pb ammunition by X-ray (mean±SE: 3.29±1.12 µg/g w.w.) than in samples without this evidence (1.28±0.61 µg/g). The percentage of Pb that was bioaccessible within the simulated intestine phase was far higher in meat cooked with vinegar (6.75%) and wine (4.51%) than in uncooked meat (0.7%). Risk assessment simulations using our results transformed to bioavailability and the Integrated Exposure Uptake Biokinetic model (IEUBK; US EPA) show that the use of wine instead of vinegar in cooking recipes may reduce the percentage of children that would be expected to have >10 µg/dl of Pb in blood from 2.08% to 0.26% when game meat represents 50% of the meat in diet. Lead from ammunition in game meat is more bioaccessible after cooking, especially when using highly acidic recipes. These results are important because existing theoretical models regarding Pb uptake and subsequent risk in humans should take such factors into account.

  10. Combining Vγ9Vδ2 T Cells with a Lipophilic Bisphosphonate Efficiently Kills Activated Hepatic Stellate Cells

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    Xiaoying Zhou

    2017-10-01

    Full Text Available Activated hepatic stellate cells (aHSCs are now established as a central driver of fibrosis in human liver injury. In the presence of chronic or repeated injury, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC can occur, so there is interest in down-regulating aHSCs activity in order to treat these diseases. Here, we report that Vγ9Vδ2 T cells are reduced in patients with liver cirrhosis, stimulating us to investigate possible interactions between Vγ9Vδ2 T cells and aHSCs. We find that Vγ9Vδ2 T cells kill aHSCs and killing is enhanced when aHSCs are pretreated with BPH-1236, a lipophilic analog of the bone resorption drug zoledronate. Cytotoxicity is mediated by direct cell-to-cell contact as shown by Transwell experiments and atomic force microscopy, with BPH-1236 increasing the adhesion between aHSCs and Vγ9Vδ2 T cells. Mechanistically, BPH-1236 functions by inhibiting farnesyl diphosphate synthase, leading to accumulation of the phosphoantigen isopentenyl diphosphate and recognition by Vγ9Vδ2 T cells. The cytolytic process is largely dependent on the perforin/granzyme B pathway. In a Rag2−/−γc−/− immune-deficient mouse model, we find that Vγ9Vδ2 T cells home-in to the liver, and when accompanied by BPH-1236, kill not only orthotopic aHSCs but also orthotopic HCC tumors. Collectively, our results provide the first proof-of-concept of a novel immunotherapeutic strategy for the treatment of fibrosis–cirrhosis–HCC diseases using adoptively transferred Vγ9Vδ2 T cells, combined with a lipophilic bisphosphonate.

  11. Gastrointestinal events and association with initiation of treatment for osteoporosis

    Directory of Open Access Journals (Sweden)

    Modi A

    2015-11-01

    Full Text Available Ankita Modi,1 Ethel S Siris,2 Jackson Tang,3 Shiva Sajjan,1 Shuvayu S Sen1 1Center for Observational and Real-World Evidence, Merck & Co., Inc, Kenilworth, NJ, 2Toni Stabile Osteoporosis Center, Columbia University Medical Center, NY Presbyterian Hospital, New York, NY, 3Asclepius Analytics Ltd, Brooklyn, NY, USA Background: Preexisting gastrointestinal (GI events may deter the use of pharmacologic treatment in patients diagnosed with osteoporosis (OP. The objective of this study was to examine the association between preexisting GI events and OP pharmacotherapy initiation among women diagnosed with OP. Methods: The study utilized claims data from a large US managed care database to identify women aged ≥55 years with a diagnosis code for OP (index date during 2002–2009. Patients with a claim for pharmacologic OP treatment in the 12-month pre-index period (baseline were excluded. OP treatment initiation in the post-index period was defined as a claim for bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid, calcitonin, raloxifene, or teriparatide. During the post-index period (up to 12 months, GI events were identified before treatment initiation. A time-dependent Cox regression model was used to investigate the likelihood of initiating any OP treatment. Among patients initiating OP treatment, a discrete choice model was utilized to assess the relationship between post-index GI events and likelihood of initiating with a bisphosphonate versus a non-bisphosphonate. Results: In total, 65,344 patients (mean age 66 years were included; 23.7% had a GI event post diagnosis and before treatment initiation. Post-index GI events were associated with a 75% lower likelihood of any treatment initiation (hazard ratio 0.25; 95% confidence interval 0.24–0.26. Among treated patients (n=23,311, those with post-index GI events were 39% less likely to receive a bisphosphonate versus a non-bisphosphonate (odds ratio 0.61; 95% confidence

  12. Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis.

    Directory of Open Access Journals (Sweden)

    Anthony Grosso

    Full Text Available A recent trial unexpectedly reported that atrial fibrillation, when defined as serious, occurred more often in participants randomized to an annual infusion of the relatively new parenteral bisphosphonate, zoledronic acid, than among those given placebo, but had limited power. Two subsequent population-based case-control studies of patients receiving a more established oral bisphosphonate, alendronic acid, reported conflicting results, possibly due to uncontrolled confounding factors.We used the United Kingdom General Practice Research Database to assess the risk of atrial fibrillation and flutter in women exposed to the oral bisphosphonates, alendronic acid and risedronate sodium. The self-controlled case-series method was used to minimise the potential for confounding. The age-adjusted incidence rate ratio for atrial fibrillation or flutter in individuals during their exposure to these oral bisphosphonates (n = 2195 was 1.07 (95% CI 0.94-1.21. The age-adjusted incidence rate ratio for alendronic acid (n = 1489 and risedronate sodium (n = 649 exposed individuals were 1.09 (95% CI 0.93-1.26 and 0.99 (95% CI 0.78-1.26 respectively. In post-hoc analyses, an increased risk of incident atrial fibrillation or flutter was detected for patients during their first few months of alendronic acid therapy.We found no robust evidence of an overall long-term increased risk of atrial fibrillation or flutter associated with continued exposure to the oral bisphosphonates, alendronic acid and risedronate sodium. A possible signal for an increase in risk during the first few months of therapy with alendronic acid needs to be re-assessed in additional studies.

  13. The effects of blue-enriched light treatment compared to standard light treatment in seasonal affective disorder

    NARCIS (Netherlands)

    Gordijn, M. C. M.; 't Mannetje, D.; Meesters, Y.

    Background: One of the most frequently investigated hypotheses of the pathophysiology underlying Seasonal Affective Disorder (SAD) is a disturbance of circadian rhythms. Since the circadian system as well as other non-visual effects is especially sensitive to blue light, a new light therapy device

  14. The reciprocal relationship between daily fatigue and catastrophizing following cancer treatment: Affect and physical activity as potential mediators.

    Science.gov (United States)

    Müller, Fabiola; Stephenson, Ellen; DeLongis, Anita; Smink, Ans; Van Ginkel, Robert J; Tuinman, Marrit A; Hagedoorn, Mariët

    2018-03-01

    Fatigue is a distressing symptom many cancer patients experience even after completion of treatment. Although theory and empirical evidence indicate that negative cognitions perpetuate fatigue after completion of treatment, insight into how this process unfolds in daily life is limited. This study used an intensive longitudinal design to investigate the reciprocal relationship between catastrophizing and fatigue in daily life and whether affective and behavioral processes mediate these relationships. Post-treatment colorectal cancer patients (n = 101) completed daily diaries (14 days, 3 times daily) regarding their fatigue, catastrophizing, positive and negative affect, and physical activity. Multilevel modeling was applied to investigate within-person associations within days. Analyses revealed a positive reciprocal relationship between fatigue and catastrophizing throughout the day. That is, high levels of catastrophizing were associated with increases in fatigue within patients. In turn, but to a lesser extent, high levels of fatigue predicted increases in catastrophizing at the next assessment. Low positive affect and high negative affect mediated the effect of catastrophizing on increases in fatigue. Only negative affect mediated the reverse relationship. Physical activity did not mediate either relationship. This study provides evidence for a mutually reinforcing relationship between catastrophizing and fatigue in daily life, which might explain the perpetuation of fatigue after completion of cancer treatment. Fatigue-specific cognitive behavior therapy could be improved by educating patients about this daily reciprocal relationship, train them to quickly replace catastrophizing thoughts in daily life, and help them to cope with affective changes induced by fatigue. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Evolution of bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma and Waldenstrom's macroglobulinemia: a retrospective multicentric study

    International Nuclear Information System (INIS)

    Andriani, A; Petrucci, M T; Caravita, T; Montanaro, M; Villivà, N; Levi, A; Siniscalchi, A; Bongarzoni, V; Pisani, F; De Muro, M; Coppetelli, U; Avvisati, G; Zullo, A; Agrillo, A; Gaglioti, D

    2012-01-01

    Bisphosphonates (BPs) are used intravenously to treat cancer-related conditions for the prevention of pathological fractures. Osteonecrosis of the jaw (BRONJ) is a rare complication reported in 4–15% of patients. We studied, retrospectively, 55 patients with multiple myeloma or Waldenstrom's macroglobulinemia followed up from different haematological departments who developed BRONJ. All patients were treated with BPs for bone lesions and/or fractures. The most common trigger for BRONJ was dental alveolar surgery. After a median observation of 26 months, no death caused by BRONJ complication was reported. In all, 51 patients were treated with antibiotic therapy, and in 6 patients, this was performed in association with surgical debridement of necrotic bone, in 16 with hyperbaric O 2 therapy/ozonotherapy and curettage and in 12 with sequestrectomy and O 2 /hyperbaric therapy. Complete response was observed in 20 cases, partial response in 21, unchanged in 9 and worsening in 3. The association of surgical treatment with antibiotic therapy seems to be more effective in eradicating the necrotic bone than antibiotic treatment alone. O 2 hyperbaric/ozonotherapy is a very effective treatment. The cumulative dosage of BPs is important for the evolution of BRONJ. Because the most common trigger for BRONJ was dental extractions, all patients, before BP treatment, must achieve an optimal periodontal health

  16. Cognitive-behavioral therapy for persistent pain: does adherence after treatment affect outcome?

    Science.gov (United States)

    Curran, Charlotte; Williams, Amanda C de C; Potts, Henry W W

    2009-02-01

    It is a tenet of cognitive behavioral treatment of persistent pain problems that ex-patients should adhere to treatment methods over the longer term, in order to maintain and to extend treatment gains. However, no research has quantified the causal influence of adherence on short-term outcome in this field. The aims of this study are to assess determinants of adherence to treatment recommendations in several domains, and to examine the extent to which cognitive and behavioral adherence predicts better outcome of cognitive behavioral treatment for persistent pain. Longitudinal data from a sample of 2345 persistent pain patients who attended a multicomponent treatment programme were subjected to structural equation modeling. Adherence emerged as a mediating factor linking post-treatment and follow-up treatment outcome, but contributed only 3% unique variance to follow-up outcomes. Combined end-of-treatment outcomes and adherence factors accounted for 72% of the variance in outcome at one-month follow-up. Notwithstanding shortcomings in the measurement of adherence, these findings question the emphasis normally given to adherence in the maintenance of behavioral and cognitive change, and clinical implications are discussed.

  17. When idols look into the future: fair treatment modulates the affective forecasting error in talent show candidates.

    Science.gov (United States)

    Feys, Marjolein; Anseel, Frederik

    2015-03-01

    People's affective forecasts are often inaccurate because they tend to overestimate how they will feel after an event. As life decisions are often based on affective forecasts, it is crucial to find ways to manage forecasting errors. We examined the impact of a fair treatment on forecasting errors in candidates in a Belgian reality TV talent show. We found that perceptions of fair treatment increased the forecasting error for losers (a negative audition decision) but decreased it for winners (a positive audition decision). For winners, this effect was even more pronounced when candidates were highly invested in their self-view as a future pop idol whereas for losers, the effect was more pronounced when importance was low. The results in this study point to a potential paradox between maximizing happiness and decreasing forecasting errors. A fair treatment increased the forecasting error for losers, but actually made them happier. © 2014 The British Psychological Society.

  18. Effectiveness of icatibant for treatment of hereditary angioedema attacks is not affected by body weight

    DEFF Research Database (Denmark)

    Caballero, Teresa; Zanichelli, Andrea; Aberer, Werner

    2018-01-01

    Background: Icatibant is a bradykinin B2-receptor antagonist used for the treatment of hereditary angioedema attacks resulting from C1-inhibitor deficiency. Treatment is not adjusted by body weight however the impact of body mass index (BMI) on the effectiveness of icatibant is not documented in ...

  19. High pressure treatment of brine enhanced pork affects endopeptidase activity, protein solubility, and peptide formation

    DEFF Research Database (Denmark)

    Grossi, Alberto Blak; Gkarane, Vasiliki; Otte, Jeanette Anita Held

    2012-01-01

    at 600 MPa following storage at 2 °C for up to 8 weeks. In this report a novel protocol for SDS gelatin zymography was established, and an increase of cathepsin B and L activity after HP treatment was shown followed by a decrease during storage. No calpain activity was detected following HP treatment. HP...

  20. Factors affecting the choice of treatment in occupational therapy practices in hospital-based care.

    NARCIS (Netherlands)

    Driessen, M.J.; Dekker, J.; Lankhorst, G.; Zee, J. van der

    1996-01-01

    The aim of this article was twofold: to describe the occurrence of treatment goals, health-care programmes and type of interventions chosen by occupational therapists; and to investigate relationships between treatment goals, health-care programmes and interventions. A survey on occupational therapy

  1. Preparation and biodistribution of 131I labeled 3-Amino-1-hydroxypropylidene-1, 1-bisphosphonate

    International Nuclear Information System (INIS)

    Lin Rushan; Yang Yuanyou; Liu Ning; Liao Jiali; Jin Jiannan; Pu Manfei

    2008-01-01

    3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (ABP) was synthesized and labeled with 131 I using N-succinimidyl-5-(tri-butylstannyl)-3-pyridinecarboxylate (SPC) as a bi-functional linker. 131 I could be coupled to ABP via a 131 I-SIPC intermediate with a labeling yield of more than 64%, and a radiochemical purity of more than 99% after HPLC purification. After 72 h at room temperature, the radiochemical purity was still more than 98.8%, implying that the 131 I-SIPC-ABP is stable in vitro. Biodistribution experiments in mice show that 131 I-SIPC-ABP has high affinity to bone and high stability in vivo as well as in vitro. (authors)

  2. Does executive dysfunction affect treatment outcome in late-life mood and anxiety disorders?

    Science.gov (United States)

    Mohlman, Jan

    2005-06-01

    Rates of treatment response among the elderly are typically lower than those found in younger samples. This article discusses specific biological and psychological aspects of aging that may impact the effectiveness of treatments for late-life mood and anxiety disorders. Although empirical evidence for the role of executive skills in treatment outcome is currently quite limited, the small number of existing studies suggest that some older adults with deficits in executive skills may respond poorly to popular treatments for depression and anxiety compared with those with intact executive functions. However, there are likely to be additional mediating factors. This article provides a definition and description of executive functions, including a summary of popular assessment tools. The literature on treatment outcome is reviewed, and future directions are discussed.

  3. Quantitative ultrasound at the hand phalanges in patients with bisphosphonate-related osteonecrosis of the jaws

    Directory of Open Access Journals (Sweden)

    Ana Carolina Fragoso MOTTA

    2015-01-01

    Full Text Available Patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ who received intravenous or oral bisphosphonates (BP were selected for determination of their bone microarchitecture as a risk predictor of BRONJ development. The diagnosis of BRONJ was made based on clinical and radiographic findings. The control group consisted of healthy patients. All patients underwent quantitative and qualitative ultrasound measurements of bone at the hand phalanges carried out using the DBM Sonic BP. Ultrasound bone profile index (UBPI, amplitude-dependent speed of sound (AD-SoS, bone biophysics profile (BBP, and bone transmission time (BTT were measured. The BRONJ group consisted of 17 patients (62 ± 4.24; range: 45-82; 10 (58.8% were male and seven (41.1% were female, of whom 11 (64.7% suffered from multiple myeloma, three (17.6% from osteoporosis, one (5.8% from prostate cancer, one (5.8% from kidney cancer, and one (5.8% from leukemia. Fourteen (82.3% of them received intravenous BP whereas three (17.6% received oral BP. Nine (9/17; 52.9% patients developed bone exposure: two in the maxilla and seven in the mandible. Regarding quantitative parameters, Ad-SoS was low in the BRONJ group, but not significant. The UBPI score was significantly reduced in BRONJ patients with exposed bone when compared to controls (0.47 ± 0.12 vs. 0.70 ± 0.15; p = 0.004. The present study demonstrated that quantitative ultrasound was able to show bone microarchitecture alterations in BRONJ patients, and suggests that these analyses may be an important tool for early detection of bone degeneration associated with BRONJ.

  4. Crystallographic and thermodynamic characterization of phenylaminopyridine bisphosphonates binding to human farnesyl pyrophosphate synthase.

    Directory of Open Access Journals (Sweden)

    Jaeok Park

    Full Text Available Human farnesyl pyrophosphate synthase (hFPPS catalyzes the production of the 15-carbon isoprenoid farnesyl pyrophosphate. The enzyme is a key regulator of the mevalonate pathway and a well-established drug target. Notably, it was elucidated as the molecular target of nitrogen-containing bisphosphonates, a class of drugs that have been widely successful against bone resorption disorders. More recently, research has focused on the anticancer effects of these inhibitors. In order to achieve increased non-skeletal tissue exposure, we created phenylaminopyridine bisphosphonates (PNP-BPs that have bulky hydrophobic side chains through a structure-based approach. Some of these compounds have proven to be more potent than the current clinical drugs in a number of antiproliferation assays using multiple myeloma cell lines. In the present work, we characterized the binding of our most potent PNP-BPs to the target enzyme, hFPPS. Co-crystal structures demonstrate that the molecular interactions designed to elicit tighter binding are indeed established. We carried out thermodynamic studies as well; the newly introduced protein-ligand interactions are clearly reflected in the enthalpy of binding measured, which is more favorable for the new PNP-BPs than for the lead compound. These studies also indicate that the affinity of the PNP-BPs to hFPPS is comparable to that of the current drug risedronate. Risedronate forms additional polar interactions via its hydroxyl functional group and thus exhibits more favorable binding enthalpy; however, the entropy of binding is more favorable for the PNP-BPs, owing to the greater desolvation effects resulting from their large hydrophobic side chains. These results therefore confirm the overall validity of our drug design strategy. With a distinctly different molecular scaffold, the PNP-BPs described in this report represent an interesting new group of future drug candidates. Further investigation should follow to

  5. Low temperature treatment affects concentration and distribution of chrysanthemum stunt viroid in Argyranthemum

    Directory of Open Access Journals (Sweden)

    Zhibo eZhang

    2016-03-01

    Full Text Available Chrysanthemum stunt viroid (CSVd can infect Argyranthemum and cause serious economic loss. Low temperature treatment combined with meristem culture has been applied to eradicate viroids from their hosts, but without success in eliminating CSVd from diseased Argyranthemum. The objectives of this work were to investigate 1 the effect of low temperature treatment combined with meristem culture on elimination of CSVd, 2 the effect of low temperature treatment on CSVd distribution pattern in shoot apical meristem (SAM, and 3 CSVd distribution in flowers and stems of two infected Argyranthemum cultivars. After treatment with low temperature combined with meristem tip culture, two CSVd-free plants were found in ‘Border Dark Red’, but none in ‘Yellow Empire’. With the help of in situ hybridization, we found that CSVd distribution patterns in the SAM showed no changes in diseased ‘Yellow Empire’ following 5oC treatment, compared with non-treated plants. However, the CSVd-free area in SAM was enlarged in diseased ‘Border Dark Red’ following prolonged 5oC treatment. Localization of CSVd in the flowers and stems of infected ‘Border Dark Red’ and ‘Yellow Empire’ indicated that seeds could not transmit CSVd in these two cultivars, and CSVd existed in phloem. Results obtained in the study contributed to better understanding of the distribution of CSVd in systemically infected plants and the combination of low temperature treatment and meristem tip culture for production of viroid-free plants.

