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  1. Osteoporosis: Therapeutic Options.

    PubMed

    Ivanova, Stefka; Vasileva, Liliya; Ivanova, Stanislava; Peikova, Lily; Obreshkova, Danka

    2016-01-01

    The definition of osteoporosis was originally formulated at a conference of the World Health Organization (WHO) in 1993 as 'a systemic skeletal disease characterized by decreased bone mass and altered micro-architecture of bone tissue, leading to enhanced bone fragility and risk of fractures'. Osteoporosis is characterized by low bone mineral density (BMD) and loss of the structural and bio-mechanical properties that are required to maintain bone homeostasis. This review aims to address the currently available options in prevention and treatment of osteoporosis. Management of osteoporosis includes non-pharmacological treatment - diet rich of calcium and vitamin D, healthy lifestyle, proper exercise plan, and pharmacological therapy. Combination of non-pharmacological and pharmacological treatment options have to be considered for prevention of osteoporosis and minimization of the risk of fractures. Given the heterogeneity of osteoporosis syndrome and lack of significant number of comparative studies, the choice of a pharmacological agents should be individualized. PMID:27180344

  2. Emerging therapeutic options for asthma.

    PubMed

    Colice, Gene L

    2011-04-01

    Asthma is characterized by eosinophilic airway inflammation and elevated serum immunoglobulin E (IgE) levels. Due to these pathologic features, the foundation of asthma treatment has historically been anti-inflammatory therapy with inhaled corticosteroids (ICSs). Numerous factors in addition to IgE and eosinophils, however, likely play important roles in mediating the airway inflammatory response characteristic of asthma. ICSs are effective therapy for some patients with persistent asthma, but clinical trials have shown that even increasing doses of ICSs under carefully controlled situations does not always result in acceptable asthma control. Consequently, other classes of medications, in addition to ICSs, are recommended in those patients with more severe asthma. The class of medication most commonly used in more severe asthma, along with ICSs, is long-acting inhaled beta2-agonists, but leukotriene modifying agents and anti-IgE monoclonal antibodies may also be used. Agents such as tiotropium, a long-acting inhaled anti-muscarinic agent, and those aimed at inhibiting cytokines, such as mepoluzimab, daclizumab, and etanercept, hold promise in the treatment of asthma. Other agents under investigation include phosphodiesterase type 4 inhibitors and oligonucleotides. Bronchial thermoplasty, a nonpharmacologic option, may also be beneficial in patients with poorly controlled asthma. As our understanding of the complex pathophysiology of asthma increases, it will enable the development of novel therapeutic approaches for patients who are not responding well to traditional treatments. Although more studies are necessary to ensure the efficacy and safety of both pharmacologic and nonpharmacologic approaches, there is future promise for therapeutic advances in severe, persistent asthma. PMID:21761958

  3. [Nystagmus. Clinical characteristics and therapeutic options].

    PubMed

    Käsmann-Kellner, B

    2016-03-01

    This article presents an overview of the pathophysiology of nystagmus and the differential diagnostics of congenital and acquired nystagmus. In addition, the principles of conservative, surgical and pharmacotherapy treatment options are described. The pathophysiological basis of nystagmus deepens the understanding of the etiology of the individual forms of nystagmus. The therapeutic approach to calming of nystagmus aims at an extension of the foveation time, which has the most significant impact on visual acuity. In congenital nystagmus this can be carried out by optimization of the retinal image, prisms or by bilateral surgical muscle repositioning to use the phenomenon of a null or neutral zone. In acquired nystagmus the off-label use of centrally acting medications can sometimes be helpful to calm the nystagmus and the associated oscillopsia. PMID:26936363

  4. Emerging therapeutic options in GERD.

    PubMed

    Woodland, Philip; Amarasinghe, Gehanjali; Sifrim, Daniel

    2013-06-01

    Gastroesophageal reflux disease (GERD) is a prevalent problem resulting in a high level of healthcare consultation and expenditure in the Western World. Although standard medical therapy (in the form of proton pump inhibitor drugs) is effective in the majority of cases, there remains a significant proportion who are refractory to treatment. In addition, surgical therapy (in the form of laparoscopic fundoplication) is not always effective, and in some can be associated with significant side-effects, particularly gas-bloat, flatulence and dysphagia. As such there remains an unmet need in GERD to develop new therapies for refractory cases, and to develop alternatives to fundoplication with fewer side-effects. This article discusses the current state of pharmacological and non-pharmacological emerging therapies for GERD. PMID:23998982

  5. 20 CFR 416.2035 - Optional supplementation: Additional State options.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Optional supplementation: Additional State options. 416.2035 Section 416.2035 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED State Supplementation Provisions; Agreement;...

  6. 20 CFR 416.2035 - Optional supplementation: Additional State options.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Optional supplementation: Additional State options. 416.2035 Section 416.2035 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED State Supplementation Provisions; Agreement;...

  7. Future therapeutic options in food allergy.

    PubMed

    Eigenmann, P A

    2003-12-01

    Up to 5% of young children and 2% of adults suffer from food allergy. Among them many have immunoglobulin E (IgE)-mediated food allergy, a condition with potentially fatal allergic reactions. Several studies have addressed possible definite treatment options for food allergy. Immunotherapy, by the oral route or by systemic injections shows promising preliminary results, but current interpretation of these therapeutic options are mostly handicapped by studies with insufficient scientific support, or by severe side-effects. Currently, no studies can support pharmacotherapy. Finally, most promising results were recently published with anti-IgE antibodies in a human trial, or various approaches in a mouse model of food allergy (chinese herbal medicine, specific modulation of the T cell response). Rapidly evolving findings might provide hope for a cure of food allergy in the near future. PMID:14616094

  8. Therapeutic options for management of endometrial hyperplasia

    PubMed Central

    2016-01-01

    Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH. PMID:26463434

  9. Therapeutic options for peritoneal metastasis arising from colorectal cancer

    PubMed Central

    Glockzin, Gabriel; Schlitt, Hans J; Piso, Pompiliu

    2016-01-01

    Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer (pmCRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standardization of oncologic treatment regimens for pmCRC. The addition of further therapeutic options such as neoadjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investigated to optimize therapeutic regimens and further improve the oncological outcome. PMID:27602235

  10. Therapeutic options for peritoneal metastasis arising from colorectal cancer.

    PubMed

    Glockzin, Gabriel; Schlitt, Hans J; Piso, Pompiliu

    2016-08-01

    Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer (pmCRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standardization of oncologic treatment regimens for pmCRC. The addition of further therapeutic options such as neoadjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investigated to optimize therapeutic regimens and further improve the oncological outcome. PMID:27602235

  11. Lagophthalmos after facial palsy: current therapeutic options.

    PubMed

    Vásquez, Luz María; Medel, Ramón

    2014-01-01

    As the facial nerve carries sensory, motor and parasympathetic fibres involved in facial muscle innervation, facial palsy results in functional and cosmetic impairment. It can result from a wide variety of causes like infectious processes, trauma, neoplasms, autoimmune diseases, and most commonly Bell's palsy, but it can also be of iatrogenic origin. The main ophthalmic sequel is lagophthalmos. The increased surface exposure increases the risk of keratitis, corneal ulceration, and potentially loss of vision. Treatment options are wide; some are temporary, some permanent. In addition to gold standard and traditional therapies and procedures, new options are being proposed aiming to improve not only lagophthalmos but also the quality of life of these patients. PMID:25342248

  12. [Multiple sclerosis: potential therapeutic options and update of ongoing studies].

    PubMed

    Wiendl, H; Lehmann, H C; Hohlfeld, R; Hartung, H-P; Kieseier, B C

    2004-06-01

    The therapeutic options for the treatment of multiple sclerosis (MS) have experienced enormous progress over recent years. Despite these encouraging developments, available therapies are only partially effective, and the ultimate goal of curing MS is still far from being attained. The improved understanding of the cellular and molecular mechanisms of MS (immune) pathogenesis together with recent shifts in paradigms led to a variety of new therapeutic targets and approaches. In addition to modulation of the inflammatory process, therapeutic approaches focussing on active neuroprotection, remyelinization, and regeneration have become increasingly important. Based on current concepts of the MS pathogenesis, this article summarizes new therapeutic approaches. Substances and strategies currently tested in clinical trials are reviewed. PMID:15257377

  13. Coronaviruses - drug discovery and therapeutic options.

    PubMed

    Zumla, Alimuddin; Chan, Jasper F W; Azhar, Esam I; Hui, David S C; Yuen, Kwok-Yung

    2016-05-01

    In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections. PMID:26868298

  14. Graves' disease. Manifestations and therapeutic options

    SciTech Connect

    McFarland, K.F.; Saleeby, G.

    1988-03-01

    Graves' disease is the most common cause of hyperthyroidism. Clinical features include thyroid enlargement, eye signs, tachycardia, heat intolerance, emotional lability, weight loss, and hyperkinesis. Three modes of therapy are available. The preferences of the patient and physician are usually prime considerations in devising the therapeutic plan. Radioactive iodine is the most frequently used and safest method of treatment for adults. Antithyroid drugs are preferred for children and pregnant women. Surgery is usually reserved for patients in whom the other forms of treatment are not acceptable. Considerable patient education during the decision-making process enhances the success of the therapeutic plan.

  15. Recurrent pericarditis: new and emerging therapeutic options.

    PubMed

    Imazio, Massimo; Lazaros, George; Brucato, Antonio; Gaita, Fiorenzo

    2016-02-01

    Recurrent pericarditis is one of the most common and troublesome complications after an episode of pericarditis, and affects 20-50% of patients treated for pericarditis. In most of these patients, the pericarditis remains idiopathic, although an immune-mediated (either autoimmune or autoinflammatory) pathogenesis is often presumed. The mainstay of therapy for recurrences is aspirin or NSAIDs, with the adjunct of colchicine. Corticosteroids are a second-line option to be considered for specific indications, such as connective tissue disease or pregnancy; contraindications or intolerance to aspirin, NSAIDs, and/or colchicine; or insufficient response to these medications. Furthermore, corticosteroids can be added to NSAIDs and colchicine in patients with persistent symptoms. In patients who do not respond adequately to any of these conventional therapies, alternative treatment options include azathioprine, intravenous human immunoglobulins, and anakinra. An improved understanding of how recurrent pericarditis develops after an initiating event is critical to prevent this complication, and further research is needed into the pathogenesis of recurrences. We discuss the aetiology and diagnosis of recurrent pericarditis, and extensively review the treatment options for this condition. PMID:26259934

  16. Secukinumab: a promising therapeutic option in spondyloarthritis.

    PubMed

    Maldonado-Ficco, Hernan; Perez-Alamino, Rodolfo; Maldonado-Cocco, José A

    2016-09-01

    Psoriatic arthritis (PsA) is the second most common chronic inflammatory joint disease. Ankylosing spondylitis (AS) is another less common but equally chronic and disabling spondyloarthritis (SpA). Therapeutic agents for the treatment of these diseases have been somewhat lacking as compared with those available for rheumatoid arthritis, which represents a significant challenge for both the treating physician and the pharmaceutical industry. A promising development for our understanding of the physiopathology of PsA and AS involves new targets to interrupt IL-17 and IL-12/IL-23 pathways. Up to 30-40 % of SpA patients have inadequate or poor response, or are intolerant to anti-TNF therapies. Therefore, there has been a clear unmet medical need in an important group of these patients. As a result, new therapeutic targets have emerged for the treatment of both axial and peripheral SpA. Interleukin 17 (IL-17) is a pro-inflammatory cytokine that is increased in psoriatic lesions as well as in the synovial fluid of patients with PsA and in sites of enthesitis in SpA. IL-23 has been shown to play an important role in the polarization of CD4+ T-cells to become IL-17 producers. Based on these evidences, blockade of the cytokine IL-17 or its receptors was considered to have therapeutic implications for the treatment of psoriasis, as well as PsA and AS.This article presents a thorough review of an IL-17 A blocking agent, its mechanism of action, its clinical efficacy and its therapeutic safety. PMID:27437696

  17. [New therapeutical options for heavy gastrointestinal bleeding].

    PubMed

    Braun, Georg; Messmann, Helmut

    2015-06-01

    The number of patients taking new oral anticoagulants is rising, so is the number of serious bleeding events. In severe bleeding, the decision to start a procoagulant therapy is difficult to take. With Idarucizumab and Andexanet Alfa, specific antidotes have been developed against both, direct thrombin inhibitors as well as direct Factor Xa inhibitors. In the endoscopic treatment of severe gastrointestinal bleeding, alternative treatment options are available with Hemospray™, Endoclot™ and new hemostasis clips. Especially in the recurrent ulcer bleeding, the newly developed clips can achieve hemostasis and prevent an operational procedure. PMID:26069913

  18. [The ketogenic diet: an underappreciated therapeutic option?].

    PubMed

    Paoli, A; Canato, M; Toniolo, L; Bargossi, A M; Neri, M; Mediati, M; Alesso, D; Sanna, G; Grimaldi, K A; Fazzari, A L; Bianco, A

    2011-01-01

    Obesity is reaching epidemic proportions in Western countries and is a strong risk factor for cardiovascular disease. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Although there is a common agreement about the concept that exercise and diet are two key factors for the control of body weight, the ideal amount and type of exercise and also the ideal diet for weight control are still under debate. A widely accepted nutritional regime is the Mediterranean diet that has evident health benefits although less attention has been paid to see if the effects are due to other lifestyle factors which may contribute to the health benefits perhaps as much as specific food choices. There are several other options available to the physician that may produce good weight loss results in the short/medium term and also for maintenance of the goal achieved. One of these strategies is the ketogenic diet or VLCKD (very low carbohydrate ketogenic diet) that has been widely studied in recent years. Most studies show that this diet has a solid physiological and biochemical basis which is able to induce effective weight loss and improvement of several parameters of cardiovascular risk. This review discusses the physiological basis of VLCKD and the main applications together with its strengths and weaknesses compared to common dietary recommendations. PMID:22041813

  19. Phytotherapy: emerging therapeutic option in urologic disease

    PubMed Central

    2012-01-01

    Phytotherapy belongs to the area of complementary and alternative medicine (CAM) and the definition of phytotherapy is the use of plants or plant extracts for medicinal uses. Interest in phytotherapy is growing in both Asian and western countries for its use in the prevention and management of disease, improvement of general health and anti-aging. And also, there are several studies about the efficacy of phytotherapy in urologic diseases like benign prostatic hyperplasia (BPH), erectile dysfunction (ED), late-onset hypogonadism (LOH) and infertility in males. Phytotherapy for BPH including saw palmetto, pygeum, and nettles, is under vigorous research for the therapeutic effect. No solid evidence showing better effective treatment modality for ED than placebo has been found yet for phytotherapy. Recently, a potent NO donor, L-arginine is under research with promising results. Phytotherapy is used by a number of patients with urological disease, and urologists need to have accurate knowledge about phytotherapy as well as keep a cautious approach. The possible effects and side effects should be defined and related to urologic patients by urologists. PMID:26816707

  20. Emerging Therapeutic Options for Celiac Disease

    PubMed Central

    Bakshi, Anita; Stephen, Sindu; Borum, Marie L.

    2012-01-01

    Celiac disease is an autoimmune disorder of the small intestine that is more common than was previously thought. This disease is caused by an inappropriate immune response to wheat gluten, barley, and rye. Three main pathways cause celiac disease: the environmental trigger (gluten), genetic susceptibility, and unusual gut permeability. The only treatment currently available is a strict gluten-free diet. Unfortunately, a majority of patients have difficulty complying with this diet, and the response to therapy is poor. Therefore, alternative treatments are being developed, and new insights into the pathophysiology of celiac disease have led to research into novel therapies. New treatments include engineering gluten-free grains, decreasing intestinal permeability by blockage of the epithelial zonulin receptor, inducing oral tolerance to gluten with a therapeutic vaccine, and degrading immunodominant gliadin peptides using probiotics with endopeptidases or transglutaminase inhibitors. These nondiet-based therapies provide hope for enhanced, lifelong celiac disease management with improved patient compliance and better quality of life. PMID:23483819

  1. Targeting α-synuclein: Therapeutic options.

    PubMed

    Dehay, Benjamin; Decressac, Mickael; Bourdenx, Mathieu; Guadagnino, Irene; Fernagut, Pierre-Olivier; Tamburrino, Anna; Bassil, Fares; Meissner, Wassilios G; Bezard, Erwan

    2016-06-01

    The discovery of the central role of α-synuclein (αSyn) in the pathogenesis of Parkinson's disease (PD) has powered, in the last decade, the emergence of novel relevant models of this condition based on viral vector-mediated expression of the disease-causing protein or inoculation of toxic species of αSyn. Although the development of these powerful tools and models has provided considerable insights into the mechanisms underlying neurodegeneration in PD, it has also been translated into the expansion of the landscape of preclinical therapeutic strategies. Much attention is now brought to the proteotoxic mechanisms induced by αSyn and how to block them using strategies inspired by intrinsic cellular pathways such as the enhancement of cellular clearance by the lysosomal-autophagic system, through proteasome-mediated degradation or through immunization. The important effort undertaken by several laboratories and consortia to tackle these issues and identify novel targets warrants great promise for the discovery not only of neuroprotective approaches but also of restorative strategies for PD and other synucleinopathies. In this viewpoint, we summarize the latest advances in this new area of PD research and will discuss promising approaches and ongoing challenges. © 2016 International Parkinson and Movement Disorder Society. PMID:26926119

  2. Therapeutic options for the management of pancreatic cancer

    PubMed Central

    Rossi, Maria L; Rehman, Azeem A; Gondi, Christopher S

    2014-01-01

    Since its initial characterization, pancreatic ductal adenocarcinoma has remained one of the most devastating and difficult cancers to treat. Pancreatic cancer is the fourth leading cause of death in the United States, resulting in an estimated 38460 deaths annually. With few screening tools available to detect this disease at an early stage, 94% of patients will die within five years of diagnosis. Despite decades of research that have led to a better understanding of the molecular and cellular signaling pathways in pancreatic cancer cells, few effective therapies have been developed to target these pathways. Other treatment options have included more sophisticated pancreatic cancer surgeries and combination therapies. While outcomes have improved modestly for these patients, more effective treatments are desperately needed. One of the greatest challenges in the future of treating this malignancy will be to develop therapies that target the tumor microenvironment and surrounding pancreatic cancer stem cells in addition to pancreatic cancer cells. Recent advances in targeting pancreatic stellate cells and the stroma have encouraged researchers to shift their focus to the role of desmoplasia in pancreatic cancer pathobiology in the hopes of developing newer-generation therapies. By combining novel agents with current cytotoxic chemotherapies and radiation therapy and personalizing them to each patient based on specific biomarkers, the goal of prolonging a patient’s life could be achieved. Here we review the most effective therapies that have been used for the treatment of pancreatic cancer and discuss the future potential of therapeutic options. PMID:25170201

  3. Therapeutic options in the treatment of benign prostatic hyperplasia

    PubMed Central

    Sandhu, Jaspreet S

    2009-01-01

    Current theraputic options for the treatment of symptomatic benign prostatic hyperplasia (BPH) are reviewed. Therapeutic options for mild lower urinary tract symptoms (LUTS), as defined by the American Urological Association, are generally treated medically. Moderate to severe LUTS can be treated medically or with surgical therapy. Current medical and surgical treatments for LUTS secondary to BPH are reviewed and evolving treatments are explored. PMID:19936164

  4. Primary Sclerosing Cholangitis: Therapeutic Options and Surveillance Management

    PubMed Central

    Kumar, Aditi; Wheatley, Daniel; Puttanna, Amar

    2016-01-01

    Primary sclerosing cholangitis is a chronic immune-mediated liver disease. Though rare, it poses several clinical concerns for the managing physician. There are currently limited therapeutic options in the management of the condition and weak evidence base behind them. Endoscopic intervention is limited to those patients with obstructing stricture-related disease, and even liver transplantation has a risk of disease recurrence. Surveillance for inflammatory bowel disorders, metabolic bone disease, and malignancy is paramount when managing such patients. This article provides an overview of the condition with further focus on current therapeutic options and guidance on surveillance management. PMID:27330336

  5. Stem cells as promising therapeutic options for neurological disorders.

    PubMed

    Yoo, Jongman; Kim, Han-Soo; Hwang, Dong-Youn

    2013-04-01

    Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell-mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed. PMID:23097262

  6. Therapeutic options in idiopathic burning mouth syndrome: literature review.

    PubMed

    Miziara, Ivan; Chagury, Azis; Vargas, Camila; Freitas, Ludmila; Mahmoud, Ali

    2015-01-01

    Introduction Burning mouth syndrome (BMS) is characterized by a burning sensation in the tongue, palate, lips, or gums of no well-defined etiology. The diagnosis and treatment for primary BMS are controversial. No specific laboratory tests or diagnostic criteria are well established, and the diagnosis is made by excluding all other possible disorders. Objective To review the literature on the main treatment options in idiopathic BMS and compare the best results of the main studies in 15 years. Data Synthesis We conducted a literature review on PubMed/MEDLINE, SciELO, and Cochrane-BIREME of work in the past 15 years, and only selected studies comparing different therapeutic options in idiopathic BMS, with preference for randomized and double-blind controlled studies. Final Comments Topical clonazepam showed good short-term results for the relief of pain, although this was not presented as a definitive cure. Similarly, α-lipoic acid showed good results, but there are few randomized controlled studies that showed the long-term results and complete remission of symptoms. On the other hand, cognitive therapy is reported as a good and lasting therapeutic option with the advantage of not having side effects, and it can be combined with pharmacologic therapy. PMID:25992157

  7. Therapeutic Options in Idiopathic Burning Mouth Syndrome: Literature Review

    PubMed Central

    Miziara, Ivan; Chagury, Azis; Vargas, Camila; Freitas, Ludmila; Mahmoud, Ali

    2014-01-01

    Introduction Burning mouth syndrome (BMS) is characterized by a burning sensation in the tongue, palate, lips, or gums of no well-defined etiology. The diagnosis and treatment for primary BMS are controversial. No specific laboratory tests or diagnostic criteria are well established, and the diagnosis is made by excluding all other possible disorders. Objective To review the literature on the main treatment options in idiopathic BMS and compare the best results of the main studies in 15 years. Data Synthesis We conducted a literature review on PubMed/MEDLINE, SciELO, and Cochrane-BIREME of work in the past 15 years, and only selected studies comparing different therapeutic options in idiopathic BMS, with preference for randomized and double-blind controlled studies. Final Comments Topical clonazepam showed good short-term results for the relief of pain, although this was not presented as a definitive cure. Similarly, α-lipoic acid showed good results, but there are few randomized controlled studies that showed the long-term results and complete remission of symptoms. On the other hand, cognitive therapy is reported as a good and lasting therapeutic option with the advantage of not having side effects, and it can be combined with pharmacologic therapy. PMID:25992157

  8. Pediatric lymphatic malformations: evolving understanding and therapeutic options.

    PubMed

    Defnet, Ann M; Bagrodia, Naina; Hernandez, Sonia L; Gwilliam, Natalie; Kandel, Jessica J

    2016-05-01

    Multimodal treatment of lymphatic malformations continues to expand as new information about the biology and genetics of these lesions is discovered, along with knowledge gained from clinical practice. A patient-centered approach, ideally provided by a multidisciplinary medical and surgical team, should guide timing and modality of treatment. Current treatment options include observation, surgery, sclerotherapy, radiofrequency ablation, and laser therapy. New medical and surgical therapies are emerging, and include sildenafil, propranolol, sirolimus, and vascularized lymph node transfer. The primary focus of management is to support and optimize these patients' quality of life. Researchers continue to study lymphatic malformations with the goal of increasing therapeutic options and developing effective clinical pathways for these complicated lesions. PMID:26815877

  9. Emerging therapeutic options for myelofibrosis: a Canadian perspective

    PubMed Central

    Gupta, Vikas; Foltz, Lynda; Sirhan, Shireen; Busque, Lambert; Turner, A Robert

    2012-01-01

    Myelofibrosis (MF) is a clonal stem cell disorder characterized by cytopenias, splenomegaly, marrow fibrosis, and systemic symptoms due to elevated inflammatory cytokines. MF is associated with decreased survival. The quality of life of patients with MF is similar to other advanced malignancies. Allogeneic hematopoietic cell transplantation is a curative treatment, but is applicable to a minority of patients with MF. None of the conventional therapies are known to alter the natural history of the disease. Significant progress has been made in the last few years in the understanding of disease biology of MF. Discovery of the JAK2V617F mutation paved the way for drug discovery in MF, and the first JAK1/2 inhibitor, ruxolitinib, has been approved by FDA and Health Canada. Several other JAK1/2 inhibitors are at various stages of clinical development. As a consequence, the therapeutic landscape of MF is changing from a disease where no effective therapies existed to one with several novel treatment options on the horizon. In this report, we assess the changing therapeutic options for MF, and critically analyze the position of novel treatments in the current armamentarium. PMID:23119228

  10. Update on therapeutic options in Waldenström macroglobulinemia

    PubMed Central

    Leleu, Xavier; Gay, Julie; Roccaro, Aldo M.; Moreau, Anne-Sophie; Poulain, Stephanie; Dulery, Remy; Champs, Berenice Bro Des; Robu, Daniela; Ghobrial, Irene M.

    2011-01-01

    Waldenström macroglobulinemia (WM) is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells (LPCs), along with demonstration of an IgM monoclonal gammopathy in the blood. WM remains incurable, with 5–6 yr median overall survival for patients with symptomatic WM. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab, either in monotherapy or in combination. Studies involving combination chemotherapy are ongoing, and preliminary results are encouraging. However, there are several limitations to these approaches. The complete response rate is low and the treatment free survival are short in many patients, no specific agent or regimen has been shown to be superior to another, and no treatment has been specifically approved for WM. As such, novel therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to develop new targeted therapeutics for this malignancy. These efforts have led to the development of proteasome inhibitors, of them bortezomib, several Akt/mTor inhibitors, such as perifosine and Rad001, and immunomodulatory agents such as thalidomide and lenalidomide. Many agents and monoclonal antibodies are currently being tested in clinical trials and seem promising. This report provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM. PMID:19087134

  11. New therapeutic options for actinic keratosis and basal cell carcinoma.

    PubMed

    Sligh, James E

    2014-06-01

    Actinic keratosis (AK) is a common premalignant skin lesion that is frequently treated by cryosurgery. Basal cell carcinoma is the most common malignancy of man, and early-stage lesions are usually cured via surgery. Advanced basal cell carcinoma may require more extensive surgery resulting in deformity, and many advanced lesions cannot be treated surgically. Several recent developments have improved therapeutic options for both conditions. Cryosurgery is still a mainstay of treatment for AK, but the introduction of effective topical agents, imiquimod cream and ingenol mebutate, has provided alternatives to cryosurgery. For advanced basal cell carcinoma, the small-molecule inhibitor vismodegib has proven to be an effective therapy for lesions that are not amenable to surgery and has demonstrated ability to achieve dramatic improvement in advanced, potentially disfiguring cancer. PMID:25268601

  12. Clostridium difficile infection: New insights into therapeutic options.

    PubMed

    Kachrimanidou, Melina; Sarmourli, Theopisti; Skoura, Lemonia; Metallidis, Symeon; Malisiovas, Nikolaos

    2016-09-01

    Clostridium difficile infection (CDI) is an important cause of mortality and morbidity in healthcare settings and represents a major social and economic burden. The major virulence determinants are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), encoded within the pathogenicity locus. Traditional therapies, such as metronidazole and vancomycin, frequently lead to a vicious circle of recurrences due to their action against normal human microbiome. New disease management strategies together with the development of novel therapeutic and containment approaches are needed in order to better control outbreaks and treat patients. This article provides an overview of currently available CDI treatment options and discusses the most promising therapies under development. PMID:25955884

  13. Hypertension in pregnancy: a review of therapeutic options

    PubMed Central

    Kernaghan, D; Duncan, A C; McKay, G A

    2012-01-01

    Hypertensive disorders in pregnancy are common and can occur as a result of pre-existing hypertension or as new onset hypertension usually in the second half of pregnancy. In either situation there is potential for considerable perinatal and maternal morbidity and mortality. This review article aims to compare therapeutic options outlined in a selection of national guidelines and to look in more detail at the most commonly prescribed drugs – labetalol, methyldopa and nifedipine – with respect to their pharmacology and the evidence for their use in pregnancy. We will also consider the rationale for identifying and treating hypertension in pregnancy and the effect this can have on short- and long-term maternal and neonatal outcomes.

  14. Inner ear symptoms and disease: Pathophysiological understanding and therapeutic options

    PubMed Central

    Ciuman, Raphael R.

    2013-01-01

    In recent years, huge advances have taken place in understanding of inner ear pathophysiology causing sensorineural hearing loss, tinnitus, and vertigo. Advances in understanding comprise biochemical and physiological research of stimulus perception and conduction, inner ear homeostasis, and hereditary diseases with underlying genetics. This review describes and tabulates the various causes of inner ear disease and defines inner ear and non-inner ear causes of hearing loss, tinnitus, and vertigo. The aim of this review was to comprehensively breakdown this field of otorhinolaryngology for specialists and non-specialists and to discuss current therapeutic options in distinct diseases and promising research for future therapies, especially pharmaceutic, genetic, or stem cell therapy. PMID:24362017

  15. Current Therapeutic Options in Sturge-Weber Syndrome.

    PubMed

    Comi, Anne

    2015-12-01

    Sturge-Weber syndrome is a vascular malformation syndrome consisting of a facial port-wine birthmark associated with malformed leptomeningeal blood vessels and a choroid "angioma" of the eye. It is a rare neurocutaneous disorder that occurs sporadically, is not inherited, and is caused by a somatic mosaic mutation in GNAQ. In patients with Sturge-Weber syndrome, brain involvement typically presents in infancy with seizures, strokes, and stroke-like episodes, and a range of neurologic impairments. Standard treatment includes laser therapy for the birthmark, control of glaucoma through eyedrops or surgery, and the use of anticonvulsants. Increasingly low-dose aspirin is offered. Treatment with propranolol has been tried generally without the dramatic results seen in hemangiomas. Treatment with an anticonvulsant or low-dose aspirin or both before the onset of seizures is an option. Surgical resection may be offered to those whose seizures are medically refractory. Endocrine, medical rehabilitation and cognitive comorbidities are important to manage. In the future, new therapeutic options are likely to be offered stemming from preclinical studies and small pilot clinical trials currently ongoing. Discovery of the causative somatic mosaic mutation suggests new insights into the pathophysiology of this vascular malformation disorder, and potential novel treatment strategies for future study. The mutation results in constitutive overactivation of the Ras-Raf-MEK-ERK and the HIPPO-YAP pathways and inhibitors of these pathways may in the future prove useful in the treatment of Sturge-Weber syndrome. PMID:26706016

  16. Current Therapeutic Options in Sturge-Weber Syndrome

    PubMed Central

    Comi, Anne

    2016-01-01

    Sturge-Weber syndrome is a vascular malformation syndrome consisting of a facial port-wine birthmark associated with malformed leptomeningeal blood vessels and a choroid “angioma” of the eye. It is a rare neurocutaneous disorder that occurs sporadically, is not inherited, and is caused by a somatic mosaic mutation in GNAQ. In patients with Sturge-Weber syndrome, brain involvement typically presents in infancy with seizures, strokes, and stroke-like episodes, and a range of neurologic impairments. Standard treatment includes laser therapy for the birthmark, control of glaucoma through eyedrops or surgery, and the use of anticonvulsants. Increasingly low-dose aspirin is offered. Treatment with propranolol has been tried generally without the dramatic results seen in hemangiomas. Treatment with an anticonvulsant or low-dose aspirin or both before the onset of seizures is an option. Surgical resection may be offered to those whose seizures are medically refractory. Endocrine, medical rehabilitation and cognitive comorbidities are important to manage. In the future, new therapeutic options are likely to be offered stemming from preclinical studies and small pilot clinical trials currently ongoing. Discovery of the causative somatic mosaic mutation suggests new insights into the pathophysiology of this vascular malformation disorder, and potential novel treatment strategies for future study. The mutation results in constitutive overactivation of the Ras-Raf-MEK-ERK and the HIPPO-YAP pathways and inhibitors of these pathways may in the future prove useful in the treatment of Sturge-Weber syndrome. PMID:26706016

  17. Skewed Epigenetics: An Alternative Therapeutic Option for Diabetes Complications

    PubMed Central

    Togliatto, Gabriele; Dentelli, Patrizia; Brizzi, Maria Felice

    2015-01-01

    Vascular complications are major causes of morbidity and mortality in type 2 diabetes patients. Mitochondrial reactive oxygen species (ROS) generation and a lack of efficient antioxidant machinery, a result of hyperglycaemia, mainly contribute to this problem. Although advances in therapy have significantly reduced both morbidity and mortality in diabetic individuals, diabetes-associated vascular complications are still one of the most challenging health problems worldwide. New healing options are urgently needed as current therapeutics are failing to improve long-term outcomes. Particular effort has recently been devoted to understanding the functional relationship between chromatin structure regulation and the persistent change in gene expression which is driven by hyperglycaemia and which accounts for long-lasting diabetic complications. A detailed investigation into epigenetic chromatin modifications in type 2 diabetes is underway. This will be particularly useful in the design of mechanism-based therapeutics which interfere with long-lasting activating epigenetics and improve patient outcomes. We herein provide an overview of the most relevant mechanisms that account for hyperglycaemia-induced changes in chromatin structure; the most relevant mechanism is called “metabolic memory.” PMID:26064979

  18. New therapeutic options for advanced non-resectable malignant melanoma.

    PubMed

    Stadler, Simone; Weina, Kasia; Gebhardt, Christoffer; Utikal, Jochen

    2015-03-01

    Melanoma is a malignant tumor which is inclined to metastasize promptly into the lymphatic system and other organs such as lung, liver, brain or bone. Therefore early diagnosis remains crucial for improving clinical outcome for melanoma patients. Current chemotherapy and chemo-immunotherapy regimes have shown little clinical benefit with no improvement in overall survival. However, new advances in melanoma biology such as the discovery of predisposed gene signatures and key somatic events have changed clinical practice. New therapeutic approaches are being tested or have been approved by the FDA/EMA recently including targeted therapies, such as BRAF- and MEK-inhibitors, and novel immunotherapies, such as anti-CTLA4 or anti-PD1 therapies. For these therapies an improvement of progression-free and overall survival has been seen in patients with advanced non-resectable melanoma. The following review summarizes recent therapeutic options after the ASCO and ESMO annual meetings 2014 for the treatment of malignant melanoma. PMID:25596540

  19. Transcriptome Sequencing of Tumor Subpopulations Reveals a Spectrum of Therapeutic Options for Squamous Cell Lung Cancer

    PubMed Central

    Barrett, Christian L.; Schwab, Richard B.; Jung, HyunChul; Crain, Brian; Goff, Daniel J.; Jamieson, Catriona H. M.; Thistlethwaite, Patricia A.; Harismendy, Olivier; Carson, Dennis A.; Frazer, Kelly A.

    2013-01-01

    Background The only therapeutic options that exist for squamous cell lung carcinoma (SCC) are standard radiation and cytotoxic chemotherapy. Cancer stem cells (CSCs) are hypothesized to account for therapeutic resistance, suggesting that CSCs must be specifically targeted. Here, we analyze the transcriptome of CSC and non-CSC subpopulations by RNA-seq to identify new potential therapeutic strategies for SCC. Methods We sorted a SCC into CD133− and CD133+ subpopulations and then examined both by copy number analysis (CNA) and whole genome and transcriptome sequencing. We analyzed The Cancer Genome Atlas (TCGA) transcriptome data of 221 SCCs to determine the generality of our observations. Results Both subpopulations highly expressed numerous mRNA isoforms whose protein products are active drug targets for other cancers; 31 (25%) correspond to 18 genes under active investigation as mAb targets and an additional 4 (3%) are of therapeutic interest. Moreover, we found evidence that both subpopulations were proliferatively driven by very high levels of c-Myc and the TRAIL long isoform (TRAILL) and that normal apoptotic responses to high expression of these genes was prevented through high levels of Mcl-1L and Bcl-xL and c-FlipL—isoforms for which drugs are now in clinical development. SCC RNA-seq data (n = 221) from TCGA supported our findings. Our analysis is inconsistent with the CSC concept that most cells in a cancer have lost their proliferative potential. Furthermore, our study suggests how to target both the CSC and non-CSC subpopulations with one treatment strategy. Conclusions Our study is relevant to SCC in particular for it presents numerous potential options to standard therapy that target the entire tumor. In so doing, it demonstrates how transcriptome sequencing provides insights into the molecular underpinnings of cancer propagating cells that, importantly, can be leveraged to identify new potential therapeutic options for cancers beyond what is

  20. Management of hepatitis delta: Need for novel therapeutic options

    PubMed Central

    Abbas, Zaigham; Abbas, Minaam

    2015-01-01

    Hepatitis D virus (HDV) is the smallest single stranded RNA virus infecting humans. The hepatitis B surface antigen envelope protein protects the HDV nucleocapsid antigen and provides a means for the virus to enter and exit the hepatocyte. Hepatitis B and D viruses exploit the human sodium taurocholate co-transporting polypeptide (NTCP), a receptor, for their entry into hepatocytes. Prenylation of the large delta antigen is a critical determinant of HDV particle assembly. Treatment with pegylated interferon results in sustained virological response six months post-treatment in one fourth of the patients. Nucleos(t)ide analogs (NAs) have been widely tested in hepatitis delta, but they appear to be ineffective. Combination treatment of NAs with interferon also proved to be disappointing so there is a need for novel therapeutic options. The receptor function of NTCP is blocked by Myrcludex B, a synthetic N-acylated preS1 lipopeptide that competes with infectious virions for receptor binding. There are already some approved drugs available, including irbesartan, ezetimibe, and ritonavir and cyclosporin A, with documented inhibitory effects on NTCP’s metabolic function. These drugs may have a role in HDV treatment. Interference with host-mediated post-translational changes of proteins that are crucial to the HDV life cycle, such as prenylation may become an important tool to control HDV infection and prevent replication. Lonafarnib, a prenylation inhibitor significantly reduces virus levels in hepatitis delta patients. Antisense oligodeoxynucleotides which are complementary to genomic HDV ribozyme self-cleavage site and stem I regions can inhibit genomic HDV ribozyme activity. PMID:26327754

  1. 45 CFR 1306.36 - Additional Head Start program option variations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 4 2014-10-01 2014-10-01 false Additional Head Start program option variations..., YOUTH AND FAMILIES, HEAD START PROGRAM HEAD START STAFFING REQUIREMENTS AND PROGRAM OPTIONS Head Start Program Options § 1306.36 Additional Head Start program option variations. In addition to the...

  2. 45 CFR 1306.36 - Additional Head Start program option variations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Additional Head Start program option variations..., YOUTH AND FAMILIES, HEAD START PROGRAM HEAD START STAFFING REQUIREMENTS AND PROGRAM OPTIONS Head Start Program Options § 1306.36 Additional Head Start program option variations. In addition to the...

  3. 45 CFR 1306.36 - Additional Head Start program option variations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 4 2011-10-01 2011-10-01 false Additional Head Start program option variations..., YOUTH AND FAMILIES, HEAD START PROGRAM HEAD START STAFFING REQUIREMENTS AND PROGRAM OPTIONS Head Start Program Options § 1306.36 Additional Head Start program option variations. In addition to the...

  4. 45 CFR 1306.36 - Additional Head Start program option variations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 4 2012-10-01 2012-10-01 false Additional Head Start program option variations..., YOUTH AND FAMILIES, HEAD START PROGRAM HEAD START STAFFING REQUIREMENTS AND PROGRAM OPTIONS Head Start Program Options § 1306.36 Additional Head Start program option variations. In addition to the...

  5. Attention deficit and hyperactivity disorder: a therapeutic option

    PubMed Central

    Topczewski, Abram

    2014-01-01

    Objective To evaluate the use of a therapeutic regimen to treat attention deficit hyperactivity disorder patients. Methods A total of 140 patients initially underwent physical, neurological and laboratory evaluation. Thereafter, treatment was initiated with a compounding product consisting of a tricyclic antidepressant and an anxiolytic. Results The response was positive in 71.43% of patients in controlling hyperactivity and improving dispersion and attention deficit. Conclusion The therapeutic regimen utilized proved to be an effective therapeutic alternative, especially for patients who do not adapt to psychostimulant drugs. PMID:25295451

  6. Calcium-activated potassium channels and endothelial dysfunction: therapeutic options?

    PubMed Central

    Félétou, Michel

    2009-01-01

    The three subtypes of calcium-activated potassium channels (KCa) of large, intermediate and small conductance (BKCa, IKCa and SKCa) are present in the vascular wall. In healthy arteries, BKCa channels are preferentially expressed in vascular smooth muscle cells, while IKCa and SKCa are preferentially located in endothelial cells. The activation of endothelial IKCa and SKCa contributes to nitric oxide (NO) generation and is required to elicit endothelium-dependent hyperpolarizations. In the latter responses, the hyperpolarization of the smooth muscle cells is evoked either via electrical coupling through myo-endothelial gap junctions or by potassium ions, which by accumulating in the intercellular space activate the inwardly rectifying potassium channel Kir2.1 and/or the Na+/K+-ATPase. Additionally, endothelium-derived factors such as cytochrome P450-derived epoxyeicosatrienoic acids and under some circumstances NO, prostacyclin, lipoxygenase products and hydrogen peroxide (H2O2) hyperpolarize and relax the underlying smooth muscle cells by activating BKCa. In contrast, cytochrome P450-derived 20-hydroxyeicosatetraenoic acid and various endothelium-derived contracting factors inhibit BKCa. Aging and cardiovascular diseases are associated with endothelial dysfunctions that can involve a decrease in NO bioavailability, alterations of EDHF-mediated responses and/or enhanced production of endothelium-derived contracting factors. Because potassium channels are involved in these endothelium-dependent responses, activation of endothelial and/or smooth muscle KCa could prevent the occurrence of endothelial dysfunction. Therefore, direct activators of these potassium channels or compounds that regulate their activity or their expression may be of some therapeutic interest. Conversely, blockers of IKCa may prevent restenosis and that of BKCa channels sepsis-dependent hypotension. PMID:19187341

  7. Emerging therapeutic options for sporadic inclusion body myositis

    PubMed Central

    Alfano, Lindsay N; Lowes, Linda P

    2015-01-01

    Sporadic inclusion body myositis is the most common inflammatory muscle disorder preferentially affecting males over the age of 40 years. Progressive muscle weakness of the finger flexors and quadriceps muscles results in loss of independence with activities of daily living and eventual wheelchair dependence. Initial signs of disease are often overlooked and can lead to mis- or delayed diagnosis. The underlying cause of disease is unknown, and disease progression appears refractory to available treatment options. This review discusses the clinical presentation of inclusion body myositis and the current efforts in diagnosis, and focuses on the current state of research for both nonpharmacological and pharmacological treatment options for this patient group. PMID:26445546

  8. [Female androgenetic alopecia, a survey of causes and therapeutic options].

    PubMed

    Duchková, Hana; Hašková, Marta

    2015-01-01

    Mesotherapy is one of the options for the treatment of androgenetic alopecia. Testing 24 women with androgenetic alopecia has demonstrated a positive effect of mesotherapy on the hair growth, hair thickness, with only insignificant increase of hair density. It is known that androgenetic alopecia represents a localized aging of hair follicles. We therefore decided to examine the different effects of mesotherapy on hair density in younger and in elderly women. In younger women mesotherapy significantly increased hair density compared with older women. For mesotherapy we used a combination of micronutrients and antioxidants. Mesotherapy achievements were evident for 6-12 months. Treatment requires a long-term care. PMID:25994911

  9. Granuloma annulare: Pathogenesis, disease associations and triggers, and therapeutic options.

    PubMed

    Piette, Evan W; Rosenbach, Misha

    2016-09-01

    Granuloma annulare (GA) represents a cutaneous reaction pattern of unknown cause with a variety of previously described potential disease associations and triggers. This review attempts to synthesize the available data regarding potential etiopathogenesis, reviews the available data on potential GA disease associations and work-up indicated for patients with GA, and discusses potential inciting triggers. In the final part, this article describes the available treatments options and supporting data, and provides a framework for approaching management of patients with GA. The previous accompanying article provided a comprehensive overview of the available information known about the clinical variants, epidemiology, genetics, and histology of GA. PMID:27543210

  10. Lactic acid bacteria as mucosal delivery vehicles: a realistic therapeutic option.

    PubMed

    Wang, Miao; Gao, Zeqian; Zhang, Yongguang; Pan, Li

    2016-07-01

    Recombinant lactic acid bacteria (LAB), in particular lactococci and lactobacilli, have gained increasing interest as mucosal delivery vehicles in recent years. With the development of mucosal vaccines, studies on LAB expression systems have been mainly focused on the generation of genetic tools for antigen expression in different locations. Recombinant LAB show advantages in a wide range of aspects over other mucosal delivery systems and represent an attractive candidate for the delivery of therapeutic and prophylactic molecules in different applications. Here, we review the recent data on the use of recombinant LAB as mucosal delivery vectors and the associated health benefits, including the prevention and treatment of inflammatory bowel diseases (IBDs), autoimmune disorders, and infections by pathogenic microorganisms from mucosal surfaces. In addition, we discuss the use of LAB as vehicles to deliver DNA directly to eukaryotic cells. Researches from the last 5 years demonstrate that LAB as vectors for mucosal delivery of therapeutic molecules seem to be a realistic therapeutic option both in human and animal diseases. PMID:27154346

  11. Pharmacologic options for reducing the shivering response to therapeutic hypothermia.

    PubMed

    Weant, Kyle A; Martin, Julia E; Humphries, Roger L; Cook, Aaron M

    2010-08-01

    Recent literature has demonstrated significant improvements in neurologic outcomes in patients who have received induced hypothermia in the setting of out-of-hospital cardiac arrest. Through multiple metabolic mechanisms, the induction of hypothermia slows the progression and devastation of transient cerebral hypoxia. Despite these benefits, the desired reduction in core temperature is often a challenging venture as the body attempts to maintain homeostasis through the induction of thermoregulatory processes aimed at elevating body temperature. Shivering is an involuntary muscular activity that enhances heat production in an attempt to restore homeostasis. For successful induction and maintenance of induced hypothermia, shivering, as well as other thermoregulatory responses, must be overcome. Several pharmacologic options are available, either used alone or in combination, that safely and effectively prevent or treat shivering after the induction of hypothermia. We conducted a PubMed search (1966-March 2009) to identify all human investigations published in English that discussed pharmacologic mechanisms for the control of shivering. Among these options, clonidine, dexmedetomidine, and meperidine have demonstrated the greatest and most clinically relevant impact on depression of the shivering threshold. More research in this area is needed, however, and the role of the clinical pharmacist in the development and implementation of this therapy needs to be defined. PMID:20653360

  12. [Orthokin as new therapeutic option for orthopedic diseases].

    PubMed

    Heyll, U

    2004-03-01

    The synthesis and introduction of interleukin-1 receptor antagonists established a promising strategy in the treatment of inflammatory diseases. This kind of therapy is claimed now to be available for osteoarthritis and other orthopedic disorders also. In the case of "orthokin", the interleukin-1 receptor antagonist is produced by stimulation of own blood-cells. It is not possible, to evaluate the practicability of this therapeutic approach because there are no published experimental data. We also found no results of clinical studies, which would allow an estimation of the effectiveness and the risks of this method. Therefore treatment with "orthokin" cannot be recommended at present. PMID:15049471

  13. Epidermolysis Bullosa Acquisita: From Pathophysiology to Novel Therapeutic Options.

    PubMed

    Kasperkiewicz, Michael; Sadik, Christian D; Bieber, Katja; Ibrahim, Saleh M; Manz, Rudolf A; Schmidt, Enno; Zillikens, Detlef; Ludwig, Ralf J

    2016-01-01

    Epidermolysis bullosa acquisita (EBA) is a prototypic organ-specific autoimmune disease induced by autoantibodies to type VII collagen causing mucocutaneous blisters. In the inflammatory (bullous pemphigoid-like) EBA variant, autoantibody binding is followed by a lesional inflammatory cell infiltration, and the overall clinical picture may be indistinguishable from that of bullous pemphigoid, the latter being the most common autoimmune bullous disease. The last decade witnessed the development of several mouse models of inflammatory EBA that facilitated the elucidation of the pathogenesis of autoantibody-induced, cell-mediated subepidermal blistering diseases and identified new therapeutic targets for these and possibly other autoantibody-driven disorders. PMID:26763420

  14. Current and Novel Therapeutic Options for Irritable Bowel Syndrome Management

    PubMed Central

    Camilleri, Michael; Andresen, Viola

    2009-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder affecting up to 3-15% of the general population in western countries. It is characterized by unexplained abdominal pain, discomfort, and bloating in association with altered bowel habits. The pathophysiology of IBS is multifactorial involving disturbances of the brain-gut-axis. The pathophysiology provides the rationale for pharmacotherapy: abnormal gastrointestinal motor functions, visceral hypersensitivity, psychosocial factors, autonomic dysfunction, and mucosal immune activation. Understanding the mechanisms, and their mediators or modulators including neurotransmitters and receptors have led to several therapeutic approaches including agents acting on the serotonin receptor or serotonin transporter system, antidepressants, novel selective anticholinergics, α-adrenergic agonists, opioid agents, cholecystokinin-antagonists, neurokinin-antagonists, somatostatin receptor agonists, corticotropin releasing factor antagonists, chloride-channel activators, guanylate-cyclase-c agonists, melatonin, atypical benzodiazepines, antibiotics, immune modulators and probiotics. The mechanisms and current evidence regarding efficacy of these agents are reviewed. PMID:19665953

  15. Acquired von Willebrand syndrome: diagnostic problems and therapeutic options.

    PubMed

    Eikenboom, Jeroen C J; Tjernberg, Pernilla; Van Marion, Vincent; Heering, Karel J

    2007-01-01

    We present a case of acquired von Willebrand syndrome (AVWS) due to a monoclonal gammopathy of undetermined significance. Initially this case was diagnosed as congenital von Willebrand disease (VWD); however, re-examination of the medical history rendered a congenital bleeding disorder unlikely. A normal plasma von Willebrand factor (VWF) propeptide level and a very short half-life of VWF after a test infusion with factor VIII/VWF concentrate confirmed the diagnosis AVWS. Two major surgical procedures were successfully managed using high-dose intravenous immunoglobulin. The differential diagnosis with congenital VWD and the diagnostic and therapeutic approaches of AVWS are discussed. We conclude that the diagnosis of AVWS relies primarily on clinical suspicion and a careful bleeding history. A correct diagnosis is essential for optimal perioperative management and treatment of bleeding episodes. PMID:16986130

  16. Papaya extract to treat dengue: a novel therapeutic option?

    PubMed

    Sarala, N; Paknikar, Ss

    2014-05-01

    Dengue is a viral disease that today affects a vast number of people in over 125 countries and is responsible for a sizable number of deaths. In the absence of an effective antiviral drug to treat the disease, various treatments are being investigated. Studies have indicated that the juice of the leaves of the Carica papaya plant from the family Caricaceae could help to increase the platelet levels in these patients. This review describes some of the published studies on this topic. The search was done independently by the two authors using PubMed, Google and the library database and included relevant articles of the last 10 years. A total of 7 studies were included in this review, which were one animal study, one case report, three case series and two randomized controlled trials. Although many of the studies and case reports published in literature lack adequate information, some of the studies do raise the possibility that this treatment could be an important option in the future. Further large-scale studies could establish the usefulness or ineffectiveness of this natural product in the treatment of dengue. PMID:24971201

  17. Treating seborrheic dermatitis: review of mechanisms and therapeutic options.

    PubMed

    Bhatia, Neal

    2013-07-01

    Seborrheic dermatitis is one of those conditions that dermatologists and patients alike tend to find a routine for, and in many cases those routines are hard to break. And, unlike the new treatment paradigms for eczema, acne, and even actinic keratoses, combination therapies for addressing the disease process typically have not been a part of the approach to treating seborrheic dermatitis. However, with the advent of new therapies and vehicles as well as a better understanding of how neutrophils and free oxygen radicals impact inflammation,1 there are new options to maintain and control the disease process of seborrheic dermatitis to minimize flares. Although the needs of the scalp, face and chest are different, as are the variations in skin types, the fundamental mechanisms of the inflammatory process are often the same. If it is understood that seborrheic dermatitis is histologically classified as a papulosquamous disorder with paucineutrophilic and lymphocytic infiltrates, and if the trigger and etiologic agent most likely is Malassezia furfur, then the ideal mechanisms of action of therapies should be directed as such PMID:23884493

  18. The potential for emerging therapeutic options for Clostridium difficile infection

    PubMed Central

    Mathur, Harsh; Rea, Mary C; Cotter, Paul D; Ross, R Paul; Hill, Colin

    2014-01-01

    Clostridium difficile is mainly a nosocomial pathogen and is a significant cause of antibiotic-associated diarrhea. It is also implicated in the majority of cases of pseudomembranous colitis. Recently, advancements in next generation sequencing technology (NGS) have highlighted the extent of damage to the gut microbiota caused by broad-spectrum antibiotics, often resulting in C. difficile infection (CDI). Currently the treatment of choice for CDI involves the use of metronidazole and vancomycin. However, recurrence and relapse of CDI, even after rounds of metronidazole/vancomycin administration is a problem that must be addressed. The efficacy of alternative antibiotics such as fidaxomicin, rifaximin, nitazoxanide, ramoplanin and tigecycline, as well as faecal microbiota transplantation has been assessed and some have yielded positive outcomes against C. difficile. Some bacteriocins have also shown promising effects against C. difficile in recent years. In light of this, the potential for emerging treatment options and efficacy of anti-C. difficile vaccines are discussed in this review. PMID:25564777

  19. Therapeutic Options for Controlling Fluids in the Visual System

    NASA Technical Reports Server (NTRS)

    Curry, Kristina M.; Wotring, Virginia E.

    2014-01-01

    Visual Impairment/Intracranial Pressure (VIIP) is a newly recognized risk at NASA. The VIIP project examines the effect of long-term exposure to microgravity on vision of crewmembers before and after they return to Earth. Diamox (acetazolamide) is a medication which is used to decrease intraocular pressure; however, it carries a 3% risk of kidney stones. Astronauts are at a higher risk of kidney stones during spaceflight and the use Diamox would only increase the risk; therefore alternative therapies were investigated. Histamine 2 (H2) antagonist acid blockers such as cimetidine, ranitidine, famotidine and nizatidine are typically used to relieve the symptoms of gastroesophageal reflux disease (GERD). H2 receptors have been found in the human visual system, which has led to research on the use of H2 antagonist blockers to control fluid production in the human eye. Another potential therapeutic strategy is targeted at aquaporins, which are water channels that help maintain fluid homeostasis. Aquaporin antagonists are also known to affect intracranial pressure which can in turn alter intraocular pressure. Studies on aquaporin antagonists suggest high potential for effective treatment. The primary objective of this investigation is to review existing research on alternate medications or therapy to significantly reduce intracranial and intraocular pressure. A literature review was conducted. Even though we do not have all the answers quite yet, a considerable amount of information was discovered, and findings were narrowed, which should allow for more conclusive answers to be found in the near future.

  20. Rocket based combined cycle (RBCC) propulsion systems offer additional options

    NASA Astrophysics Data System (ADS)

    Czysz, Paul A.