  6. Subtrochanteric Fracture In A Chinese Woman With Paget’s Disease Of Bone And On Long Term Bisphosphonate Therapy: Could It Be An Insufficiency Fracture?

    Directory of Open Access Journals (Sweden)

    CK Lee

    2011-03-01

    Full Text Available Paget’s disease is common in Western countries but is very rare in Chinese populations. Although bisphosphonate has been widely used to treat symptomatic Paget’s disease, prolonged use may be associated with insufficiency fracture. We highlight this rare case of Paget’s disease in a Chinese lady who presented with an insufficiency fracture following long-term use of bisphosphonate.

  7. Timing of growth hormone treatment affects trabecular bone microarchitecture and mineralization in growth hormone deficient mice.

    Science.gov (United States)

    Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W; Boyd, Steven K

    2010-08-01

    Growth hormone (GH) is essential in the development of bone mass, and a growth hormone deficiency (GHD) in childhood is frequently treated with daily injections of GH. It is not clear what effect GHD and its treatment has on bone. It was hypothesized that GHD would result in impaired microarchitecture, and an early onset of treatment would result in a better recovery than late onset. Growth hormone deficient homozygous (lit/lit) mice of both sexes were divided into two treatment groups receiving daily injections of GH, starting at an early (21 days of age) or a late time point (35 days of age, corresponding to the end of puberty). A group of heterozygous mice with normal levels of growth hormone served as controls. In vivo micro-computed tomography scans of the fourth lumbar vertebra were obtained at five time points between 21 and 60 days of age, and trabecular morphology and volumetric BMD were analyzed to determine the effects of GH on bone microarchitecture. Early GH treatment led to significant improvements in bone volume ratio (p=0.006), tissue mineral density (p=0.005), and structure model index (p=0.004) by the study endpoint (day 60), with no detected change in trabecular thickness. Trabecular number increased and trabecular separation decreased in GHD mice regardless of treatment compared to heterozygous mice. This suggests fundamental differences in the structure of trabecular bone in GHD and GH treated mice, reflected by an increased number of thinner trabeculae in these mice compared to heterozygous controls. There were no significant differences between the late treatment group and GHD mice except for connectivity density. Taken together, these results indicate that bone responds to GH treatment initiated before puberty but not to treatment commencing post-puberty, and that GH treatment does not rescue the structure of trabecular bone to that of heterozygous controls. Copyright 2010 Elsevier Inc. All rights reserved.

  8. [Pharmacologic treatment of osteoporosis--2011].

    Science.gov (United States)

    Lakatos, Péter

    2011-08-14

    Osteoporosis affects approximately 9% of the population in Hungary resulting in about 100 000 osteoporotic fractures annually. Thirty-five percent of patients with hip fractures due to osteoporosis will die within 1 year. Direct costs of osteoporosis exceed 25 billion forints per year. Apparently, cost-effective reduction of bone loss and consequent fracture risk will add up to not only financial savings but improvement in quality of life, as well. A number of pharmacological modalities are available for this purpose. The mainstay of the treatment of osteoporosis is the bisphosphonate group that includes effective anti-resorptive compounds mitigating bone loss and fragility. The recently registered denosumab exhibits similar efficacy by neutralizing RANK ligand, however, marked differences can be observed between the two drug classes. Strontium has a unique mechanism of action by rebalancing bone turnover, and thus, providing an efficient treatment option for the not fast bone losers who are at high fracture risk. The purely anabolic teriparatide is available for the extremely severe osteoporotic patients and for those who do not respond to other types of therapy. Older treatment options such as hormone replacement therapy, raloxifene, tibolone or calcitonin may also have a restricted place in the management of osteoporosis.

  9. Chronic dihydroergotoxine treatment affects the number of dopamine recognition sites in rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Battaini, F.; Govoni, S.; Rius, R.A.; Spano, P.F.; Trabucchi, M.

    1984-06-01

    Ergot derivatives have been proposed to have ameliorative effects in various pathological conditions where dopaminergic transmission is believed to be impaired, namely Parkinson's disease, amenorrhea-galactorrhea syndrome, and in the treatment of behavioural disturbances of the elderly. To get more insight into a possible involvement of a direct action of ergot derivatives on dopamine receptors we studied the effect of acute and chronic dihydroergotoxine (DHT) treatment on 3H-Spiroperidol and 3H-N-Propylnorapomorphine (3H-NPA) binding to rat striatal membrane preparations. The results are in favor of an interaction of ergot derivatives with dopamine recognition sites both after acute and chronic treatment.

  10. Chronic dihydroergotoxine treatment affects the number of dopamine recognition sites in rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Battaini, F; Govoni, S; Rius, R A; Spano, P F; Trabucchi, M

    1984-06-01

    Ergot derivatives have been proposed to have ameliorative effects in various pathological conditions where dopaminergic transmission is believed to be impaired, namely Parkinson's disease, amenorrhea-galactorrhea syndrome, and in the treatment of behavioural disturbances of the elderly. To get more insight into a possible involvement of a direct action of ergot derivatives on dopamine receptors we studied the effect of acute and chronic dihydroergotoxine (DHT) treatment on 3H-Spiroperidol and 3H-N-Propylnorapomorphine (3H-NPA) binding to rat striatal membrane preparations. The results are in favor of an interaction of ergot derivatives with dopamine recognition sites both after acute and chronic treatment.

  11. The Range and Impact of Postmigration Stressors During Treatment of Trauma-Affected Refugees

    DEFF Research Database (Denmark)

    Bruhn, Maja; Rees, Susan; Mohsin, Mohammed

    2018-01-01

    . Postmigration stressors were deemed to impact on 39.1% of treatment sessions with medical personnel. Issues related to work, finances, and family were the most frequently identified stressors. Postmigration stressors interfering with treatment were more common among male refugees, those living alone, those from...... for trauma-related mental distress. A total of 116 patients completed 6 months of multidisciplinary treatment. Clinician-rated postmigration stressors were registered at each session. Outcome measures were Harvard Trauma Questionnaire and Global Assessment of Functioning, function (GAF-F) and symptom...

  12. Improvement in cognitive and affective theory of mind with observation and imitation treatment in subjects with schizophrenia

    Directory of Open Access Journals (Sweden)

    Maria C. Pino

    2015-06-01

    Full Text Available Objective: the main objective of this study is to consider Theory of Mind (ToM, i.e. the ability to perceive other people in terms of thinking, believing and emotions, as a target for effective rehabilitative intervention, using Emotion and ToM Imitation Training (ETIT, aimed at improving social cognition and social functioning in schizophrenia. ToM impairment is a key feature of schizophrenia. According to recent literature, ToM is a multidimensional process requiring at least two components: cognitive and affective. Cognitive ToM seems to be a prerequisite for affective ToM, which requires intact empathic ability. Method: seven patients with schizophrenia completed ETIT treatment and were compared to 7 patients who participated in Problem Solving Training (PST. The participants were assessed at pre and post treatment regarding measures of cognitive (Advanced Theory of Mind Task and Social Situation Test and affective (Emotion Attribution Task and Eyes Task ToM and also empathy (Empathy Quotient. Results: our results showed that when compared to the control group, ETIT participants improved in three social cognition components evaluated (cognitive and affective ToM and empathy. Improvement in cognitive and affective ToM was found within the ETIT group pre and post treatment. Conclusions: Action observation and imitation could be important goals for future “low cost” rehabilitation treatment in several disorders in which the deficit of social cognition is considered as “core” to the disease. This represents a new perspective in the rehabilitation field.

  13. Vitamin D supplementation for treatment of seasonal affective symptoms in healthcare professionals

    DEFF Research Database (Denmark)

    Frandsen, Tenna Bloch; Pareek, Manan; Hansen, Jens Peter

    2014-01-01

    BACKGROUND: Low serum 25-hydroxyvitamin D levels (25(OH)D) have been associated with a higher likelihood of seasonal affective disorder (SAD) and poor mental well-being, yet firm evidence for either remains lacking. Thus, vitamin D supplementation may alleviate symptoms associated with SAD. METHODS...... for the Hamilton Depression Rating Scale, Seasonal Affective Disorders (SIGH-SAD). The secondary outcome was World Health Organization-Five Well-Being Index (WHO-5) of the healthcare professionals during the winter period and the exploratory outcome measures were weight, waist circumference, blood pressure...

  14. Hospital specific factors affect quality of blood pressure treatment in chronic kidney disease

    NARCIS (Netherlands)

    Zuilen, A.D. van; Blankestijn, P.J.; Buren, M. van; Dam, M.A. ten; Kaasjager, K.A.; Ligtenberg, G.; Sijpkens, Y.W.; Sluiter, H.E.; Ven, P.J. van der; Vervoort, G.M.M.; Vleming, L.; Bots, M.L.; Wetzels, J.F.M.

    2011-01-01

    BACKGROUND: Blood pressure (BP) is the most important modifiable risk factor for cardiovascular (CV) disease and progression of kidney dysfunction in patients with chronic kidney disease. Despite extensive antihypertensive treatment possibilities, adequate control is notoriously hard to achieve.

  15. Marijuana Use in Hepatitis C Infection does not Affect Liver Biopsy Histology or Treatment Outcomes

    Directory of Open Access Journals (Sweden)

    Theresa Liu

    2014-01-01

    Full Text Available BACKGROUND: Marijuana smoking is prevalent among hepatitis C virus-infected patients. The literature assessing the influence of marijuana on liver disease progression and hepatitis C virus antiviral treatment outcomes is conflicting.

  16. Access and completion of a Web-based treatment in a population-based sample of tornado-affected adolescents.

    Science.gov (United States)

    Price, Matthew; Yuen, Erica K; Davidson, Tatiana M; Hubel, Grace; Ruggiero, Kenneth J

    2015-08-01

    Although Web-based treatments have significant potential to assess and treat difficult-to-reach populations, such as trauma-exposed adolescents, the extent that such treatments are accessed and used is unclear. The present study evaluated the proportion of adolescents who accessed and completed a Web-based treatment for postdisaster mental health symptoms. Correlates of access and completion were examined. A sample of 2,000 adolescents living in tornado-affected communities was assessed via structured telephone interview and invited to a Web-based treatment. The modular treatment addressed symptoms of posttraumatic stress disorder, depression, and alcohol and tobacco use. Participants were randomized to experimental or control conditions after accessing the site. Overall access for the intervention was 35.8%. Module completion for those who accessed ranged from 52.8% to 85.6%. Adolescents with parents who used the Internet to obtain health-related information were more likely to access the treatment. Adolescent males were less likely to access the treatment. Future work is needed to identify strategies to further increase the reach of Web-based treatments to provide clinical services in a postdisaster context. (c) 2015 APA, all rights reserved).

  17. Comparing a Cognitive Model and Phototherapy in the Treatment of Seasonal Affective Disorder.

    Science.gov (United States)

    Krantz, Sandra

    Seasonal affective disorder (SAD) is characterized by recurrent major depression or bipolar disorder that occurs annually, usually later in fall as the daylight hours decrease, and that alternates with euthymic or hypomanic moods in the spring and summer. Pioneering research by Dr. Norman Rosenthal and associates has found phototherapy to be…

  18. The duration of light treatment and therapy outcome in seasonal affective disorder

    NARCIS (Netherlands)

    Knapen, S. E.; van de Werken, M.; Gordijn, Marijke; Meesters, Y.

    Background: Seasonal affective disorder (SAD) is characterized by recurrent episodes of major depression with a seasonal pattern, treated with light therapy (LT). Duration of light therapy differs. This study investigates retrospectively whether a single week of LT is as effective as two weeks,

  19. Clinical evaluation of a nutraceutical diet as an adjuvant to pharmacological treatment in dogs affected by Keratoconjunctivitis sicca.

    Science.gov (United States)

    Destefanis, Simona; Giretto, Daniela; Muscolo, Maria Cristina; Di Cerbo, Alessandro; Guidetti, Gianandrea; Canello, Sergio; Giovazzino, Angela; Centenaro, Sara; Terrazzano, Giuseppe

    2016-09-22

    Canine keratoconjunctivitis sicca (cKCS) is an inflammatory eye condition related to a deficiency in the tear aqueous fraction. Etiopathogenesis of such disease is substantially multifactorial, combining the individual genetic background with environmental factors that contribute to the process of immunological tolerance disruption and, as a consequence, to the emergence of autoimmunity disease. In this occurrence, it is of relevance the role of the physiological immune-dysregulation that results in immune-mediated processes at the basis of cKCS. Current therapies for this ocular disease rely on immunosuppressive treatments. Clinical response to treatment frequently varies from poor to good, depending on the clinical-pathological status of eyes at diagnosis and on individual response to therapy. In the light of the variability of clinical response to therapies, we evaluated the use of an anti-inflammatory/antioxidant nutraceutical diet with potential immune-modulating activity as a therapeutical adjuvant in cKCS pharmacological treatment. Such combination was administered to a cohort of dogs affected by cKCS in which the only immunosuppressive treatment resulted poorly responsive or ineffective in controlling the ocular symptoms. Fifty dogs of different breeds affected by immune-mediated cKCS were equally distributed and randomly assigned to receive either a standard diet (control, n = 25) or the nutraceutical diet (treatment group, n = 25) both combined with standard immunosuppressive therapy over a 60 days period. An overall significant improvement of all clinical parameters (tear production, conjunctival inflammation, corneal keratinization, corneal pigment density and mucus discharge) and the lack of food-related adverse reactions were observed in the treatment group (p metabolic changes could affect the immune response orchestration in a model of immune-mediated ocular disease, as represented by cKCS.

  20. Osteonecrosis of the jaw associated to bisphosphonates treatment in osteoporosis patients: a review

    OpenAIRE

    Gutiérrez Restrepo, Johnayro

    2013-01-01

    La osteonecrosis de mandíbula es una entidad que se viene describiendo desde 2003 y se define como la presencia de un defecto en la mucosa oral que lleva a exposición del hueso de la mandíbula y del maxilar que falla en cicatrizar en un periodo de ocho semanas, en un paciente en tratamiento con bifosfonatos y sin exposición previa a radioterapia en cuello o en la cabeza. En este artículo se hace una revisión de la literatura respecto a la epidemiología, la fisiopatología, los estudios diagnós...

  1. Intracerebroventricular ghrelin treatment affects lipid metabolism in liver of rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Velasco, Cristina; Librán-Pérez, Marta; Otero-Rodiño, Cristina; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2016-03-01

    We aimed to elucidate in rainbow trout (Oncorhynchus mykiss) the effects of central ghrelin (GHRL) treatment on the regulation of liver lipid metabolism, and the possible modulatory effect of central GHRL treatment on the simultaneous effects of raised levels of oleate. Thus, we injected intracerebroventricularly (ICV) rainbow trout GHRL in the presence or absence of oleate and evaluated in liver variables related to lipid metabolism. Oleate treatment elicited in liver of rainbow trout decreased lipogenesis and increased oxidative capacity in agreement with previous studies. Moreover, as demonstrated for the first time in fish in the present study, GHRL also acts centrally modulating lipid metabolism in liver, resulting in increased potential for lipogenesis and decreased potential for fatty acid oxidation, i.e. the converse effects to those elicited by central oleate treatment. The simultaneous treatment of GHRL and oleate confirmed these counteractive effects. Thus, the nutrient sensing mechanisms present in hypothalamus, particularly those involved in sensing of fatty acid, are involved in the control of liver energy metabolism in fish, and this control is modulated by the central action of GHRL. These results give support to the notion of hypothalamus as an integrative place for the regulation of peripheral energy metabolism in fish. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Multidisciplinary Treatment of Severe Osteogenesis Imperfecta: Functional Outcomes at Skeletal Maturity.

    Science.gov (United States)

    Montpetit, Kathleen; Palomo, Telma; Glorieux, Francis H; Fassier, François; Rauch, Frank

    2015-10-01

    To determine the functional outcomes associated with long-term multidisciplinary treatment, intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation in children with severe osteogenesis imperfecta (OI) (diagnosed clinically as OI types III or IV). Retrospective study where outcomes were measured prospectively. Pediatric orthopedic hospital. Adolescents (N=41; age range, 15-21y) with severe OI (OI type III: n=17; OI type IV: n=24) who had started therapy before the age of 6 years, had received treatment for at least 10 years, and had achieved final height. Intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation. Pediatric Evaluation of Disability Inventory. At the time of the last available follow-up examination, none of the individuals diagnosed with OI type III (most severely affected group) was able to ambulate without ambulation aids, whereas 20 (83%) patients with OI type IV were able to ambulate without ambulation aids. Regarding self-care, we specifically assessed 8 skills that we deemed essential for living independently (grooming; dressing; toileting; bed, chair, toilet, tub, and car transfers). Only 6 (35%) of the youths with OI type III were able to complete all 8 items, whereas 23 (96%) individuals with OI type IV managed to perform all tasks. Teens with OI type III often needed assistance for the transfer to toilet, tub, and car and for personal hygiene and clothing management associated with toileting, usually because of limitations in upper-extremity function. These observations suggest that further improvements in the functional status of the most severely affected children with OI are contingent on advances in the clinical management of upper-extremity issues. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  3. Shade treatment affects structure and recovery of invasive C4 African grass Echinochloa pyramidalis.

    Science.gov (United States)

    López Rosas, Hugo; Moreno-Casasola, Patricia; Espejel González, Verónica E

    2015-03-01

    Echinochloa pyramidalis (Lam.) Hitchc. & Chase is an African grass with C4 photosynthesis, high biomass production, and high vegetative propagation that is tolerant to grazing and able to grow in flooded and dry conditions. Thus, it is highly invasive in tropical freshwater marshes where it is intentionally planted by ranchers to increase cattle production. This invasion is reducing plant biodiversity by increasing the invader's aerial coverage, changing wetland hydrology and causing soil physicochemical changes such as vertical accretion. Reducing the dominance of this species and increasing the density of native wetland species is a difficult, expensive, and time-consuming process. We applied a series of disturbance treatments aimed at eliminating E. pyramidalis and recovering the native vegetation of a partially invaded freshwater marsh. Treatments included physical (cutting, soil disking, transplanting individuals of the key native species Sagittaria lancifolia subsp. media (Micheli) Bogin, and/or reducing light with shade mesh) and/or chemical (spraying Round-Up™ herbicide) disturbances. At the end of the experiment, four of the five treatments used were effective in increasing the cover and biomass of native species and reducing that of E. pyramidalis. The combination of these treatments should be used to generate a proposal for the restoration of tropical wetlands invaded by non-native grasses. A promising treatment is using soil disked to soften the soil and destroy belowground structures such as roots and rhizomes. This treatment would be more promising if combined with the use of shade cloth. If it is desirable not to impact the soil or if there is not enough budget to make an effort to include active restoration disking soil, the use of shade cloth will suffice, although the recovery of native vegetation will be slower.

  4. Stroke and TIA survivors’ cognitive beliefs and affective responses regarding treatment and future stroke risk differentially predict medication adherence and categorised stroke risk

    OpenAIRE

    Phillips, L. Alison; Diefenbach, Michael A.; Abrams, Jessica; Horowitz, Carol R.

    2014-01-01

    Cognitive beliefs and affective responses to illness and treatment are known to independently predict health behaviours. The purpose of the current study is to assess the relative importance of four psychological domains – specifically, affective illness, cognitive illness, affective treatment and cognitive treatment – for predicting stroke and transient ischemic attack (TIA) survivors’ adherence to stroke prevention medications as well as their objective, categorised stroke risk. We assessed...

  5. Search for genetic markers determining the efficiency of therapy with bisphosphonates in Russian women with postmenopausal osteoporosis: A pilot study

    Directory of Open Access Journals (Sweden)

    M. Yu. Krylov

    2016-01-01

    Full Text Available Many clinical observations show that patient’s genetic background is of great importance in determining the efficiency of treatment.Subjects and methods. The instigation included 50 postmenopausal women with osteoporosis (OP, who were followed up at the Laboratory of osteoporosis, V.A. Nasonova Research Institute of Rheumatology. Body mineral density (BMD in the lumbar spine (LI-IV, femoral neck (FN, and total hip was measured using dual-energy X-ray absorptiometry before and 12 months after treatment with bisphosphonates (BP. To estimate BMD changes, the investigators used ΔBMD in percent (Δ, %.Results and discussion. The whole group showed a positive effect of BP therapy during a year, which was most pronounced in the lumbar spine (mean ΔBMD, about 4%, and a small increment in the proximal hip BMD (mean ΔBMD, about 2%. An analysis indicated a statistically significant correlation of MCP1 -2518A>G polymorphism with changes in LI-IV BMD after 12-month BP therapy. Thus, the female patients who were A allele carriers had a twice lower increase in LI-IV BMD due to BP therapy than those without this allele. The genetic variants of the CCR5 gene, which were related to Δ32 deletion, and IL1β -511C/T polymorphism were also associated with changes in FN BMD following 12-month BP therapy. The BMD increase due to BP therapy in the carriers of the CCR5 Δ32 mutation (wt/Δ32 genotype was 3.5-fold than that in the carriers of the wild type gene (wt/wt genotype. Examination of IL1 -511C/T polymorphism demonstrated that the FN BMD increment in the carriers of the CC genotype was significantly higher than in those of the CT genotype (4.2±4.8 and 1.0±3.7%, respectively; р = 0.023. Our investigation revealed no significant relationship between VDR, LEPR, IL10, MHTFR, PPARG, SPP1, and CCR5(G/A gene polymorphisms and 12-month BP therapy-induced BMD changes in the three study skeletal regions. The findings may suggest that genetic testing may be used to

  6. MK-801 treatment affects glycolysis in oligodendrocytes more than in astrocytes and neuronal cells: insights for schizophrenia

    Science.gov (United States)

    Guest, Paul C.; Iwata, Keiko; Kato, Takahiro A.; Steiner, Johann; Schmitt, Andrea; Turck, Christoph W.; Martins-de-Souza, Daniel

    2015-01-01

    Schizophrenia is a debilitating mental disorder, affecting more than 30 million people worldwide. As a multifactorial disease, the underlying causes of schizophrenia require analysis by multiplex methods such as proteomics to allow identification of whole protein networks. Previous post-mortem proteomic studies on brain tissues from schizophrenia patients have demonstrated changes in activation of glycolytic and energy metabolism pathways. However, it is not known whether these changes occur in neurons or in glial cells. To address this question, we treated neuronal, astrocyte, and oligodendrocyte cell lines with the NMDA receptor antagonist MK-801 and measured the levels of six glycolytic enzymes by Western blot analysis. MK-801 acts on the glutamatergic system and has been proposed as a pharmacological means of modeling schizophrenia. Treatment with MK-801 resulted in significant changes in the levels of glycolytic enzymes in all cell types. Most of the differences were found in oligodendrocytes, which had altered levels of hexokinase 1 (HK1), enolase 2 (ENO2), phosphoglycerate kinase (PGK), and phosphoglycerate mutase 1 after acute MK-801 treatment (8 h), and HK1, ENO2, PGK, and triosephosphate isomerase (TPI) following long term treatment (72 h). Addition of the antipsychotic clozapine to the cultures resulted in counter-regulatory effects to the MK-801 treatment by normalizing the levels of ENO2 and PGK in both the acute and long term cultures. In astrocytes, MK-801 affected only aldolase C (ALDOC) under both acute conditions and HK1 and ALDOC following long term treatment, and TPI was the only enzyme affected under long term conditions in the neuronal cells. In conclusion, MK-801 affects glycolysis in oligodendrocytes to a larger extent than neuronal cells and this may be modulated by antipsychotic treatment. Although cell culture studies do not necessarily reflect the in vivo pathophysiology and drug effects within the brain, these results suggest that

  7. Surgical Orthodontic Treatment of a Patient Affected by Type 1 Myotonic Dystrophy (Steinert Syndrome)

    OpenAIRE

    Cacucci, Laura; Ricci, Beatrice; Moretti, Maria; Gasparini, Giulio; Pelo, Sandro; Grippaudo, Cristina

    2017-01-01

    Myotonic dystrophy, or Steinert’s disease, is the most common form of muscular dystrophy that occurs in adults. This multisystemic form involves the skeletal muscles but affects also the eye, the endocrine system, the central nervous system, and the cardiac system. The weakness of the facial muscles causes a characteristic facial appearance frequently associated with malocclusions. Young people with myotonic dystrophy, who also have severe malocclusions, have bad oral functions such as chewin...

  8. TREATMENT PLANNING, PACING, AND COUNTERTRANSFERENCE: PERSPECTIVES ON THE PSYCHOTHERAPY OF EARLY AFFECT-CONFUSION

    Directory of Open Access Journals (Sweden)

    Richard G. Erskine

    2012-12-01

    Full Text Available This article is a rejoinder and elaboration on the article “Early Affect-Confusion: The ‘Borderline’ Between Despair and Rage: Part 1 of a Case Study Trilogy” and addresses the distinction between personality style, pattern, and disorder. It describes the pacing of a time-limited psychotherapy, the use of phenomenological inquiry in resolving transferential enactments, and the psychological function of idealization.

  9. Implications of bisphosphonate calcium ion depletion interfering with desmosome epithelial seal in osseointegrated implants and pressure ulcers.

    Science.gov (United States)

    Touyz, Louis Z G; Afrashtehfar, Kelvin I

    2017-09-01

    Osteoporosis (OP) is a global bone disease prevalent in aging in humans, especially in older women. Bisphosphonates (BPs) are commonly used as therapy for OP as it influences hard and soft tissues calcium metabolism. Mucosal and dermal ulceration with exposure of underlying bone arises from incomplete epithelial recovery due to reduced desmosome formation deriving from lack of available calcium. Pathological situations such as bisphosphonate-related osteonecrosis of the jaw have been described. This hypothesis states other situations which demand intact functional desmosomes such as healing skin over chronic pressure points leading to pressure ulcers (as well-known as bedsores, pressure sores, pressure injuries, decubitus ulcers), and hemidesmosomes such as epithelial seals in contact with titanium surfaces will have a higher prevalence of breakdown among patients being treated with BPs. This may be proven through the diminished modulation of calcium ions due to BPs, and its effect on the formation of intercellular gap junctions. Copyright © 2017. Published by Elsevier Ltd.

  10. Bis-phosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation

    Energy Technology Data Exchange (ETDEWEB)

    Sawicki, M.; Lecercle, D.; Taran, F. [CEA Saclay, IBiTecS, Serv Chim Bioorgan et Marquage, F-91191 Gif Sur Yvette (France); Grillon, G.; Le Gall, B.; Serandour, A.L.; Poncy, J.L. [CEA, DSV, DRR, Lab Radiotoxicol, F-91680 Bruyeres Le Chatel (France); Bailly, T.; Burgada, R.; Lecouvey, M.; Challeix, V. [CNRS, Lab Chim Struct Biomol, UMR 7033, F-93017 Bobigny (France); Leydier, A.; Pellet-Rostaing, S. [Univ Lyon 1, ICBMS, UMR 5246, Lab Catalyse et Synth Organ, F-69622 Villeurbanne (France); Ansoborlo, E. [CEA, DEN, DRCP, CETAMA, VRH Marcoule, F-30207 Bagnols Sur Ceze (France)

    2008-07-01

    A library of bis-phosphonate-based ligands was prepared using solution-phase parallel synthesis and tested for its uranium-binding properties. With the help of a screening method, based on a chromo-phoric complex displacement procedure, 23 dipodal and tripodal chelates bearing bis-phosphonate chelating functions were found to display very high affinity for the uranyl ion and were selected for evaluation of their in vivo uranyl-removal efficacy. Among them, 11 ligands induced a huge modification of the uranyl biodistribution by deviating the metal from kidney and bones to liver. Among the other ligands, the most potent was the dipodal bis-phosphonate 3C which reduced the retention of uranyl and increased its excretion by around 10% of the injected metal. (authors)

  11. Do Pharmacological and Behavioral Interventions Differentially Affect Treatment Outcome for Children with Social Phobia?

    Science.gov (United States)

    Scharfstein, Lindsay A.; Beidel, Deborah C.; Rendon Finnell, Laura; Distler, Aaron; Carter, Nathan T.

    2011-01-01

    In a randomized trial for children with social phobia (SP), Social Effectiveness Therapy for Children (SET-C; a treatment consisting of exposure and social skills training) and fluoxetine were more effective than pill placebo in reducing social distress and behavioral avoidance, but only SET-C demonstrated significantly improved overall social…

  12. Overstory removal and residue treatments affect soil surface, air, and soil temperature: implications for seedling survival

    Science.gov (United States)

    Roger D. Hungerford; Ronald E. Babbitt

    1987-01-01

    Potentially lethal ground surface temperatures were measured at three locations in the Northern Rocky Mountains but occurred more frequently under treatments with greater overstory removal. Observed maximum and minimum temperatures of exposed surfaces are directly related to the thermal properties of the surface materials. Survival of planted seedlings was consistent...

  13. Some physiological changes in faba bean seedlings as affected by the treatment with the fungicide zineb

    International Nuclear Information System (INIS)

    Kamel, H.A.; Aly, M.A.S.; Afifi, L.M.

    2002-01-01

    The toxic effect of 10 ppm of the fungicide zineb (zine ethylene -1,2-bis dithiocarbamate) on photosynthesis, respiration and endogenous hormones levels of faba bean seedlings were studied after seed treatment or foliar application utilizing radiotracer techniques. A suggested scheme for faba bean treatment with zineb and a flow diagram for extraction, purification and separation of endogenous hormones are presented. The data obtained (seed treatment) revealed a marked reduction (41.8%) in the amount of 14C O 2 fixed or incorporated in different cell components of seedlings. On the other hand, respiratory activity was significantly increased recording 176.5% and manifesting a respired/fixed radio about 4 times of the corresponding control. In case of foliar application, the amount of 14C O 2 fixed showed remarkable decrease (50%) after 24 h of application then declined to reach almost control values after 72 h. The respiratory 14C O 2 showed a continuos increase with time reaching 398% after 72 h. Respired/fixed ratio amounted 0.8 after 72 h. Both treatments led to an increase in the amounts of endogenous hormones; cytokinines, auxins and ABA when compared with control values recording the highest values after 24 h. A substational reduction in the amount of gibberellin-like substances was observed. Zineb induced high stress on faba bean seedlings and had the impact to reduce the intensity of certain natural processes such as photosynthesis and respiration and increased the endogenous hormones

  14. Analysis of factors affecting the early hypothyroidism following 131I treatment of Graves' disease

    International Nuclear Information System (INIS)

    Tian Rong; Kuang Anren; Qin Weishi

    2001-01-01

    Objective: It is a retrospective study designed to evaluate the early therapeutic outcome of radioiodine therapy in patients with Graves' disease and determine whether the outcome of radioiodine therapy in Graves' disease depends on thyroid volume, function, thyreo-stasis, therapeutic dosage, 131 I uptake, age, sex, and absorbed doses by per gram of thyroid tissue. Methods: One year after treatment, 342 patients were divided into two groups according to whether there was hypothyroidism, t test and x 2 test were used to compare the variable parameters between the two groups. Results: 92.1% were cured with a single dose of 131 I, and 21.2% contracted hypothyroidism at 12 months after treatment. The outcome of treatment at 12 months depended on the volume of thyroid and the absorbed doses by per gram of thyroid tissue. And pretreatment with thyreo-stasis did not reduce the therapeutic efficacy of 131 I in hyperthyroidism if antithyroid drugs were discontinued at least 3 days before 131 I treatment. Conclusions: Since most hypothyroidism occurred in patients whose thyroid volume is small, appropriate reduction of target dose is recommended here for those patients

  15. Ruminal biohydrogenation kinetics of defatted flaxseed and sunflower is affected by heat treatment

    DEFF Research Database (Denmark)

    Lashkari, Saman; Hymøller, Lone; Jensen, Søren Krogh

    2017-01-01

    The effect of heat treatment on biohydrogenation of linoleic acid (LA) and linolenic acid (LNA) and formation of stearic acid (SA), cis-9, trans-11 conjugated LA (CLA), trans-10, cis-12 CLA and trans-vaccenic acid (VA) was studied in in vitro incubations with diluted rumen fluid as inoculum...

  16. From lifting to planting: Root dip treatments affect survival of loblolly pine (Pinus taeda)

    Science.gov (United States)

    Tom E. Starkey; David B. South

    2009-01-01

    Hydrogels and clay slurries are the materials most commonly applied to roots of pines in the southern United States. Most nursery managers believe such applications offer a form of "insurance" against excessive exposure during planting. The objective of this study was to examine the ability of root dip treatments to: (1) support fungal growth; and (2) protect...

  17. Applications of text messaging, and bibliotherapy for treatment of patients affected by depressive symptoms

    Directory of Open Access Journals (Sweden)

    Roya Taleban

    2016-01-01

    Conclusions: It seems that bibliotherapy could efficiently decrease the intensity of depressive symptoms. Nevertheless, in comparison with our booklet trial, the text messaging group achieved neither durable nor significant success; thus, bibliotherapy could be utilized as a complementary methodology aiming depression treatment.

  18. Environmental Parameters Affecting the Algal Diversity in a Sewage Water Treatment Plant

    International Nuclear Information System (INIS)

    Hammad, D.M.; Tawfik, T.A.; Ismail, G.A.; Abou El-Khair, W.S.; Abou El-Nour, F.

    2008-01-01

    The present investigation was carried out at a tertiary sewage water treatment plant located at El-Kattameya city, Cairo, Egypt, for a duration period of 12 months during 2004. The present work aimed to study the algal diversity (phyto benthos and phytoplankton) of the different tanks (collector, oxidation, settling and effluent) included in the tertiary sewage treatment system with respect to changes in physico-chemical characteristics of sewage water during the different seasons to be used for golf course irrigation. The treatment system is of the physico-biological type. Representing data of the physico-chemical parameters are air and water temperatures, ph, electrical conductivity (EC), dissolved oxygen (DO), chemical oxygen demand (COD), biological oxygen demand (BOD), total suspended salts (TSS), total alkalinity, nutrients (nitrate, ammonia, phosphate, ortho-phosphorus, phosphorus and silicate), as well as major ions (calcium, potassium, sodium, magnesium, sulfate and chloride). In addition, the treatment efficiency of the system was evaluated and the suitability of using the effluent in irrigation purposes was discussed

  19. Ruby laser for treatment of tattoos: technical considerations affecting clinical use

    Science.gov (United States)

    Grove, Robert E.

    1990-06-01

    Recent clinical research on the use of ruby lasers for the treatment of tattoos and FIlk approval of a commercial system have renewed interest in this device. In this paper the principles of Q-switched ruby laser operation are reviewed, and potential sources of error in the estimation of delivered fluence are discussed.

  20. Transcranial magnetotherapy in the complex treatment of affective disorders in patients with alcoholism.

    Science.gov (United States)

    Staroverov, A T; Vil'yanov, V B; Raigorodskii, Yu M; Rogozina, M A

    2009-06-01

    Transcranial magnetotherapy (TMT) was used in 32 patients with alcoholism (study group) on the background of basal treatment (nootropes, hepatoprotectors, vitamin/mineral formulations, etc.). The influence of this treatment was compared with a control group (30 subjects), in which TMT was replaced with an appropriate (placebo) procedure. All patients, who were aged from 35 to 64 years, had second-degree alcoholism with disease durations of 4-12 years. Patients were in a post-abstinence state during the treatment period. Courses of TMT consisted of 10 daily procedures with exposures of 10-20 min. Somatic, neurological, and laboratory studies were performed before and after treatment and included cardiointervalography, electroencephalography, assessments of the state of the autonomic nervous system, and use of psychometric scales to evaluate levels of anxiety and depression. TMT was followed by improvements in wellbeing, mood, and sleep, with increases in physical exercise tolerance and decreases in alcohol craving in 75% of patients in the study group and 30% of patients in the control group. Improvements in patients' status were supported by paraclinical investigations (electrophysiological, measures of the state of the autonomic nervous system, etc.) and psychometric scales.

  1. Treatment with Entinostat Heals Experimental Cholera by Affecting Physical and Chemical Barrier Functions of Intestinal Epithelia.

    Science.gov (United States)

    Sarker, Protim; Banik, Atanu; Stromberg, Roger; Gudmundsson, Gudmundur H; Raqib, Rubhana; Agerberth, Birgitta

    2017-07-01

    We have shown previously that oral treatment with sodium butyrate or phenylbutyrate in an experimental model of shigellosis improves clinical outcomes and induces the expression of the antimicrobial peptide CAP-18 in the large intestinal epithelia. In a subsequent study, we found that entinostat, an aroylated phenylenediamine compound, has similar therapeutic potential against shigellosis. In this study, we aimed to evaluate entinostat as a potential candidate for host-directed therapy against cholera in an experimental model. Vibrio cholerae -infected rabbits were treated with two different dose regimens of entinostat: either 0.5 mg twice daily for 2 days or 1 mg once daily for 2 days. The effects of treatment on clinical outcomes and V. cholerae shedding (CFU count in stool) were observed. Immunohistochemical analysis was carried out to assess CAP-18 expression in ileal and jejunal mucosae. The serum zonulin level was measured by an enzyme-linked immunosorbent assay (ELISA) to evaluate gut permeability. Infection of rabbits with V. cholerae downregulated CAP-18 expression in the ileal epithelium; the expression was replenished by oral treatment with entinostat at either dose regimen. The level of zonulin, a marker of gut permeability, in serum was upregulated after infection, and this upregulation was counteracted after treatment with entinostat. Entinostat treatment also led to recovery from cholera and a decline in the V. cholerae count in stool. In conclusion, the improved clinical outcome of cholera for rabbits treated with entinostat is associated with the induction of CAP-18 and the reduction of gut epithelial permeability. Copyright © 2017 American Society for Microbiology.