    The propulsion cycles presented at the 1991 IAF Congress in Montreal, and at The World Hydrogen Conference 1992 in Paris were the subject of an IAF paper for the 1992 World Space Conference in Washington DC. RBCC propulsion systems from several nations were analyzed in terms of a SSTO space launcher with a 7-Mg payload. The RBCC concept emerged from the advanced injector ramjet research of the early 1960s. The performance of the current RBCC propulsion systems such that the specific thrust of a rocket is combined with the specific impulse of an airbreather. This performance offers a new perspective to the options available. In a brief review of the present RBCC the reasons for these options are developed. The spectrum of the system options is presented in three examples, a LACE VTOL SSTO, an HTOL SSTO and a HTOL TSTO. Results using the present RBCC are dramatically different from the past concept of the Conventional Combined Cycle propulsion system, i.e., combinations of separate engines. The integration of the engine cycles into a single thermodynamically integrated system significantly changes the propulsion performance.

  1. Endovascular Therapeutic Options for Isolated Iliac Aneurysms with a Working Classification

    SciTech Connect

    Fahrni, Markus; Lachat, Mario M; Wildermuth, Simon; Pfammatter, Thomas

    2003-09-15

    The purpose of this paper is to demonstrate a variety of stent-grafting and embolization techniques and describe a new classification for endovascular treatment of isolated iliac artery aneurysms. A total of 19 patients were treated for isolated iliac aneurysms. Depending on the proximal iliac neck and the uni-/bilaterality of common iliac artery aneurysms (CIAA's) the patient may be treated by a tube (Type Ia) or a bifurcated stent-graft (Type Ib) in addition to internal iliac artery embolization. Neck anatomy is also critical in determining therapeutical options for internal iliac artery aneurysms (IIAA's). These are tube stent-grafting plus internal iliac branch embolization (Type IIa), coiling of afferent and efferent internal iliac vessels (Type IIb) and IIAA packing (Type IIc). The average length of stay for these procedures was 3.8 days. During the mean follow-up of 20.9 months, aneurysm size remained unchanged in all but 4 patients. Reinterventions were necessary in option Type Ib (3/8 pat.) and Type Ia (1/7 pat.) due to extender stent-graft migration (n = 2) or reperfusion leaks (n 2). We conclude that Iliac artery aneurysms may be successfully and safely treated by a tailored approach using embolization or a combination of embolization and stent-grafting. Long-term CT imaging follow-up is necessary, particularly in patients treated with bifurcated stent-grafts (Type Ib)

  2. Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options.

    PubMed

    Iglesias, Pedro; Carrero, Juan J; Díez, Juan J

    2012-01-01

    Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men. Although there are encouraging data suggesting plausible benefits from testosterone replacement therapy, further studies are needed with regards to safety and effectiveness of this therapy. PMID:21748720

  3. Electrical Storms in Brugada Syndrome: Review of Pharmacologic and Ablative Therapeutic Options

    PubMed Central

    P, Maury; M, Hocini; M, Haïssaguerre

    2005-01-01

    Electrical storm occurring in a patient with the Brugada syndrome is an exceptional but malignant and potentially lethal event. Efficient therapeutic solutions should be known and urgently applied because of the inability of usual antiarrhythmic means in preventing multiple recurrences of ventricular arrhythmias. Isoproterenol should be immediately infused while oral quinidine should be further administrated when isoproterenol is not effective. In case of failure of these therapeutic options, ablation of the triggering ventricular ectopies should be attempted. PMID:16943940

  4. Lysosomal storage disorders: emerging therapeutic options require early diagnosis.

    PubMed

    Meikle, Peter J; Hopwood, John J

    2003-12-01

    Lysosomal storage disorders have been recognised as one of the major groups of genetic disorders affecting children and adults. With over 40 different disorders and a combined prevalence of up to 1:5000 births, this group of disorders is a major public health problem and places an enormous burden on the individuals and families affected. Since the introduction of enzyme replacement therapy for Gaucher disease over 10 years ago there has been considerable progress in the development of enzyme based therapies for other disorders, in addition to alternate therapies including substrate deprivation and gene based therapies. Early diagnosis of these disorders before the onset of irreversible pathologies will lead to better outcomes for current and proposed therapies. In this review we describe the strategies and technology being used for the development of newborn screening for lysosomal storage disorders and discuss the future requirements for the early diagnosis and effective therapy of this group of disorders. PMID:14610674

  5. Transcatheter device closure of pseudoaneurysms of the left ventricular wall: An emerging therapeutic option.

    PubMed

    Madan, Tarun; Juneja, Manish; Raval, Abhishek; Thakkar, Bhavesh

    2016-02-01

    Left ventricular pseudoaneurysm is a rare but serious complication of acute myocardial infarction and cardiac surgery. While surgical intervention is the conventional therapeutic option, transcatheter closure can be considered in selected patients with suitable morphology of the pseudoaneurysm. We report a case of successful transcatheter closure of a left ventricular pseudoaneurysm orifice and isolation of the sac using an Amplatzer septal occluder. PMID:26852302

  6. ICORE: Image Co-addition with Optional Resolution Enhancement

    NASA Astrophysics Data System (ADS)

    Masci, Frank

    2013-02-01

    ICORE is a command-line driven co-addition, mosaicking, and resolution enhancement (HiRes) tool for creating science quality products from image data in FITS format and with World Coordinate System information following the FITS-WCS standard. It includes preparatory steps such as image background matching, photometric gain-matching, and pixel-outlier rejection. Co-addition and/or HiRes'ing can be performed in either the inertial WCS or in the rest frame of a moving object. Three interpolation methods are supported: overlap-area weighting, drizzle, and weighting by the detector Point Response Function (PRF). The latter enables the creation of matched-filtered products for optimal point-source detection, but most importantly allows for resolution enhancement using a spatially-dependent deconvolution method. This is a variant of the classic Richardson-Lucy algorithm with the added benefit to simultaneously register and co-add multiple images to optimize signal-to-noise and sampling of the instrumental PSF. It can assume real (or otherwise "flat") image priors, mitigate "ringing" artifacts, and assess the quality of image solutions using statistically-motivated convergence criteria. Uncertainties are also estimated and internally validated for all products. The software supports multithreading that can be configured for different architectures. Numerous example scripts are included (with test data) to co-add and/or HiRes image data from Spitzer-IRAC/MIPS, WISE, and Herschel-SPIRE.

  7. Acute respiratory distress syndrome: new definition, current and future therapeutic options

    PubMed Central

    Vlachou, Aikaterini; Ghannadian, Shirin; Simonetti, Umberto; Slutsky, Arthur S.; Zhang, Haibo

    2013-01-01

    Since acute respiratory distress syndrome (ARDS) was first described in 1967 there has been large number of studies addressing its pathogenesis and therapies. Despite this intense research activity, there are very few effective therapies for ARDS other than the use of lung protection strategies. This lack of therapeutic modalities is not only related to the complex pathogenesis of this syndrome but also the insensitive and nonspecific diagnostic criteria to diagnose ARDS. This review article will summarize the key features of the new definition of ARDS, and provide a brief overview of innovative therapeutic options that are being assessed in the management of ARDS. PMID:23825769

  8. [Inner Ear Hearing Loss Part II: Sudden Sensorineural Hearing Loss, Therapeutic Options].

    PubMed

    Hesse, Gerhard

    2016-07-01

    The great majority of hearing disorders generates from pathologies in the inner ear, mainly the outer hair cells, as mentioned in the first part of this review. Very often, however, hearing loss appears suddenly and even without external causes like noise exposure. This sudden hearing loss is mostly unilateral, recovers very often spontaneously and should be treated, if persisting. Only in this acute stage there are therapeutic options available. If the inner ear hearing loss is chronic there is no curative therapy, an effective management of the hearing disorder is only possible through rehabilitation. This is due to the fact, that hair cells of all mammals, incl. humans, have no regenerative capacity and neither pharmaceutic agents nor other means can induce regeneration and recovery of hair cells. Even a gen-therapy is not available yet. In the second part of this review the main focus lies in sudden hearing loss and general therapeutic options for inner ear hearing loss. PMID:27392187

  9. Herbal Medicine Offered as an Initiative Therapeutic Option for the Management of Hepatocellular Carcinoma.

    PubMed

    Chen, Shao-Ru; Qiu, Hong-Cong; Hu, Yang; Wang, Ying; Wang, Yi-Tao

    2016-06-01

    Hepatocellular carcinoma (HCC) is a common malignant cancer and is the third leading cause of death worldwide. Effective treatment of this disease is limited by the complicated molecular mechanism underlying HCC pathogenesis. Thus, therapeutic options for HCC management are urgently needed. Targeting the Wnt/β-catenin, Hedgehog, Notch, and Hippo-YAP signaling pathways in cancer stem cell development has been extensively investigated as an alternative treatment. Herbal medicine has emerged as an initiative therapeutic option for HCC management because of its multi-level, multi-target, and coordinated intervention effects. In this article, we summarized the recent progress and clinical benefits of targeting the above mentioned signaling pathways and using natural products such as herbal medicine formulas to treat HCC. Proving the clinical success of herbal medicine is expected to deepen the knowledge on herbal medicine efficiency and hasten the adoption of new therapies. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26879574

  10. Ocular Manifestations and Therapeutic Options in Patients with Familial Amyloid Polyneuropathy: A Systematic Review

    PubMed Central

    Martins, A. C.; Rosa, A. M.; Costa, E.; Tavares, C.; Quadrado, M. J.; Murta, J. N.

    2015-01-01

    Purpose. This paper aims to review the morphological and functional characteristics of patients affected by familial amyloid polyneuropathy (FAP), with greater focus on type I and its progression after liver transplantation. We also analyse therapeutic options for the ophthalmic manifestations. Methods. The literature from 2002 through 2015 was reviewed, with a total of 45 articles studied, using the key terms related to amyloidosis and its therapeutic approaches. Information was collated, evaluated, critically assessed, and then summarised in its present form. Pathophysiology and Treatment. FAP results from mutation of the transthyretin gene, with Val30Met being the most frequent substitution. The symptoms are those typical of a sensorimotor autonomic neuropathy and can be halted with liver transplantation. Nowadays there are new medical therapies that delay the progression of the systemic neuropathy. However, there are still no options to avoid ocular disease. Conclusion. The main ocular manifestations in patients with FAP type I are amyloid deposition in the vitreous, dry eye, and secondary glaucoma. Despite liver transplantation, eye synthesis of amyloid persists and is associated with progressive ocular manifestations, which require continued ophthalmologic follow-up. New therapeutic strategies are therefore needed, particularly to target the ocular synthesis of the abnormal protein. PMID:26558262

  11. Therapeutic options in pediatric non alcoholic fatty liver disease: current status and future directions

    PubMed Central

    2012-01-01

    The epidemics of overweight and obesity has resulted in a significant increase of non alcoholic fatty liver disease (NAFLD), a potentially progressive condition. Currently, obesity related hepatopathy represents therefore the main cause of pediatric chronic liver disease. The first choice treatment at all ages is weight loss and/or lifestyle changes, however compliance is very poor and a pharmacological approach has become necessary. In the present article we present a systematic literature review focusing on established pediatric NALFD drugs (ursodeoxycholic acid, insulin sensitizers, and antioxidants) and on innovative therapeutic options as well. Regarding the former ones, a pediatric pilot study highlighted that ursodeoxycholic acid is not efficient on transaminases levels and bright liver. Similarly, a recent large scale, multicenter randomized clinical trial (TONIC study) showed that also insulin sensitizers and antioxidant vitamin E have scarce effects on serum transaminase levels. Among a large series of novel therapeutic approaches acting on recently proposed different pathomechanisms, probiotics seem hitherto the most interesting and reasonable option for their safety and tolerability. Toll-like receptors modifiers, Pentoxifylline, and Farnesoid X receptors agonists have been still poorly investigated, and will need further studies before becoming possible promising innovative therapeutic strategies. PMID:23075296

  12. Novel therapeutic options for second-line therapy in metastatic renal cell carcinoma

    PubMed Central

    VON KLOT, CHRISTOPH-A. J.; MERSEBURGER, AXEL S.; KUCZYK, MARKUS A.

    2016-01-01

    Metastatic renal cell carcinoma (mRCC) has gained a variety of therapeutic options since the introduction of targeted therapy, starting in 2007. The basic molecular mechanisms included predominantly the targeting of vascular endothelial growth factor or the inhibition of the mammalian target of rapamycin. Recently, results from two randomized controlled trials, the CheckMate-25 and the METEOR trial, regarding therapy for RCC in the second-line setting have been published. In the present review, the current status of second-line therapy in mRCC is discussed, together with results from the two newly introduced substances, nivolumab and cabozantinib. PMID:27313856

  13. Current and emerging therapeutic options for the treatment of chronic chagasic cardiomyopathy

    PubMed Central

    Muratore, Claudio A; Baranchuk, Adrian

    2010-01-01

    Chagas’ disease is an endemic disease in Latin America caused by a unicellular parasite (Trypanosoma cruzi) that affects almost 18 million people. This condition involves the heart, causing heart failure, arrhythmias, heart block, thromboembolism, stroke, and sudden death. In this article, we review the current and emerging treatment of Chagas’ cardiomyopathy focusing mostly on management of heart failure and arrhythmias. Heart failure therapeutical options including drugs, stem cells and heart transplantation are revised. Antiarrhythmic drugs, catheter ablation, and intracardiac devices are discussed as well. Finally, the evidence for a potential role of specific antiparasitic treatment for the prevention of cardiovascular disease is reviewed. PMID:20730015

  14. Addition of flexible body option to the TOLA computer program, part 1

    NASA Technical Reports Server (NTRS)

    Dick, J. W.; Benda, B. J.

    1975-01-01

    This report describes a flexible body option that was developed and added to the Takeoff and Landing Analysis (TOLA) computer program. The addition of the flexible body option to TOLA allows it to be used to study essentially any conventional type airplane in the ground operating environment. It provides the capability to predict the total motion of selected points on the analytical methods incorporated in the program and operating instructions for the option are described. A program listing is included along with several example problems to aid in interpretation of the operating instructions and to illustrate program usage.

  15. New therapeutic option for irritable bowel syndrome: Serum-derived bovine immunoglobulin

    PubMed Central

    Good, Larry; Rosario, Roxanne; Panas, Raymond

    2015-01-01

    Oral prescription medical foods have long been used in hospital settings but are also appropriate therapies for gastrointestinal disorders in outpatient medical practice. Oral serum-derived bovine immunoglobulin/protein isolate (SBI) has been shown in clinical studies to reduce loose stools and improve stool consistency as well as other symptoms (i.e., abdominal pain, bloating, and urgency) in patients with irritable bowel syndrome with diarrhea (IBS-D) and human immunodeficiency virus-associated enteropathy. This case series reports the outcomes of 14 IBS patients who received SBI as an addition to standard of care at an individual physician’s clinical practice. The patients: 2 IBS with constipation (IBS-C), 7 IBS-D, 2 mixed diarrhea and constipation IBS (IBS-M) and 3 undefined IBS (IBS-U; also described by some physicians as IBS-Bloating), ranged in age from 22-87 years. SBI (5 g or 10 g daily dose) was added to the patient’s current standard care and followed for several weeks to determine if symptoms were improved with the addition of SBI. Overall, 12 of the 14 patients indicated some level of improvement through direct questioning of the patients regarding changes from the prior visit. One IBS-Bloating patient had a resolution of symptoms and two patients (1 IBS-Bloating and 1 IBS-C) discontinued therapy because of insufficient relief. The 12 patients who continued on therapy reported an overall improvement in symptoms with better stool consistency, decreased frequency as well as reductions in abdominal pain, bloating, distention, and incontinence. In most cases, therapeutic effects of SBI were seen within the first four weeks of therapy with continued improvements at subsequent visits. SBI has a multifaceted mechanism of action and may help to manage IBS by providing a distinct protein source required to normalize bowel function, gastrointestinal microbiota, and nutritionally enhance tight junction protein expression between intestinal epithelial cells

  16. New therapeutic option for irritable bowel syndrome: serum-derived bovine immunoglobulin.

    PubMed

    Good, Larry; Rosario, Roxanne; Panas, Raymond

    2015-03-21

    Oral prescription medical foods have long been used in hospital settings but are also appropriate therapies for gastrointestinal disorders in outpatient medical practice. Oral serum-derived bovine immunoglobulin/protein isolate (SBI) has been shown in clinical studies to reduce loose stools and improve stool consistency as well as other symptoms (i.e., abdominal pain, bloating, and urgency) in patients with irritable bowel syndrome with diarrhea (IBS-D) and human immunodeficiency virus-associated enteropathy. This case series reports the outcomes of 14 IBS patients who received SBI as an addition to standard of care at an individual physician's clinical practice. The patients: 2 IBS with constipation (IBS-C), 7 IBS-D, 2 mixed diarrhea and constipation IBS (IBS-M) and 3 undefined IBS (IBS-U; also described by some physicians as IBS-Bloating), ranged in age from 22-87 years. SBI (5 g or 10 g daily dose) was added to the patient's current standard care and followed for several weeks to determine if symptoms were improved with the addition of SBI. Overall, 12 of the 14 patients indicated some level of improvement through direct questioning of the patients regarding changes from the prior visit. One IBS-Bloating patient had a resolution of symptoms and two patients (1 IBS-Bloating and 1 IBS-C) discontinued therapy because of insufficient relief. The 12 patients who continued on therapy reported an overall improvement in symptoms with better stool consistency, decreased frequency as well as reductions in abdominal pain, bloating, distention, and incontinence. In most cases, therapeutic effects of SBI were seen within the first four weeks of therapy with continued improvements at subsequent visits. SBI has a multifaceted mechanism of action and may help to manage IBS by providing a distinct protein source required to normalize bowel function, gastrointestinal microbiota, and nutritionally enhance tight junction protein expression between intestinal epithelial cells. SBI

  17. Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer: how the latest results are improving therapeutic options

    PubMed Central

    Jiang, Hanfang; Rugo, Hope S.

    2015-01-01

    Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (MBC) remains an incurable disease, and approximately 25% of patients with HER2+ early breast cancer still relapse after adjuvant trastuzumab-based treatment. HER2 is a validated therapeutic target that remains relevant throughout the disease process. Recently, a number of novel HER2 targeted agents have become available, including lapatinib (a small molecule tyrosine kinase inhibitor of both HER2 and the epidermal growth factor receptor), pertuzumab (a new anti-HER2 monoclonal antibody) and ado-trastuzumab emtansine (T-DM1, a novel antibody–drug conjugate), which provide additional treatment options for patients with HER2+ MBC. The latest clinical trials have demonstrated improved outcome with treatment including pertuzumab or T-DM1 compared with standard HER2 targeted therapy. Here we review the clinical development of approved and investigational targeted agents for the treatment of HER2+ MBC, summarize the latest results of important clinical trials supporting use of these agents in the treatment of HER2+ MBC, and discuss how these results impact therapeutic options in clinical practice. PMID:26557900

  18. 24 CFR 982.629 - Homeownership option: Additional PHA requirements for family search and purchase.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Homeownership option: Additional PHA requirements for family search and purchase. 982.629 Section 982.629 Housing and Urban Development...: Additional PHA requirements for family search and purchase. (a) The PHA may establish the maximum time for...

  19. 24 CFR 982.629 - Homeownership option: Additional PHA requirements for family search and purchase.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Homeownership option: Additional PHA requirements for family search and purchase. 982.629 Section 982.629 Housing and Urban Development...: Additional PHA requirements for family search and purchase. (a) The PHA may establish the maximum time for...

  20. 24 CFR 982.629 - Homeownership option: Additional PHA requirements for family search and purchase.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Homeownership option: Additional PHA requirements for family search and purchase. 982.629 Section 982.629 Housing and Urban Development...: Additional PHA requirements for family search and purchase. (a) The PHA may establish the maximum time for...

  1. 24 CFR 982.629 - Homeownership option: Additional PHA requirements for family search and purchase.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Homeownership option: Additional PHA requirements for family search and purchase. 982.629 Section 982.629 Housing and Urban Development...: Additional PHA requirements for family search and purchase. (a) The PHA may establish the maximum time for...

  2. 24 CFR 982.629 - Homeownership option: Additional PHA requirements for family search and purchase.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Homeownership option: Additional PHA requirements for family search and purchase. 982.629 Section 982.629 Housing and Urban Development...: Additional PHA requirements for family search and purchase. (a) The PHA may establish the maximum time for...

  3. Endometriosis: Survey of Current Diagnostic and Therapeutic Options and Latest Research Work

    PubMed Central

    Juhasz-Böss, I.; Laschke, M. W.; Müller, F.; Rosenbaum, P.; Baum, S.; Solomayer, E. F.; Ulrich, U.

    2014-01-01

    Endometriosis is one of the most frequent benign diseases in women of child-bearing age. The main symptoms are chronic upper abdominal pain and infertility. However, the aetiology and pathogenesis of endometriosis are as yet insufficiently clarified. Thus, therapy is mainly symptomatic with laparoscopic surgery being the gold standard. The aim of drug therapy is to achieve a hypo-oestrogenic condition. In cases of severe endometriosis and a desire to have children there is often an indication for assisted reproduction. The present article illustrates almost all current aspects on the diagnosis of and therapy of endometriosis. From the clinical viewpoint, emphasis is placed on the rare cases of deeply infiltrating endometriosis that are, however, accompanied with a high morbidity. Current therapeutic options in cases of infertility are also presented in more detail. Furthermore, special attention is paid to the latest research results from both clinical and basic research fields in order to demonstrate our current knowledge on the pathogenesis and, where possible, potentially related therapeutic options. PMID:25221341

  4. Coronary Sinus Reducer system™: A new therapeutic option in refractory angina patients unsuitable for revascularization.

    PubMed

    Ielasi, Alfonso; Todaro, Maria Chiara; Grigis, Giulietta; Tespili, Maurizio

    2016-04-15

    A challenge of modern cardiovascular medicine is to find new, effective treatments for patients with refractory angina pectoris (RAP), a clinical condition characterized by severe angina despite optimal medical therapy and "no option" for a surgical or percutaneous revascularization. Although the relevant advance of both pharmaceutical and interventional treatments for patients affected by symptomatic coronary artery disease has greatly contributed to prolong survival, the increasing number of patients experimenting persistent and invalidating angina symptoms, highlights that quality of life of these patients has not been equally improved. Clinical limitations of the efficiency of conventional and relatively new approaches justify the search for new therapeutic options. In this review, we will focus on the epidemiology of RAP, and we will provide a brief update on the different options actually available to these patients with particular interest to an innovative device that narrow the coronary sinus: the Reducer system (Neovasc Inc., Richmond B.C., Canada). The efforts of present and future clinical studies will ultimately answer the question of whether this intriguing therapy is a suitable strategy for treatment of patients with RAP. PMID:26889595

  5. Natural Nuclear Factor Kappa Beta Inhibitors: Safe Therapeutic Options for Inflammatory Bowel Disease.

    PubMed

    Tambuwala, Murtaza M

    2016-03-01

    Inflammatory bowel disease (IBD) is a chronic and debilitating condition classified as ulcerative colitis and Crohn's disease. IBD usually happens as result of immune dysfunction in the intestinal mucosa resulting in epithelial barrier dysfunction, which leads to exposure of the mucosal immune system to luminal antigenic material. This results in activation of inflammation, which is our bodies natural defense system; however, chronic inflammation leads to barrier dysfunction, which triggers a cycle of inflammation and further barrier dysfunction. This barrier breakdown results in the uncontrolled progression of IBD throughout the intestine. Despite the therapeutic advances made over the last decade, the current first line of treatment of IBD is limited to immunosuppressive and anti-inflammatory drugs, which need to be taken regularly and have significant side effects to the patients. Prolonged inflammation may increase the risk of intestinal malignancy. The role of nuclear factor kappa beta (NF-κβ) has been established in the regulation of innate immunity and inflammation. NF-κβ has also shown to be involved in critical events linking inflammation and cancer development. Recent investigations suggest that the NF-κβ signaling cascade may be the central mediator of gastrointestinal inflammation in IBD and malignancies including esophageal, gastric, and colorectal cancers. In this review, the therapeutic potential of natural NF-κβ inhibitors as safe therapeutic options for the treatment of IBD will be discussed. PMID:26717321

  6. A new therapeutic option for postoperative pain management with oxycodone HCI injection

    PubMed Central

    2016-01-01

    Fentanyl is the most commonly used opioid analgesic in intravenous patient-controlled analgesia (IV PCA) in Korea. IV oxycodone was approved for postoperative IV PCA by the Ministry of Food and Drug Safety of Korea in 2013. The approved dosage regimen for postoperative pain relief with IV oxycodone is IV bolus loading of 2 mg followed by PCA composed of demand boluses of 1 mg and no background infusion with an oxycodone concentration of 1 mg/ml. However, a simulation study indicated that the minimum effective analgesic concentration (MEAC, as indicated by relief of pain by administering rescue analgesics) of oxycodone was reached most quickly with a higher loading dose of 0.1 mg/kg and IV PCA with background infusion. Oxycodone is a therapeutic option as an analgesic for postoperative pain management. It is necessary to reduce the analgesic dose of oxycodone in elderly patients because metabolic clearance decreases with age. PMID:27274364

  7. Antihypertensive therapy versus alternative therapeutic options for prehypertension: an evidence-based approach.

    PubMed

    Gaddam, Krishna K; Ventura, Hector; Lavie, Carl J

    2012-01-01

    The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) defines hypertension as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg. The JNC-7 defines 'prehypertension' to include systolic BP values between 120 and 139 mmHg and diastolic BP values between 80 and 89 mmHg. Individuals with blood pressure in the prehypertension range are clearly at increased risk of developing hypertension in the future and have an increased risk of cardiovascular morbidity and mortality, compared with those with normal BP. However, there is paucity of evidence to intervene in these patients. In this article we discuss an evidence-based approach to therapeutic options in patients with prehypertension. PMID:22185450

  8. A new therapeutic option for postoperative pain management with oxycodone HCI injection.

    PubMed

    Choi, Byung Moon

    2016-06-01

    Fentanyl is the most commonly used opioid analgesic in intravenous patient-controlled analgesia (IV PCA) in Korea. IV oxycodone was approved for postoperative IV PCA by the Ministry of Food and Drug Safety of Korea in 2013. The approved dosage regimen for postoperative pain relief with IV oxycodone is IV bolus loading of 2 mg followed by PCA composed of demand boluses of 1 mg and no background infusion with an oxycodone concentration of 1 mg/ml. However, a simulation study indicated that the minimum effective analgesic concentration (MEAC, as indicated by relief of pain by administering rescue analgesics) of oxycodone was reached most quickly with a higher loading dose of 0.1 mg/kg and IV PCA with background infusion. Oxycodone is a therapeutic option as an analgesic for postoperative pain management. It is necessary to reduce the analgesic dose of oxycodone in elderly patients because metabolic clearance decreases with age. PMID:27274364

  9. Therapeutic options for old world cutaneous leishmaniasis and new world cutaneous and mucocutaneous leishmaniasis.

    PubMed

    Monge-Maillo, Begoña; López-Vélez, Rogelio

    2013-11-01

    Estimated worldwide incidence of tegumentary leishmaniasis (cutaneous leishmaniasis [CL] and mucocutaneous leishmaniasis [MCL]) is over 1.5 million cases per year in 82 countries, with 90 % of cases occurring in Afghanistan, Brazil, Iran, Peru, Saudi Arabia and Syria. Current treatments of CL are poorly justified and have sub-optimal effectiveness. Treatment can be based on topical or systemic regimens. These different options must be based on Leishmania species, geographic regions, and clinical presentations. In certain cases of Old World CL (OWCL), lesions can spontaneously heal without any need for therapeutic intervention. Local therapies (thermotherapy, cryotherapy, paromomycin ointment, local infiltration with antimonials) are good options with less systemic toxicity, reserving systemic treatments (azole drugs, miltefosine, antimonials, amphotericin B formulations) mainly for complex cases. The majority of New World CL (NWCL) types require systemic treatment (mainly with pentavalent antimonials), either to speed the healing or to prevent dissemination to oral-nasal mucosa as MCL (NWMCL). These types of lesions are potentially serious and always require systemic-based regimens, mainly antimonials and pentamidine; however, the associated immunotherapy is promising. This paper is an exhaustive review of the published literature on the treatment of OWCL, NWCL and NWMCL, and provides treatment recommendations stratified according to their level of evidence regarding the species of Leishmania implicated and the geographical location of the infection. PMID:24170665

  10. Cystosarcoma phylloides of the breast: a review of clinical, pathological and therapeutic option in 18 cases.

    PubMed

    Sheen-Chen, S M; Chou, F F; Chen, W J

    1991-01-01

    The clinical and pathological findings and therapeutic options in 18 patients with cystosarcoma phylloides were retrospectively studied and analysed. Painless breast lump was the most common clinical penetration. An accurate pre-operative diagnosis was obtained in only six patients (33.3%). Intraoperative frozen section examination was performed in nine patients and the diagnosis was cystosarcoma phylloides in five patients, benign breast tumor in four patients with a 55.5% yield. The final pathological results revealed benign form cystosarcoma phylloides in 17 patients and malignant form in one patient. Seven patients, including the one with malignant form tumor, underwent wide excision with an adequate margin of normal breast tissue. One patient underwent subcutaneous mastectomy due to the huge size of tumor. The remaining 11 patients with presumed diagnosis of fibroadenoma or breast cancer underwent simple excision. There was no local recurrence or distant metastasis in any of the 18 patients, with a mean follow-up time of 31.5 months. On the basis of this data, wide excision with an adequate margin of normal breast tissue may be the preferred initial therapy for cystosarcoma phylloides. For those patients undergoing simple excision, the follow-up option may be acceptable if microscopic examination reveals no unrecognised amputation of tumor. PMID:1651293

  11. Technical options for processing additional light tight oil volumes within the United States

    EIA Publications

    2015-01-01

    This report examines technical options for processing additional LTO volumes within the United States. Domestic processing of additional LTO would enable an increase in petroleum product exports from the United States, already the world’s largest net exporter of petroleum products. Unlike crude oil, products are not subject to export limitations or licensing requirements. While this is one possible approach to absorbing higher domestic LTO production in the absence of a relaxation of current limitations on crude exports, domestic LTO would have to be priced at a level required to encourage additional LTO runs at existing refinery units, debottlenecking, or possible additions of processing capacity.

  12. The nitric oxide pathway and possible therapeutic options in pre-eclampsia

    PubMed Central

    Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

    2014-01-01

    Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide–soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3′,5′-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. PMID:24313856

  13. Evolving concepts of liver fibrogenesis provide new diagnostic and therapeutic options

    PubMed Central

    Gressner, Olav A; Weiskirchen, Ralf; Gressner, Axel M

    2007-01-01

    Despite intensive studies, the clinical opportunities for patients with fibrosing liver diseases have not improved. This will be changed by increasing knowledge of new pathogenetic mechanisms, which complement the "canonical principle" of fibrogenesis. The latter is based on the activation of hepatic stellate cells and their transdifferentiation to myofibroblasts induced by hepatocellular injury and consecutive inflammatory mediators such as TGF-β. Stellate cells express a broad spectrum of matrix components. New mechanisms indicate that the heterogeneous pool of (myo-)fibroblasts can be supplemented by epithelial-mesenchymal transition (EMT) from cholangiocytes and potentially also from hepatocytes to fibroblasts, by influx of bone marrow-derived fibrocytes in the damaged liver tissue and by differentiation of a subgroup of monocytes to fibroblasts after homing in the damaged tissue. These processes are regulated by the cytokines TGF-β and BMP-7, chemokines, colony-stimulating factors, metalloproteinases and numerous trapping proteins. They offer innovative diagnostic and therapeutic options. As an example, modulation of TGF-β/BMP-7 ratio changes the rate of EMT, and so the simultaneous determination of these parameters and of connective tissue growth factor (CTGF) in serum might provide information on fibrogenic activity. The extension of pathogenetic concepts of fibrosis will provide new therapeutic possibilities of interference with the fibrogenic mechanism in liver and other organs. PMID:17663771

  14. [PCSK9 - "missing link" in familial hypercholesterolemia : New therapeutic options in hypercholesterolemia and coronary artery disease].

    PubMed

    Thiery, J; Burkhardt, R

    2016-06-01

    Lowering plasma low-density lipoprotein cholesterol (LDL-C) levels to individual therapeutic goals is one of the most effective measures for the prevention of cardiovascular disease. Besides dietary measures, this can be achieved pharmaceutically by inhibition of hepatic cholesterol synthesis with statins or inhibition of intestinal cholesterol absorption (e.g., ezetimibe and bile acid sequestrants). Decisive for lowering LDL is an increased hepatic uptake of circulating LDL via an increase in LDL receptors (LDLR) in hepatic cell membranes. The formation of new LDLR and recirculation of existing LDLR play a decisive role in this process. An important modulator of LDLR is proprotein convertase subtilisin/kexin type 9 (PCSK9). In the last years genetic studies have identified several mutations in the PCSK9 gene leading to a gain of function and carriers of these mutations suffer from autosomal dominant hypercholesterolemia. In contrast, carriers of PCSK9 loss of function mutations show very low plasma LDL-C concentrations and a markedly reduced risk for coronary artery disease. These fundamental discoveries have sparked the development of a completely novel therapeutic approach to treating hypercholesterolemia. At present, inhibition of PCSK9 by monoclonal antibodies presents the most promising therapeutic approach. First human antibodies were recently approved as the first immunotherapeutic agents for the treatment of severe hypercholesterolemia and in patients with statin intolerance. An additional PCSK9 antibody is presently being studied in phase III clinical trials. PMID:27215417

  15. Beyond first-line chemotherapy for advanced pancreatic cancer: An expanding array of therapeutic options?

    PubMed Central

    Walker, Evan J; Ko, Andrew H

    2014-01-01

    While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer, the optimal choice for treatment in the second-line setting and beyond is less well defined. A variety of cytotoxic agents, either alone or in combination, have been evaluated, although primarily in the context of small single-arm or retrospective studies. Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8 mo, highlighting the very poor prognosis of patients who are candidates for such treatment. Targeted therapies studied in this chemotherapy-refractory setting, meanwhile, have produced even worse efficacy results. In the current article, we review the clinical evidence for treatment of refractory disease, primarily in patients who have progressed on front-line gemcitabine-based chemotherapy. In the process, we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting, including how to select an appropriate control arm given the absence of a well-established reference standard, and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design. PMID:24605022

  16. Surgical strategies and modern therapeutic options in the treatment of craniopharyngiomas.

    PubMed

    Mortini, Pietro; Gagliardi, Filippo; Boari, Nicola; Losa, Marco

    2013-12-01

    The optimal treatment of patients with craniopharyngioma remains controversial. In particular, the role of aggressive treatment compared to less aggressive therapeutic options is poorly understood. Radical resection is the therapy of choice at any age, because it is associated with the best outcome in terms of survival. Nevertheless, aggressive behaviour, location, involvement of critical structures, tumour size, calcifications, and patient age may limit the extent of resection. Surgery can also carry significant morbidity in terms of visual, hypothalamic, and endocrinological disturbances. Long term sequelae reduce the quality of life in 50% of long-term survivors, notably obesity and neurobehavioral impairment due to hypthalamic involvement and iatrogenic induced lesions. The quality of life should be considered as a clinically important endpoint in patients, who currently experience good overall survival rates, regardless of the degree of surgical resection. Tendency to recur despite negative postoperative imaging led many authors to advocate a less aggressive surgical treatment followed by radiation therapy. We review the data reported in the literature, especially early outcome after surgical treatment and factors affecting the risk of tumour recurrence, to elucidate the role of attempted radical resection in the treatment of craniopharyngioma and to identify the clinical and morphological characteristics predictive for the best surgical prognosis. PMID:23932582

  17. Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks.

    PubMed

    Haque, Azizul; Hober, Didier; Blondiaux, Joel

    2015-10-01

    Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients. PMID:26248374

  18. Nitroglycerin patch for the treatment of chondrodermatitis nodularis helicis: a new therapeutic option.

    PubMed

    Garrido Colmenero, Cristina; Martínez García, Eliseo; Blasco Morente, Gonzalo; Tercedor Sánchez, Jesús

    2014-01-01

    Chondrodermatitis nodularis helicis (CNH) is an inflammatory process that affects the skin and cartilage of the ear. At present, there are many treatment options, although they are not always effective. Based on previous studies where nitroglycerin 2% gel was used, we propose the use of nitroglycerin patches. The purpose of this study was to evaluate the effectiveness of nitroglycerin patches in treating CNH. We performed a prospective study in 11 patients diagnosed with CNH treated with nitroglycerin patches 5 mg, 12 hours a day for 2 months. The therapeutic effectivity was determined by the improvement in the appearance and symptoms of the lesion. Seven of 11 patients (63.6%) had a complete response. One of 11 patients (9%) did not respond completely and surgical treatment was performed. Two of 11 patients (18.1%) stopped the treatment because of headache. One of 11 patients (9%) did not complete the treatment because the said patient forgot to apply the patch every night. Transdermal nitroglycerin has demonstrated efficacy in the treatment of the symptoms and lesional appearance of CNH noninvasive manner. The success rate is comparable with other published methods and the rate of adverse effects is acceptable. PMID:24909052

  19. Influenza virus pathogenicity regulated by host cellular proteases, cytokines and metabolites, and its therapeutic options

    PubMed Central

    KIDO, Hiroshi

    2015-01-01

    Influenza A virus (IAV) causes significant morbidity and mortality. The knowledge gained within the last decade on the pandemic IAV(H1N1)2009 improved our understanding not only of the viral pathogenicity but also the host cellular factors involved in the pathogenicity of multiorgan failure (MOF), such as cellular trypsin-type hemagglutinin (HA0) processing proteases for viral multiplication, cytokine storm, metabolic disorders and energy crisis. The HA processing proteases in the airway and organs for all IAV known to date have been identified. Recently, a new concept on the pathogenicity of MOF, the “influenza virus–cytokine–trypsin” cycle, has been proposed involving up-regulation of trypsin through pro-inflammatory cytokines, and potentiation of viral multiplication in various organs. Furthermore, the relationship between causative factors has been summarized as the “influenza virus–cytokine–trypsin” cycle interconnected with the “metabolic disorders–cytokine” cycle. These cycles provide new treatment concepts for ATP crisis and MOF. This review discusses IAV pathogenicity on cellular proteases, cytokines, metabolites and therapeutic options. PMID:26460316

  20. Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks

    PubMed Central

    Hober, Didier; Blondiaux, Joel

    2015-01-01

    Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients. PMID:26248374

  1. Vogt-Koyanagi-Harada syndrome: Perspectives for immunogenetics, multimodal imaging, and therapeutic options.

    PubMed

    Silpa-Archa, Sukhum; Silpa-Archa, Narumol; Preble, Janine M; Foster, C Stephen

    2016-08-01

    Vogt-Koyanagi-Harada syndrome (VKH) is a bilateral, diffuse granulomatous uveitis associated with neurological, audiovestibular, and dermatological systems. The primary pathogenesis is T-cell-mediated autoimmune response directed towards melanocyte or melanocyte-associated antigens causing inflammation of the choroidal layer. This phenomenon usually leads to diffuse inflammatory conditions throughout most parts of eye before ocular complications ensue. The diagnosis is achieved mainly by clinical features according to the revised diagnostic criteria of VKH published in 2001, without confirmatory serologic tests as a requirement. However, ancillary tests, especially multimodal imaging, can reliably provide supportive evidence for the diagnosis of early cases, atypical presentations, and evaluation of management. Prompt treatment with systemic corticosteroids and early non-steroidal immunosuppressive drug therapy can lessen visually threatening ocular complications and bring about good visual recovery. Close monitoring warrants visual stabilization from disease recurrence and ocular complications. This article review aims not only to update comprehensive knowledge regarding VKH but also to emphasize three major perspectives of VKH: immunogenetics as the major pathogenesis of the disease, multimodal imaging, and therapeutic options. The role of anti-vascular endothelial growth factor therapy and drug-induced VKH is also provided. PMID:27060382

  2. The practicing physician's current perspective on therapeutic options in coronary artery disease

    PubMed Central

    Drenth, D.J.; Zijlstra, F.; Boonstra, P.W.

    2005-01-01

    Over the past decades the management of patients with stable as well as unstable manifestations of coronary artery disease has evolved in every aspect of routine clinical practice. Modern diagnostic modalities allow reliable and objective assessment of both the anatomical and functional consequences of the early as well as advanced stages of this disease, which remains one of the most important causes of morbidity and mortality worldwide. Pharmacological therapy now includes several classes of drugs with mortality benefits documented by randomised controlled trials. Surgical and percutaneous revascularisation techniques have shown rapid technical improvements and are now applicable in a wide range of clinical conditions. In this paper we will attempt to place the current status of the three therapeutic options for patients with coronary artery disease into perspective. It is important to realise that it is impossible to write a complete overview, a Pubmed search: 'PCI or drug therapy or surgery for coronary artery disease' results in 1,152,117 hits. Therefore, we have chosen the viewpoint of the practicing physician to synthesise this abundance of information in the context of modern clinical practice in a high volume cardiothoracic and cardiological practice. PMID:25696508

  3. Rectal cancer and Fournier’s gangrene - current knowledge and therapeutic options

    PubMed Central

    Bruketa, Tomislav; Majerovic, Matea; Augustin, Goran

    2015-01-01

    Fournier’s gangrene (FG) is a rapid progressive bacterial infection that involves the subcutaneous fascia and part of the deep fascia but spares the muscle in the scrotal, perianal and perineal region. The incidence has increased dramatically, while the reported incidence of rectal cancer-induced FG is unknown but is extremely low. Pathophysiology and clinical presentation of rectal cancer-induced FG per se does not differ from the other causes. Only rectal cancer-specific symptoms before presentation can lead to the diagnosis. The diagnosis of rectal cancer-induced FG should be excluded in every patient with blood on digital rectal examination, when urogenital and dermatological causes are excluded and when fever or sepsis of unknown origin is present with perianal symptomatology. Therapeutic options are more complex than for other forms of FG. First, the causative rectal tumor should be removed. The survival of patients with rectal cancer resection is reported as 100%, while with colostomy it is 80%. The preferred method of rectal resection has not been defined. Second, oncological treatment should be administered but the timing should be adjusted to the resolution of the FG and sometimes for the healing of plastic reconstructive procedures that are commonly needed for the reconstruction of large perineal, scrotal and lower abdominal wall defects. PMID:26290629

  4. Relapsed and refractory Hodgkin lymphoma: transplantation strategies and novel therapeutic options.

    PubMed

    David, Kevin A; Mauro, Lauren; Evens, Andrew M

    2007-10-01

    Many patients with Hodgkin lymphoma are cured with initial therapy, although a portion of patients will experience primary induction failure or disease relapse. Pathologic confirmation of refractory or relapsed Hodgkin lymphoma is important. Following two to four cycles of non-cross-resistant salvage chemotherapy, the standard of care is high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT), which is associated with long-term event-free survival rates of 45-68%. Of note, survival rates for studies integrating total lymphoid irradiation into the autologous HSCT-conditioning regimen are among the highest reported for relapsed/refractory Hodgkin lymphoma. Further treatment options are available for patients not fit to proceed to HSCT, for relapsed disease after autologous HSCT, and for 'high-risk' Hodgkin lymphoma including chemotherapy-resistant disease. Allogeneic HSCT is a valid treatment option, as a graft-vs.-Hodgkin-lymphoma effect has been demonstrated. In addition, novel targeted treatments are being investigated such as receptor-specific antibodies, radiolabeled antibodies, antiapoptotic agents including inhibitors of the nuclear factor-kappaB complex or X-linked inhibitor of apoptosis proteins, transcription pathway modulators such as histone deacetylase and mTOR inhibitors, and Epstein-Barr virus-directed therapy. Continued translational and collaborative prospective clinical research efforts are needed in order to continue to increase the survival rates for Hodgkin lymphoma and to lessen the toxicities associated with lymphoma-related therapy. PMID:18214690

  5. Therapeutic options for sleep-maintenance and sleep-onset insomnia.

    PubMed

    Morin, Anna K; Jarvis, Courtney I; Lynch, Ann M

    2007-01-01

    Insomnia, defined as difficulty falling asleep, staying asleep, and/or experiencing restorative sleep with associated impairment or significant distress, is a common condition resulting in significant clinical and economic consequences. Many options are available to treat insomnia, to assist with either falling asleep (sleep onset) or maintaining sleep. We searched MEDLINE for articles published between January 1996 and January 2006, evaluated abstracts from recent professional meetings, and contacted the manufacturer of the most recent addition to the pharmacologic armamentarium for insomnia treatment (ramelteon) to gather information. Nonpharmacologic options include stimulus control, sleep hygiene education, sleep restriction, paradoxical intention, relaxation therapy, biofeedback, and cognitive behavioral therapy. Prescription and over-the-counter drug therapies include benzodiazepine and nonbenzodiazepine sedative-hypnotic agents; ramelteon, a melatonin receptor agonist; trazodone; and sedating antihistamines. Herbal and alternative preparations include melatonin and valerian. Before recommending any treatment, clinicians should consider patient-specific criteria such as age, medical history, and other drug use, as well as the underlying cause of the sleep disturbance. All pharmacotherapy should be used with appropriate caution, at minimum effective doses, and for minimum duration of time. PMID:17192164

  6. Antibiotic therapeutic options for infections caused by drug-resistant Gram-positive cocci.

    PubMed

    Banwan, K; Senok, A C; Rotimi, V O

    2009-01-01

    Serious infections caused by Gram-positive bacteria are currently difficult to treat because many of these pathogens are now resistant to standard antimicrobial agents. As a result of the emergence and spread of multidrug-resistant Gram-positive pathogens, new antimicrobial agents are urgently needed for clinical use. In recent years, there has been an increase in the number of drugs that have activity against these Gram-positive pathogens. Daptomycin, tigecycline, linezolid, quinupristin/dalfopristin and dalbavancin are five antimicrobial agents that are useful for the treatment of infections due to drug-resistant Gram-positive cocci. This review focuses on their mechanism of action, pharmacokinetics, spectrum of activity, clinical effectiveness, drug interaction and safety. These antimicrobial agents provide the clinician with additional treatment options among the limited therapies for resistant Gram-positive bacterial infection. PMID:20701863

  7. Lisdexamfetamine dimesylate: a new therapeutic option for attention-deficit hyperactivity disorder.

    PubMed

    Steer, Christopher; Froelich, Jan; Soutullo, César A; Johnson, Mats; Shaw, Monica

    2012-08-01

    Attention-deficit hyperactivity disorder (ADHD) is associated with substantial functional, clinical and economic burdens. It is among the most common psychiatric disorders in children and adolescents, and often persists into adulthood. Both medication and psychosocial interventions are recommended for the treatment of ADHD. However, ADHD treatment practices vary considerably, depending on medication availability, reimbursement and the evolution of clinical practice in each country. In Europe, stimulants and atomoxetine are widely available medications for the treatment of ADHD, whereas in the US approved treatment options also include extended-release formulations of clonidine and guanfacine. Lisdexamfetamine dimesylate (lisdexamfetamine) is a long-acting, prodrug formulation of dexamfetamine. It is currently licensed in the US, Canada and Brazil, and is undergoing phase III studies in Europe. We performed a PubMed/MEDLINE search looking for recent (2005-2012) scientific papers regarding the pharmacokinetics, pharmacodynamics, efficacy and safety of lisdexamfetamine. The lisdexamfetamine molecule is therapeutically inactive and is enzymatically hydrolysed, primarily in the blood, to the active dexamfetamine. This conversion is unaffected by gastrointestinal pH and variations in normal transit times. Lisdexamfetamine was developed with the goal of providing an extended duration of effect that is consistent throughout the day. Clinical trials have demonstrated robust clinical efficacy of lisdexamfetamine in the treatment of children, adolescents and adults with ADHD with dose-dependent improvements in the core symptoms of ADHD. Studies have further shown that the duration of action of lisdexamfetamine continues for 13 hours post-dosing in children and for 14 hours in adults. The tolerability profile of lisdexamfetamine is consistent with those of other stimulant medications, with decreased appetite, insomnia, abdominal pain and irritability among the more frequent

  8. Management of frontotemporal dementia: targeting symptom management in such a heterogeneous disease requires a wide range of therapeutic options

    PubMed Central

    Jicha, Gregory A; Nelson, Peter T

    2011-01-01

    SUMMARY There are no US FDA-approved therapies for the management of frontotemporal dementia (FTD). Evidence-based medicine that would support a FDA indication for the treatment of FTD requires large-scale, randomized, double-blind, placebo-controlled trials that do not currently exist. Progress in obtaining approval and therapeutic indications for FTD has been severely hampered by the heterogeneity of clinical and pathological phenotypes seen in various FTD disease states. These issues are often misinterpreted by clinicians, caregivers and patients suggesting that potential treatment options are nonexistent for this devastating disease. This article discusses these issues in the context of recent studies and publications investigating therapeutic options in FTD, and further suggests a rationale for individualized therapy in FTD. Targeting the myriad of symptoms seen in FTD requires recognition of such symptoms that may play primary or secondary roles in the spectrum of deficits that lead to functional disability in FTD, and the availability of a wide range of therapeutic options that may be helpful in alleviating such symptomatology. Fortunately, agents targeting the many cognitive, behavioral, psychiatric and motor symptoms that can be seen in FTD are readily available, having been previously developed and approved for symptomatic benefit in other disease states. In contrast to the widespread belief that beneficial treatments are not available for FTD today, our therapeutic armament is stocked with pharmacological tools that may improve quality of life for those suffering from this devastating and incurable class of degenerative diseases. PMID:21927623

  9. B-cell development and functions and therapeutic options in adenosine deaminase–deficient patients

    PubMed Central

    Brigida, Immacolata; Sauer, Aisha V.; Ferrua, Francesca; Giannelli, Stefania; Scaramuzza, Samantha; Pistoia, Valentina; Castiello, Maria Carmina; Barendregt, Barbara H.; Cicalese, Maria Pia; Casiraghi, Miriam; Brombin, Chiara; Puck, Jennifer; Müller, Klaus; Notarangelo, Lucia Dora; Montin, Davide; van Montfrans, Joris M.; Roncarolo, Maria Grazia; Traggiai, Elisabetta; van Dongen, Jacques J. M.; van der Burg, Mirjam; Aiuti, Alessandro

    2015-01-01

    Background Adenosine deaminase (ADA) deficiency causes severe cellular and humoral immune defects and dysregulation because of metabolic toxicity. Alterations in B-cell development and function have been poorly studied. Enzyme replacement therapy (ERT) and hematopoietic stem cell (HSC) gene therapy (GT) are therapeutic options for patients lacking a suitable bone marrow (BM) transplant donor. Objective We sought to study alterations in B-cell development in ADA-deficient patients and investigate the ability of ERT and HSC-GT to restore normal B-cell differentiation and function. Methods Flow cytometry was used to characterize B-cell development in BM and the periphery. The percentage of gene-corrected B cells was measured by using quantitative PCR. B cells were assessed for their capacity to proliferate and release IgM after stimulation. Results Despite the severe peripheral B-cell lymphopenia, patients with ADA-deficient severe combined immunodeficiency showed a partial block in central BM development. Treatment with ERT or HSC-GT reverted most BM alterations, but ERT led to immature B-cell expansion. In the periphery transitional B cells accumulated under ERT, and the defect in maturation persisted long-term. HSC-GT led to a progressive improvement in B-cell numbers and development, along with increased levels of gene correction. The strongest selective advantage for ADA-transduced cells occurred at the transition from immature to naive cells. B-cell proliferative responses and differentiation to immunoglobulin secreting IgM after B-cell receptor and Toll-like receptor triggering were severely impaired after ERT and improved significantly after HSC-GT. Conclusions ADA-deficient patients show specific defects in B-cell development and functions that are differently corrected after ERT and HSC-GT. PMID:24506932

  10. Restless Leg Syndrome in ADHD children: levetiracetam as a reasonable therapeutic option.

    PubMed

    Gagliano, Antonella; Aricò, Irene; Calarese, Tiziana; Condurso, Rosaria; Germanò, Eva; Cedro, Clemente; Spina, Edoardo; Silvestri, Rosalia

    2011-06-01

    The comorbidity of Attention Deficit Hyperactivity Disorder (ADHD) with sleep disorders has been extensively studied. In particular, Restless Legs Syndrome (RLS) appears to be consistently more frequent in children with ADHD. Several papers also draw attention to the frequent occurrence of epileptic seizures and EEG abnormalities in ADHD children. We performed a preliminary open label study to evaluate the efficacy of Levetiracetam (LEV) to ameliorate the sleep pattern and reduce RLS symptoms in children with a complex comorbidity between Attention Deficit Hyperactivity Disorder (ADHD), RLS and focal interictal epileptic discharges (IEDs) on EEG. We recruited seven children (all males, aged between 5 and 12years) who fulfilled the following criteria: ADHD diagnosis combined subtype; presence of idiopathic RLS; and presence of focal IEDs on EEG. All children were given LEV at a starting dose of approximately 10-20mg/kg/day followed by 10mg/kg/day incrementing at 1-week intervals up to 50-60mg/kg/day given in two separate doses. At a 3 and 6month follow-up, all children showed significant improvement (p<0.05) in global International RLS Rating Scale (IRLS-RS). Parents' reports revealed improved sleep quality with fewer awakenings and restorative sleep in their children. LEV was well tolerated and no major side effects were reported. With an accessory report we observed the reduction of epileptiform EEG activity during sleep. In most patients (6 on 7) the discharges completely disappeared; in the last patient epileptiform EEG activity was significantly reduced. These children may represent a subgroup of ADHD patients in which the hyperactivity and attention difficulties might be aggravated by sleep disturbances and by IEDs. LEV could represent a therapeutic option for these comorbid conditions. PMID:20950971

  11. Adhesion molecules in peritoneal dissemination: function, prognostic relevance and therapeutic options.

    PubMed

    Sluiter, Nina; de Cuba, Erienne; Kwakman, Riom; Kazemier, Geert; Meijer, Gerrit; Te Velde, Elisabeth Atie

    2016-06-01

    Peritoneal dissemination is diagnosed in 10-25 % of colorectal cancer patients. Selected patients are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. For these patients, earlier diagnosis, optimised selection criteria and a personalised approach are warranted. Biomarkers could play a crucial role here. However, little is known about possible candidates. Considering tumour cell adhesion as a key step in peritoneal dissemination, we aim to provide an overview of the functional importance of adhesion molecules in peritoneal dissemination and discuss the prognostic, diagnostic and therapeutic options of these candidate biomarkers. A systematic literature search was conducted according to the PRISMA guidelines. In 132 in vitro, ex vivo and in vivo studies published between 1995 and 2013, we identified twelve possibly relevant adhesion molecules in various cancers that disseminate peritoneally. The most studied molecules in tumour cell adhesion are integrin α2β1, CD44 s and MUC16. Furthermore, L1CAM, EpCAM, MUC1, sLe(x) and Le(x), chemokine receptors, Betaig-H3 and uPAR might be of clinical importance. ICAM1 was found to be less relevant in tumour cell adhesion in the context of peritoneal metastases. Based on currently available data, sLe(a) and MUC16 are the most promising prognostic biomarkers for colorectal peritoneal metastases that may help improve patient selection. Different adhesion molecules appear expressed in haematogenous and transcoelomic spread, indicating two different attachment processes. However, our extensive assessment of available literature reveals that knowledge on metastasis-specific genes and their possible candidates is far from complete. PMID:27074785

  12. Improving Response to Hormone Therapy in Breast Cancer: New Targets, New Therapeutic Options.

    PubMed

    Rugo, Hope S; Vidula, Neelima; Ma, Cynthia

    2016-01-01

    The majority of breast cancer expresses the estrogen and or progesterone receptors (ER and PR). In tumors without concomitant HER2 amplification, hormone therapy is a major treatment option for all disease stages. Resistance to hormonal therapy is associated with disease recurrence and progression. Recent studies have identified a number of resistance mechanisms leading to estrogen-independent growth of hormone receptor-positive (HR+) breast cancer as a result of genetic and epigenetic alterations, which could be exploited as novel therapeutic targets. These include acquired mutations in ER-alpha (ESR1) in response to endocrine deprivation; constitutive activation of cyclin-dependent kinases (CDK) 4 and 6; cross talk between ER and growth factor receptor signaling such as HER family members, fibroblast growth factor receptor (FGFR) pathways, intracellular growth, and survival signals PI3K/Akt/mTOR; and epigenetic modifications by histone deacetylase (HDAC) as well as interactions with tumor microenvironment and host immune response. Inhibitors of these pathways are being developed to improve efficacy of hormonal therapy for treatment of both metastatic and early-stage disease. Two agents are currently approved in the United States for the treatment of metastatic HR+ breast cancer, including the mTOR inhibitor everolimus and the CDK4/6 inhibitor palbociclib. Management of toxicity is a critical aspect of treatment; the primary toxicity of everolimus is stomatitis (treated with topical steroids) and of palbociclib is neutropenia (treated with dose reduction/delay). Many agents are in clinical trials, primarily in combination with hormone therapy; novel combinations are under active investigation. PMID:27249746

  13. Contemporary management of lymph node metastases from an unknown primary to the neck: II. a review of therapeutic options.