  2. EFFECTIVENESS OF NITROGEN-CONTAINING BISPHOSPHONATES IN THE REGULATION OF MINERAL METABOLISM DISTURBANCES ASSOCIATED WITH ALIMENTARY OSTEOPOROSIS IN RATS

    OpenAIRE

    Komisarenko S. V.; Volochnyuk D. M.; Shymanskyy I. O.; Ivonin S. P.; Veliky M. M.1

    2015-01-01

    The aim of the study was to investigate the effectiveness of nitrogen-containing bisphosphonates synthesized as promising substances for correction of mineral metabolism in osteoporosis. The study was carried out on a model of alimentary osteoporosis that was characterized by hypocalcaemia, hypophosphatemia, decreased 25-Hydroxyvitamin D3 content in blood serum and severe bone tissue demineralization (reduced ash content and mineral components). It was found that synthesized novel nitrogen bi...

  3. Acyclic nucleoside bisphosphonates: Synthesis and properties of chiral 2-amino-4,6-bis[(phosphonomethoxy)alkoxy]pyrimidines

    Czech Academy of Sciences Publication Activity Database

    Doláková, Petra; Dračínský, Martin; Masojídková, Milena; Šolínová, Veronika; Kašička, Václav; Holý, Antonín

    2009-01-01

    Roč. 44, č. 6 (2009), s. 2408-2424 ISSN 0223-5234 R&D Projects: GA MŠk 1M0508 Grant - others:NIH(US) 1UC1AIO62540-01 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * pyrimidine * bisphosphonates Subject RIV: CC - Organic Chemistry Impact factor: 3.269, year: 2009

  4. Structural and thermodynamic basis of the inhibition of Leishmania major farnesyl diphosphate synthase by nitrogen-containing bisphosphonates

    Energy Technology Data Exchange (ETDEWEB)

    Aripirala, Srinivas [Johns Hopkins University, 725 North Wolfe Street WBSB 605, Baltimore, MD 21210 (United States); Gonzalez-Pacanowska, Dolores [López-Neyra Institute of Parasitology and Biomedicine, 18001 Granada (Spain); Oldfield, Eric [University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Kaiser, Marcel [University of Basel, Petersplatz 1, CH-4003 Basel (Switzerland); Amzel, L. Mario, E-mail: mamzel@jhmi.edu [Johns Hopkins University School of Medicine, 725 N. Wolfe Street WBSB 604, Baltimore, MD 21205 (United States); Gabelli, Sandra B., E-mail: mamzel@jhmi.edu [Johns Hopkins University School of Medicine, 725 N. Wolfe Street WBSB 604, Baltimore, MD 21205 (United States); Johns Hopkins University School of Medicine, Baltimore, MD 21205 (United States); Johns Hopkins University, 725 North Wolfe Street WBSB 605, Baltimore, MD 21210 (United States)

    2014-03-01

    Structural insights into L. major farnesyl diphosphate synthase, a key enzyme in the mevalonate pathway, are described. Farnesyl diphosphate synthase (FPPS) is an essential enzyme involved in the biosynthesis of sterols (cholesterol in humans and ergosterol in yeasts, fungi and trypanosomatid parasites) as well as in protein prenylation. It is inhibited by bisphosphonates, a class of drugs used in humans to treat diverse bone-related diseases. The development of bisphosphonates as antiparasitic compounds targeting ergosterol biosynthesis has become an important route for therapeutic intervention. Here, the X-ray crystallographic structures of complexes of FPPS from Leishmania major (the causative agent of cutaneous leishmaniasis) with three bisphosphonates determined at resolutions of 1.8, 1.9 and 2.3 Å are reported. Two of the inhibitors, 1-(2-hydroxy-2,2-diphosphonoethyl)-3-phenylpyridinium (300B) and 3-butyl-1-(2,2-diphosphonoethyl)pyridinium (476A), co-crystallize with the homoallylic substrate isopentenyl diphosphate (IPP) and three Ca{sup 2+} ions. A third inhibitor, 3-fluoro-1-(2-hydroxy-2,2-diphosphonoethyl)pyridinium (46I), was found to bind two Mg{sup 2+} ions but not IPP. Calorimetric studies showed that binding of the inhibitors is entropically driven. Comparison of the structures of L. major FPPS (LmFPPS) and human FPPS provides new information for the design of bisphosphonates that will be more specific for inhibition of LmFPPS. The asymmetric structure of the LmFPPS–46I homodimer indicates that binding of the allylic substrate to both monomers of the dimer results in an asymmetric dimer with one open and one closed homoallylic site. It is proposed that IPP first binds to the open site, which then closes, opening the site on the other monomer, which closes after binding the second IPP, leading to the symmetric fully occupied FPPS dimer observed in other structures.

  5. Hyperparathyroidism Associated with Long-Term Proton Pump Inhibitors Independent of Concurrent Bisphosphonate Therapy in Elderly Adults.

    Science.gov (United States)

    Hinson, Andrew M; Wilkerson, Bekka M; Rothman-Fitts, Ivy; Riggs, Ann T; Stack, Brendan C; Bodenner, Donald L

    2015-10-01

    To measure the effect of proton pump inhibitors (PPIs), with and without concurrent bisphosphonates, on parathyroid hormone (PTH), vitamin D, and calcium. Retrospective chart review of individuals 60 years and older. Subjects with reduced renal function (creatinine >1.3 mg/dL) and low vitamin D (hyperparathyroidism regardless of concurrent oral BP administration. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  6. Factors affecting ambulance utilization for asthma attack treatment: understanding where to target interventions.

    Science.gov (United States)

    Raun, L H; Ensor, K B; Campos, L A; Persse, D

    2015-05-01

    Asthma is a serious, sometimes fatal condition, in which attacks vary in severity, potentially requiring emergency medical services (EMS) ambulance treatment. A portion of asthma attacks requiring EMS ambulance treatment may be prevented with improved education and access to care. The aim of this study was to identify areas of the city with high rates of utilization of EMS ambulance for treatment, and the demographics, socio-economic status, and time of day associated with these rates, to better target future interventions to prevent emergencies and reduce cost. A cross-sectional study was conducted on individuals in Houston, TX (USA) requiring ambulance treatment for asthma attacks from 2004 to 2011. 12,155 EMS ambulance-treated asthma attack cases were linked to census tracts. High rate treatment areas were identified with geospatial mapping. Census tract demographic characteristics of these high rate areas were compared with the remainder of the city using logistic regression. The association between case level demographics and the time of day of asthma attack within the high rate area was also assessed with logistic regression. EMS ambulance-treated high rate areas were identified and found to have a utilization incidence rate over six times higher per 100,000 people than the remainder of the city. There is an increased risk of location in this high rate area with a census tract level increase of percent of population: earning less than $10,000 yearly income (RR 1.21, 1.16-1.26), which is black (RR 1.08, 1.07-1.10), which is female (RR 1.34, 1.20-1.49) and have obtained less than a high school degree (RR 1.02, 1.01-1.03). Within the high rate area, case level data indicates an increased risk of requiring an ambulance after normal doctor office hours for men compared with women (RR 1.13, 1.03-1.22), for black compared with Hispanic ethnicity (RR 1.31, 1.08-1.59), or for adults (less than 41 and greater than 60) compared with children. Interventions to prevent

  7. Wastewater treatment in tsunami affected areas of Thailand by constructed wetlands

    DEFF Research Database (Denmark)

    Brix, Hans; Koottatep, H.; Laugesen, C.H.

    2007-01-01

    the systems which have been built at three locations: (a) Baan Pru Teau: A newly-built township for tsunami victims which was constructed with the contribution of the Thai Red Cross. Conventional septic tanks were installed for the treatment of blackwater from each household and its effluent and grey water...... system and a system for reuse of treated wastewater. The constructed wetland system (capacity 400 m3/day) consists of vertical flow, horizontal subsurface flow, free water surface flow and pond units. Because the treatment plant is surrounded by resorts, restaurants and shops, the constructed wetland...... systems are designed with terrains as scenic landscaping. (c) Patong: A 5,000 m2 constructed wetland system has been established to treat polluted water from drainage canals which collect overflow from septic tanks and grey water from residential areas. It is envisaged that these three systems will serve...

  8. Laparoscopic Cryoablation Of Small Renal Tumors – Does Anatomical Tumor Complexity Affect Treatment Outcome?

    DEFF Research Database (Denmark)

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Andersen, Gratien

    risk in relation to nephron sparing surgery, but they may also be useful when planning cryoablation. Aim: The aim of the present study was to investigate whether patients with an anatomical complex tumor, represented by a high PADUA-score (≥10), carried a higher risk of residual unablated tumor...... compared to patients with a less anatomical complex tumor when treated with laparoscopic cryoablation. Material and methods: A retrospective review of Aarhus Cryoablation Register identified 120 patients with a single biopsy-verified pT1a renal tumor, treated with primary laparoscopic cryoablation between....... This relative risk of 2.9 (95%CI 1.1;7.6) was statistically significant (p=0.03). The mean follow-up time from treatment to diagnosis of treatment failure was 13 months (95%CI 8;18), which was not significantly different between the two groups. Conclusion: Patients with an anatomical complex tumor, represented...

  9. An evaluation of factors affecting duration of treatment with repetitive transcranial magnetic stimulation for depression

    Directory of Open Access Journals (Sweden)

    Roni Broder Cohen

    2007-12-01

    Full Text Available Objective: To investigate the effects of repetitive transcranialmagnetic stimulation in patients with major depression who weresubmitted to this treatment during the period from 2000 to 2006.Methods: A retrospective study with 204 patients who underwenttreatment with repetitive transcranial magnetic stimulation, collectingdata from those who experienced remission (defined as a HDRS scoreequal to or lower than 7. The patients were followed for up to 6 monthsafter treatment. Mean duration of remission for this cohort of patientswas 70.2 (± 58.4 days. Results: The only variable associated withthe duration of remission in the linear regression model was numberof repetitive transcranial magnetic stimulation sessions. Conclusion:Our findings suggest that the greater the number of sessions, the longerthe duration of repetitive transcranial magnetic stimulation effects.Consequently, future research investigating the effects of repetitivetranscranial magnetic stimulation should explore this variable in orderto maximize the therapeutic effects of this new brain stimulationtechnique.

  10. An analysis of vascular surgery in elderly patients to determine whether age affects treatment strategy.

    LENUS (Irish Health Repository)

    O'Brien, G

    2012-03-01

    The incidence of arterial disease increases with age. Increasing life expectancy in the western world will intensify demands on vascular surgeons with regard to increasing caseload, expanding patient selection criteria, and more complex and minimally-invasive treatment options. We analysed our arterial cases over the past 31 years (n = 6,144) and compared our methods of intervention and complication rates in the elderly population (>75) with the younger cohort, in order to determine whether age should influence our management strategies.

  11. Marijuana use in hepatitis C infection does not affect liver biopsy histology or treatment outcomes

    OpenAIRE

    Liu, Theresa; Howell, Glen T; Turner, Lucy; Corace, Kimberley; Garber, Gary; Cooper, Curtis

    2014-01-01

    BACKGROUND: Marijuana smoking is prevalent among hepatitis C virus-infected patients. The literature assessing the influence of marijuana on liver disease progression and hepatitis C virus antiviral treatment outcomes is conflicting.METHODS: The authors evaluated hepatitis C virus RNA-positive patients followed at The Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario) from 2000 to 2009. Using The Ottawa Hospital Viral Hepatitis Clinic database and charts, information regarding demograph...

  12. An ontology for factors affecting tuberculosis treatment adherence behavior in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Ogundele OA

    2016-04-01

    Full Text Available Olukunle Ayodeji Ogundele,1 Deshendran Moodley,1 Anban W Pillay,1 Christopher J Seebregts1,2 1UKZN/CSIR Meraka Centre for Artificial Intelligence Research and Health Architecture Laboratory, School of Mathematics, Statistics and Computer Science, University of KwaZulu-Natal, Durban, KwaZulu-Natal, 2Jembi Health Systems NPC, Cape Town, South Africa Purpose: Adherence behavior is a complex phenomenon influenced by diverse personal, cultural, and socioeconomic factors that may vary between communities in different regions. Understanding the factors that influence adherence behavior is essential in predicting which individuals and communities are at risk of nonadherence. This is necessary for supporting resource allocation and intervention planning in disease control programs. Currently, there is no known concrete and unambiguous computational representation of factors that influence tuberculosis (TB treatment adherence behavior that is useful for prediction. This study developed a computer-based conceptual model for capturing and structuring knowledge about the factors that influence TB treatment adherence behavior in sub-Saharan Africa (SSA.Methods: An extensive review of existing categorization systems in the literature was used to develop a conceptual model that captured scientific knowledge about TB adherence behavior in SSA. The model was formalized as an ontology using the web ontology language. The ontology was then evaluated for its comprehensiveness and applicability in building predictive models. Conclusion: The outcome of the study is a novel ontology-based approach for curating and structuring scientific knowledge of adherence behavior in patients with TB in SSA. The ontology takes an evidence-based approach by explicitly linking factors to published clinical studies. Factors are structured around five dimensions: factor type, type of effect, regional variation, cross-dependencies between factors, and treatment phase. The ontology is

  13. Relative binding affinity of carboxylate-, phosphonate-, and bisphosphonate-functionalized gold nanoparticles targeted to damaged bone tissue

    Energy Technology Data Exchange (ETDEWEB)

    Ross, Ryan D. [Rush University Medical Center, Department of Anatomy and Cell Biology (United States); Cole, Lisa E.; Roeder, Ryan K., E-mail: rroeder@nd.edu [University of Notre Dame, Department of Aerospace and Mechanical Engineering Bioengineering Graduate Program (United States)

    2012-10-15

    Functionalized Au NPs have received considerable recent interest for targeting and labeling cells and tissues. Damaged bone tissue can be targeted by functionalizing Au NPs with molecules exhibiting affinity for calcium. Therefore, the relative binding affinity of Au NPs surface functionalized with either carboxylate (l-glutamic acid), phosphonate (2-aminoethylphosphonic acid), or bisphosphonate (alendronate) was investigated for targeted labeling of damaged bone tissue in vitro. Targeted labeling of damaged bone tissue was qualitatively verified by visual observation and backscattered electron microscopy, and quantitatively measured by the surface density of Au NPs using field-emission scanning electron microscopy. The surface density of functionalized Au NPs was significantly greater within damaged tissue compared to undamaged tissue for each functional group. Bisphosphonate-functionalized Au NPs exhibited a greater surface density labeling damaged tissue compared to glutamic acid- and phosphonic acid-functionalized Au NPs, which was consistent with the results of previous work comparing the binding affinity of the same functionalized Au NPs to synthetic hydroxyapatite crystals. Targeted labeling was enabled not only by the functional groups but also by the colloidal stability in solution. Functionalized Au NPs were stabilized by the presence of the functional groups, and were shown to remain well dispersed in ionic (phosphate buffered saline) and serum (fetal bovine serum) solutions for up to 1 week. Therefore, the results of this study suggest that bisphosphonate-functionalized Au NPs have potential for targeted delivery to damaged bone tissue in vitro and provide motivation for in vivo investigation.

  14. Treatment of trauma-affected refugees with Venlafaxine versus Sertraline combined with psychotherapy – a randomised study

    DEFF Research Database (Denmark)

    Sonne, Charlotte Kærgaard; Carlsson, Jessica; Bech, P

    2016-01-01

    Background: The prevalence of trauma-related psychiatric disorders is high among refugees. Despite this, little is known about the effect of pharmacological treatment for this patient group. The objective of the present study was therefore to examine differences in the effects of venlafaxine...... and sertraline on Post-Traumatic Stress Disorder (PTSD), depression and functional impairment in trauma-affected refugees. Methods: The study was a randomised pragmatic trial comparing venlafaxine and sertraline in combination with psychotherapy and social counselling. PTSD symptoms were measured on the Harvard......: Two hundred seven adult refugee patients were included in the trial (98 in the venlafaxine and 109 in the sertraline group). Of these, 195 patients were eligible for intention-to-treat analyses. Small but significant pre-treatment to post-treatment differences were found on the Harvard Trauma...

  15. Affective predictors of the severity and change in eating psychopathology in residential eating disorder treatment: The role of social anxiety.

    Science.gov (United States)

    Smith, Kathryn E; Mason, Tyler B; Leonard, Rachel C; Wetterneck, Chad T; Smith, Brad E R; Farrell, Nicholas R; Riemann, Brad C

    2018-01-01

    Despite evidence documenting relationships between eating disorder (ED) psychopathology, depression, and anxiety, little is known regarding how social anxiety is related to ED symptoms in treatment. Therefore this study examined associations between depression, general anxiety, social anxiety, and ED psychopathology at the beginning and end of treatment (EOT) among patients (N = 380) treated in a residential ED program. Participants completed measures of ED psychopathology and affective variables. Higher depression and general anxiety, but not social anxiety, were related to higher ED psychopathology at baseline. However, social anxiety emerged as a unique predictor of ED psychopathology at EOT such that participants with higher social anxiety evidenced less improvement in ED psychopathology. Findings suggest that social anxiety has specific relevance to treatment in EDs, which may reflect shared mechanisms and underlying deficits in emotion regulation.

  16. Nandrolone decanoate treatment affects sarcoplasmic reticulum Ca(2+) ATPase function in skinned rat slow- and fast-twitch fibres.

    Science.gov (United States)

    Bouhlel, Aicha; Joumaa, Wissam H; Léoty, Claude

    2003-09-01

    The effects of anabolic-androgenic steroid administration on the function of the sarcoplasmic reticulum (SR) pump were investigated in chemically skinned fibres from the extensor digitorum longus (EDL) and soleus muscles of sedentary rats. Twenty male rats were divided into two groups, one group received an intramuscular injection of nandrolone decanoate (15 mg x kg(-1)) weekly for 8 weeks, the second received similar weekly doses of vehicle (sterile peanut oil). Compared with control muscles, nandrolone decanoate treatment reduced SR Ca(2+) loading in EDL and soleus fibres by 49% and 29%, respectively. In control and treated muscles, the rate of Ca(2+) leakage depended on the quantity of Ca(2+) loaded. Furthermore, for similar SR Ca(2+) contents, the Ca(2+) leakage rate was not significantly modified by nandrolone decanoate treatment. Nandrolone decanoate treatment thus affects Ca (2+) uptake by the SR in a fibre-type dependent manner.