    PubMed

    Strojan, Primož; Ferlito, Alfio; Langendijk, Johannes A; Corry, June; Woolgar, Julia A; Rinaldo, Alessandra; Silver, Carl E; Paleri, Vinidh; Fagan, Johannes J; Pellitteri, Phillip K; Haigentz, Missak; Suárez, Carlos; Robbins, K Thomas; Rodrigo, Juan P; Olsen, Kerry D; Hinni, Michael L; Werner, Jochen A; Mondin, Vanni; Kowalski, Luiz P; Devaney, Kenneth O; de Bree, Remco; Takes, Robert P; Wolf, Gregory T; Shaha, Ashok R; Genden, Eric M; Barnes, Leon

    2013-02-01

    Although uncommon, cancer of an unknown primary (CUP) metastatic to cervical lymph nodes poses a range of dilemmas relating to optimal treatment. The ideal resolution would be a properly designed prospective randomized trial, but it is unlikely that this will ever be conducted in this group of patients. Accordingly, knowledge gained from retrospective studies and experience from treating patients with known head and neck primary tumors form the basis of therapeutic strategies in CUP. This review provides a critical appraisal of various treatment approaches described in the literature. Emerging treatment options for CUP with metastases to cervical lymph nodes are discussed in view of recent innovations in the field of head and neck oncology and suitable therapeutic strategies for particular clinical scenarios are presented. For pN1 or cN1 disease without extracapsular extension (ECE), selective neck dissection or radiotherapy offer high rates of regional control. For more advanced neck disease, intensive combined treatment is required, either a combination of neck dissection and radiotherapy, or initial (chemo)radiotherapy followed by neck dissection if a complete response is not recorded on imaging. Each of these approaches seems to be equally effective. Use of extensive bilateral neck/mucosal irradiation must be weighed against toxicity, availability of close follow-up with elective neck imaging and guided fine-needle aspiration biopsy (FNAB) when appropriate, the human papillomavirus (HPV) status of the tumor, and particularly against the distribution pattern (oropharynx in the majority of cases) and the emergence rate of hidden primary lesions (<10% after comprehensive workup). The addition of systemic agents is expected to yield similar improvement in outcome as has been observed for known head and neck primary tumors. PMID:22034062

  14. Therapeutic Options and Multifaceted Treatment Paradigms In Metastatic Castrate Resistant Prostate Cancer

    PubMed Central

    Vaishampayan, Ulka

    2014-01-01

    Purpose of Review The field of prostate cancer therapeutics has undergone a rapid and dramatic change in the last few years. Multiple agents with very distinct mechanisms of actions and unique toxicities and efficacies have become available for clinical use. The focus of this review is to give a summary of clinical perspectives of the indications, including pros and cons of the currently approved regimens. The next generation of novel targets and agents are also highlighted. Recent Findings Addition of docetaxel based chemotherapy to conventional androgen suppression therapy in hormone sensitive advanced prostate cancer demonstrated overall survival benefit in recently released results of ECOG 3805. In castrate resistant metastatic disease, development of novel immunotherapy (Sipuleucel T), chemotherapy (docetaxel and cabazitaxel), radiation (alpharadin) and hormone therapy (abiraterone and enzalutamide) agents has created a range of choices for treatment, palliation and improved life expectancy. Summary A paradigm shift has occurred in the management of advanced prostate cancer, with multiple novel agents addressing distinct pathways, and demonstrating powerful efficacy. The judicious use of the available agents, with finesse of sequencing, and concomitant palliative care has prolonged survival and made living with the disease more reasonable and tolerable. PMID:24626129

  15. Therapeutic management of fetal anemia: review of standard practice and alternative treatment options.

    PubMed

    Papantoniou, Nikos; Sifakis, Stavros; Antsaklis, Aris

    2013-01-01

    Fetal anemia, mainly due to red cell alloimmunization, is still a significant cause of fetal and neonatal mortality and morbidity. The focus of current clinical research has shifted from an invasive approach to non-invasive management and treatment of affected pregnancies, and the progress in this field is associated with a major improvement in perinatal outcome. During the last 50 years, intrauterine red cells transfusion (IUT), fi rst via the intraperitoneal route and later directly to fetal circulation, is the standard practice in most centers, with survival rates that exceed 90 % , particularly if anemia is diagnosed early and treated in a timely manner. In addition, plasmapheresis and intravenous administration of highdose immunoglobulin have been implicated in the treatment of pregnancies complicated with early-onset severe red cell alloimmunization, alone or in combination with IUTs before the 20(th) week of pregnancy, but there are still issues to be clarified further. This review article aims to provide an overview of the current standard therapeutic management and alternative treatment modalities in pregnancies complicated by fetal anemia. PMID:23093258

  16. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options.

    PubMed

    Uttara, Bayani; Singh, Ajay V; Zamboni, Paolo; Mahajan, R T

    2009-03-01

    Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced defense mechanism of antioxidants, overproduction or incorporation of free radicals from environment to living system leads to serious penalty leading to neuro-degeneration. Neural cells suffer functional or sensory loss in neurodegenerative diseases. Apart from several other environmental or genetic factors, oxidative stress (OS) leading to free radical attack on neural cells contributes calamitous role to neuro-degeneration. Though, oxygen is imperative for life, imbalanced metabolism and excess reactive oxygen species (ROS) generation end into a range of disorders such as Alzheimer's disease, Parkinson's disease, aging and many other neural disorders. Toxicity of free radicals contributes to proteins and DNA injury, inflammation, tissue damage and subsequent cellular apoptosis. Antioxidants are now being looked upon as persuasive therapeutic against solemn neuronal loss, as they have capability to combat by neutralizing free radicals. Diet is major source of antioxidants, as well as medicinal herbs are catching attention to be commercial source of antioxidants at present. Recognition of upstream and downstream antioxidant therapy to oxidative stress has been proved an effective tool in alteration of any neuronal damage as well as free radical scavenging. Antioxidants have a wide scope to sequester metal ions involved in neuronal plaque formation to prevent oxidative stress. In addition, antioxidant therapy is vital in scavenging free radicals and ROS preventing neuronal degeneration in post-oxidative stress scenario. PMID:19721819

  17. Therapeutic options to minimize allogeneic blood transfusions and their adverse effects in cardiac surgery: A systematic review

    PubMed Central

    dos Santos, Antônio Alceu; da Silva, José Pedro; da Silva, Luciana da Fonseca; de Sousa, Alexandre Gonçalves; Piotto, Raquel Ferrari; Baumgratz, José Francisco

    2014-01-01

    Introdution Allogeneic blood is an exhaustible therapeutic resource. New evidence indicates that blood consumption is excessive and that donations have decreased, resulting in reduced blood supplies worldwide. Blood transfusions are associated with increased morbidity and mortality, as well as higher hospital costs. This makes it necessary to seek out new treatment options. Such options exist but are still virtually unknown and are rarely utilized. Objective To gather and describe in a systematic, objective, and practical way all clinical and surgical strategies as effective therapeutic options to minimize or avoid allogeneic blood transfusions and their adverse effects in surgical cardiac patients. Methods A bibliographic search was conducted using the MeSH term “Blood Transfusion” and the terms “Cardiac Surgery” and “Blood Management.” Studies with titles not directly related to this research or that did not contain information related to it in their abstracts as well as older studies reporting on the same strategies were not included. Results Treating anemia and thrombocytopenia, suspending anticoagulants and antiplatelet agents, reducing routine phlebotomies, utilizing less traumatic surgical techniques with moderate hypothermia and hypotension, meticulous hemostasis, use of topical and systemic hemostatic agents, acute normovolemic hemodilution, cell salvage, anemia tolerance (supplementary oxygen and normothermia), as well as various other therapeutic options have proved to be effective strategies for reducing allogeneic blood transfusions. Conclusion There are a number of clinical and surgical strategies that can be used to optimize erythrocyte mass and coagulation status, minimize blood loss, and improve anemia tolerance. In order to decrease the consumption of blood components, diminish morbidity and mortality, and reduce hospital costs, these treatment strategies should be incorporated into medical practice worldwide. PMID:25714216

  18. [Nasal Highflow (NHF): A New Therapeutic Option for the Treatment of Respiratory Failure].

    PubMed

    Bräunlich, J; Nilius, G

    2016-01-01

    The therapy of choice in hypoxemic respiratory failure (type 1) is the application of supplemental oxygen at flow rates of 1 to 15 l/min via nasal prongs or mask. Non-invasive or invasive positive pressure ventilation will be initiated when the oxygen therapy effects are not sufficient or if hypercapnic respiratory failure (type 2) is the underlying problem. Recently, an alternative therapy option is available, from the pathophysiology it can be classified between oxygen therapy and positive pressure ventilation. The therapy called Nasal High Flow (NHF) is based on the nasal application of a heated and humidified air oxygen mixture with a flow range of up to 60 l/min. The precise pathophysiological principles of NHF are only partly understood, yet various aspects are well studied already: it is possible to deliver high oxygen concentrations, airway dryness can be avoided, dead space ventilation reduced and clearance of nasal dead space is achieved. Additionally, an end expiratory positive pressure is built up, which helps to prevent airway collapse, thus resulting in an improvement of respiratory efficiency and reduction of breathing work. Current studies demonstrate improvement in gas exchange and reduction of reintubation rate when applying the NHF treatment in acute respiratory failure. Thus the NHF therapy attracts attention in intensive care medicine. The application in other fields like chronic respiratory insufficiency is less well clarified. The objectives of this review are to present the pathophysiological effects and mechanisms of NHF, as far as understood, and to give an overview over the current state of relevant studies. PMID:26789432

  19. 46 CFR Appendix F to Subpart C of... - Optional Rider for Additional NVOCC Financial Responsibility for Group Bonds [Optional Rider to...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 9 2010-10-01 2010-10-01 false Optional Rider for Additional NVOCC Financial Responsibility for Group Bonds F Appendix F to Subpart C of Part 515 Shipping FEDERAL MARITIME COMMISSION REGULATIONS AFFECTING OCEAN SHIPPING IN FOREIGN COMMERCE LICENSING, FINANCIAL RESPONSIBILITY REQUIREMENTS, AND GENERAL DUTIES FOR OCEAN...

  20. Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options

    PubMed Central

    Uttara, Bayani; Singh, Ajay V.; Zamboni, Paolo; Mahajan, R.T

    2009-01-01

    Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced defense mechanism of antioxidants, overproduction or incorporation of free radicals from environment to living system leads to serious penalty leading to neuro-degeneration. Neural cells suffer functional or sensory loss in neurodegenerative diseases. Apart from several other environmental or genetic factors, oxidative stress (OS) leading to free radical attack on neural cells contributes calamitous role to neuro-degeneration. Though, oxygen is imperative for life, imbalanced metabolism and excess reactive oxygen species (ROS) generation end into a range of disorders such as Alzheimer’s disease, Parkinson’s disease, aging and many other neural disorders. Toxicity of free radicals contributes to proteins and DNA injury, inflammation, tissue damage and subsequent cellular apoptosis. Antioxidants are now being looked upon as persuasive therapeutic against solemn neuronal loss, as they have capability to combat by neutralizing free radicals. Diet is major source of antioxidants, as well as medicinal herbs are catching attention to be commercial source of antioxidants at present. Recognition of upstream and downstream antioxidant therapy to oxidative stress has been proved an effective tool in alteration of any neuronal damage as well as free radical scavenging. Antioxidants have a wide scope to sequester metal ions involved in neuronal plaque formation to prevent oxidative stress. In addition, antioxidant therapy is vital in scavenging free radicals and ROS preventing neuronal degeneration in post-oxidative stress scenario. PMID:19721819

  1. Addition of flexible body option to the TOLA computer program. Part 2: User and programmer documentation

    NASA Technical Reports Server (NTRS)

    Dick, J. W.; Benda, B. J.

    1975-01-01

    User and programmer oriented documentation for the flexible body option of the Takeoff and Landing Analysis (TOLA) computer program are provided. The user information provides sufficient knowledge of the development and use of the option to enable the engineering user to successfully operate the modified program and understand the results. The programmer's information describes the option structure and logic enabling a programmer to make major revisions to this part of the TOLA computer program.

  2. Passive solar addition to therapeutic pre-school. Final technical report

    SciTech Connect

    Not Available

    1983-10-01

    This project consisted of designing and constructing a passive solar system on a new classroom addition to the Peanut Butter and Jelly Therapeutic Pre-School in Albuquerque, NM. The purpose of this project was to demonstrate the applicability of solar space heating systems to large institutional buildings, and to demonstrate the energy and cost savings available through the use of such systems. Preliminary estimates indicated that the passive solar systems will provide about 90 percent of the heating and cooling needs for the new classroom addition to the school.

  3. Endovascular Therapeutic Occlusion of the Posterior Cerebral Artery: An Option for Ruptured Giant Aneurysm in a Child.

    PubMed

    Demartini, Zeferino; Matos, Luiz Afonso Dias; Dos Santos, Marcio Luis Tostes; Cardoso-Demartini, Adriane de Andre

    2016-01-01

    The incidence of intracranial aneurysms in the pediatric population is low, and surgical clipping remains a good long-term treatment option. However, posterior circulation aneurysms are even more complex to manage in children than in adults. We report a case of a giant aneurysm of the posterior cerebral artery in a 10-year-old boy presenting with subarachnoid hemorrhage. Endovascular treatment with platinum coils was performed with total occlusion of the aneurysm and the affected arterial segment without complications. The patient achieved good recovery, and a late control angiogram confirmed exclusion of the aneurysm. Occurrence of special features of cerebral aneurysm in children, in comparison to adults, is also described. Parent artery sacrifice is an effective therapeutic option, but long-term follow-up is necessary to avoid recurrence and rebleeding. PMID:26974558

  4. Rivaroxaban – a safe therapeutic option in patients with antiphospholipid syndrome? Our experience in 23 cases

    PubMed Central

    Olesińska, Marzena

    2016-01-01

    In the therapeutic approach to patients with antiphospholipid syndrome (APS) with thrombotic manifestations, oral vitamin K antagonists (VKA) remain the standard of care. However, the use of VKA is very often associated with inability to achieve a therapeutic dose even in patients maintaining nutritional and therapeutic restrictions. The non-vitamin-K oral anticoagulants (NOAC) have a lot of advantages, but their efficacy and safety in APS have not been proven. We present 23 patients with APS treated with rivaroxaban in our department. Recurrence of thrombosis was observed only in 1 patient. No major or minor bleeding occurred. It proves the efficacy of treatment with rivaroxaban, but our observations require further prospective, randomized studies. PMID:27504026

  5. Rivaroxaban - a safe therapeutic option in patients with antiphospholipid syndrome? Our experience in 23 cases.

    PubMed

    Haładyj, Ewa; Olesińska, Marzena

    2016-01-01

    In the therapeutic approach to patients with antiphospholipid syndrome (APS) with thrombotic manifestations, oral vitamin K antagonists (VKA) remain the standard of care. However, the use of VKA is very often associated with inability to achieve a therapeutic dose even in patients maintaining nutritional and therapeutic restrictions. The non-vitamin-K oral anticoagulants (NOAC) have a lot of advantages, but their efficacy and safety in APS have not been proven. We present 23 patients with APS treated with rivaroxaban in our department. Recurrence of thrombosis was observed only in 1 patient. No major or minor bleeding occurred. It proves the efficacy of treatment with rivaroxaban, but our observations require further prospective, randomized studies. PMID:27504026

  6. CD20-negative diffuse large B-cell lymphomas: biology and emerging therapeutic options.

    PubMed

    Castillo, Jorge J; Chavez, Julio C; Hernandez-Ilizaliturri, Francisco J; Montes-Moreno, Santiago

    2015-06-01

    CD20-negative diffuse large B-cell lymphoma (DLBCL) is a rare and heterogeneous group of lymphoproliferative disorders. Known variants of CD20-negative DLBCL include plasmablastic lymphoma, primary effusion lymphoma, large B-cell lymphoma arising in human herpesvirus 8-associated multicentric Castleman disease and anaplastic lymphoma kinase-positive DLBCL. Given the lack of CD20 expression, atypical cellular morphology and aggressive clinical behavior characterized by chemotherapy resistance and inferior survival rates, CD20-negative DLBCL represents a challenge from the diagnostic and therapeutic perspectives. The goals of the present review are to summarize the current knowledge on the biology of the distinct variants of CD20-negative DLBCL, provide future therapeutic directions based on the limited preclinical and clinical data available, and increase awareness concerning these rare malignancies among pathologists and clinicians. PMID:25641215

  7. Assessment of therapeutic options for reducing alkali burn-induced corneal neovascularization and inflammation.

    PubMed

    Bakunowicz-Łazarczyk, Alina; Urban, Beata

    2016-03-01

    This article aims to review and provide the current knowledge of the possibilities of topical treatment of corneal neovascularization due to alkali burns, evidenced by laboratory experiments, in vitro studies, and clinical trials published in the specialized literature. Authors present clinically relevant treatment of corneal neovascularization used in clinical practice, potential antiangiogenic topical therapeutics against corneal neovascularization, which are under investigation, and anti-angiogenic gene-therapy. PMID:26651127

  8. Treatment of hyperuricemia in gout: current therapeutic options, latest developments and clinical implications

    PubMed Central

    Sattui, Sebastian E.; Gaffo, Angelo L.

    2016-01-01

    Despite being the most common type of inflammatory arthritis, gout is often poorly managed. Except for febuxostat and pegloticase, research in new therapeutic agents for the management of hyperuricemia in gout remained insufficient for several decades. With emerging evidence of possible roles of hyperuricemia in cardiometabolic comorbidities, as well as more convincing evidence regarding poor outcomes (e.g. disability, recurrent hospital admissions) in patients with uncontrolled gout, several agents are current under development. Increasing knowledge regarding renal urate transporters has resulted in the development of new generation uricosurics such as lesinurad and arhalofenate. This review aims at discussing current therapeutic strategies for gout, as well as their limitations and the possible role of emerging agents in the chronic management of hyperuricemia in gout. Drugs in phases I and II of development will be discussed, along with new agents and therapeutic classes, such as purine nucleoside phosphorylase inhibitors and dual-action drugs. These new developments are encouraging, and will hopefully contribute to a more adequate management of hyperuricemia in gout. PMID:27493693

  9. Is the medical use of cannabis a therapeutic option for children?

    PubMed

    Rieder, Michael J

    2016-01-01

    Cannabis is a psychoactive compound with a long history of recreational and therapeutic use. Current considerations regarding cannabis use for medical purposes in children have been stimulated by recent case reports describing its beneficial effect with refractory epilepsy. Overall, there are insufficient data to support either the efficacy or safety of cannabis use for any indications in children, and an increasing body of data suggests possible harm, most importantly in specific conditions. The potential for cannabis as a therapeutic agent must be evaluated carefully for both efficacy and safety in treating specific paediatric health conditions. Smoking is not an acceptable mode of drug delivery for children. The use of cannabis for medical purposes in specific cases should not be construed as a justification for recreational cannabis use by adolescents. Recommendations for therapeutic use in exceptional paediatric cases are offered, always providing that this treatment course is carefully evaluated in individuals and in ongoing, well-designed research studies to determine safety and efficacy. PMID:26941559

  10. Treatment of hyperuricemia in gout: current therapeutic options, latest developments and clinical implications.

    PubMed

    Sattui, Sebastian E; Gaffo, Angelo L

    2016-08-01

    Despite being the most common type of inflammatory arthritis, gout is often poorly managed. Except for febuxostat and pegloticase, research in new therapeutic agents for the management of hyperuricemia in gout remained insufficient for several decades. With emerging evidence of possible roles of hyperuricemia in cardiometabolic comorbidities, as well as more convincing evidence regarding poor outcomes (e.g. disability, recurrent hospital admissions) in patients with uncontrolled gout, several agents are current under development. Increasing knowledge regarding renal urate transporters has resulted in the development of new generation uricosurics such as lesinurad and arhalofenate. This review aims at discussing current therapeutic strategies for gout, as well as their limitations and the possible role of emerging agents in the chronic management of hyperuricemia in gout. Drugs in phases I and II of development will be discussed, along with new agents and therapeutic classes, such as purine nucleoside phosphorylase inhibitors and dual-action drugs. These new developments are encouraging, and will hopefully contribute to a more adequate management of hyperuricemia in gout. PMID:27493693

  11. Tacrolimus combined with low-dose corticosteroids is an effective and safe therapeutic option for refractory IgA nephropathy

    PubMed Central

    Wan, Qi-Jun; Hu, Hao-Fei; He, Yong-Cheng; Luan, Shao-Dong; Chen, Hong-Tao; Li, Tong; Xu, Yi; Xu, Hui-Li; Liao, Ying

    2016-01-01

    -dose corticosteroids may be an effective and safe therapeutic option for the treatment of refractory IgAN. However, given the small number of patients in this study, further prospective randomized controlled trials are required with a larger sample of participants and longer follow-up period. PMID:27602099

  12. Current state of evidence on 'off-label' therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents, in Germany, Austria and Switzerland--a consensus report.

    PubMed

    Aringer, M; Burkhardt, H; Burmester, G R; Fischer-Betz, R; Fleck, M; Graninger, W; Hiepe, F; Jacobi, A M; Kötter, I; Lakomek, H J; Lorenz, H M; Manger, B; Schett, G; Schmidt, R E; Schneider, M; Schulze-Koops, H; Smolen, J S; Specker, C; Stoll, T; Strangfeld, A; Tony, H P; Villiger, P M; Voll, R; Witte, T; Dörner, T

    2012-04-01

    Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include 'off-label' use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors' own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence. PMID:22072024

  13. New direct oral anticoagulants--current therapeutic options and treatment recommendations for bleeding complications.

    PubMed

    Miesbach, Wolfgang; Seifried, Erhard

    2012-10-01

    To date, clinical studies show that the incidence of spontaneous bleeding with new direct oral anticoagulants (DOAs) is comparable to that of established anticoagulants. However, unlike vitamin K antagonists, there are currently no clinically available antidotes or approved reversal agents for new DOAs. Restoring normal coagulation is important in many cases, such as emergency surgeries, serious bleedings, or anticoagulant overdosing. Attempts have been made to restore normal coagulation after treatment with new DOAs using compounds such as recombinant activated factor VII (rFVIIa), prothrombin complex concentrate (PCC), or FEIBA (factor eight inhibitor bypassing activity). Limited pre-clinical data and even less clinical evidence are available on the usefulness of these methods in restoring normal coagulation for the emergency management of critical bleeding episodes. Evaluating the utility of DOAs is further complicated by the fact that it is unknown how predictive established test systems are of the bleeding risks. Clinical practice requires further evaluation of the emergency management options for the new DOAs to define the agents and the doses that are most useful. Furthermore, patients receiving long-term treatment with a DOA are likely to undergo elective surgery at some point, and there is lack of evidence regarding perioperative treatment regimens under such conditions. This review summarises potential bleeding management options and available data on the new DOAs. PMID:22782297

  14. [Novel therapeutic options in patients with type 2 diabetes and high cardiovascular risk].

    PubMed

    Laubner, Katharina; Seufert, Jochen

    2016-06-01

    SGLT2 inhibitors represent a novel therapeutic approach for the tretment of type 2 diabetes mellitus. Beyond glucose control, these drugs also induce weight loss and blod pressure reduction. In a specific cardiovascular outcome trial (EMPA-REG-OUTCOME), the SGLT 2 inhibitor empagliflozin has for the first time demonstrated to reduce cardiovascular and overall mortality as well as hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk. These results will drastically affect future recommendations for the treatment of type 2 diabetes mellitus.). PMID:27176455

  15. Therapeutic options for lymphangioleiomyomatosis (LAM): where we are and where we are going

    PubMed Central

    Steagall, Wendy K; Moss, Joel

    2009-01-01

    Lymphangioleiomyomatosis (LAM), a multisystem disease affecting predominantly premenopausal and middle-aged women, causes progressive respiratory failure due to cystic lung destruction and is associated with lymphatic and kidney tumors. In the past, the treatment of LAM comprised exclusively anti-estrogen and related hormonal therapies. These treatments, however, have not been proven effective. In this article, we discuss new findings regarding the molecular mechanisms involved in the regulation of LAM cell growth, which may offer opportunities to develop effective and targeted therapeutic agents. PMID:20948684

  16. Extracellular vesicles derived from mesenchymal stromal cells: a therapeutic option in respiratory diseases?

    PubMed

    Abreu, Soraia C; Weiss, Daniel J; Rocco, Patricia R M

    2016-01-01

    Extracellular vesicles (EVs) are plasma membrane-bound fragments released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. EVs derived from MSCs and other cell types transfer molecules (such as DNA, proteins/peptides, mRNA, microRNA, and lipids) and/or organelles with reparative and anti-inflammatory properties to recipient cells. The paracrine anti-inflammatory effects promoted by MSC-derived EVs have attracted significant interest in the regenerative medicine field, including for potential use in lung injuries. In the present review, we describe the characteristics, biological activities, and mechanisms of action of MSC-derived EVs. We also review the therapeutic potential of EVs as reported in relevant preclinical models of acute and chronic respiratory diseases, such as pneumonia, acute respiratory distress syndrome, asthma, and pulmonary arterial hypertension. Finally, we discuss possible approaches for potentiating the therapeutic effects of MSC-derived EVs so as to enable use of this therapy in clinical practice. PMID:27075363

  17. Systemic minocycline as a therapeutic option in predominantly oral mucous membrane pemphigoid: a cautionary report.

    PubMed

    Carrozzo, M; Arduino, P; Bertolusso, G; Cozzani, E; Parodi, A

    2009-10-01

    The aim of this study was to evaluate the therapeutic benefit of minocycline in mucous membrane pemphigoid (MMP) predominantly involving the oral cavity. A descriptive, open clinical study with no control group, including 9 patients, was developed. The diagnosis was confirmed by histopathological examination and direct and salt-split-skin indirect immunofluorescence analysis. Target antigens were sought by immunoblotting. Patients received minocycline (200mg/day) for a variable period. All patients were followed up for at least 2 years after initial diagnosis. Therapeutic response was assessed by clinical improvement in three categories: major response, minor response and no response. A major response was observed in 3 patients (33%), a minor response in 4 (44%) and 2 (22%) patients showed no improvement. Two of the 3 patients with a major response showed no immunoblot reactivity; 80% of patients with circulating autoantibodies (autoAb) against BP180 had a minor or no response. Permanent remission of signs with no relapse was only obtained in one patient. 5 patients (55%) stopped the drug because of adverse effects, such as vertigo and gastralgia. The results revealed temporary clinical benefits in MMP predominantly involving the oral cavity with minocycline, although frequently side effects led to drug withdrawal. PMID:19628373

  18. Therapeutic options for chronic myeloid leukemia: focus on imatinib (Glivec®, Gleevec™)

    PubMed Central

    Henkes, Martin; van der Kuip, Heiko; Aulitzky, Walter E

    2008-01-01

    Treatment options for chronic myeloid leukemia (CML) have changed dramatically during the last decades. Interferon-α treatment and stem cell transplantation (SCT) clearly improved survival over conventional chemotherapy and offered the possibility of complete and durable responses. With the advent of the small molecule inhibitor imatinib mesylate (Glivec®, Gleevec™) targeting the causative Bcr-Abl oncoprotein, the era of molecular cancer therapy began with remarkable success especially in chronic phase patients. Today, imatinib is the first-line treatment for CML. However, imatinib does not appear to be capable to eliminate all leukemia cells in the patients and pre-existing as well as acquired resistance to the drug has been increasingly recognized. To overcome these problems, several strategies involving dose escalation, combinations with other agents, and novel Bcr-Abl inhibitors have been developed. PMID:18728706

  19. Inhibition of STAT5: A therapeutic option in BCR-ABL1-driven leukemia

    PubMed Central

    Berger, Angelika; Sexl, Veronika; Valent, Peter; Moriggl, Richard

    2014-01-01

    The two transcription factors STAT5A and STAT5B are central signaling molecules in leukemias driven by Abelson fusion tyrosine kinases and they fulfill all criteria of drug targets. STAT5A and STAT5B display unique nuclear shuttling mechanisms and they have a key role in resistance of leukemic cells against treatment with tyrosine kinase inhibitors (TKI). Moreover, STAT5A and STAT5B promote survival of leukemic stem cells. We here discuss the possibility of targeting up-stream kinases with TKI, direct STAT5 inhibition via SH2 domain obstruction and blocking nuclear translocation of STAT5. All discussed options will result in a stop of STAT5 transport to the nucleus to block STAT5-mediated transcriptional activity. In summary, recently described shuttling functions of STAT5 are discussed as potentially druggable pathways in leukemias. PMID:25333255

  20. Quinine sulfate as a therapeutic option in a patient with slow channel congenital myasthenic syndrome.

    PubMed

    Peyer, Anne-Kathrin; Abicht, Angela; Heinimann, Karl; Sinnreich, Michael; Fischer, Dirk

    2013-07-01

    Slow channel congenital myasthenic syndrome is caused by a genetically determined kinetic anomaly of the acetylcholine receptor at the neuromuscular junction leading to its prolonged open state. Patients typically present with fatigability and static weakness of neck, hand and finger extensors. The open-channel blockers fluoxetine and quinidine have been used as standard treatment, although the former is limited by its side effects. We describe a patient with a novel "de novo" mutation in the α subunit of acetylcholine receptor with clinical and electrophysiological hallmarks of the disease. The patient showed marked treatment response to fluoxetine as well as quinine, a stereoisomer of quinidine, expanding the treatment options for this hereditary disorder. PMID:23688972

  1. Genome Integrity in Aging: Human Syndromes, Mouse Models, and Therapeutic Options.

    PubMed

    Vermeij, Wilbert P; Hoeijmakers, Jan H J; Pothof, Joris

    2016-01-01

    Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular communication, loss of proteostasis, cellular senescence and adult stem cell exhaustion. However, whether and how these instigators of aging interrelate or whether they have one root cause is currently largely unknown. Rare human progeroid syndromes and corresponding mouse mutants with resolved genetic defects highlight the dominant importance of genome maintenance for aging. A second class of aging-related disorders reveals a cross connection with metabolism. As genome maintenance and metabolism are closely interconnected, they may constitute the main underlying biology of aging. This review focuses on the role of genome stability in aging, its crosstalk with metabolism, and options for nutritional and/or pharmaceutical interventions that delay age-related pathology. PMID:26514200

  2. SGLT2 inhibitors provide an effective therapeutic option for diabetes complicated with insulin antibodies.

    PubMed

    Hayashi, Akinori; Takano, Koji; Kawai, Sayuki; Shichiri, Masayoshi

    2016-02-29

    Diabetes mellitus complicated with insulin antibodies is rare in clinical practice but usually difficult to control. A high amount of insulin antibodies, especially with low affinity and high binding capacity, leads to unstable glycemic control characterized by hyperglycemia unresponsive to large volume of insulin and unanticipated hypoglycemia. There are several treatment options, such as changing insulin preparation, immunosupression with glucocorticoids, and plasmapheresis, most of which are of limited efficacy. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of drug which decrease renal glucose reabsorption and lowers plasma glucose level independent of insulin action. We report here a case with diabetes complicated with insulin antibodies who was effectively controlled by an SGLT2 inhibitor. A 47-year-old man with type 2 diabetes treated with insulin had very poor glycemic control characterized by postprandial hyperglycemia unresponsive to insulin therapy and repetitive hypoglycemia due to insulin antibodies. Treatment with ipragliflozin, an SGLT2 inhibitor, improved HbA1c from 8.4% to 6.0% and glycated albumin from 29.4% to 17.9%. Continuous glucose monitoring revealed improvement of glycemic profile (average glucose level from 212 mg/dL to 99 mg/dL and glycemic standard deviation from 92 mg/dL to 14 mg/dL) with disappearance of hypoglycemic events. This treatment further ameliorated the characteristics of insulin antibodies and resulted in reduced insulin requirement. SGLT2 inhibitors may offer an effective treatment option for managing the poor glycemic control in diabetes complicated with insulin antibodies. PMID:26549210

  3. Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options

    PubMed Central

    Rodrigues, Daniela; Longatto-Filho, Adhemar

    2016-01-01

    Colorectal cancer (CRC) is one of the most frequent cancers and is a leading cause of cancer death worldwide. Treatments used for CRC may include some combination of surgery, radiation therapy, chemotherapy, and targeted therapy. The current standard drugs used in chemotherapy are 5-fluorouracil and leucovorin in combination with irinotecan and/or oxaliplatin. Most recently, biologic agents have been proven to have therapeutic benefits in metastatic CRC alone or in association with standard chemotherapy. However, patients present different treatment responses, in terms of efficacy and toxicity; therefore, it is important to identify biological markers that can predict the response to therapy and help select patients that would benefit from specific regimens. In this paper, authors review CRC genetic markers that could be useful in predicting the sensitivity/resistance to chemotherapy. PMID:27563673

  4. Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options.

    PubMed

    Rodrigues, Daniela; Longatto-Filho, Adhemar; Martins, Sandra F

    2016-01-01

    Colorectal cancer (CRC) is one of the most frequent cancers and is a leading cause of cancer death worldwide. Treatments used for CRC may include some combination of surgery, radiation therapy, chemotherapy, and targeted therapy. The current standard drugs used in chemotherapy are 5-fluorouracil and leucovorin in combination with irinotecan and/or oxaliplatin. Most recently, biologic agents have been proven to have therapeutic benefits in metastatic CRC alone or in association with standard chemotherapy. However, patients present different treatment responses, in terms of efficacy and toxicity; therefore, it is important to identify biological markers that can predict the response to therapy and help select patients that would benefit from specific regimens. In this paper, authors review CRC genetic markers that could be useful in predicting the sensitivity/resistance to chemotherapy. PMID:27563673

  5. Therapeutic options for acute cough due to upper respiratory infections in children.

    PubMed

    Paul, Ian M

    2012-02-01

    Cough due to upper respiratory tract infections (URIs) is one of the most frequent complaints encountered by pediatric health-care providers, and one of the most disruptive symptoms for children and families. Despite the frequency of URIs, there is limited evidence to support the few therapeutic agents currently available in the United States (US) to treat acute cough due to URI. Published, well-designed, contemporary research supporting the efficacy of narcotics (codeine, hydrocodone) and US Food and Drug Administration (FDA)-approved over-the-counter (OTC) oral antitussives and expectorants (dextromethorphan, diphenhydramine, chlophedianol, and guaifenesin) is absent for URI-associated pediatric cough. Alternatively, honey and topically applied vapor rubs may be effective antitussives. PMID:21892785

  6. Searching for additional endocrine functions of the skeleton: genetic approaches and implications for therapeutics

    PubMed Central

    Wei, Jianwen; Flaherty, Stephen; Karsenty, Gerard

    2016-01-01

    Our knowledge of whole organism physiology has greatly advanced in the past decades through mouse genetics. In particular, genetic studies have revealed that most organs interact with one another through hormones in order to maintain normal physiological functions and the homeostasis of the entire organism. Remarkably, through these studies many unexpected novel endocrine means to regulate physiological functions have been uncovered. The skeletal system is one example. In this article, we review a series of studies that over the years have identified bone as an endocrine organ. The mechanism of action, pathological relevance, and therapeutic implications of the functions of the bone-derived hormone osteocalcin are discussed. In the last part of this review we discuss the possibility that additional endocrine functions of the skeleton may exist.

  7. New Therapeutic Option for Drop Foot with the ActiGait Peroneal Nerve Stimulator--a Technical Note.

    PubMed

    Martin, K Daniel; Polanski, Witold; Schackert, Gabriele; Sobottka, Stephan B

    2015-12-01

    A drop foot occurs in up to 20% of stroke patients and leads to an increased risk of falls. Until recently, only a foot orthosis or surface stimulation was able to improve the gait of these patients. Recent studies have shown that direct peroneal nerve stimulation with an implantable 4-channel peroneal nerve stimulator (ActiGait) allows independent electrode adjustment and leads to better functional results and an improved quality of life. The application of this therapeutic option is restricted to patients with a drop foot attributable to a lesion of the first motor neuron caused by stroke, multiple sclerosis, or tumors. In this paper, we present the first technical note with possible pitfalls of the surgical procedure and the perioperative care after implantation of ActiGait drop foot stimulators in 50 patients. PMID:26164191

  8. [Vitamin D and Alzheimer's disease: from an intriguing idea to a therapeutic option].

    PubMed

    Annweiler, Cédric

    2014-01-01

    Beyond the classically described regulation of calcium and bone metabolism, vitamin D is a neurosteroid hormone essential to neurophysiological function (regulation of neurotransmitters and neurotrophins) with anti-inflammatory and antioxidant neuroprotective action. In contrast, hypovitaminosis D, which is extremely frequent in the elderly, may result in neurological dysfunction and may explain part of the cognitive disorders in this population. Epidemiology is consistent with this notion and has repeatedly shown an association between hypovitaminosis D and cognitive decline, either in the general population or in Alzheimer's patients. Preliminary intervention trials confirm the causal relationship and quantify the cognitive effect of vitamin D supplementation in the elderly. This raises prospects for primary/secondary prevention of cognitive decline by exogenous supplies of vitamin D. In particular, although current anti-dementia drugs are only symptomatic, future treatment options could rely on drug combinations preventing several neurodegenerative mechanisms at once. As such, vitamin D enhances the efficacy of memantine in terms of neuronal protection and prevention of cognitive decline in Alzheimer's disease. PMID:24948022

  9. Emerging novel and antimicrobial-resistant respiratory tract infections: new drug development and therapeutic options.

    PubMed

    Zumla, Alimuddin; Memish, Ziad A; Maeurer, Markus; Bates, Matthew; Mwaba, Peter; Al-Tawfiq, Jaffar A; Denning, David W; Hayden, Frederick G; Hui, David S

    2014-11-01

    The emergence and spread of antimicrobial-resistant bacterial, viral, and fungal pathogens for which diminishing treatment options are available is of major global concern. New viral respiratory tract infections with epidemic potential, such as severe acute respiratory syndrome, swine-origin influenza A H1N1, and Middle East respiratory syndrome coronavirus infection, require development of new antiviral agents. The substantial rise in the global numbers of patients with respiratory tract infections caused by pan-antibiotic-resistant Gram-positive and Gram-negative bacteria, multidrug-resistant Mycobacterium tuberculosis, and multiazole-resistant fungi has focused attention on investments into development of new drugs and treatment regimens. Successful treatment outcomes for patients with respiratory tract infections across all health-care settings will necessitate rapid, precise diagnosis and more effective and pathogen-specific therapies. This Series paper describes the development and use of new antimicrobial agents and immune-based and host-directed therapies for a range of conventional and emerging viral, bacterial, and fungal causes of respiratory tract infections. PMID:25189352

  10. Human Umbilical Cord Mesenchymal Stem Cells: A New Therapeutic Option for Tooth Regeneration

    PubMed Central

    Chen, Yuanwei; Yu, Yongchun; Chen, Lin; Ye, Lanfeng; Cui, Junhui; Sun, Quan; Li, Kaide; Li, Zhiyong; Liu, Lei

    2015-01-01

    Tooth regeneration is considered to be an optimistic approach to replace current treatments for tooth loss. It is important to determine the most suitable seed cells for tooth regeneration. Recently, human umbilical cord mesenchymal stem cells (hUCMSCs) have been regarded as a promising candidate for tissue regeneration. However, it has not been reported whether hUCMSCs can be employed in tooth regeneration. Here, we report that hUCMSCs can be induced into odontoblast-like cells in vitro and in vivo. Induced hUCMSCs expressed dentin-related proteins including dentin sialoprotein (DSP) and dentin matrix protein-1 (DMP-1), and their gene expression levels were similar to those in native pulp tissue cells. Moreover, DSP- and DMP-1-positive calcifications were observed after implantation of hUCMSCs in vivo. These findings reveal that hUCMSCs have an odontogenic differentiation potency to differentiate to odontoblast-like cells with characteristic deposition of dentin-like matrix in vivo. This study clearly demonstrates hUCMSCs as an alternative therapeutic cell source for tooth regeneration. PMID:26136785

  11. The challenge of Clostridium difficile infection: Overview of clinical manifestations, diagnostic tools and therapeutic options.

    PubMed

    Postma, Nynke; Kiers, Dorien; Pickkers, Peter

    2015-12-01

    The most important infectious cause of antibiotic-associated diarrhoea and colitis is Clostridium difficile, which is a Gram-positive, anaerobic, spore-forming, toxin-producing bacillus. In this overview we will discuss the diagnostic and therapeutic management of patients presenting with suspected or proven C. difficile infection (CDI). The clinical spectrum varies from asymptomatic C. difficile carriers to fulminant colitis with multi-organ failure. The onset of symptoms is usually within 2 weeks after initiation of antibiotic treatment. Diagnosis is based on the combination of clinical symptoms and either a positive stool test for C. difficile toxins or endoscopic or histological findings of pseudomembranous colitis. There is no indication for treatment of asymptomatic carriers, but patients with proven CDI should be treated. Treatment consists of cessation of the provoking antibiotic treatment, secondary prevention by infection control strategies, and treatment with metronidazole or vancomycin. Treatment of recurring CDI, severe infection, the need for surgery, and novel alternative potential treatment strategies will be discussed. The concurrent increase in multiresistant colonisation and increasing numbers of asymptomatic carriers of C. difficile will lead to an increase of the situation in which patients with severe infections, treated with broad-spectrum antibiotics, will develop concurrent severe CDI. We will discuss possible therapy strategies for these patients. PMID:26612229

  12. Unmet treatment needs in schizophrenia patients: is asenapine a potential therapeutic option?

    PubMed

    Pompili, Maurizio; Serafini, Gianluca; Innamorati, Marco; Ambrosi, Elisa; Telesforo, Ludovica; Venturini, Paola; Giordano, Gloria; Battuello, Michele; Lester, David; Girardi, Paolo

    2011-07-01

    Adverse metabolic events, such as increased adiposity, hyperglycemia, diabetes mellitus and dyslipidemia, have been associated with treatment using atypical antipsychotic medications. However, the complexity of some of the reports on this problem and marketing efforts in this area may make it difficult for psychiatrists to remain fully and accurately informed about the metabolic complications of atypical antipsychotic therapy. Little is currently known about how psychiatrists view what they have read or heard, how they perceive the available information and how this affects their management of patients with schizophrenia. A number of studies have demonstrated that nonadherence to the medication regimen in schizophrenia is associated with poor symptomatic outcome, increased risk of relapse, more frequent use of compulsory treatment and increased risk of suicide and severe self-harm. Suicide is a major cause of death among schizophrenic patients, and their attitude toward medication can make the difference between a proper therapeutic regimen that protects patients from suicide risk versus discontinuation of treatments that are associated with disabling symptoms, some of which are risk factors for suicide. We review the characteristics of a new drug, asenapine, that may improve adherence in patients as a result of a distinctive receptor profile that may be associated with fewer side effects than other second-generation antipsychotic drugs. PMID:21721916

  13. [Lower urinary tract obstruction (LUTO)--clinical picture, prenatal diagnostics and therapeutic options].

    PubMed

    Bildau, J; Enzensberger, C; Degenhardt, J; Kawecki, A; Tenzer, A; Kohl, T; Stressig, R; Ritgen, J; Utsch, B; Axt-Fliedner, R

    2014-02-01

    The aetiology of urinary tract obstructions (LUTO) is heterogeneous. The most common entities are isolated posterior urethral valves or urethral atresia in male foetuses. In female foetuses LUTO is frequently a part of complex malformations. The natural history of LUTO is characterised by high morbidity and mortality due to the development of severe pulmonary hypoplasia caused by oligo- or anhydramnios affecting the cannalicular phase (16-24 weeks of gestation) of pulmonary development. The degree of renal damage is variable and ranges from mild renal impairment in infancy to end-stage renal insufficiency, necessitating dialysis and transplantation. Foetal interventions in order to bypass the obstruction are biologically plausible and technically feasible. Vesico-amniotic shunting as well as (currently less frequent) foetoscopic cystoscopy and laser ablation of posterior urethral valves are minimally invasive treatment options. Previous reports indicate that prenatal therapy is suitable to reduce perinatal mortality but does not improve postnatal renal function. Selection of foetuses who may profit from prenatal intervention is aggravated by the lack of reliable prognostic criteria for the prediction of postnatal renal function in both ultrasound and foetal urine analysis. Furthermore, there is no randomised trial available at the time of writing. Because of a relevant complication rate and still no clear evidence for foetal benefit, interventions should be performed in specialised centres. Further studies are necessary to improve case selection of affected foetuses and to evaluate the impact of interventions in earlier gestational weeks. The data from the PLUTO trial (percutaneous shunting in lower urinary tract obstruction) conducted by the University of Birmingham may help to answer these questions. In the meantime selection of foetuses for prenatal intervention puts high requirements on interdisciplinary counselling in every case. A general treatment algorithm

  14. Allele-Specific Suppression of Mutant Huntingtin Using Antisense Oligonucleotides: Providing a Therapeutic Option for All Huntington Disease Patients

    PubMed Central

    Skotte, Niels H.; Southwell, Amber L.; Østergaard, Michael E.; Carroll, Jeffrey B.; Warby, Simon C.; Doty, Crystal N.; Petoukhov, Eugenia; Vaid, Kuljeet; Kordasiewicz, Holly; Watt, Andrew T.; Freier, Susan M.; Hung, Gene; Seth, Punit P.; Bennett, C. Frank; Swayze, Eric E.; Hayden, Michael R.

    2014-01-01

    Huntington disease (HD) is an inherited, fatal neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The mutant protein causes neuronal dysfunction and degeneration resulting in motor dysfunction, cognitive decline, and psychiatric disturbances. Currently, there is no disease altering treatment, and symptomatic therapy has limited benefit. The pathogenesis of HD is complicated and multiple pathways are compromised. Addressing the problem at its genetic root by suppressing mutant huntingtin expression is a promising therapeutic strategy for HD. We have developed and evaluated antisense oligonucleotides (ASOs) targeting single nucleotide polymorphisms that are significantly enriched on HD alleles (HD-SNPs). We describe our structure-activity relationship studies for ASO design and find that adjusting the SNP position within the gap, chemical modifications of the wings, and shortening the unmodified gap are critical for potent, specific, and well tolerated silencing of mutant huntingtin. Finally, we show that using two distinct ASO drugs targeting the two allelic variants of an HD-SNP could provide a therapeutic option for all persons with HD; allele-specifically for roughly half, and non-specifically for the remainder. PMID:25207939

  15. Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma.

    PubMed

    Mimura, Naoya; Fulciniti, Mariateresa; Gorgun, Gullu; Tai, Yu-Tzu; Cirstea, Diana; Santo, Loredana; Hu, Yiguo; Fabre, Claire; Minami, Jiro; Ohguchi, Hiroto; Kiziltepe, Tanyel; Ikeda, Hiroshi; Kawano, Yutaka; French, Maureen; Blumenthal, Martina; Tam, Victor; Kertesz, Nathalie L; Malyankar, Uriel M; Hokenson, Mark; Pham, Tuan; Zeng, Qingping; Patterson, John B; Richardson, Paul G; Munshi, Nikhil C; Anderson, Kenneth C

    2012-06-14

    Multiple myeloma (MM) cells are characterized by high protein synthesis resulting in chronic endoplasmic reticulum (ER) stress, which is adaptively managed by the unfolded protein response. Inositol-requiring enzyme 1α (IRE1α) is activated to splice X-box binding protein 1 (XBP1) mRNA, thereby increasing XBP1s protein, which in turn regulates genes responsible for protein folding and degradation during the unfolded protein response. In this study, we examined whether IRE1α-XBP1 pathway is a potential therapeutic target in MM using a small-molecule IRE1α endoribonuclease domain inhibitor MKC-3946. MKC-3946 triggered modest growth inhibition in MM cell lines, without toxicity in normal mononuclear cells. Importantly, it significantly enhanced cytotoxicity induced by bortezomib or 17-AAG, even in the presence of bone marrow stromal cells or exogenous IL-6. Both bortezomib and 17-AAG induced ER stress, evidenced by induction of XBP1s, which was blocked by MKC-3946. Apoptosis induced by these agents was enhanced by MKC-3946, associated with increased CHOP. Finally, MKC-3946 inhibited XBP1 splicing in a model of ER stress in vivo, associated with significant growth inhibition of MM cells. Taken together, our results demonstrate that blockade of XBP1 splicing by inhibition of IRE1α endoribonuclease domain is a potential therapeutic option in MM. PMID:22538852

  16. Mycoplasma genitalium infection: current treatment options, therapeutic failure, and resistance-associated mutations.

    PubMed

    Couldwell, Deborah L; Lewis, David A

    2015-01-01

    determine the optimal therapeutic dosing schedules for both agents to effect clinical cure and minimize the risk of emergent antimicrobial resistance. Continual inappropriate M. genitalium treatments will likely lead to untreatable infections in the future. PMID:26060411

  17. [Cell-based therapies - an innovative therapeutic option in ophthalmology: Treating corneal diseases with stem cells].

    PubMed

    Bakker, Ann-Christin; Langer, Barbara

    2015-11-01

    Pathological changes and disorders of the cornea are a major cause of severe visual impairment and blindness. Replacement of a pathologically altered cornea with healthy corneal tissue from the eye of a suitable donor is among the most common and successful transplantation procedures in medicine. In Germany, approximately 5000-6000 corneal transplantations are performed each year, but the total demand per year is estimated to be twice as high. With a success rate of 90%, the outcome of cornea transplantation is very favourable. However, long-term maintenance and regeneration of a healthy new cornea requires tissue-specific corneal stem cells residing at the basal layer of the limbus, which is the annular transition zone between the cornea and sclera. When this important limbal stem cell population is destroyed or dysfunctional, a pathological condition known as limbal stem cell deficiency (LSCD) manifests. Limbal stem cell deficiency describes conditions associated with impaired corneal wound healing and regeneration. In this situation, transplantation of healthy limbal stem cells is the only curative treatment approach for restoration of an intact and functional ocular surface. To date, treatment of LSCD presents a great challenge for ophthalmologists. However, innovative, cell-therapeutic approaches may open new, promising treatment perspectives. In February 2015, the European Commission granted marketing authorization to the first stem cell-based treatment in the European Union. The product named Holoclar® is an advanced therapy medicinal product (ATMP) for the treatment of moderate to severe LSCD due to physical and chemical burns in adults. Further cell-based treatment approaches are in clinical development. PMID:26459569

  18. Mycoplasma genitalium infection: current treatment options, therapeutic failure, and resistance-associated mutations

    PubMed Central

    Couldwell, Deborah L; Lewis, David A

    2015-01-01

    determine the optimal therapeutic dosing schedules for both agents to effect clinical cure and minimize the risk of emergent antimicrobial resistance. Continual inappropriate M. genitalium treatments will likely lead to untreatable infections in the future. PMID:26060411

  19. Transfusion of sickle cells may be a therapeutic option for patients suffering metastatic disease.

    PubMed

    Goldberg, Joel S

    2010-04-01

    Red blood cells from patients with sickle cell disease will sickle under conditions of hypoxemia and acidosis which is a similar milieu found in malignant tumors. While control of tumor angiogenesis has long been a goal of cancer therapy, selective occlusion of tumor blood supply may be achieved by transfusion of sickle cells into patients who suffer metastatic cancer. Although this potential therapy has not been previously reported in the medical literature, the concept may have been elusive to medical mainstream thinking because it requires transfusion of diseased cells. For this therapy to be effective, other environmental factors may need to be manipulated such inducing mild hypoxemia or hypercarbia (respiratory acidosis) to induce red cell sickling. Preliminary evidence supportive of this therapeutic approach to cancer treatment is provided by case evidence that sickle cell occlusion of a malignant brain tumor (glioma) produced tumor necrosis. Also sickle cells have been successfully transfused into primates. Furthermore, donor blood is crossmatched and transfused into patients suffering from sickle cell disease regularly in clinics and this procedure is associated with acceptable morbidity. Most importantly, animal models of sickle cell disease and cancer currently exist, and this theory could be tried with available technologies including ultrasound detection of vaso-occlusion. While the proposed therapy may not cure metastatic cancer, this treatment could prove useful for decreasing the size and perhaps the pain from metastatic tumor burden. Therefore, it is hypothesized that ABO Rh compatible crossmatched sickle cells transfused into patients who suffer metastatic cancer under controlled conditions of blood oxygenation and pH will selectively produce vaso-occlusive infarcts in malignant tumors and be a useful therapy. The author hopes for further investigations. PMID:20022432

  20. [Weighing use and safety of therapeutic agents and feed additives (author's transl)].

    PubMed

    van der Wal, P

    1982-02-01

    (1) The pros and cons of using feed additives and therapeutic agents may be successfully weighed in the light of carefully considered consumer requirements. (2) The socio-economic interests of the producer and the welfare of the animal will also determine the response of the production apparatus to consumer requirements. (3) Consumption of the current amounts of products of animal origin and maintenance of price and quality will only be feasible in the event of rational large-scale production in which constituents used in nutrition, prophylaxis and therapeutics are highly important factors. (4) Using these ingredients should be preceded by accurate evaluation of their use and safety. Testing facilities, conduct of studies and reporting should be such as to make the results nationally and internationally acceptable to all those concerned. (5) In deciding whether feed constituents are acceptable in view of the established use and safety, compliance will have to be sought with those standards which are accepted in other fields of society. Measures which result in raising the price of food without actually helping to reduce the risks to the safety of man, animals and environment, are likely to be rejected by any well-informed consumer who is aware of the facts. (6) For accurate weighing of use and safety at a national level, possibilities are hardly adequate in Europe. Decisions reached within the framework of the European Community, also tuned to U.S.A.- conditions are rightly encouraged. A centrally managed professionally staffed and equipped test system in the European Community would appear to be indispensable. PMID:7058519

  1. New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials

    PubMed Central

    Kotova, Svetlana; Wong, Raymond M; Cameron, Robert B

    2015-01-01

    Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease. PMID:25670913

  2. Inflammatory Acne Treatment: Review of Current and New Topical Therapeutic Options.

    PubMed

    Zeichner, Joshua A

    2016-01-01

    Acne vulgaris (AV) is an inflammatory skin disease characterized by the presence of comedones, papules, pustules, and nodules. Consensus guidelines recommend the use of combination therapy using different drugs with complementary mechanisms of action to best address as many acne pathogenic factors as possible at the same time. Topical acne medications exist as individual agents that may be combined in physician-recommended regimens or as pre-formulated fixed-dose combination products. In addition, there are several new and promising topical therapies currently being developed that work by different mechanisms of action from traditionally used acne therapies. The following review will cover commonly used drugs, newcomers to the market, and what the future holds for the topical treatment of AV. PMID:26741391

  3. Certolizumab pegol - A new therapeutic option for refractory disseminated pyoderma gangrenosum associated with Crohn's disease.