  17. Insomnia complaints in lean patients with obstructive sleep apnea negatively affect positive airway pressure treatment adherence.

    Science.gov (United States)

    Eysteinsdottir, Bjorg; Gislason, Thorarinn; Pack, Allan I; Benediktsdottir, Bryndís; Arnardottir, Erna S; Kuna, Samuel T; Björnsdottir, Erla

    2017-04-01

    The objective of this study was to evaluate the determinants of long-term adherence to positive airway pressure treatment among patients with obstructive sleep apnea, with special emphasis on patients who stop positive airway pressure treatment within 1 year. This is a prospective long-term follow-up of subjects in the Icelandic Sleep Apnea Cohort who were diagnosed with obstructive sleep apnea between 2005 and 2009, and started on positive airway pressure treatment. In October 2014, positive airway pressure adherence was obtained by systematically evaluating available clinical files (n = 796; 644 males, 152 females) with moderate to severe obstructive sleep apnea (apnea-hypopnea index ≥15 events per h). The mean follow-up time was 6.7 ± 1.2 years. In total, 123 subjects (15.5%) returned their positive airway pressure device within the first year, 170 (21.4%) returned it later and 503 (63.2%) were still using positive airway pressure. The quitters within the first year had lower body mass index, milder obstructive sleep apnea, less sleepiness, and more often had symptoms of initial and late insomnia compared with long-term positive airway pressure users at baseline. Both initial and late insomnia were after adjustment still significantly associated with being an early quitter among subjects with body mass index insomnia are associated with early quitting on positive airway pressure among non-obese subjects. © 2016 European Sleep Research Society.

  18. An ontology for factors affecting tuberculosis treatment adherence behavior in sub-Saharan Africa.

    Science.gov (United States)

    Ogundele, Olukunle Ayodeji; Moodley, Deshendran; Pillay, Anban W; Seebregts, Christopher J

    2016-01-01

    Adherence behavior is a complex phenomenon influenced by diverse personal, cultural, and socioeconomic factors that may vary between communities in different regions. Understanding the factors that influence adherence behavior is essential in predicting which individuals and communities are at risk of nonadherence. This is necessary for supporting resource allocation and intervention planning in disease control programs. Currently, there is no known concrete and unambiguous computational representation of factors that influence tuberculosis (TB) treatment adherence behavior that is useful for prediction. This study developed a computer-based conceptual model for capturing and structuring knowledge about the factors that influence TB treatment adherence behavior in sub-Saharan Africa (SSA). An extensive review of existing categorization systems in the literature was used to develop a conceptual model that captured scientific knowledge about TB adherence behavior in SSA. The model was formalized as an ontology using the web ontology language. The ontology was then evaluated for its comprehensiveness and applicability in building predictive models. The outcome of the study is a novel ontology-based approach for curating and structuring scientific knowledge of adherence behavior in patients with TB in SSA. The ontology takes an evidence-based approach by explicitly linking factors to published clinical studies. Factors are structured around five dimensions: factor type, type of effect, regional variation, cross-dependencies between factors, and treatment phase. The ontology is flexible and extendable and provides new insights into the nature of and interrelationship between factors that influence TB adherence.

  19. Modulating affect, cognition and behavior – prospects of deep brain stimulation for treatment resistant psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Thomas E. Schlaepfer

    2011-06-01

    Full Text Available Most patients suffering from psychiatric disorders respond to combina-tions of psycho- and psychopharmacotherapy, however there are patients who profit little if anything even after many years of treatment. Since about a decade different modalities of targeted neuromodulation – among them most prominently – Deep Brain Stimulation (DBS - are being actively researched as putative approaches to very treatment resistant forms of those disorders. Recently, promising pilot data have been re-ported both for Major Depression (MD and Obsessive-Compulsive Disor-der (OCD. Given the fact that patients studied had been treated unsuc-cessfully for many years renders these findings remarkable. Remarkable is the fact, that in case of the long-term studies underway for MD, patients show a stable response. This gives hope to a substantial percentage of therapy-resistant psychiatric patients requiring new therapy approaches. There are no fundamental ethic objections to its use in psychiatric disor-ders, but until substantial clinical data is available, mandatory standards are needed. DBS is a unique and very promising method for the treat-ment of therapy-resistant psychiatric patients. The method allows ma-nipulating pathological neuronal networks in a very precise way.

  20. Hospital treatment as a foal does not adversely affect future sales performance in Thoroughbred horses.

    Science.gov (United States)

    Corley, K T T; Corley, M M B

    2012-02-01

    Many Thoroughbred foals are intended to be sold at public auction. The impact of disease conditions necessitating hospital treatment as a foal on future sales performance is unknown. To determine whether Thoroughbred horses that were treated in a hospital before age 125 days and presented to public auction sell for a different mean price than controls. Foals aged horses that were presented to the same sale immediately before and immediately after the subject. Results were controlled for the sale at which the animal presented and the sex of the subject and controls. Sixty-three subjects were presented to public auction: 19 at the foal sales, 39 at the yearling sales and 5 at the 2-year-old sales. Forty-five subjects were sold. There was no difference in the mean sales price (subjects Euros 38,207; controls Euros 35,026) or percentage of animals sold (subjects 71.4%; controls 66.4%) between subjects and controls. If Thoroughbred horses are presented for public auction following hospital treatment as a foal, there is no impact on sales outcome. This information may help commercial breeders of Thoroughbred foals make informed decisions about treatment of their foals.

  1. Treatment modalities in children with teeth affected by molar-incisor enamel hypomineralisation (MIH): A systematic review.

    Science.gov (United States)

    Lygidakis, N A

    2010-04-01

    This was to review the literature concerning the treatment of permanent teeth with molar-incisor hypomineralised enamel (MIH), comment about possible shortcomings and propose areas of future research. A search of MedLine, Scopus, ResearchGate, Isis and Google Scholar databases was conducted using all terms relevant to the subject. Relevant papers published in English were identified after a review of their titles, abstracts or full reading of the papers. Of 189 references initially found, 66 papers were included; 34 directly relevant to the subject. From the latter, only 14 concerned laboratory or clinical studies dealing with treatment for MIH. Since 2000 11 reviews evaluated, to a certain extent, treatment options for affected teeth. Analysis of the proposed treatment modalities indicated options for prevention, restorations, and adhesion to hypomineralised enamel, full coronal coverage and extraction followed by orthodontics. Based on these findings, a treatment decision plan is proposed. Although treatment approaches for MIH have started to be clearer, long-term clinical trials, supported by laboratory studies, should be conducted to further facilitate the clinical management of this dental defect.

  2. Analysis of soybean root proteins affected by gibberellic acid treatment under flooding stress.

    Science.gov (United States)

    Oh, Myeong Won; Nanjo, Yohei; Komatsu, Setsuko

    2014-01-01

    Flooding is a serious abiotic stress for soybean because it restricts growth and reduces grain yields. To investigate the effect of gibberellic acid (GA) on soybean under flooding stress, root proteins were analyzed using a gel-free proteomic technique. Proteins were extracted from the roots of 4-days-old soybean seedlings exposed to flooding stress in the presence and absence of exogenous GA3 for 2 days. A total of 307, 324, and 250 proteins were identified from untreated, and flooding-treated soybean seedlings without or with GA3, respectively. Secondary metabolism- and cell-related proteins, and proteins involved in protein degradation/synthesis were decreased by flooding stress; however, the levels of these proteins were restored by GA3 supplementation under flooding. Fermentation- and cell wall-related proteins were not affected by GA3 supplementation. Furthermore, putative GA-responsive proteins, which were identified by the presence of a GA-responsive element in the promoter region, were less abundant by flooding stress; however, these proteins were more abundant by GA3 supplementation under flooding. Taken together, these results suggest that GA3 affects the abundance of proteins involved in secondary metabolism, cell cycle, and protein degradation/synthesis in soybeans under flooding stress.

  3. How medical treatment affects mean platelet volume as a cardiovascular risk marker in polycystic ovary syndrome?

    Science.gov (United States)

    Kabil Kucur, Suna; Gozukara, Ilay; Aksoy, Aysenur; Uludag, Eda U; Keskin, Havva; Kamalak, Zeynep; Carlioglu, Ayse

    2015-12-01

    Polycystic ovary syndrome (PCOS) is a prevalent disease with many potential long-term metabolic and cardiovascular risks if not managed appropriately. Mean platelet volume (MPV) is a marker associated with adverse cardiovascular events. In this study, we aimed to investigate MPV levels under ethinyl estradiol/cyproterone acetate or metformin therapy for the previous 6 months in PCOS. A total of 114 individuals [metformin treatment (n = 18), ethinyl estradiol/cyproterone acetate treatment (n = 29), newly diagnosed PCOS patient with no treatment (n = 35), and control group of eumenorrheic healthy individuals (n = 32)] were included in the current study. Hematologic parameters other than MPV were similar in all groups. The MPV value was significantly higher in the newly diagnosed PCOS patients compared with the other three groups independent of age, BMI, and C-reactive protein level in multiple regression analysis (P < 0.01). The MPV value of control group was comparable to the groups under ethinyl estradiol/cyproterone acetate or metformin therapy (P = 1.0). There was no statistically significant difference in the white blood cell count among the groups. The MPV values were positively correlated with the homeostatic model assessment-insulin resistance and Ferriman-Gallwey Score (P = 0.044, r = 0.261; P = 0.037, r = 0.229, respectively). Ethinyl estradiol/cyproterone acetate and metformin similarly appear to decrease MPV, a marker of cardiovascular risk. Therefore, a possible beneficial effect of ethinyl estradiol/cyproterone acetate and metformin on long-term cardiovascular morbidities in PCOS may be suggested.

  4. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments.

    Science.gov (United States)

    Stambaugh, Cassandra; Nelms, Benjamin E; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2013-09-01

    The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments. VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤ 8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D99%), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found. For the motion amplitudes and periods obtained from the 4DCT, the interplay effect

  5. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments

    International Nuclear Information System (INIS)

    Stambaugh, Cassandra; Nelms, Benjamin E.; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2013-01-01

    Purpose: The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments.Methods: VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D 99% ), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found.Results: For the motion amplitudes and periods obtained from the

  6. Anti-tumor effect of bisphosphonate (YM529 on non-small cell lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Date Hiroshi

    2007-01-01

    Full Text Available Abstract Background YM529 is a newly developed nitrogen-containing bisphosphonate (BP classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both in vitro or/and in vivo. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC. Methods Direct anti-tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI-H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous cell carcinoma: NCI-H157 were measured by MTS assay and calculated inhibition concentration 50 % (IC50 values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G1 method. We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis. Results We found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC50 values were 2.1 to 7.9 μM and YM529 induced apoptosis and G1 arrest cell cycle with dose-dependent manner and YM529 caused down regulation of phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819. Conclusion Our study demonstrate that YM529 showed direct anti-tumor effect on NSCLC cell lines in vitro, which supports the possibility that third-generation BPs including YM529 can be one of therapeutic options for NSCLC.

  7. Sewage Treatment Systems of Cruise Ships and The Parameters Affect on Dilution of Effluent at Sea

    Directory of Open Access Journals (Sweden)

    Volkan ŞAHİN

    2015-11-01

    Full Text Available Cruise ships play an inevitable role in tourism sector across the world. Increasing in cruise ship tourism accompanies with significant environmental problems. Due to both size of cruise ships and the amount of passengers and consumables, cruise ships have a great potential for producing considerable amounts of wastes. Various types of wastes are produced in cruise ships depending on the daily consumptions of these wastes. Sewage, which consists mainly the toilet wastes, is the most important problem. Sewage contains various types of heavy metal, chemicals and pathogens that have harmful effects on marine species and ecosystem. Many national and international regulations and conventions are established in order to prevent the harmful effects of wastes. Studies on preventing and minimizing ship-related pollution contribute to both developing new waste management systems and forming new procedures for removing the wastes in both ship and port. In this study, Marine Sanitation Device (MSD and Advanced Wastewater Treatment (AWT and treatment procedures are investigated. ‘Dilution factor’ obtained by theoretical and experimental studies is explained in detail and variation of dilution factor depending on ship dimensions and velocity is investigated.

  8. Nutritive values of brassica campestris L. oil as affected by growth regulator treatments

    International Nuclear Information System (INIS)

    Bano, A.; Khan, N.

    2009-01-01

    The effects of plant growth regulators, viz. Indole acetic acid (IAA), Gibberellic acid (GA) and Abscisic acid (ABA) were studied on fatty acid compositions, glucosinolate content and protein content of Brassica campestris L subsp. Oleifera (common name yellow sarson). Growth regulators were applied in seed soaking solution as well as foliar spray during vegetative phase and at flowering stage. There were reductions in the amount of long chain fatty acids viz erucic acid, eicosenoic acid and increase in the amount of unsaturated fatty acid viz. linoleic acid by lAA applications. The stimulating effect of lAA which reduced amount of unsaturated fatty acid was more pronounced when applied as foliar spray at vegetative stage. But, foliar spray of ABA during flowering increased the concentration of linoleic acid and reduced the eicosenoic acid and erucic acid. The glucosinolate content was greater in seeds soaked in 10/sup -5/ M lAA than that of control but less in 10/sup -5/ M GA treated seeds than that of control. The ABA treatment (10/sup -5/M) increased the concentration of glucosinolates in the seeds IAA treatments (10/sup -5/M) increased the protein percentage in the seeds. Foliar application of GA (10/sup -5/M) during vegetative growth and ABA (10/sup -5/M) as seed soaking prior to sowing as well as foliar spry during flowering decreased the protein content of seeds. (author)

  9. How sociodemographics, presence of oncology specialists, and hospital cancer programs affect accrual to cancer treatment trials.

    Science.gov (United States)

    Sateren, Warren B; Trimble, Edward L; Abrams, Jeffrey; Brawley, Otis; Breen, Nancy; Ford, Leslie; McCabe, Mary; Kaplan, Richard; Smith, Malcolm; Ungerleider, Richard; Christian, Michaele C

    2002-04-15

    We chose to examine the impact of socioeconomic factors on accrual to National Cancer Institute (NCI)-sponsored cancer treatment trials. We estimated the geographic and demographic cancer burden in the United States and then identified 24,332 patients accrued to NCI-sponsored cancer treatment trials during a 12-month period. Next, we examined accrual by age, sex, geographic residence, health insurance status, health maintenance organization market penetration, several proxy measures of socioeconomic status, the availability of an oncologist, and the presence of a hospital with an approved multidisciplinary cancer program. Pediatric patients were accrued to clinical trials at high levels, whereas after adolescence, only a small percentage of cancer patients were enrolled onto clinical trials. There were few differences by sex. Black males as well as Asian-American and Hispanic adults were accrued to clinical trials at lower rates than white cancer patients of the same age. Overall, the highest observed accrual was in suburban counties. Compared with the United States population, patients enrolled onto clinical trials were significantly less likely to be uninsured and more like to have Medicare health insurance. Geographic areas with higher socioeconomic levels had higher levels of clinical trial accruals. The number of oncologists and the presence of approved cancer programs both were significantly associated with increased accrual to clinical trials. We must work to increase the number of adults who enroll onto trials, especially among the elderly. Ongoing partnership with professional societies may be an effective approach to strengthen accrual to clinical trials.

  10. Understanding the operational parameters affecting NDMA formation at Advanced Water Treatment Plants.

    Science.gov (United States)

    Farré, Maria José; Döderer, Katrin; Hearn, Laurence; Poussade, Yvan; Keller, Jurg; Gernjak, Wolfgang

    2011-01-30

    N-nitrosodimethylamine (NDMA) can be formed when secondary effluents are disinfected by chloramines. By means of bench scale experiments this paper investigates operational parameters than can help Advanced Water Treatment Plants (AWTPs) to reduce the formation of NDMA during the production of high quality recycled water. The formation of NDMA was monitored during a contact time of 24h using dimethylamine as NDMA model precursor and secondary effluent from wastewater treatment plants. The three chloramine disinfection strategies tested were pre-formed and in-line formed monochloramine, and pre-formed dichloramine. Although the latter is not employed on purpose in full-scale applications, it has been suggested as the main contributing chemical generating NDMA during chloramination. After 24h, the NDMA formation decreased in both matrices tested in the order: pre-formed dichloramine>in-line formed monochloramine≫pre-formed monochloramine. The most important parameter to consider for the inhibition of NDMA formation was the length of contact time between disinfectant and wastewater. Formation of NDMA was initially inhibited for up to 6h with concentrations consistently NDMA concentrations were reduced by a factor of 20 by optimizing the disinfection strategy. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. [Transcranial magnetic therapy in the complex treatment of affective disorders in patients with alcoholism].

    Science.gov (United States)

    Staroverov, A T; Vil'ianov, V B; Raĭgorodskiĭ, Iu M; Rogozina, M A

    2008-01-01

    A main group--32 patients receiving transcranial magnetic therapy (TMT) in addition to the basic treatment (nootrops, hepatoprotectors, vitamins/minerals etc)--was compared to a control group (30 patients) receiving placebo instead of TMT. All patients, aged from 35 to 64 years, had the second stage of alcoholism with illness duration from 4 to 12 years and were in the postabstinent state at the moment of treatment. The TMT course included 10 daily sessions with a 10-20 min exposure. A somatic, neurological and instrumental study, including cardiointervalography, electroencephalography, assessment of autonomic system state and psychometric scales for depression and anxiety, was conducted before, during and after the therapy. The improvement of health, mood and sleep, increase of tolerability to physical loading and reduction of alcohol craving were observed after TMT in 75% of patients in the main group and in 30% in the control one. The improvement of patient's state was correlated with the data of the paraclinical study (electrophysiological parameters of the autonomic nervous system and psychometric scales scores).

  12. Roughness and compressive strength of FDM 3D printed specimens affected by acetone vapour treatment

    Science.gov (United States)

    Beniak, Juraj; Križan, Peter; Šooš, Ľubomír; Matúš, Miloš

    2018-01-01

    Rapid Prototyping technologies are the fastest growing technologies in the manufacturing of components and parts. There are many techniques which can be used with different materials and different purposes of produced part. Gradually, Rapid Prototyping systems have grown into Additive Manufacturing, because technology expansion brings faster production, improved manufactured components, and expanded palette of used materials. So now this techniques are also used for regular production of special parts, where is usual change of part design, where is necessary to produce variety of different designs and shapes. The following article deals with Fused Deposition Modelling (FDM) technology, the core of which is the manufacture models and components from thermoplastic polymers by deposition single fibres of semi-molten plastic material layer by layer. The article focuses on the results of research for testing of manufactured specimens by FDM technology. Components are modified by acetone vapour for surface smoothing. The purpose is to point out how the additional specimen treatment influence the strength properties. Presented paper shows realized experiments and measurements of compressive force on specimens and surface roughness which are influenced by acetone vapour treatment.

  13. [An easy, safe and affective method for the treatment of intussusception: ultrasound-guided hydrostatic reduction].