    PubMed

    Hurabielle, Charlotte; Schneider, Pierre; Baudry, Clotilde; Bagot, Martine; Allez, Matthieu; Viguier, Manuelle

    2016-01-01

    Systemic steroids, in association or not with cyclosporin, are indicated for the treatment of large or widespread Pyoderma gangrenosum (PG). We report the case of a 27-year-old woman with a 15-year history of severe Crohn's disease, who developed a severe and disseminated PG, refractory to multiple lines of treatment. Infliximab and adalimumab were contraindicated, either because of allergy or of ineffectiveness on Crohn's disease. The addition of certolizumab pegol to the baseline treatment, associating systemic steroids and tacrolimus, finally allowed the complete healing of PG. Oral prednisone was stopped and tacrolimus was decreased, without any cutaneous or digestive relapse. Certolizumab pegol could be an alternative therapy in the treatment of PG in case of intolerance or ineffectiveness of the other anti-tumor necrosis factor (anti-TNF) therapies. PMID:25909366

  4. Early Treatment with Addition of Low Dose Prednisolone to Methotrexate Improves Therapeutic Outcome in Severe Psoriatic Arthritis

    PubMed Central

    Mahajan, Vikram K; Sharma, Anju Lath; Chauhan, Pushpinder S; Mehta, Karaninder S; Sharma, Nand Lal

    2013-01-01

    Psoriatic arthritis (PsA) is increasingly being recognized to cause progressive joint damage and disability. PsA unresponsive to non-steroidal anti-inflammatory drugs (NSAIDs), the conventional first-line choice of treatment, is usually managed with disease-modifying antirheumatic drugs (DMARDs) especially methotrexate. An 18-year-old HIV-negative male had progressively severe PsA of 4-month duration that was nearly confining him to a wheel chair. He did not respond to multiple NSAIDs, alone or in combination with methotrexate (15 mg/week), given for 4 weeks. Addition of prednisolone (10 mg on alternate days) controlled his symptoms within a week. The NSAIDs could be withdrawn after 4 weeks as the treatment progressed. The doses were tapered for methotrexate (5 mg/week) and prednisolone (2.5 mg on alternate days) every 8 weekly subsequently during 15 months of follow-up without recurrence/deformities or drug toxicity. For years, the use of corticosteroids in psoriasis has been criticized for their propensity to exacerbate the skin disease on withdrawal. However, monitored use of corticosteroids, even in low doses, combined with DMARDs may be a good therapeutic option in early stage of the PsA rather than ‘steroid rescue’ later. This will help in early control of joint inflammation, prevent joint damage and maintain long-term good functional capacity and quality of life. This may be useful when the cost or availability of biologics precludes their use. However, we discourage the use of corticosteroids as monotherapy. PMID:23723489

  5. RPGR-associated retinopathy: clinical features, molecular genetics, animal models and therapeutic options.

    PubMed

    Tee, James J L; Smith, Alexander J; Hardcastle, Alison J; Michaelides, Michel

    2016-08-01

    Retinitis pigmentosa GTPase regulator (RPGR) gene sequence variants account for the vast majority of X linked retinitis pigmentosa (RP), which is one of the most severe forms of RP. Symptoms of nyctalopia typically begin in childhood, with increasing loss of peripheral visual field during teenage years, and progressive central visual loss during the second to fourth decade of life. There is however marked intrafamilial and interfamilial phenotypic heterogeneity in affected males and carrier females. There is now a far greater understanding of the range of phenotypes associated with variants in this gene; including rod-cone dystrophy, cone-rod dystrophy, cone dystrophy, macular dystrophy and non-ocular phenotypes. There are also increasingly established genotype-phenotype associations and structure-function correlations. RPGR is involved in ciliary function, with ciliary dysfunction now recognised as the mechanism underlying a large proportion of inherited retinal disease. There has been significant progress in identifying naturally occurring animal models and developing novel models to define the underlying disease mechanisms and to test gene replacement therapy, in addition to advances in human retinal imaging, culminating in completed and planned clinical trials. These significant developments will be discussed. PMID:26843488

  6. In-patient, short-term group psychotherapy – a therapeutic option for Bundeswehr soldiers?

    PubMed Central

    Zimmermann, Peter; Kröger, Norbert; Willmund, Gerd; Ströhle, Andreas; Heinz, Andreas; Hahne, Hans Heiner

    2008-01-01

    Objective: This study is to assess the efficacy of short-term group psychotherapy rooted in depth psychology for Bundeswehr soldiers suffering from depressive, neurotic, stress, or personality disorders. Method: 103 participants in the in-patient, closed group setting were evaluated prospectively and compared with a non-randomized waitlisted control group. Results: In all relevant SCL-90-R (Symptom-Check-List-90) and MMPI-K (Minnesota-Multiphasic-Personality-Inventory short-form) scales therapy resulted in significant improvements as compared with the initial values. The control group did not show any significant changes, the therapy group was significantly superior to the control group in the scales of MMPI-K and the GSI-Scale of the SCL-90-R. For soldiers with a stress-reactive disorder (F43), no differences in efficacy could be identified compared with the other diagnosis groups. Conclusion: The results were considered to indicate that in-patient, short-term group psychotherapy may, in combination with additional setting components, be helpful in improving psychological symptoms in German soldiers. The indication range of group therapy offered to Bundeswehr soldiers should be expanded to also include primary prophylaxis and the treatment of mental-health problems following deployments abroad, if applicable. PMID:19742280

  7. ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability

    PubMed Central

    Teixido, Cristina; Michels, Sebastian; Morales-Espinosa, Daniela; Viteri, Santiago; Hartmann, Wolfgang; Merkelbach-Bruse, Sabine; Fischer, Rieke; Schildhaus, Hans-Ulrich; Fassunke, Jana; Sebastian, Martin; Serke, Monika; Kaminsky, Britta; Randerath, Winfried; Gerigk, Ulrich; Ko, Yon-Dschun; Krüger, Stefan; Schnell, Roland; Rothe, Achim; Kropf-Sanchen, Cornelia; Heukamp, Lukas; Rosell, Rafael

    2015-01-01

    Background While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. Patients and Methods 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. Results 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations. Conclusion ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC. PMID:25868855

  8. Covered Biodegradable Stent: New Therapeutic Option for the Management of Esophageal Perforation or Anastomotic Leak

    SciTech Connect

    Cerna, Marie; Koecher, Martin Valek, Vlastimil; Aujesky, Rene; Neoral, Cestmir; Andrasina, Tomas; Panek, Jiri; Mahathmakanthi, Shankari

    2011-12-15

    Purpose: This study was designed to evaluate our experience with the treatment of postoperative anastomotic leaks and benign esophageal perforations with covered biodegradable stents. Materials and Methods: From 2008 to 2010, we treated five men with either an anastomotic leak or benign esophageal perforation by implanting of covered biodegradable Ella-BD stents. The average age of the patients was 60 (range, 38-74) years. Postoperative anastomotic leaks were treated in four patients (1 after esophagectomy, 1 after resection of diverticulum, 2 after gastrectomy). In one patient, perforation occurred as a complication of the treatment of an esophageal rupture (which occurred during a balloon dilatation of benign stenosis) with a metallic stent. Results: Seven covered biodegradable stents were implanted in five patients. Primary technical success was 100%. Clinical success (leak sealing) was achieved in four of the five patients (80%). Stent migration occurred in three patients. In two of these patients, the leak had been sealed by the time of stent migration, therefore no reintervention was necessary. In one patient an additional stent had to be implanted. Conclusion: The use of biodegradable covered stents for the treatment of anastomotic leaks or esophageal perforations is technically feasible and safe. The initial results are promising; however, larger number of patients will be required to evaluate the capability of these biodegradable stents in the future. The use of biodegradable material for coverage of the stent is essential.

  9. Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins

    PubMed Central

    Tenenbaum, Alexander; Fisman, Enrique Z; Motro, Michael; Adler, Yehuda

    2006-01-01

    Lowering of low-density lipoprotein cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is clearly efficacious in the treatment and prevention of coronary artery disease. However, despite increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is being paid now to combined atherogenic dyslipidemia which typically presents in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or "lipid quartet"): hypertriglyceridemia, low high-density lipoprotein cholesterol levels, a preponderance of small, dense low-density lipoprotein particles and an accumulation of cholesterol-rich remnant particles (e.g. high levels of apolipoprotein B) – emerged as the greatest "competitor" of low-density lipoprotein-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP – Bezafibrate Infarction Prevention study, HHS – Helsinki Heart Study, VAHIT – Veterans Affairs High-density lipoprotein cholesterol Intervention Trial and FIELD – Fenofibrate Intervention and Event Lowering in Diabetes) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants and cholesteryl ester transfer protein inhibition. In addition, bezafibrate as pan-peroxisome proliferator activated receptor activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism and insulin sensitivity. Because fibrates, niacin, ezetimibe and statins each regulate serum lipids by different mechanisms, combination therapy

  10. Diagnosis, Management, and New Therapeutic Options in Childhood Neurofibromatosis Type 2 and Related Forms.

    PubMed

    Ruggieri, Martino; Praticò, Andrea Domenico; Evans, Dafydd Gareth

    2015-12-01

    Neurofibromatosis type 2 (NF2; MIM # 101000) is an autosomal dominant disorder characterized by the development of vestibular schwannomas (VSs); schwannomas of other cranial, spinal, and cutaneous nerves; cranial and spinal meningiomas or other central nervous system tumors (eg, ependymomas and astrocytomas) or both. Additional features include eye (eg, early onset cataracts, optic nerve sheath meningiomas, retinal or pigment epithelial hamartomas or both, and epithelial retinal membranes) and skin abnormalities (eg, flat dermal [NF2 plaques] or spherical subcutaneous nodular schwannomas or both, and few, atypical café-au-lait spots). Clinically, children with NF2 fall into 2 main groups: (1) congenital NF2 with bilateral VSs detected as early as the first days to months of life, which can be stable or asymptomatic for 1-2 decades and suddenly progress; and (2) severe prepubertal (Wishart type) NF2 with multiple (and rapidly progressive) central nervous system tumors other-than-VS, which usually presents first, years before VSs, both associated with more marked skin and eye involvement (vs the classical mild adult [Gardner type] NF2, with bilateral VSs presenting in young adulthood, sometimes as the only disease feature). Individuals manifesting unilateral VS associated with ipsilateral meningiomas or multiple schwannomas localized to a part of the peripheral nervous system have mosaic or segmental NF2; individuals developing multiple nonVS, nonintradermal cranial, spinal, and peripheral schwannomas (histologically proven) have schwannomatosis (SWNTS). NF2 is caused by mutations in the NF2 gene at chromosome 22q12.1, which encodes for a protein called merlin or schwannomin, most similar to the exrin-readixin-moesin proteins; mosaic or segmental NF2 is because of mosaic phenomena for the NF2 gene, whereas SWNTS is caused by germline and possibly mosaic mutations either in the SMARCB1 gene (SWNTS1; MIM # 162091) or the LZTR1 gene (SWNTS2; MIM # 615670), both falling

  11. Enhanced external counterpulsation--a therapeutic option for patients with chronic cardiovascular problems.

    PubMed

    Linnemeier, Georgiann

    2002-01-01

    EECP is a non-invasive outpatient treatment for cardiovascular disease refractory to medical and/or surgical therapy. It has been cleared by the Food and Drug Administration for the treatment of a variety of cardiac conditions including congestive heart failure and chronic stable angina. A course of therapy consists of 35 one-hour treatments given once or twice daily. Augmented diastolic pressure and retrograde flow improve myocardial perfusion, while systolic unloading reduces cardiac workload and oxygen requirements. As a result of this treatment, most patients experience increased time to onset of ischemia, increased exercise tolerance, a reduction in the number and severity of anginal episodes, and improved quality of life. Evidence has been presented that this effect lasts well beyond the immediate post-treatment period with some patients symptom-free for several years. Because patients principally seek medical care to live longer or feel better, heart programs need to offer their patients the latest medical advances which have the potential of improving patient survival and health status (symptoms, functioning, and quality of life). Heart programs face a challenging economic future. Increased competition makes it necessary to implement strategies for market differentiation. Those programs most attuned to what their patients define as critical to quality would be most likely to succeed. Over the past decade, there have been a growing number of patients with chronic angina who have exhausted the standard revascularization armamentarium. Because coronary artery bypass grafts occlude and restenosis occurs at angioplasty sites, many patients no longer have suitable coronary anatomy for additional procedures. Also, as the population ages, the proportion of patients with diffuse coronary disease, congestive heart failure, significant co-morbid illness, and poor functional status increases. The incapacitating effects of angina on patients' abilities to work, maintain

  12. Percutaneous transluminal angioplasty and stenting of coeliac artery stenosis in the treatment of mesenteric angina: a case report and review of therapeutic options.

    PubMed

    Mohammed, A; Teo, N B; Pickford, I R; Moss, J G

    2000-12-01

    We report the case of a 72-year-old gentleman with mesenteric angina who was successfully treated with stenting of a coeliac artery stenosis using a Palmaz stent, and review the therapeutic options in the management of mesenteric angina. PMID:11153434

  13. Diabetic gastroparesis: Therapeutic options.

    PubMed

    Alam, Uazman; Asghar, Omar; Malik, Rayaz Ahmed

    2010-08-01

    Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient's quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG. PMID:22127672

  14. 75 FR 29680 - Importation of Mexican Hass Avocados; Additional Shipping Options

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... specify that the boxes, bins, or crates would have to be safeguarded from insects by covering with a lid, insect-proof mesh, or by some other barrier that prevents insects from entering the boxes or bins. Those... provide an additional layer of protection against insects of concern. The regulations also contain...

  15. Alteration of the intestinal microbiota as a cause of and a potential therapeutic option in irritable bowel syndrome.

    PubMed

    König, J; Brummer, R J

    2014-09-01

    The intestinal microbiota forms a complex ecosystem that is in close contact with its host and has an important impact on health. An increasing number of disorders are associated with disturbances in this ecosystem. Also patients suffering from irritable bowel syndrome (IBS) show an altered composition of their gut microbiota. IBS is a multifactorial chronic disorder characterised by various abdominal complaints and a worldwide prevalence of 10-20%. Even though its aetiology and pathophysiology are complex and not well understood, it is widely accepted that aberrations along the microbe-gut-brain axis are involved. In this review, it will be discussed how exogenous factors, e.g. antibiotics, can cause disbalance in the intestinal microbiota and thereby contribute to the development of IBS. In addition, several new IBS treatment options that aim at re-establishing a healthy, beneficial ecosystem will be described. These include antibiotics, probiotics, prebiotics and faecal transplantation. PMID:24583610

  16. 46 CFR Appendix E to Subpart C of... - Optional Rider for Additional NVOCC Financial Responsibility (Optional Rider to Form FMC-48...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Responsibility (Optional Rider to Form FMC-48) E Appendix E to Subpart C of Part 515 Shipping FEDERAL MARITIME...; Claims Against Ocean Transportation Intermediaries Pt. 515, Subpt. C, App. E Appendix E to Subpart C of... Commission, 800 North Capitol Street, NW., Washington, DC 20573-0001 or e-mail: secretary@fmc.gov....

  17. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  18. [The potential role of microbiota in major psychiatric disorders: Mechanisms, preclinical data, gastro-intestinal comorbidities and therapeutic options].

    PubMed

    Fond, Guillaume; Chevalier, Grégoire; Eberl, Gerard; Leboyer, Marion

    2016-01-01

    While forecasts predict an increase in the prevalence of mental health disorders in the worldwide general population, the response rate to classical psychiatric treatment remains unsatisfactory. Resistance to psychotropic drugs can be due to clinical, pharmacological, pharmacokinetic, and pharmacodynamic factors. Among these factors, recent animal findings suggest that microbiota may have an underestimated influence on its host's behavior and on drug metabolism that may explain ineffectiveness or increased side effects of psychiatric medications such as weight gain. The following issues were identified in the present review: (i) microbiota dysbiosis and putative consequences on central nervous system functioning; (ii) chronic microbiota dysbiosis-associated illnesses in humans; (iii) microbiota-oriented treatments and their potential therapeutic applications in psychiatry. PMID:26653939

  19. Hedgehog signaling pathway: A novel target for cancer therapy: Vismodegib, a promising therapeutic option in treatment of basal cell carcinomas

    PubMed Central

    Abidi, Afroz

    2014-01-01

    The Hedgehog signaling pathway is one of the major regulators of cell growth and differentiation during embryogenesis and early development. It is mostly quiescent in adults but inappropriate mutation or deregulation of the pathway is involved in the development of cancers. Therefore; recently it has been recognized as a novel therapeutic target in cancers. Basal cell carcinomas (BCC) and medulloblastomas are the two most common cancers identified with mutations in components of the hedgehog pathway. The discovery of targeted Hedgehog pathway inhibitors has shown promising results in clinical trials, several of which are still undergoing clinical evaluation. Vismodegib (GDC-0449), an oral hedgehog signaling pathway inhibitor has reached the farthest in clinical development. Initial clinical trials in basal cell carcinoma and medulloblastoma have shown good efficacy and safety and hence were approved by U.S. FDA for use in advanced basal cell carcinomas. This review highlights the molecular basis and the current knowledge of hedgehog pathway activation in different types of human cancers as well as the present and future prospects of the novel drug vismodegib. PMID:24550577

  20. Combination of JAK2 and HSP90 inhibitors: an effective therapeutic option in drug-resistant chronic myelogenous leukemia

    PubMed Central

    Perazzona, Bastianella; Sun, Xiaoping; Lin, Yu-Hsi; Arlinghaus, Ralph B.

    2016-01-01

    Recent studies suggest that JAK2 serves as a novel therapeutic target in Bcr-Abl+ chronic myelogenous leukemia (CML). We have reported the existence of an HSP90- associated high molecular weight network complex (HMWNC) that is composed of HSP90 client proteins BCR-ABL, JAK2, and STAT3 in wild type Bcr-Abl+ leukemic cells. Here we showed that the HSP90-HMWNC is present in leukemia cells from CML patients in blast stage, and in Imatinib (IM)-resistant 32Dp210 (T315I) leukemia cells. We found that the HSP90-HMWNC could be disassembled by depleting JAK2 with either Jak2-specific shRNA or treatment with JAK2 inhibitors (TG101209 or Ruxolitinib) and HSP90 inhibitor (AUY922). Combinational treatment with JAK2 and HSP90 inhibitors diminished the activation of BCR-ABL, JAK2 and its downstream targets. As a result, the IM-resistant 32Dp210 T315I cells underwent apoptosis. When administered in mice bearing 32Dp210 T315I leukemia, combinational therapy using Ruxolitinib and AUY922 prolonged the survival significantly. Thus, a combination of JAK2 and HSP90 inhibitors could be a powerful strategy for the treatment of CML, especially in IM-resistant patients. PMID:27551334

  1. Disease modeling and cell based therapy with iPSC: future therapeutic option with fast and safe application

    PubMed Central

    2014-01-01

    Induced pluripotent stem cell (iPSC) technology has shown us great hope to treat various human diseases which have been known as untreatable and further endows personalized medicine for future therapy without ethical issues and immunological rejection which embryonic stem cell (hES) treatment has faced. It has been agreed that iPSCs knowledge can be harnessed from disease modeling which mimics human pathological development rather than trials utilizing conventional rodent and cell lines. Now, we can routinely generate iPSC from patient specific cell sources, such as skin fibroblast, hair follicle cells, patient blood samples and even urine containing small amount of epithelial cells. iPSC has both similarity and dissimilarity to hES. iPSC is similar enough to regenerate tissue and even full organism as ES does, however what we want for therapeutic advantage is limited to regenerated tissue and lineage specific differentiation. Depending on the lineage and type of cells, both tissue memory containing (DNA rearrangement/epigenetics) and non-containing iPSC can be generated. This makes iPSC even better choice to perform disease modeling as well as cell based therapy. Tissue memory containing iPSC from mature leukocytes would be beneficial for curing cancer and infectious disease. In this review, the benefit of iPSC for translational approaches will be presented. PMID:24724061

  2. Sarcomatoid mesothelioma: future advances in diagnosis, biomolecular assessment, and therapeutic options in a poor-outcome disease.

    PubMed

    Galetta, Domenico; Catino, Annamaria; Misino, Andrea; Logroscino, Antonio; Fico, Maria

    2016-04-18

    Malignant pleural mesothelioma (MPM) is the most frequent pleural neoplasm, with asbestos exposure as one of the recognized carcinogen agents, causative in 80% of cases. The prognosis is poor; median survival of untreated cases is 6-9 months, with fewer than 5% of patients surviving 5 years. Sarcomatoid mesothelioma (SM) represents the subtype with the worst outcome and median survival ranging from 3.5 to 8 months. In the last few years, an accurate differentiation between the subtypes of MPM has become a crucial issue, due to differences in chemosensitivity and clinical outcome, and several studies have evaluated different immunohistochemical markers to better define the diagnosis. The different and worse outcome of patients with SM and, in general, nonepithelioid subtypes makes it intriguing to select these cases to better study the biomolecular profile in order to find factors linked to prognosis and/or predictive of therapeutic response. Considering recent studies on miRNA and genetic mapping, further investigation of this rare subtype might represent a field for basic and clinical-translational research providing for more tailored therapies. PMID:26108245

  3. Combination of JAK2 and HSP90 inhibitors: an effective therapeutic option in drug-resistant chronic myelogenous leukemia.

    PubMed

    Chakraborty, Sandip N; Leng, Xiaohong; Perazzona, Bastianella; Sun, Xiaoping; Lin, Yu-Hsi; Arlinghaus, Ralph B

    2016-05-01

    Recent studies suggest that JAK2 serves as a novel therapeutic target in Bcr-Abl+ chronic myelogenous leukemia (CML). We have reported the existence of an HSP90- associated high molecular weight network complex (HMWNC) that is composed of HSP90 client proteins BCR-ABL, JAK2, and STAT3 in wild type Bcr-Abl+ leukemic cells. Here we showed that the HSP90-HMWNC is present in leukemia cells from CML patients in blast stage, and in Imatinib (IM)-resistant 32Dp210 (T315I) leukemia cells. We found that the HSP90-HMWNC could be disassembled by depleting JAK2 with either Jak2-specific shRNA or treatment with JAK2 inhibitors (TG101209 or Ruxolitinib) and HSP90 inhibitor (AUY922). Combinational treatment with JAK2 and HSP90 inhibitors diminished the activation of BCR-ABL, JAK2 and its downstream targets. As a result, the IM-resistant 32Dp210 T315I cells underwent apoptosis. When administered in mice bearing 32Dp210 T315I leukemia, combinational therapy using Ruxolitinib and AUY922 prolonged the survival significantly. Thus, a combination of JAK2 and HSP90 inhibitors could be a powerful strategy for the treatment of CML, especially in IM-resistant patients. PMID:27551334

  4. [Are there alternative therapeutical options other than CPAP in the treatment of the obstructive sleep apnea syndrome].

    PubMed

    Randerath, W; Bauer, M; Blau, A; Fietze, I; Galetke, W; Hein, H; Maurer, J T; Orth, M; Rasche, K; Rühle, K-H; Sanner, B; Stuck, B A; Verse, T

    2007-07-01

    Many patients with the obstructive sleep apnea syndrome (OSAS) look for alternative conservative or surgical therapies to avoid to be treated with continuous positive airway pressure. In view of the high prevalence and the relevant impairment of the patients lots of methods are offered which promise definitive cure or relevant improvement of OSAS. The working group "Apnea" in the German Society of Sleep Medicine and Research established a task force to evaluate the scientific literature on non-CPAP therapies in the treatment of OSAS according to the standards of evidence-based medicine. This paper summarizes the results of the task force. The data were unsatisfactorily for most of the methods. Sufficient data were available for intraoral appliances (IOA) and the maxillomandibular osteotomy (MMO). IOA's can reduce mild to moderate respiratory disturbances, MMO are efficient in the short and long term but are performed only in special situations such as craniofacial dysmorphias. Weight reduction and body positioning cannot be recommended as a single treatment of OSAS. Most surgical procedures still lack sufficient data according to the criteria of evidence based medicine. Resections of muscular tissue within the soft palate have to be strictly avoided. But even success following gentle soft palate procedures is difficult to predict and often decreases after years. Results in other anatomical regions seem to be more stable over time. Today combined surgeries in the sense of multi-level surgery concepts are of increasing interest in the secondary treatment after failure of nasal ventilation therapy although more data from prospective controlled studies are needed. There is no evidence for any other treatment options. PMID:17538860

  5. MitraClip therapy in mitral regurgitation: a Markov model for the cost-effectiveness of a new therapeutic option.

    PubMed

    Guerin, Patrice; Bourguignon, Sandrine; Jamet, Nicolas; Marque, Sébastien

    2016-07-01

    Introduction Mitral regurgitation is a heart condition resulting from blood flowing from the left ventricle towards the left atrium, increasing the risk of heart failure and mortality. While surgery can greatly reduce these risks, some patients are not eligible, resulting in medication being their only therapeutic alternative. The MitraClip (Abbot Vascular) is a medical device that is percutaneously implanted and designed to eliminate leaking of the mitral valve. Methods The efficacy of the MitraClip strategy vs medical management was assessed using a 4-state Markov model based on the mitral regurgitation grade (mitral regurgitation grade 0, I/II, and III/IV, and death). At each 1-month cycle, patients were or were not hospitalized. The model analyzed a fictional population of 1000 patients over a 5-year period from a national Health Insurance perspective. The primary end-point was the number of deaths avoided. Data from the EVEREST II High Risk Study patients were used along with a literature review. Results At 5 years, among the 1000 patients, 276 deaths were found to be avoidable with the MitraClip strategy. The incremental cost-effectiveness ratio (ICER) was €93,363 per death avoided. The annual ICER was calculated to take into consideration excess costs resulting from the MitraClip over the first year (€29,984 vs €8557 for the reference strategy) and the reduction of costs in following years (€3122 for MitraClip vs €8557 for reference strategy). Thus, the mean ICER was calculated to be €20,720 per death avoided. Conclusion The MitraClip is a novel alternative therapy for mitral insufficiency in patients ineligible for surgery that may offer a medico-economic advantage. PMID:26909557

  6. The Role of Topical Brimonidine Tartrate Gel as a Novel Therapeutic Option for Persistent Facial Erythema Associated with Rosacea.