    Science.gov (United States)

    Ülger, Fatma Esra Bahadır; Ülger, Aykut; Karakaya, Ali Erdal; Tüten, Fatih; Katı, Ömer; Çolak, Mustafa

    2014-03-01

    Intussusception is one of the important causes of intestinal obstruction in children. Hydrostatic reduction under ultrasound guidance is a popular treatment method for intussusception. In the present study, we aimed to explain the demographic characteristics of and treatment approaches in patients diagnosed with intussusception by ultrasound. Forty-one patients diagnosed with intussusception by ultrasound between August 2011 and May 2013 were retrospectively analyzed. Twenty-four of these patients who had no contraindications had been treated with ultrasound-guided hydrostatic reduction. Twenty-four of the patients were male and 17 were female, a 1.4/1 male-to-female ratio. The majority of the patients were between the ages of 6-24 months and 2-5 years. The mean age was 31.12±26.32 months (range 3-125). Patients were more frequently diagnosed in April and May. Seventeen patients who had clinical contraindications enrolled directly for surgery. In 20 of the 24 patients who underwent ultrasound-guided hydrostatic reduction, reduction was achieved. Three experienced recurrence. In two of these patients, successful reduction was achieved with the second attempt. The remaining patient was enrolled for surgery. Hydrostatic reduction was performed 26 times on these 24 patients, and in 22, success was achieved (84.6%). No procedure-related complications occurred in the patients. Ultrasound-guided hydrostatic reduction, with its high success rates and lack of radiation risk, should be the first choice therapeutic approach for children diagnosed with intussusception.

  14. Treatment of the depressive phase of bipolar affective disorder: a review

    International Nuclear Information System (INIS)

    Muneer, A.

    2013-01-01

    Bipolar disorder is a chronic mood disorder which usually has its onset in adolescence and young adulthood. The disorder is typified by a remitting and relapsing course. While remissions are often partial in nature, relapses are frequent and manifested as manic, mixed, hypomanic and depressive episodes. Rapid cycling is a particularly disabling form of bipolar disorder, characterised by four or more episodes in a 12-month period. Bipolar disorder inevitably causes impairment in social and occupational functioning. Many patients experience severe hopelessness and suicidal ideation and the disorder is associated with one of the highest mortality rates of all psychiatric disorders. The treatment of bipolar depression is particularly challenging and numerous patients achieve incomplete benefit even with complex psychopharmacological strategies. In recent years, many new pharmacological options have become available for the treatment of bipolar depression and the field has seen significant progress. In order to achieve better outcome for the patients, it is mandatory that treating physicians have an up to date knowledge of recent advances in the management of this condition. (author)

  15. Bisphosphonate Drug Holiday and Fracture Risk: A Population-Based Cohort Study.

    Science.gov (United States)

    Adams, Annette L; Adams, John L; Raebel, Marsha A; Tang, Beth T; Kuntz, Jennifer L; Vijayadeva, Vinutha; McGlynn, Elizabeth A; Gozansky, Wendolyn S

    2018-03-12

    Holidays from bisphosphonates (BPs) may help to prevent rare adverse events like atypical femoral fractures, but may be appropriate only if risk of osteoporosis-related fractures does not increase. Our objective was to compare the incidence of osteoporosis-related fractures among women who had a bisphosphonate (BP) holiday to those who continued use BPs. This retrospective cohort study, conducted within 4 Kaiser Permanente integrated health system regions, included 39,502 women aged ≥45 years with ≥3 years exposure to BP. Participants with a BP holiday (≥12 months with no use) were compared to persistent (use with ≥50% adherence) and non-persistent (use with holiday (n = 11,497), non-persistent user (n = 10,882), and persistent user groups (n = 17,123) were observed for 156,657 person-years. A total of 5,199 osteoporosis-related fractures (including 1,515 hip fractures and 2,147 vertebral fractures) were observed. Compared to the persistent use group, there was a slight difference in overall osteoporosis-related fracture risk (HR 0.92, 95% CI 0.84-0.99)and no difference in hip fracture risk (HR 0.95, 95% CI 0.83-1.10) for the BP holiday group. A slight reduction in risk of vertebral fracture was observed (HR 0.83, 95% CI 0.74-0.95). Compared to the non-persistent user group, the BP holiday group was at decreased risk for osteoporosis-related fractures (HR 0.71, 95% CI 0.65-0.79), vertebral fractures (HR 0.68, 95% CI 0.59-0.78), and hip fractures (HR 0.59; 95% CI 0.50-0.70). Women who undertake a BP holiday from BP of ≥12 months duration for any reason after ≥3 years of BP use do not appear to be at greater risk of osteoporosis-related fragility fracture, hip, or vertebral fractures compared to ongoing BP users. In our cohort, BP holiday remains a viable strategy for balancing the benefits and potential harms associated with long-term BP use. This article is protected by copyright. All rights reserved. This article is protected by copyright

  16. Structure of human farnesyl pyrophosphate synthase in complex with an aminopyridine bisphosphonate and two molecules of inorganic phosphate

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jaeok [McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6 (Canada); Lin, Yih-Shyan [McGill University, 801 Rue Sherbrooke Ouest, Montreal, QC H3A 0B8 (Canada); Tsantrizos, Youla S. [McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6 (Canada); McGill University, 801 Rue Sherbrooke Ouest, Montreal, QC H3A 0B8 (Canada); McGill University, 3649 Promenade Sir William Osler, Montreal, QC H3G 0B1 (Canada); Berghuis, Albert M., E-mail: albert.berghuis@mcgill.ca [McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6 (Canada); McGill University, 3649 Promenade Sir William Osler, Montreal, QC H3G 0B1 (Canada); McGill University, 3775 Rue University, Montreal, QC H3A 2B4 (Canada)

    2014-02-19

    A co-crystal structure of human farnesyl pyrophosphate synthase in complex with an aminopyridine bisphosphonate, YS0470, and two molecules of inorganic phosphate has been determined. The identity of the phosphate ligands was confirmed by anomalous diffraction data. Human farnesyl pyrophosphate synthase (hFPPS) produces farnesyl pyrophos@@phate, an isoprenoid essential for a variety of cellular processes. The enzyme has been well established as the molecular target of the nitrogen-containing bisphosphonates (N-BPs), which are best known for their antiresorptive effects in bone but are also known for their anticancer properties. Crystal structures of hFPPS in ternary complexes with a novel bisphosphonate, YS0470, and the secondary ligands inorganic phosphate (P{sub i}), inorganic pyrophosphate (PP{sub i}) and isopentenyl pyrophosphate (IPP) have recently been reported. Only the co-binding of the bisphosphonate with either PP{sub i} or IPP resulted in the full closure of the C-@@terminal tail of the enzyme, a conformational change that is required for catalysis and that is also responsible for the potent in vivo efficacy of N-BPs. In the present communication, a co-crystal structure of hFPPS in complex with YS0470 and two molecules of P{sub i} is reported. The unusually close proximity between these ligands, which was confirmed by anomalous diffraction data, suggests that they interact with one another, with their anionic charges neutralized in their bound state. The structure also showed the tail of the enzyme to be fully disordered, indicating that simultaneous binding of two P{sub i} molecules with a bisphosphonate cannot induce the tail-closing conformational change in hFPPS. Examination of homologous FPPSs suggested that this ligand-dependent tail closure is only conserved in the mammalian proteins. The prevalence of P{sub i}-bound hFPPS structures in the PDB raises a question regarding the in vivo relevance of P{sub i} binding to the function of the enzyme.

  17. Agonistic anti-TIGIT treatment inhibits T cell responses in LDLr deficient mice without affecting atherosclerotic lesion development.

    Directory of Open Access Journals (Sweden)

    Amanda C Foks

    Full Text Available OBJECTIVE: Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis. METHODS AND RESULTS: TIGIT was upregulated on CD4(+ T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr(-/- mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production. CONCLUSIONS: Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells.

  18. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments

    Energy Technology Data Exchange (ETDEWEB)

    Stambaugh, Cassandra [Department of Physics, University of South Florida, Tampa, Florida 33612 (United States); Nelms, Benjamin E. [Canis Lupus LLC, Merrimac, Wisconsin 53561 (United States); Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida 33612 (United States)

    2013-09-15

    Purpose: The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments.Methods: VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D{sub 99%}), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found.Results: For the motion amplitudes and periods obtained from

  19. The factors affecting effectiveness of treatment in phages therapy, mini review

    Directory of Open Access Journals (Sweden)

    Mai Huong eCHATAIN-LY

    2014-02-01

    Full Text Available In recent years, the use of lytic bacteriophages as antimicrobial agents controlling pathogenic bacteria has appeared as a promising new alternative strategy in the face of growing antibiotic resistance which has caused problems in many fields including medicine, veterinary medicine and aquaculture. The use of bacteriophages has numerous advantages over traditional antimicrobials. The effectiveness of phage applications in fighting against pathogenic bacteria depends on several factors such as the bacteriophages/target bacteria ratio, the mode and moment of treatment, environmental conditions (pH, temperature ..., the neutralization of phage and accessibility to target bacteria, amongst others. This report presents these factors and the challenges involved in developing phage therapy applications

  20. Metformin treatment does not affect the risk of ruptured abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Kristensen, Katrine L.; Pottegård, Anton; Hallas, Jesper

    2017-01-01

    Objective: Diabetes counteracts formation and rupture of abdominal aortic aneurysms, possibly through arterial matrix accumulation. Use of metformin, on the other hand, reduces arterial accumulation of matrix molecules. Consequently, we hypothesized that metformin treatment may reverse...... the protective role of diabetes on the development and course of aneurysms, that is, that metformin would be associated with aneurysm rupture among individuals with diabetes. Methods: Using nationwide Danish registry data, we performed a nested case-control study on the association between long-term use....... In total, 22.4% of the case population were long-term metformin users compared with 28.8% of the controls. We found a statistically nonsignificant protective effect of long-term metformin use toward RAAA with crude odds ratio (OR) of 0.74 (confidence interval, 0.54-1.00). When adjusted for covariates...

  1. Keeping quality of raisins as affected by irradiation, storage environments and combination treatments

    International Nuclear Information System (INIS)

    Hussain, B.; Afridi, S.; Durrani, M.J.

    1989-01-01

    Influence of irradiation and storage environments on the quality of raisins was investigated during storage at room temperature for six months. Storage environment included: packaging in clear polyethylene bags in the presence of normal air, nitrogen and vacuum. Insect infestation appeared after two months storage and reached to 5.8, 8.6, 11.7 and 25.8% in the control samples stored in normal air for 3, 4, 5 and 6 months storage, respectively. No infestation was observed in vacuum nitrogen and packed samples. In irradiated samples no infestation was observed during storage in normal air and also vacuum and nitrogen packed samples. Raisin samples packed under vacuum were better in quality than other treatments. (author)

  2. Clonorchis sinensis Co-infection Could Affect the Disease State and Treatment Response of HBV Patients.

    Directory of Open Access Journals (Sweden)

    Wenfang Li

    2016-06-01

    Full Text Available Clonorchis sinensis (C. sinensis is considered to be an important parasitic zoonosis because it infects approximately 35 million people, while approximately 15 million were distributed in China. Hepatitis B virus (HBV infection is a major public health issue. Two types of pathogens have the potential to cause human liver disease and eventually hepatocellular carcinoma. Concurrent infection with HBV and C. sinensis is often observed in some areas where C. sinensis is endemic. However, whether C. sinensis could impact HBV infection or vice versa remains unknown.Co-infection with C. sinensis and HBV develops predominantly in males. Co-infected C. sinensis and HBV patients presented weaker liver function and higher HBV DNA titers. Combination treatment with antiviral and anti-C. sinensis drugs in co-infected patients could contribute to a reduction in viral load and help with liver function recovery. Excretory-secretory products (ESPs may, in some ways, increase HBV viral replication in vitro. A mixture of ESP and HBV positive sera could induce peripheral blood mononuclear cells (PBMCs to produce higher level of Th2 cytokines including IL-4, IL-6 and IL-10 compared to HBV alone, it seems that due to presence of ESP, the cytokine production shift towards Th2. C. sinensis/HBV co-infected patients showed higher serum IL-6 and IL-10 levels and lower serum IFN-γ levels.Patients with concomitant C. sinensis and HBV infection presented weaker liver function and higher HBV DNA copies. In co-infected patients, the efficacy of anti-viral treatment was better in patients who were prescribed with entecavir and praziquantel than entecavir alone. One possible reason for the weaker response to antiviral therapies in co-infected patients was the shift in cytokine production from Th1 to Th2 that may inhibit viral clearance. C. sinensis/HBV co-infection could exacerbate the imbalance of Th1/Th2 cytokine.

  3. Clonorchis sinensis Co-infection Could Affect the Disease State and Treatment Response of HBV Patients.

    Science.gov (United States)

    Li, Wenfang; Dong, Huimin; Huang, Yan; Chen, Tingjin; Kong, Xiangzhan; Sun, Hengchang; Yu, Xinbing; Xu, Jin

    2016-06-01

    Clonorchis sinensis (C. sinensis) is considered to be an important parasitic zoonosis because it infects approximately 35 million people, while approximately 15 million were distributed in China. Hepatitis B virus (HBV) infection is a major public health issue. Two types of pathogens have the potential to cause human liver disease and eventually hepatocellular carcinoma. Concurrent infection with HBV and C. sinensis is often observed in some areas where C. sinensis is endemic. However, whether C. sinensis could impact HBV infection or vice versa remains unknown. Co-infection with C. sinensis and HBV develops predominantly in males. Co-infected C. sinensis and HBV patients presented weaker liver function and higher HBV DNA titers. Combination treatment with antiviral and anti-C. sinensis drugs in co-infected patients could contribute to a reduction in viral load and help with liver function recovery. Excretory-secretory products (ESPs) may, in some ways, increase HBV viral replication in vitro. A mixture of ESP and HBV positive sera could induce peripheral blood mononuclear cells (PBMCs) to produce higher level of Th2 cytokines including IL-4, IL-6 and IL-10 compared to HBV alone, it seems that due to presence of ESP, the cytokine production shift towards Th2. C. sinensis/HBV co-infected patients showed higher serum IL-6 and IL-10 levels and lower serum IFN-γ levels. Patients with concomitant C. sinensis and HBV infection presented weaker liver function and higher HBV DNA copies. In co-infected patients, the efficacy of anti-viral treatment was better in patients who were prescribed with entecavir and praziquantel than entecavir alone. One possible reason for the weaker response to antiviral therapies in co-infected patients was the shift in cytokine production from Th1 to Th2 that may inhibit viral clearance. C. sinensis/HBV co-infection could exacerbate the imbalance of Th1/Th2 cytokine.

  4. Oral muscles are progressively affected in Duchenne muscular dystrophy: implications for dysphagia treatment.

    Science.gov (United States)

    van den Engel-Hoek, Lenie; Erasmus, Corrie E; Hendriks, Jan C M; Geurts, Alexander C H; Klein, Willemijn M; Pillen, Sigrid; Sie, Lilian T; de Swart, Bert J M; de Groot, Imelda J M

    2013-05-01

    Dysphagia is reported in advanced stages of Duchenne muscular dystrophy (DMD). The population of DMD is changing due to an increasing survival. We aimed to describe the dysphagia in consecutive stages and to assess the underlying mechanisms of dysphagia in DMD, in order to develop mechanism based recommendations for safe swallowing. In this cross-sectional study, participants were divided into: early and late ambulatory stage (AS, n = 6), early non-ambulatory stage (ENAS, n = 7), and late non-ambulatory stage (LNAS, n = 11). Quantitative oral muscle ultrasound was performed to quantify echo intensity. Swallowing was assessed with a video fluoroscopic swallow study, surface electromyography (sEMG) of the submental muscle group and tongue pressure. Differences in outcome parameters among the three DMD stages were tested with analysis of variance. Oral muscles related to swallowing were progressively affected, starting in the AS with the geniohyoid muscle. Tongue (pseudo) hypertrophy was found in 70 % of patients in the ENAS and LNAS. Oral phase problems and post-swallow residue were observed, mostly in the LNAS with solid food. sEMG and tongue pressure data of swallowing solid food revealed the lowest sEMG amplitude, the longest duration and lowest tongue pressure in the LNAS. In case of swallowing problems in DMD, based on the disturbed mechanisms of swallowing, it is suggested to (1) adjust meals in terms of less solid food, and (2) drink water after meals to clear the oropharyngeal area.

  5. Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment.

    Science.gov (United States)

    Alboni, Silvia; Poggini, Silvia; Garofalo, Stefano; Milior, Giampaolo; El Hajj, Hassan; Lecours, Cynthia; Girard, Isabelle; Gagnon, Steven; Boisjoly-Villeneuve, Samuel; Brunello, Nicoletta; Wolfer, David P; Limatola, Cristina; Tremblay, Marie-Ève; Maggi, Laura; Branchi, Igor

    2016-11-01

    It has been hypothesized that selective serotonin reuptake inhibitors (SSRIs), the most common treatment for major depression, affect mood through changes in immune function. However, the effects of SSRIs on inflammatory response are contradictory since these act either as anti- or pro-inflammatory drugs. Previous experimental and clinical studies showed that the quality of the living environment moderates the outcome of antidepressant treatment. Therefore, we hypothesized that the interplay between SSRIs and the environment may, at least partially, explain the apparent incongruence regarding the effects of SSRI treatment on the inflammatory response. In order to investigate such interplay, we exposed C57BL/6 mice to chronic stress to induce a depression-like phenotype and, subsequently, to fluoxetine treatment or vehicle (21days) while being exposed to either an enriched or a stressful condition. At the end of treatment, we measured the expression levels of several anti- and pro-inflammatory cytokines and inflammatory mediators in the whole hippocampus and in isolated microglia. We also determined microglial density, distribution, and morphology to investigate their surveillance state. Results show that the effects of fluoxetine treatment on inflammation and microglial function, as compared to vehicle, were dependent on the quality of the living environment. In particular, fluoxetine administered in the enriched condition increased the expression of pro-inflammatory markers compared to vehicle, while treatment in a stressful condition produced anti-inflammatory effects. These findings provide new insights regarding the effects of SSRIs on inflammation, which may be crucial to devise pharmacological strategies aimed at enhancing antidepressant efficacy by means of controlling environmental conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Does comorbid alcohol and substance abuse affect electroconvulsive therapy outcome in the treatment of mood disorders?

    Science.gov (United States)

    Moss, Lori; Vaidya, Nutan

    2014-03-01

    Antidepressant medications remain the principal agents used to treat patients with mood disorders, although 30% to 40% of these patients do not improve. One of the factors associated with poor medication response is alcohol and substance abuse. Persons with mood disorders are at the greatest risk for suicide, and alcoholism is a significant additional risk factor. Electroconvulsive therapy (ECT) is shown to be the most effective treatment for major depression especially when associated with psychosis, catatonia, and suicide intent. However, similar to most antidepressant trials, patients with depression and comorbid alcohol and substance abuse are excluded from ECT efficacy studies. Through a retrospective chart review, we compared response to ECT in patients with mood disorder and comorbid alcohol and drug abuse to those with mood disorder only. From 2004 to 2010, 80 patients with mood disorder received ECT. Fifty of these had comorbid alcohol or drug abuse. Using a 10-item psychopathology scale, we compared pre- and post-ECT symptom severity between the 2 groups. Outcome was determined by measuring a decrease in the pre-ECT and post-ECT score using Wilcoxon rank tests, with statistical significance at P = 0.05. There was no difference between the 2 groups in most demographics, ECT medication, or seizure quality. There was no difference in ECT outcome between those with comorbid alcohol abuse and those without based on percent decrease in pre- and post-ECT symptom scores (abuse: mean [SD], 0.89 [0.2] vs nonabuse: mean [SD], 0.93 [0.16]; Wilcoxon, 1332; P = 0.086). When we compared those who met the criteria for alcohol or drug dependence (19 patients) with those with no abuse, there was a trend for the dependence group to not do as well (dependence: mean [SD], 0.83 [0.25] vs nonabuse: mean [SD], 0.93 [0.16]; Wilcoxon, 405; P = 0.053). Those with combined drug and alcohol abuse (18 patients) did have a significantly worse outcome (combined: mean [SD], 0.82 [0

  7. Adherence to diet and fluid restriction of individuals on hemodialysis treatment and affecting factors in Turkey.

    Science.gov (United States)

    Efe, Dilek; Kocaöz, Semra

    2015-04-01

    This study was conducted to determine adherence to diet and fluid restriction in hemodialysis-treated individuals and the affecting factors in Turkey. This descriptive study was conducted between 15 October 2010 and 15 January 2011 in subjects who voluntarily agreed to participate in the study from three dialysis centers in a city located in the Central Anatolia Region of Turkey. One hundred and twenty-one individuals treated with hemodialysis made up the study sample. The data were collected using a questionnaire consisting of 41 questions and the Dialysis Diet and Fluid Non-adherence Questionnaire. The data were evaluated with percentage, median, Mann-Whitney U-test, Kruskal-Wallis test, Student's t-test in independent samples and Spearman's rank correlation coefficient. The authors found that 98.3% of the individuals experienced non-adherence to diet and 95.0% with fluid restriction. The authors found a weak and negative relationship between calcium levels and non-adherence to fluid restriction, a weak relationship between phosphorus levels and diet non-adherence frequency and degree and the fluid non-adherence frequency scores, and a moderate positive relationship between phosphorus levels and fluid restriction non-adherence degree scores (P < 0.05). Based on these results, regular training and information regarding diet and fluid restriction must be provided to individuals aged 21-35 years with no one in the family to help with their care, those who consumed salted food, or had interdialytic weight gain of 4.5 kg or more. © 2014 The Authors. Japan Journal of Nursing Science © 2014 Japan Academy of Nursing Science.

  8. Country report: United Kingdom. Bifunctional bisphosphonate complexes with {sup 99m}Tc and {sup 188}Re for the diagnosis and therapy of bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Torres Martin de Rosales, Rafael; Blower, P.J., E-mail: rafael.torres@kcl.ac.uk, E-mail: philip.blower@kcl.ac.uk [Division of Imaging Sciences, King' s College London, 4th Floor, Lambeth Wing, St. Thomas Hospital, London (United Kingdom)

    2010-07-01

    1,1-Bisphosphonates (BPs) are a family of compounds extensively used in the management of disorders of bone metabolism.{sup 1} They accumulate in areas of high bone metabolism, such as bone metastases, and consequently have been receiving increasing attention as molecular imaging probes and pain palliation treatments.{sup 2} Imaging bone metastases with BPs using single photon emission computed tomography (SPECT) or planar scintigraphy is one of the most often-performed clinical imaging procedures. Beta-emitting analogues capable of producing a therapeutic effect have also been developed.{sup 3} In particular, the rhenium compounds {sup 186/188}Re-hydroxyethylidene-1,1-diphosphonate ({sup 186/188}Re-HEDP) have shown promise as palliative agents for bone metastases in recent clinical trials.{sup 4} The radiochemicals consist of a complex of a BP (e.g. methylene diphosphonate, MDP) with gamma- ({sup 99m}Tc) or beta- ({sup 186/186}Re) emitters.

  9. Issues related to symptomatic and disease-modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy

    Science.gov (United States)

    Brooks-Kayal, Amy R.; Bath, Kevin G.; Berg, Anne T.; Galanopoulou, Aristea S.; Holmes, Gregory L.; Jensen, Frances E.; Kanner, Andres M.; O’Brien, Terence J.; Whittemore, Vicky H.; Winawer, Melodie R.; Patel, Manisha; Scharfman, Helen E.

    2014-01-01

    Summary Many symptoms of neurologic or psychiatric illness—such as cognitive impairment, depression, anxiety, attention deficits, and migraine—occur more frequently in people with epilepsy than in the general population. These diverse comorbidities present an underappreciated problem for people with epilepsy and their caregivers because they decrease quality of life, complicate treatment, and increase mortality. In fact, it has been suggested that comorbidities can have a greater effect on quality of life in people with epilepsy than the seizures themselves. There is increasing recognition of the frequency and impact of cognitive and behavioral comorbidities of epilepsy, highlighted in the 2012 Institute of Medicine report on epilepsy. Comorbidities have also been acknowledged, as a National Institutes of Health (NIH) Benchmark area for research in epilepsy. However, relatively little progress has been made in developing new therapies directed specifically at comorbidities. On the other hand, there have been many advances in understanding underlying mechanisms. These advances have made it possible to identify novel targets for therapy and prevention. As part of the International League Against Epilepsy/American Epilepsy Society workshop on preclinical therapy development for epilepsy, our working group considered the current state of understanding related to terminology, models, and strategies for therapy development for the comorbidities of epilepsy. Herein we summarize our findings and suggest ways to accelerate development of new therapies. We also consider important issues to improve research including those related to methodology, nonpharmacologic therapies, biomarkers, and infrastructure. PMID:23909853

  10. Physiological factors affecting renal radiation tolerance: a guide to the treatment of late effects

    International Nuclear Information System (INIS)

    Robbins, M.E.C.; Hopewell, J.W.

    1986-01-01

    The results presented provide preliminary information concerning the ability of vasoactive compounds to modify the reduction in renal haemodynamics following renal irradiation. The two compounds are widely used in the clinical treatment of hypertension. The radiation-induced changes in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) observed in bilaterally irradiated pigs which received 150 mg indoramin daily were similar to those seen in pigs which received radiation alone: if anything the former exhibited greater decline in renal function. Two of the three Captopril-treated animals appeared to show a reduced impairment of renal function compared with irradiated controls. It is not known why the remaining pig did not show a similar response. However, plasma renin levels in this pig, measured 10 weeks after irradiation, were markedly higher than in the other two animals, i.e. 10.7 compared with 2.3 and 4.5 pmol -1 ml -1 , possibly reflecting greater renal damage. The total renal weight at postmortem of this pig was considerably reduced (approx. 50%), whereas the renal weights of the remaining Captopril-treated pigs were similar to those of age-related controls. (UK)

  11. Antioxidant Capacity and Phenolic Content in Olive Leaf Tisane as Affected by Boiling Treatment

    Directory of Open Access Journals (Sweden)

    Fathia AOUIDI

    2016-06-01

    Full Text Available This paper investigated the effect of preparation method on the quality of olive leaf tisane. Secondly, it aimed at evaluating and understanding the effect of boiling treatment on phenolic compounds and antioxidant capacity of an aqueous extract of olive leaves. The Phenolic content was determined by Folin-Ciocalteu method. The antioxidant capacity was assessed by ABTS+ method. The Phenolic content and antioxidant capacity depended on extraction procedure of olive leaf tisane. It was found that boiling leads to a decrease in the phenolic content and a rise of antioxidant capacity of aqueous extract from olive leaves. The mass molecular distribution of the polymeric aromatic fraction was analyzed by gel filtration chromatography on Sephadex G50. Results suggested the hydrolysis of phenolic polymers following boiling. Moreover, HPLC analyses showed an increase in rutin, oleuropein and caffeic acid levels in treated sample. As a conclusion, thermal processing could be useful for enhancing the antioxidant capacity and the extractability of phenolic compounds in olive leaf tisane.

  12. EC treatment for reuse of tissue paper wastewater: aspects that affect energy consumption.

    Science.gov (United States)

    Terrazas, Eduardo; Vázquez, Armando; Briones, Roberto; Lázaro, Isabel; Rodríguez, Israel

    2010-09-15

    The need for more rational use of water also calls for more efficient usage. An example is the production of tissue paper, where large amounts of water are discharged into the drain because its turbidity does not allow for recirculation. While this is a serious problem, even worse is the fact that the quality of such wastewater makes it difficult not only to recirculate but also to discharge due to environmental law restrictions. In this paper, electrocoagulation is proposed as a suitable technology to meet standards of water discharge, and even better, as a treatment option for removal of turbidity. Since energy consumption has been a drawback for EC applications, relevant aspects that contribute to increase it such as cell voltage and current density have been reviewed. For this purpose a systematic micro-electrolysis study combined with macro-electrolysis experiments have provided evidence that shows it is possible to achieve a turbidity removal of 92% with an energy consumption of 0.68 kWh/m(3). Thus, the results presented in this paper support the use of EC to obtain water of acceptable quality for reuse in the tissue paper industry. Copyright 2010 Elsevier B.V. All rights reserved.

  13. Electrochemical extraction of chlorides from reinforced concrete: variables affecting treatment efficiency

    Directory of Open Access Journals (Sweden)

    Climent, M. A.

    2006-12-01

    Full Text Available This paper reports the results of applying electrochemical chloride extraction (ECE to a series of chloride-contaminated concrete specimens. Experimental conditions were varied to study the efficiency of this technique under different circumstances. The survey covered the possible relationship between efficiency and the location of the sampling point, current density, type of concrete and treatment intermittence. Experiments were also conducted with different reinforcement configurations used in standard structural members such as columns and beams to ascertain the impact of rebar geometry.Este documento aporta los resultados de investigaciones realizadas en diferentes estudios en los que se aplicó la técnica de Extracción Electroquímica de Cloruros (EEC a diferentes estructuras de hormigón contaminado con cloruros. Se cambiaron las condiciones experimentales con el fin de estudiar la eficiencia de la misma en cada una de ellas. Se estudió la dependencia con la posición del punto de toma de las muestras, con la densidad de corriente aplicada, con el tipo de hormigón utilizado y con las paradas realizadas en etapas intermedias del tratamiento. Para ver la influencia de la disposición geométrica de las armaduras,se realizó una experiencia con tipos diferentes de disposiciones de las armaduras, correspondiente a componentes estructurales típicos como los pilares y las vigas.

  14. Radiation treatment of glottic squamous cell carcinoma, Stage I and II: analysis of factors affecting prognosis

    International Nuclear Information System (INIS)

    Franchin, Giovanni; Minatel, Emilio; Gobitti, Carlo; Talamini, Renato; Sartor, Giovanna; Caruso, Giuseppe; Grando, Giuseppe; Politi, Doriano; Gigante, Marco; Toffoli, Giuseppe; Trovo, Mauro G.; Barzan, Luigi

    1998-01-01

    Purpose: At least in some European Countries, there is still considerable controversy regarding the choice between surgery and radiotherapy for the treatment of patients with early laryngeal-glottic carcinoma. Methods and Materials: Two hundred and forty-six patients with laryngeal-glottic neoplasms, Stage I-II, were treated with radical radiotherapy. Before radiotherapy the patients were evaluated to determine the surgical procedure of choice. Either 66-68.4 Gy (33-38 fractions) or 63-65 Gy (28-29 fractions) of radiation therapy (RT) were administered. The overall disease free survival was determined for each subgroup of patients. Univariate and multivariate analyses were performed to determine significant prognostic variables. Results: Five- and 10-year overall survival rates were 83 and 72%, respectively. At a median follow-up of 6 years 204 patients are alive and disease free. No patient developed distant metastases. One patient died of a large local recurrence, 38 patients died of causes unrelated to their tumor, and 3 patients were lost to follow-up. The multivariate analysis confirmed that performance status (PS), macroscopic presentation of the lesion, and persistence of dysphonia after radiotherapy are significant prognostic factors. Conclusions: According to the multivariate analysis, the patients with PS >80 and with exophytic lesions are eligible for radical RT. The surgical procedure proposed for each patient was not found to be an independent prognostic factor

  15. Combined treatment with progesterone and magnesium sulfate positively affects traumatic brain injury in immature rats.

    Science.gov (United States)

    Uysal, Nazan; Baykara, Basak; Kiray, Muge; Cetin, Ferihan; Aksu, Ilkay; Dayi, Ayfer; Gurpinar, Tugba; Ozdemir, Durgul; Arda, M Nuri

    2013-01-01

    It is well known that head trauma results in damage in hippocampal and cortical areas of the brain and impairs cognitive functions. The aim of this study is to explore the neuroprotective effect of combination therapy with magnesium sulphate (MgSO4) and progesterone in the 7-days-old rat pups subjected to contusion injury. Progesterone (8 mg/kg) and MgSO4 (150 mg/kg) were injected intraperitoneally immediately after induction of traumatic brain injury. Half of groups were evaluated 24 hours later, the remaining animals 3 weeks after trauma or sham surgery. Anxiety levels were assessed with open field activity and elevated plus maze; learning and memory performance were evaluated with Morris Water maze in postnatal 27 days. Combined therapy with progesterone and magnesium sulfate significantly attenuated trauma-induced neuronal death, increased brain VEGF levels and improved spatial memory deficits that appear later in life. Brain VEGF levels were higher in rats that received combined therapy compared to rats that received either medication alone. Moreover, rats that received combined therapy had reduced hipocampus and prefrontal cortex apoptosis in the acute period. These results demonstrate that combination of drugs with different mechanisms of action may be preferred in the treatment of head trauma.

  16. The effectiveness of external beam radiotherapy for acromegaly is not affected by previous pituitary ablative treatments

    International Nuclear Information System (INIS)

    Reed, P.I.; Joplin, G.F.; Speirs, C.J.; Morrison, R.; Aber, V.

    1990-01-01

    Thirty-three acromegalic patients were treated with radiotherapy and followed up for at least 3 years (mean 6 years, range 3 to 12). Seventeen had not had previous pituitary ablative therapy and 16 had. The mean GH level for these two groups before radiotherapy was comparable at 98 and 119 mlU/l. The observed frequency of reaching <10 mlU/L was 53% and 75% of patients in the two groups, respectively, the mean observed falls in growth hormone level were 81 and 85% of the initial level, and the calculated exponential decline rate of GH level was 72 and 52% per fyear. Considering all 35 patients, requirement for pituitary hormone replacement therapy increased from 15 patients before radiotherapy to 20 after radiotherapy, being mostly those who had had prior ablative therapies. There were no complications attributable to the radiotherapy treatment. It appears that radiotherapy is equally efficacious whether a prior unsuccessful ablative procedure had been used or not. (author)

  17. The effectiveness of external beam radiotherapy for acromegaly is not affected by previous pituitary ablative treatments

    Energy Technology Data Exchange (ETDEWEB)

    Reed, P.I.; Joplin, G.F. (Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London (UK)); Speirs, C.J. (Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London (UK)); Morrison, R. (Department of Radiotherapy, Royal Postgraduate Medical School, Hammersmith Hospital, London (UK)); Aber, V. (Department of Medical Physics, Royal Postgraduate Medical School, Hammersmith Hospital, London (UK))

    1990-01-01

    Thirty-three acromegalic patients were treated with radiotherapy and followed up for at least 3 years (mean 6 years, range 3 to 12). Seventeen had not had previous pituitary ablative therapy and 16 had. The mean GH level for these two groups before radiotherapy was comparable at 98 and 119 mlU/l. The observed frequency of reaching <10 mlU/L was 53% and 75% of patients in the two groups, respectively, the mean observed falls in growth hormone level were 81 and 85% of the initial level, and the calculated exponential decline rate of GH level was 72 and 52% per fyear. Considering all 35 patients, requirement for pituitary hormone replacement therapy increased from 15 patients before radiotherapy to 20 after radiotherapy, being mostly those who had had prior ablative therapies. There were no complications attributable to the radiotherapy treatment. It appears that radiotherapy is equally efficacious whether a prior unsuccessful ablative procedure had been used or not. (author).

  18. High-Pressure Treatment of Non-Hydrated Flour Affects Structural Characteristics and Hydration

    Directory of Open Access Journals (Sweden)

    Sabina Jakobi

    2018-05-01

    Full Text Available In recent years, high-pressure treatment (HPT has become an established process concerning the preservation of food. However, studies dealing with the structural, and consequently functional modification of non-hydrated starchy matrices (moisture content ≤ 15% by HPT are missing. To close this knowledge gap, pressure (0–600 MPa, 10 min and pressurization time depending (0–20 min, 450 MPa alterations of wheat flour were investigated. Pressure rise from 0 to 600 MPa or pressurization time rise from 0 to 20 min resulted in a decline of amylopectin content from 68.3 ± 2.0% to 59.7 ± 1.5% (linearly, R2 = 0.83 and 59.6 ± 0.7% (sigmoidal, respectively. Thereby, detectable total amount of starch decreased from 77.7 ± 0.8% linearly to 67.6 ± 1.7%, and sigmoidal, to 69.4 ± 0.4%, respectively. Increase in pressure caused a linear decrease in gelatinization enthalpy of 33.2 ± 5.6%, and linear increase in hydration properties by 11.0 ± 0.6%. The study revealed structural and technological relevant alterations of starch-based food matrices with low moisture content by HPT, which must be taken into consideration during processing and preservation of food.

  19. Renal function affects absorbed dose to the kidneys and haematological toxicity during {sup 177}Lu-DOTATATE treatment

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Johanna; Berg, Gertrud [Sahlgrenska University Hospital, Department of Oncology, Goeteborg (Sweden); Waengberg, Bo [Sahlgrenska University Hospital, Department of Surgery, Goeteborg (Sweden); Larsson, Maria [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Forssell-Aronsson, Eva; Bernhardt, Peter [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Sahlgrenska University Hospital, Department of Medical Physics and Medical Bioengineering, Goeteborg (Sweden)

    2015-05-01

    Peptide receptor radionuclide therapy (PRRT) has become an important treatment option in the management of advanced neuroendocrine tumours. Long-lasting responses are reported for a majority of treated patients, with good tolerability and a favourable impact on quality of life. The treatment is usually limited by the cumulative absorbed dose to the kidneys, where the radiopharmaceutical is reabsorbed and retained, or by evident haematological toxicity. The aim of this study was to evaluate how renal function affects (1) absorbed dose to the kidneys, and (2) the development of haematological toxicity during PRRT treatment. The study included 51 patients with an advanced neuroendocrine tumour who received {sup 177}Lu-DOTATATE treatment during 2006 - 2011 at Sahlgrenska University Hospital in Gothenburg. An average activity of 7.5 GBq (3.5 - 8.2 GBq) was given at intervals of 6 - 8 weeks on one to five occasions. Patient baseline characteristics according to renal and bone marrow function, tumour burden and medical history including prior treatment were recorded. Renal and bone marrow function were then monitored during treatment. Renal dosimetry was performed according to the conjugate view method, and the residence time for the radiopharmaceutical in the whole body was calculated. A significant correlation between inferior renal function before treatment and higher received renal absorbed dose per administered activity was found (p < 0.01). Patients with inferior renal function also experienced a higher grade of haematological toxicity during treatment (p = 0.01). The residence time of {sup 177}Lu in the whole body (range 0.89 - 3.0 days) was correlated with grade of haematological toxicity (p = 0.04) but not with renal absorbed dose (p = 0.53). Patients with inferior renal function were exposed to higher renal absorbed dose per administered activity and developed a higher grade of haematological toxicity during {sup 177}Lu-DOTATATE treatment. The study confirms the

  20. Does bony hip morphology affect the outcome of treatment for patients with adductor-related groin pain?

    DEFF Research Database (Denmark)

    Hölmich, Per; Thorborg, Kristian; Nyvold, Per

    2014-01-01

    BACKGROUND: Adductor-related groin pain and bony morphology such as femoroacetabular impingement (FAI) or hip dysplasia can coexist clinically. A previous randomised controlled trial in which athletes with adductor-related groin pain underwent either passive treatment (PT) or active treatment (AT......) showed good results in the AT group. The primary purpose of the present study was to evaluate if radiological signs of FAI or hip dysplasia seem to affect the clinical outcome, initially and at 8-12 years of follow-up. METHODS: 47 patients (80%) were available for follow-up. The clinical result......, there was no significant difference in the distribution of Tönnis grades between hips that had an unchanged or improved outcome compared with hips that had a worse outcome over time (p=0.145). CONCLUSIONS: No evidence was found that bony hip morphology related to FAI or dysplasia prevents successful outcome...

  1. Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain.

    Science.gov (United States)

    Palasz, Artur; Rojczyk, Ewa; Golyszny, Milosz; Filipczyk, Lukasz; Worthington, John J; Wiaderkiewicz, Ryszard

    2016-04-01

    The brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression. We assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction. Chronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum. This stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.

  2. XPS and bioactivity study of the bisphosphonate pamidronate adsorbed onto plasma sprayed hydroxyapatite coatings

    International Nuclear Information System (INIS)

    McLeod, Kate; Kumar, Sunil; Smart, Roger St.C.; Dutta, Naba; Voelcker, Nicolas H.; Anderson, Gail I.; Sekel, Ron

    2006-01-01

    This paper reports the use of X-ray photoelectron spectroscopy (XPS) to investigate bisphosphonate (BP) adsorption onto plasma sprayed hydroxyapatite (HA) coatings commonly used for orthopaedic implants. BPs exhibit high binding affinity for the calcium present in HA and hence can be adsorbed onto HA-coated implants to exploit their beneficial properties for improved bone growth at the implant interface. A rigorous XPS analysis of pamidronate, a commonly used nitrogenous BP, adsorbed onto plasma sprayed HA-coated cobalt-chromium substrates has been carried out, aimed at: (a) confirming the adsorption of this BP onto HA; (b) studying the BP diffusion profile in the HA coating by employing the technique of XPS depth profiling; (c) confirming the bioactivity of the adsorbed BP. XPS spectra of plasma sprayed HA-coated discs exposed to a 10 mM aqueous BP solution (pamidronate) for periods of 1, 2 and 24 h showed nitrogen and phosphorous photoelectron signals corresponding to the BP, confirming its adsorption onto the HA substrate. XPS depth profiling of the 2 h BP-exposed HA discs showed penetration of the BP into the HA matrix to depths of at least 260 nm. The bioactivity of the adsorbed BP was confirmed by the observed inhibition of osteoclast (bone resorbing) cell activity. In comparison to the HA sample, the HA sample with adsorbed BP exhibited a 25-fold decrease in primary osteoclast cells

  3. Aspects of osseous, peritoneal and renal handling of bisphosphonate during peritoneal dialysis: a methodological study

    DEFF Research Database (Denmark)

    Joffe, P; Henriksen, Jens Henrik Sahl

    1996-01-01

    to continuous ambulatory peritoneal dialysis (CAPD). The aims were: to assess the kinetics of 99m-technetium MBP (99mTc-MBP) in CAPD, and to evaluate the correctness of the assumption that the peritoneal and renal clearances of 99mTc-MBP equal the total plasma clearance of 51-chromium ethylenediamine tetra......-acetic acid (51Cr-EDTA). Eight patients on CAPD were studied cross-sectionally. The mean plasma clearances of 99mTc-MBP and 51Cr-EDTA in the steady state (4h) were 38.2 and 12.2 ml min-1 (p peritoneal clearances (0-4 h) were 5.2 and 7.2 ml min-1 (p ....5 and 2.8 ml min-1 (not significant), respectively. The bone bisphosphonate clearance (BBC) at steady state was 26.0 ml min-1, a value which was significantly higher than that at infinity (16.5 ml min-1, p peritoneal and renal clearances of 99m...

  4. USE OF ZOLEDRONIC ACID AND A RАNK LIGAND INHIBITOR IN THE PALLIATIVE TREATMENT OF CANCERS OF THE PROSTATE WITH BONE METASTASES

    Directory of Open Access Journals (Sweden)

    S. V. Mushigin

    2013-01-01

    Full Text Available In the metastatic patterns of the cancer, the tumor foci are located more frequently in the tubular bones and vertebral column, just less frequently in the bones of the pelvis, and even more rarely in those of the shoulder and skull. Bone pain is usually related to the involvement of the periosteum that has an extensive network of nociceptors. Auxiliary exposures that directly affect the intensity of pain syndrome and the strength of bone structures are used in addition to basic therapy options for cancer of the prostate. Among these agents there are bisphosphonates. Once ingested, bisphosphonates are transported by blood to the areas of active bone tissue rearrangement where they are tightly bound to the mineral matrix. Their administration causes a considerable reduction in pain syndrome, a decrease in the frequency of complications of bone metastases, and an increase in time before a first bone complication. Antiresorptive therapy including particularly zoledronic acid (resorba or denosumab is a necessary treatment option in the above category of patients with bone metastases.

  5. USE OF ZOLEDRONIC ACID AND A RАNK LIGAND INHIBITOR IN THE PALLIATIVE TREATMENT OF CANCERS OF THE PROSTATE WITH BONE METASTASES

    Directory of Open Access Journals (Sweden)

    S. V. Mushigin

    2014-07-01

    Full Text Available In the metastatic patterns of the cancer, the tumor foci are located more frequently in the tubular bones and vertebral column, just less frequently in the bones of the pelvis, and even more rarely in those of the shoulder and skull. Bone pain is usually related to the involvement of the periosteum that has an extensive network of nociceptors. Auxiliary exposures that directly affect the intensity of pain syndrome and the strength of bone structures are used in addition to basic therapy options for cancer of the prostate. Among these agents there are bisphosphonates. Once ingested, bisphosphonates are transported by blood to the areas of active bone tissue rearrangement where they are tightly bound to the mineral matrix. Their administration causes a considerable reduction in pain syndrome, a decrease in the frequency of complications of bone metastases, and an increase in time before a first bone complication. Antiresorptive therapy including particularly zoledronic acid (resorba or denosumab is a necessary treatment option in the above category of patients with bone metastases.

  6. SU-E-J-175: Comparison of the Treatment Reproducibility of Tumors Affected by Breathing Motion

    Energy Technology Data Exchange (ETDEWEB)

    Adamczyk, M; Piotrowski, T; Adamczyk, S [Medical Physics Department, Greater Poland Cancer Centre, Poznan (Poland)

    2015-06-15

    Purpose: The aim of the dose distribution simulations was to form a global idea of intensity-modulated radiation therapy (IMRT) realization, by its comparison to three-dimensional conformal radiation therapy (3DCRT) delivery for tumors affected by respiratory motion. Methods: In the group of 10patients both 3DCRT and IMRT plans were prepared.For each field the motion kernel was generated with the largest movement amplitude of 4;6 and 8mm.Additionally,the sets of reference measurements were made in no motion conditions(0 mm).The evaluation of plan delivery,using a diode array placed on moving platform,was based on the Gamma Index analysis with distance to agreement of 3mm and dose difference of 3%. Results: IMRT plans tended to spare doses delivered to lungs compared to 3DCRT.Nonetheless,analyzed volumes showed no significant difference between the static and dynamic techniques,except for the volumes of both lungs receiving 10 and 15Gy.After adding the components associated with the respiratory movement,all IMRT lung parameters evaluated for the ipsilateral,contralateral and both lungs together,revealed considerable differences between the 0vs.6, 0vs.8 and 4vs.8-mm amplitudes.Similar results were obtained for the 3DCRT lung measurements,but without significance between the 0vs.6-mm amplitude.Taking into account the CTV score parameter in 3DCRT and IMRT plans,there was no statistically significant difference between the motion patterns with the smallest amplitudes.The differences were found for the 8-mm amplitude when it was compared both with static conditions and 4-mm amplitude (for 3DCRT) and between 0vs.6, 0vs.8 and 4vs.8-mm amplitudes (for IMRT).All accepted and measured 3DCRT and IMRT doses to spinal cord,esophagus and heart were always below the QUANTEC limits. Conclusion: The application of IMRT technique in lung radiotherapy affords possibilities for reducing the lung doses.For maximal amplitudes of breathing trajectory below 4mm,the disagreement between CTV

  7. Factors affecting decisions to seek treatment for sick children in Kerala, India.

    Science.gov (United States)

    Pillai, Rajamohanan K; Williams, Sankey V; Glick, Henry A; Polsky, Daniel; Berlin, Jesse A; Lowe, Robert A

    2003-09-01

    The purpose of this study was to measure the effects of social and economic variables, disease-related variables, and child gender on the decisions of parents in Kerala, India, to seek care for their children and on their choice of providers in the allopathic vs. the alternative system. A case-control analysis was done using data from the Kerala section of the 1996 Indian National Family Health Survey, a cross-sectional survey of a probability sample of households conducted by trained interviewers with a close-ended questionnaire. Of the 469 children who were eligible for this study because they had at least one common symptom suggestive of acute respiratory illness or diarrhea during the 2 weeks before the interview, 78 (17%) did not receive medical care, while the remaining 391 (83%) received medical care. Of the 391 children who received medical care, 342 (88%) received allopathic medical care, and 48 (12%) received alternative medical care. In multivariable analyses, parents chose not to seek medical care for their children significantly more often when the illness was mild, the child had a specific diagnosis, the mother had previously made fewer antenatal visits, and the family had a higher economic status. When parents sought medical care for their children, care was sought significantly more often in the alternative provider system when the child was a boy, the family lived in a rural area, and the family had a lower social class. We conclude that, in Kerala, disease severity and economic status predict whether children with acute respiratory infection or diarrhea are taken to medical providers. In contrast, most studies of this issue carried out in other populations have identified economic status as the primary predictor of medical system utilization. Also in Kerala, the gender of the child did not influence whether or not the child was taken for treatment but did influence whether care was sought in the alternative or the allopathic system.

  8. Fractionation of Uranium Forms as Affected by Spiked Soil Treatment and Soil Type

    International Nuclear Information System (INIS)

    Lotfy, S.M.; Mostafa, A.Z.; Abdel-Sabour, M.F.

    2012-01-01

    In a fractionation experiment Uranium forms were compared in two soil types (Mostorud and Elgabalelasfar soil). Also, the variation of U forms due to soil treatment (spiking) were studied. In case of Mostorud soil the initial U - fractions were 45.63 % as residual form, 20.69 % organically bound 16.36 % Mn and Fe oxides bound, 9.76% Carbonate form, 7.41 % exchangeable fractions and 0.15% water soluble fractions. These fractions varied significantly when the soil was spiked with 200 mg U/Kg soil to 46.88 %, 23.19 %, 9.97 %, 16.07 %, 3.79% and 0.10% for residual, organically, Mn- Fe oxide, carbonate, exchangeable and water soluble fractions respectively. These result showed significant reduction in U-ex fraction forms and Mn- Fe bound forms with significant increase in U- carbonate form due to U application. In case of Elgabalelasfar soil, the main U - fractions were 57.42% as residual form (relatively higher residual - U form in the clayey soil) 16.10 % organically bound, 13.78% Mn and Fe oxides bound, 7.22 % Carbonate form, 5.23 % exchangeable fractions and 0.25 % water soluble fractions The application of 200 mg U/Kg soil resulted in a significant changes in U - Fractions distribution as follows : 59.26 % , 11.27 % , 19.59 % , 6.84 % , 2.90 % and 0.14 % for residual , organic , Mn- Fe oxides , carbonate, exchangeable and water soluble fractions , respectively.

  9. Management options for food production systems affected by a nuclear accident. Task 7: biological treatment of contaminated milk

    International Nuclear Information System (INIS)

    Nisbet, A.F.; Marchant, J.K.; Woodman, R.F.M.; Wilkins, B.T.; Mercer, J.A.

    2003-01-01

    In the event of a nuclear accident affecting the UK, regulation of contamination in the foodchain would involve both the Food Standards Agency (FSA) and the Environment Agency (EA). Restrictions would be based on intervention levels imposed by the Council of the European Communities (often referred to as Council Food Intervention Levels, CFILs). FSA would be responsible for preventing commercial foodstuffs with concentrations of radionuclides above the CFILs from entering the foodchain, while EA would regulate the storage and disposal of the waste food. Milk is particularly important in this respect because it is produced continually in large quantities in many parts of the UK. An evaluation of various options for the management of waste foodstuffs has been carried out by NRPB, with support from FSA and its predecessor, the Ministry of Agriculture, Fisheries and Food, and EA. This report describes an evaluation of the practicability of one of those options, namely the biological treatment of contaminated milk. Whole milk has a high content of organic matter and in consequence a high biochemical oxygen demand (BOD) and chemical oxygen demand (COD). If not disposed of properly, releases of whole milk into the environment can have a substantial detrimental effect because of the high BOD. Biological treatments are therefore potentially an attractive management option because the fermentation by bacteria reduces the BOD in the resultant liquid effluent. The objectives of this study were as follows: a. To compile information about the options available for the biological treatment of milk; b. To establish the legal position; c. To assess practicability in terms of technical feasibility, capacity, cost, environmental and radiological impacts and acceptability; d. To assess the radiation doses that might be received by process operators, contractors, farmers and the general public from the biological treatment of contaminated milk. The radionuclides of interest were 131II

  10. Osteogenesis imperfecta: diagnosis and treatment.

    Science.gov (United States)

    Palomo, Telma; Vilaça, Tatiane; Lazaretti-Castro, Marise

    2017-12-01

    Here we summarize the diagnosis of osteogenesis imperfecta, discuss newly discovered genes involved in osteogenesis imperfecta, and review the management of this disease in children and adults. Mutations in the two genes coding for collagen type I, COL1A1 and COL1A2, are the most common cause of osteogenesis imperfecta. In the past 10 years, defects in at least 17 other genes have been identified as responsible for osteogenesis imperfecta phenotypes, with either dominant or recessive transmission. Intravenous bisphosphonate infusions are the most widely used medical treatment. This has a marked effect on vertebra in growing children and can lead to vertebral reshaping after compression fractures. However, bisphosphonates are less effective for preventing long-bone fractures. At the moment, new therapies are under investigation. Despite advances in the diagnosis and treatment of osteogenesis imperfecta, more research is needed. Bisphosphonate treatment decreases long-bone fracture rates, but such fractures are still frequent. New antiresorptive and anabolic agents are being investigated but efficacy and safety of these drugs, especially in children, need to be better established before they can be used in clinical practice.

  11. Imidacloprid seed treatments affect individual ant behavior and community structure but not egg predation, pest abundance or soybean yield.

    Science.gov (United States)

    Penn, Hannah J; Dale, Andrew M

    2017-08-01

    Neonicotinoid seed treatments are under scrutiny because of their variable efficacy against crop pests and for their potential negative impacts on non-target organisms. Ants provide important biocontrol services in agroecosystems and can be indicators of ecosystem health. This study tested for effects of exposure to imidacloprid plus fungicide or fungicide-treated seeds on individual ant survival, locomotion and foraging capabilities and on field ant community structure, pest abundance, ant predation and yield. Cohorts of ants exposed to either type of treated seed had impaired locomotion and a higher incidence of morbidity and mortality but no loss of foraging capacity. In the field, we saw no difference in ant species richness, regardless of seed treatment. Blocks with imidacloprid did have higher species evenness and diversity, probably owing to variable effects of the insecticide on different ant species, particularly Tetramorium caespitum. Ant predation on sentinel eggs, pest abundance and soybean growth and yield were similar in the two treatments. Both seed treatments had lethal and sublethal effects on ant individuals, and the influence of imidacloprid seed coating in the field was manifested in altered ant community composition. Those effects, however, were not strong enough to affect egg predation, pest abundance or soybean yield in field blocks. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  12. Postnatal treatment factors affecting craniofacial morphology of unilateral cleft lip and palate (UCLP) patients in a Japanese population.

    Science.gov (United States)

    Alam, M K; Iida, J; Sato, Y; Kajii, Takashi S

    2013-12-01

    We have evaluated the craniofacial morphology of Japanese patients with unilateral cleft lip and palate (UCLP) and assessed the various postnatal factors that affect it. Lateral cephalograms of 140 subjects (mean (SD) aged 7 (2) years) with UCLP were taken before orthodontic treatment. Surgeons from Hokkaido University Hospital had done the primary operations. The craniofacial morphology was assessed by angular and linear cephalometric measurements. Cheiloplasty, palatoplasty, and preoperative orthopaedic treatment were chosen as postnatal factors. To compare the assessments of the postnatal factors, we made angular and linear cephalometric measurements for each subject and converted them into Z scores in relation to the mean (SD) of the two variables. Subjects treated by the modified Millard cheiloplasty had larger sella-nasion-point A (SNA) and nasion-point A-pogonion (NA-POG) measurements than subjects treated by the modified Millard with a vomer flap cheiloplasty. Two-stage palatoplasty showed consistently better craniofacial morphology than the other palatoplasty. Subjects who had preoperative orthopaedic treatment with a Hotz plate had significantly larger upper incisor/sella-nasion (U1-SN) measurements than who had no preoperative orthopaedic treatment or an active plate. We conclude that in subjects treated by a modified Millard type of cheiloplasty, a two-stage palatoplasty, and a Hotz plate there were fewer adverse effects on craniofacial morphology. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  13. Treatment of scoliosis in patients affected with Prader-Willi syndrome using various techniques

    Directory of Open Access Journals (Sweden)

    Cioni Alfredo

    2010-06-01

    Full Text Available Abstract Background The incidence of spinal deformity in children with Prader-Willi syndrome (PWS is high, with 86% of these patients found to have a significant structural scoliosis; however, there are very few case reports describing surgical treatment for this deformity. Methods The authors reviewed a case series consisting of 6 patients who underwent spine surgery for scoliosis. Children's mean age at index surgery was 12 years and 10 months (range, 10 to 15 yrs. Clinical evaluation