    PubMed

    Johnson, Andrew William; Johnson, Sandra Marchese

    2015-09-01

    Rosacea is a chronic inflammatory skin condition that commonly presents with persistent facial erythema with or without the coincident presence of flushing, telangiectasias, inflammatory papules or pustules, phymatous changes, or ocular involvement. Patients often present with a constellation of various signs and symptoms of the disease, and an individualized treatment plan should be tailored to a patient's unique clinical presentation. Previously available medications for rosacea have all targeted the inflammatory erythematous papules and pustules frequently associated with the disease, leaving a therapeutic gap for the common manifestation of persistent facial erythema. Brimonidine tartrate 0.33% gel was approved by the US Food and Drug Administration in August 2013 as the first medication available for the topical treatment of persistent facial erythema associated with rosacea. Brimonidine gel is a highly selective α2-adrenergic receptor agonist with potent vasoconstrictive effects, which leads to significant reduction of persistent facial erythema in the majority of patients when applied once daily. Based on large-scale clinical trials and post-marketing reports, brimonidine gel has maintained a good safety profile with a minority of patients experiencing adverse effects from its use, most of which are cutaneous in nature, mild-to-moderate in degree, occur early after initiation of treatment, often resolve spontaneously with continued use, and generally resolve after discontinuation of use. Among the reported adverse effects, two distinct manifestations of worsened erythema have been described. Brimonidine gel can be integrated into a treatment regimen along with concomitant therapies for facial papules and pustules with no increased risk of adverse events with combination therapy. Education about optimal application methods, setting reasonable expectations for treatment, and minimizing inflammation are important factors for the successful use of brimonidine

  7. Impaired IGF1-GH axis and new therapeutic options in Alström Syndrome patients: a case series

    PubMed Central

    2009-01-01

    Background Defects of the primary cilium and its anchoring structure, the basal body, cause a number of human genetic disorders, collectively termed ciliopathies: primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration. Alström syndrome is an extremely rare, autosomal recessive genetic disorder characterized by a group of signs and symptoms including infantile onset dilated cardiomyopathy, blindness, hearing impairment/loss, obesity, diabetes, hepatic and renal dysfunction. Because adult growth hormone deficiency and Alström Syndrome share some clinical and metabolic features, we studied the GH-IGF1 axis, using MRI techniques and dynamic tests in 3 unrelated patients with Alström syndrome. Case presentation The patients were hospitalized and the growth hormone stimulatory tests were made, as well as brain MRI. Insulin provocative test revealed a severe GH deficiency in these patients, defined by a peak response to insulin-induced hypoglycemia less than 3 ng/dl and IGF1 concentrations less than – 2SDS. We didn't find multiple pituitary hormone deficiency and we noticed only a severe GH deficiency in all three patients. The MRI study of the diencephalic and pituitary region was suggestive for the diagnosis of empty sella in one patient. One patient received Recombinant-GH replacement for one year with very good results, one underwent a gastric sleeve with a satisfactory outcome, one patient died due to the progression of the cardiac myopathy. Conclusion Future studies are needed to assses if the substitution therapy with Recombinant Growth hormone is cost-effective and without risk in such patients with Alström Syndrome and severe insulin resistance, despite our good results in one patient. Also, careful clinical and genetic studies can contribute to a better understanding of the evolution after different therapeutical attempt in

  8. Therapeutic options or antiretroviral anarchy?

    PubMed

    Mascolini, M

    1999-01-01

    The number of drug combinations being used to treat HIV infections may produce a public health nightmare by creating multidrug resistance. The issue of whether to use aggressive multidrug combinations early in the infectious cycle or whether to delay treatment as long as possible remains controversial and unresolved. The use of viral markers to track disease progression is discussed. Tables illustrate the relationships between CD4+ counts and opportunistic infections, disease progression, and long-term viral load reduction. The effectiveness of different drugs combinations is discussed. Results of various clinical trials are presented. PMID:11366158

  9. [Therapeutic options for synovial sarcoma].

    PubMed

    Deme, Dániel; Telekes, András

    2015-05-31

    Synovial sarcomas account for approximately 5 to 10% of soft tissue sarcomas and 0.05 to 0.1% of all malignant neoplasms. They predominantly affect the extremities but can occur in any part of the body. More than 50% of the patients are expected to develop metastatic disease within 3-5 years. In some patients disease recurrence may develop after 20 years. The 5-year overall survival rate is 10% for patients with metastatic disease and 76% for patients with localized one. Age, tumour size, histological subtype, and adjuvant radiotherapy influence prognosis. The role of adjuvant chemotherapy has not been proven yet. There are several ongoing clinical trials to determine the efficacy of active agents used for therapy of locally advanced, relapsed/refractory or metastatic disease. Better understanding of the biological behaviour of synovial sarcomas would provide the future way for the targeted therapy in combination with conventional treatments. PMID:26004546

  10. Anti-IL-31 receptor antibody is shown to be a potential therapeutic option for treating itch and dermatitis in mice

    PubMed Central

    Kasutani, K; Fujii, E; Ohyama, S; Adachi, H; Hasegawa, M; Kitamura, H; Yamashita, N

    2014-01-01

    Background and Purpose IL-31, which is described as a pruritogenic cytokine, is linked to the itching that is associated with allergic and non-allergic eczema, but the precise pruritogenic mechanism of IL-31 and its potential as a therapeutic target for atopic dermatitis (AD) have not been determined. Experimental Approach We investigated the effects of existing drugs on the scratching behaviour induced by an i.v. injection of IL-31 to clarify whether IL-31 induced pruritus indirectly. In addition, we studied the effects of an anti-IL-31 receptor α subunit (anti-IL-31 receptor α) neutralizing antibody on chronic pruritus-inducing dermatitis in an AD-like model to determine whether IL-31 not only induces scratching behaviour, but is also the causative factor in an AD phenotype. Key Results The scratching behaviour induced by an i.v. injection of IL-31 was inhibited by pretreatment with an anti-IL-31 receptor α-neutralizing antibody. In contrast, it was not inhibited significantly by a non-sedative antihistamine (terfenadine), immunosuppressants (dexamethasone and tacrolimus), or a μ-opioid receptor antagonist (naloxone). The anti-IL-31 receptor α-neutralizing antibody reduced the ear swelling and dermatitis score in a chronic pruritus-inducing AD-like model. Moreover, treatment with the anti-IL-31 receptor α-neutralizing antibody showed therapeutic effects on the dermatitis even if it was injected after the disease had developed. Conclusions and Implications Anti-IL-31 receptor α is a potential novel therapeutic approach for escaping from the itch–scratch cycle and also a treatment for dermatitis in AD. PMID:24946165

  11. State of the art of Ready-to-Use Therapeutic Food: a tool for nutraceuticals addition to foodstuff.

    PubMed

    Santini, Antonello; Novellino, Ettore; Armini, Vincenzo; Ritieni, Alberto

    2013-10-15

    Therapeutic foodstuff are a challenge for the use of food and functional food ingredients in the therapy of different pathologies. Ready-to-Use Therapeutic Food (RUTF) are a mixture of nutrients designed and primarily addressed to the therapy of the severe acute malnutrition. The main ingredients of the formulation are powdered milk, peanuts butter, vegetal oil, sugar, and a mix of vitamins, salts, and minerals. The potential of this food are the low percentage of free water and the high energy and nutritional density. The high cost of the powdered milk, and the food safety problems connected to the onset of toxigenic moulds on the peanuts butter, slowed down considerably the widespread and homogenous diffusion of this product. This paper presents the state of the art of RUTF, reviews the different proposed recipes, suggests some possible new formulations as an alternative of novel recipes for this promising food. PMID:23692774

  12. Radiation Therapy: Additional Treatment Options

    MedlinePlus

    ... This is refered to as immunotherapy . Intraoperative Radiation Therapy Radiation therapy given during surgery is called intraoperative ... external beam therapy or as brachytherapy . Novel Targeted Therapies Cancer doctors now know much more about how ...

  13. Spermine metabolism and radiation-derived reactive oxygen species for future therapeutic implications in cancer: an additive or adaptive response.

    PubMed

    Amendola, Roberto; Cervelli, Manuela; Tempera, Giampiero; Fratini, Emiliano; Varesio, Luigi; Mariottini, Paolo; Agostinelli, Enzo

    2014-03-01

    Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalyzed reactions. Thus, combination therapy targeting polyamine metabolism could represent a promising strategy to fight hyper-proliferative disease. The aim of this work is to discuss and evaluate whether the presence of a DNA damage provoked by enzymatic ROS overproduction may act as an additive or adaptive response upon radiation and combination of hyperthermia with lysosomotropic compounds may improve the cytocidal effect of polyamines oxidation metabolites. Low level of X-irradiations delivers challenging dose of damage and an additive or adaptive response with the chronic damage induced by spermine oxidase overexpression depending on the deficiency of the DNA repair mechanisms. Since reactive oxygen species lead to membrane destabilization and cell death, we discuss the effects of BSAO and spermine association in multidrug resistant cells that resulted more sensitive to spermine metabolites than their wild-type counterparts, due to an increased mitochondrial activity. Since mammal spermine oxidase is differentially activated in a tissue specific manner, and cancer cells can differ in term of DNA repair capability, it could be of interest to open a scientific debate to use combinatory treatments to alter spermine metabolism and deliver differential response. PMID:23999645

  14. Energy metabolic disorder is a major risk factor in severe influenza virus infection: Proposals for new therapeutic options based on animal model experiments.

    PubMed

    Kido, Hiroshi; Indalao, Irene L; Kim, Hyejin; Kimoto, Takashi; Sakai, Satoko; Takahashi, Etsuhisa

    2016-09-01

    Severe influenza is characterized by cytokine storm and multiorgan failure. Influenza patients with underlying diseases show a rapid progression in disease severity. The major mechanism that underlies multiorgan failure during the progressive stage of infection, particularly in patients with underlying risk factors, is mitochondrial energy crisis. The relationship between the factors that determine infection severity, such as influenza virus, cytokines, cellular trypsin as a hemagglutinin processing protease for viral multiplication, accumulation of metabolic intermediates and ATP crisis in mitochondria, is termed the "influenza virus-cytokine-trypsin" cycle. This occurs during the initial stages of infection, and is interconnected with the "metabolic disorders-cytokine" cycle in the middle to late phase of infection. Experiments using animal models have highlighted the complex relationship between these two cycles. New treatment options have been proposed that target the ATP crisis and multiorgan failure during the late phase of infection, rather than antiviral treatments with neuraminidase inhibitors that work during the initial phase. These options are (i) restoration of glucose oxidation in mitochondria by diisopropylamine dichloroacetate, which inhibits infection-induced pyruvate dehydrogenase kinase 4 activity, and (ii) restoration of long-chain fatty acid oxidation in mitochondria by l-carnitine and bezafibrate, an agonist of peroxisome proliferation-activated receptors-β/δ, which transcriptionally upregulates carnitine palmitoyltransferase II. The latter is particularly effective in patients with influenza-associated encephalopathy who have thermolabile and short half-life compound variants of carnitine palmitoyltransferase II. PMID:27566378

  15. Therapeutic options to enhance coma arousal after traumatic brain injury: state of the art of current treatments to improve coma recovery.

    PubMed

    Cossu, Giulia

    2014-04-01

    Traumatic brain injury is a leading cause of death and disability. Optimizing the recovery from coma is a priority in seeking to improve patients' functional outcomes. Standards of care have not been established: pharmacological interventions, right median nerve and sensory stimulation, dorsal column stimulation (DCS), deep brain stimulation, transcranial magnetic stimulation, hyperbaric oxygen therapy and cell transplantation have all been utilized with contrasting results. The aim of this review is to clarify the indications for the various techniques and to guide the clinical practice towards an earlier coma arousal. A systematic bibliographic search was undertaken using the principal search engines (Pubmed, Embase, Ovid and Cochrane databases) to locate the most pertinent studies. Traumatic injury is a highly individualized process, and subsequent impairments are dependent on multiple factors: this heterogeneity influences and determines therapeutic responses to the various interventions. PMID:24090192

  16. Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options

    PubMed Central

    Bornhauser, Beat; Gombert, Michael; Kratsch, Christina; Stütz, Adrian M.; Sultan, Marc; Tchinda, Joelle; Worth, Catherine L.; Amstislavskiy, Vyacheslav; Badarinarayan, Nandini; Baruchel, André; Bartram, Thies; Basso, Giuseppe; Canpolat, Cengiz; Cario, Gunnar; Cavé, Hélène; Dakaj, Dardane; Delorenzi, Mauro; Dobay, Maria Pamela; Eckert, Cornelia; Ellinghaus, Eva; Eugster, Sabrina; Frismantas, Viktoras; Ginzel, Sebastian; Haas, Oskar A.; Heidenreich, Olaf; Hemmrich-Stanisak, Georg; Hezaveh, Kebria; Höll, Jessica I.; Hornhardt, Sabine; Husemann, Peter; Kachroo, Priyadarshini; Kratz, Christian P.; te Kronnie, Geertruy; Marovca, Blerim; Niggli, Felix; McHardy, Alice C.; Moorman, Anthony V.; Panzer-Grümayer, Renate; Petersen, Britt S.; Raeder, Benjamin; Ralser, Meryem; Rosenstiel, Philip; Schäfer, Daniel; Schrappe, Martin; Schreiber, Stefan; Schütte, Moritz; Stade, Björn; Thiele, Ralf; von der Weid, Nicolas; Vora, Ajay; Zaliova, Marketa; Zhang, Langhui; Zichner, Thomas; Zimmermann, Martin; Lehrach, Hans; Borkhardt, Arndt; Bourquin, Jean-Pierre; Franke, Andre; Korbel, Jan O.; Stanulla, Martin; Yaspo, Marie-Laure

    2015-01-01

    TCF3-HLF-fusion positive acute lymphoblastic leukemia (ALL) is currently incurable. Employing an integrated approach, we uncovered distinct mutation, gene expression, and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. Recurrent intragenic deletions of PAX5 or VPREB1 were identified in constellation with TCF3-HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin towards a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics, but sensitivity towards glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease. PMID:26214592

  17. Innovative therapeutic strategies for recessive dystrophic epidermolysis bullosa.

    PubMed

    Larcher, F; Del Río, M

    2015-06-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is among the most serious rare skin diseases. It is also the rare skin disease for which most effort has been expended in developing advanced therapeutic interventions. RDEB is caused by collagen VII deficiency resulting from COL7A1 mutations. Therapeutic approaches seek to replenish collagen VII and thus restore dermal-epidermal adhesion. Therapeutic options under development include protein therapy and different cell-based and gene-based therapies. In addition to treating skin defects, some of these therapies may also target internal mucosa. In the coming years, these novel therapeutic approaches should substantially improve the quality of life of patients with RDEB. PMID:25796272

  18. Rehabilitation Options

    MedlinePlus

    ... Speech Pathology Occupational Therapy Art Therapy Recreational therapy Neuropsychology Home Care Options Advanced Care Planning Palliative Care ... Speech Pathology Occupational Therapy Art Therapy Recreational therapy Neuropsychology Home Care Options Advanced Care Planning Palliative Care ...

  19. A novel in vitro platform for the study of SN38-induced mucosal damage and the development of Toll-like receptor 4-targeted therapeutic options.

    PubMed

    Wardill, Hannah R; Gibson, Rachel J; Van Sebille, Ysabella Za; Secombe, Kate R; Logan, Richard M; Bowen, Joanne M

    2016-07-01

    metabolize SN38 as well as expressing TLR4, making this an excellent platform to study clinically relevant therapeutic interventions for SN38-induced mucosal damage by targeting TLR4. PMID:27037276

  20. Combination therapy of angiotensin II receptor blocker and calcium channel blocker exerts pleiotropic therapeutic effects in addition to blood pressure lowering: amlodipine and candesartan trial in Yokohama (ACTY).

    PubMed

    Maeda, Akinobu; Tamura, Kouichi; Kanaoka, Tomohiko; Ohsawa, Masato; Haku, Sona; Azushima, Kengo; Dejima, Toru; Wakui, Hiromichi; Yanagi, Mai; Okano, Yasuko; Fujikawa, Tetsuya; Toya, Yoshiyuki; Mizushima, Shunsaku; Tochikubo, Osamu; Umemura, Satoshi

    2012-01-01

    Recent guidelines recommend combination antihypertensive therapy to achieve the target blood pressure (BP) and to suppress target organ damage. This study aimed to examine the beneficial effects of combination therapy with candesartan and amlodipine on BP control and markers of target organ function in Japanese essential hypertensive patients (N = 20) who did not achieve the target BP level during the monotherapy period with either candesartan or amlodipine. After the monotherapy period, for patients already being treated with amlodipine, a once-daily 8 mg dose of candesartan was added on during the combination therapy period (angiotensin II receptor blocker [ARB] add-on group, N = 10), and a once-daily 5 mg dose of amlodipine was added on for those already being treated with candesartan (calcium channel blocker [CCB] add-on group, N = 10). Combination therapy with candesartan and amlodipine for 12 weeks significantly decreased clinic and home systolic blood pressure (SBP) and diastolic blood pressure (DBP). In addition, the combination therapy was able to significantly reduce urine albumin excretion without decrease in estimated glomerular filtration ratio and resulted in significant improvements in brachial-ankle pulse wave velocity, central SBP, and insulin sensitivity. Furthermore, the CCB add-on group showed a significantly greater decrease in clinic and home DBP than the ARB add-on group. The calcium channel blocker add-on group also exhibited better improvements in vascular functional parameters than the ARB add-on group. These results suggest that combination therapy with candesartan and amlodipine is an efficient therapeutic strategy for hypertension with pleiotropic benefits. PMID:22571446

  1. Pricing Options.

    ERIC Educational Resources Information Center

    Tenopir, Carol

    1998-01-01

    Presents results of a recent survey of over 100 public and academic libraries about pricing options from online companies. Most options fall into three categories: pay-as-you-go, fixed-rate, and user-based. Results are discussed separately for public and academic libraries and for consortial discounts. Trends in pricing options preferred by…

  2. Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: a review of the literature.

    PubMed

    Ito, Matthew K

    2015-10-01

    Hypertriglyceridemia affects approximately 33% of the US population. Elevated triglyceride levels are independently associated with cardiovascular disease (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute pancreatitis. Guidelines for the management of severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) recommend immediate use of triglyceride-lowering agents; however, statins remain the first line of therapy for the management of mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]). Statins primarily target elevated low-density lipoprotein cholesterol levels, but have also been shown to reduce mean triglyceride levels by up to 18% (or 43% in patients with triglyceride levels≥3.1 mmol/L [≥273 mg/dL]). However, individuals with hypertriglyceridemia may need additional reduction in triglyceride-rich lipoproteins and remnant particles to further reduce residual CVD risk. A number of guidelines recommend the addition of fibrates, niacin, or long-chain omega-3 fatty acids if elevated triglyceride or non-high-density lipoprotein cholesterol levels persist despite the use of high-intensity statin therapy. This review evaluates the impact of fibrates, niacin, and long-chain omega-3 fatty acids on lipid profiles and cardiovascular outcomes in patients with hypertriglyceridemia. It also assesses the adverse effects and drug-drug interactions associated with these triglyceride-lowering agents, because although they have all been shown to effectively reduce triglyceride levels in patients with hypertriglyceridemia, they differ with regard to their associated benefit-risk profiles. Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin, yet further large-scale clinical studies are required to evaluate their effects on cardiovascular outcomes and CVD risk reduction in patients with hypertriglyceridemia. PMID:26296750

  3. [Percutaneous mitral valve annuloplasty with the carillon mitral contour system by cardiac dimensions. A minimally invasive therapeutic option for the treatment of severe functional mitral valve regurgitation].

    PubMed

    Degen, Hubertus; Lickfeld, Thomas; Stoepel, Carsten; Haude, Michael

    2009-09-01

    Morbidity in patients with systolic heart failure is significantly increased by functional mitral valve regurgitation. In addition to pharmaceutical treatment or surgical reconstruction of the impaired valve, minimally invasive procedures have continuously advanced into the focus of interest. The Carillon Mitral Contour System (Cardiac Dimensions) is a new catheter-based method to converge dehiscent mitral valve leaflets with implantation of a nitinol clip into the coronary sinus, leading to a closer approach of the valve leaflets with subsequent decrease in mitral regurgitation. The device is implanted via a central venous catheter, using a special delivery system under fluoroscopy. The immediate success of minimizing mitral valve regurgitation is verified by online transesophageal echocardiography (TEE), device-related impairment of perfusion of contiguous coronary vessels is ruled out by coronary angiography performed simultaneously during deployment of the device. As soon as reduction of the mitral valve regurgitation is demonstrated in TEE, the Carillon System is disconnected from the delivery system, before, however, the Carillon device can be withdrawn into the delivery system as necessary. Following the successful implantation of the Carillon Mitral Contour System, a left ventricular lead for cardiac resynchronization therapy can still be successfully placed alongside through the coronary sinus. PMID:19784563

  4. Human albumin eye drops as a therapeutic option for the management of keratoconjunctivitis sicca secondary to chronic graft-versus-host disease after stem-cell allografting

    PubMed Central

    Seki, J.T.; Sakurai, N.; Moldenhauer, S.; Dam, J.; Atenafu, E.G.; Yip, P.M.; Mazzulli, T.; Henderson, T.; Pendergrast, J.; Cserti, C.; Velazquez, J.P.; Simpson, R.; Felluga, G.; Messner, H.A.; Lipton, J.H.

    2015-01-01

    Background Keratoconjunctivitis sicca from chronic graft-versus-host disease (cgvhd) after allogeneic stem cell transplantation is common, leading to severe corneal damage and blindness if not treated. We retrospectively examined the efficacy and safety of pooled human albumin eye drops (haeds) for symptom relief in 40 stem-cell transplantation patients after other alternatives had failed. Methods The Common Terminology Criteria for Adverse Events (version 4.0) and the cgvhd grading scale were used to compare response in the patients during January 2000 and July 2013. In addition, on days 1 and 30, the haeds were subjected to quality assurance testing for sterility, oncotic pressure, albumin measurement, viscosity, pH, and purity by protein electrophoresis. Results Use of haeds resulted in symptom relief for 37 patients (92.5%); 3 patients (7.5%) failed to improve with use of haeds (p ≤ 0.0001). Of the 37 patients having symptom relief, 7 (19%) improved from grade 3 to no dry eye symptoms. Proportionately, post-treatment symptom improvement by two grade levels, from 3 to 1 (70%), was significantly higher than improvement by one grade level, from 3 to 2 (11%) or from 2 to 1 (19%, p ≤ 0.0001). Time to symptom relief ranged from 2 weeks to 28 weeks. Of the 40 patients, 38 (95%) had no adverse reactions. Days 1 and 30 quality assurance testing results were equivalent. Conclusions Complications of keratoconjunctivitis sicca were well managed and well tolerated with haeds when other remedies failed. Quality assurance testing confirmed that haeds were safe and stable in extreme conditions. PMID:26628876

  5. Prehypertension: Underlying pathology and therapeutic options

    PubMed Central

    Albarwani, Sulayma; Al-Siyabi, Sultan; Tanira, Musbah O

    2014-01-01

    Prehypertension (PHTN) is a global major health risk that subjects individuals to double the risk of cardiovascular disease (CVD) independent of progression to overt hypertension. Its prevalence rate varies considerably from country to country ranging between 21.9% and 52%. Many hypotheses are proposed to explain the underlying pathophysiology of PHTN. The most notable of these implicate the renin-angiotensin system (RAS) and vascular endothelium. However, other processes that involve reactive oxygen species, the inflammatory cytokines, prostglandins and C-reactive protein as well as the autonomic and central nervous systems are also suggested. Drugs affecting RAS have been shown to produce beneficial effects in prehypertensives though such was not unequivocal. On the other hand, drugs such as β-adrenoceptor blocking agents were not shown to be useful. Leading clinical guidelines suggest using dietary and lifestyle modifications as a first line interventional strategy to curb the progress of PHTN; however, other clinically respected views call for using drugs. This review provides an overview of the potential pathophysiological processes associated with PHTN, abridges current intervention strategies and suggests investigating the value of using the “Polypill” in prehypertensive subjects to ascertain its potential in delaying (or preventing) CVD associated with raised blood pressure in the presence of other risk factors. PMID:25228952

  6. Therapeutic options in peripheral T cell lymphoma.

    PubMed

    Zhang, Yaping; Xu, Wei; Liu, Hong; Li, Jianyong

    2016-01-01

    Peripheral T cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphomas with a very poor prognosis. The standard first-line treatments have resulted in unsatisfactory patient outcomes. With the exception of low-risk anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), the majority of patients relapse rapidly; the current 5-year overall survival rates are only 10-30%. Novel targeted therapies and combination chemotherapies are required for the treatment of patients with PTCL. In recent years, some retrospective and prospective studies have been performed concerning PTCL. Consequently, a number of novel agents and their relevant combination therapies have been identified, including histone deacetylase inhibitors, immunoconjugates, antifolates, monoclonal antibodies, immunomodulatory agents, nucleoside analogs, proteasome inhibitors, kinase inhibitors, bendamustine, L-asparaginase, and other targeted agents. It is hoped that these innovative approaches will finally improve outcomes in patients with PTCL. This review summarizes the currently available approaches for the treatment of PTCL with an emphasis on potential new agents, including the role of stem cell transplantation. PMID:27071634

  7. Sporotrichosis: An Overview and Therapeutic Options

    PubMed Central

    Mahajan, Vikram K.

    2014-01-01

    Sporotrichosis is a chronic granulomatous mycotic infection caused by Sporothrix schenckii, a common saprophyte of soil, decaying wood, hay, and sphagnum moss, that is endemic in tropical/subtropical areas. The recent phylogenetic studies have delineated the geographic distribution of multiple distinct Sporothrix species causing sporotrichosis. It characteristically involves the skin and subcutaneous tissue following traumatic inoculation of the pathogen. After a variable incubation period, progressively enlarging papulo-nodule at the inoculation site develops that may ulcerate (fixed cutaneous sporotrichosis) or multiple nodules appear proximally along lymphatics (lymphocutaneous sporotrichosis). Osteoarticular sporotrichosis or primary pulmonary sporotrichosis are rare and occur from direct inoculation or inhalation of conidia, respectively. Disseminated cutaneous sporotrichosis or involvement of multiple visceral organs, particularly the central nervous system, occurs most commonly in persons with immunosuppression. Saturated solution of potassium iodide remains a first line treatment choice for uncomplicated cutaneous sporotrichosis in resource poor countries but itraconazole is currently used/recommended for the treatment of all forms of sporotrichosis. Terbinafine has been observed to be effective in the treatment of cutaneous sporotrichosis. Amphotericin B is used initially for the treatment of severe, systemic disease, during pregnancy and in immunosuppressed patients until recovery, then followed by itraconazole for the rest of the therapy. PMID:25614735

  8. Gallbladder carcinoma: Prognostic factors and therapeutic options

    PubMed Central

    Goetze, Thorsten Oliver

    2015-01-01

    The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ‘‘incidental or occult gallbladder carcinoma’’ (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a formally R0 situation is either occult invasion or hepatic spread with unknown lymphogenic dissemination. Unfortunately, there are diverse interpretations and practices regarding stage-adjusted therapy for gallbladder carcinoma. The current data suggest that more radical therapy is warranted. PMID:26604631

  9. Natural Therapeutic Options in Endodontics - A Review

    PubMed Central

    Venkateshbabu, Nagendrababu; Anand, Suresh; Abarajithan, Mohan; Sheriff, Sultan O.; Jacob, Pulikkotil S.; Sonia, Nath

    2016-01-01

    Complete eradication of microbial biofilms and elimination of the smear layer are the key factors during endodontic treatment. Various chemical irrigants have been proposed in the literature for the same. The major setback with these chemical irrigants is that they are not bio-friendly to the dental and peri-radicular tissues. In the recent years, research to use natural products for root canal disinfection has gained importance. The aim of this article is to compile various herbal products that have been used as an irrigants and intracanal medicaments in the field of Endodontics to eradicate the biofilm and remove smear layer. PMID:27386007

  10. Cryptococcal meningitis: epidemiology and therapeutic options

    PubMed Central

    Sloan, Derek J; Parris, Victoria

    2014-01-01

    Cryptococcal meningitis causes morbidity and mortality worldwide. The burden of disease is greatest in middle- and low-income countries with a high incidence of human immunodeficiency virus (HIV) infection. Patients taking immunosuppressive drugs and some immunocompetent hosts are also at risk. Treatment of cryptococcal meningitis consists of three phases: induction, consolidation, and maintenance. Effective induction therapy requires potent fungicidal drugs (amphotericin B and flucytosine), which are often unavailable in low-resource, high-endemicity settings. As a consequence, mortality is unacceptably high. Wider access to effective treatment is urgently required to improve outcomes. For human immunodeficiency virus-infected patients, judicious management of asymptomatic cryptococcal antigenemia and appropriately timed introduction of antiretroviral therapy are important. PMID:24872723

  11. Natural Therapeutic Options in Endodontics - A Review.

    PubMed

    Venkateshbabu, Nagendrababu; Anand, Suresh; Abarajithan, Mohan; Sheriff, Sultan O; Jacob, Pulikkotil S; Sonia, Nath

    2016-01-01

    Complete eradication of microbial biofilms and elimination of the smear layer are the key factors during endodontic treatment. Various chemical irrigants have been proposed in the literature for the same. The major setback with these chemical irrigants is that they are not bio-friendly to the dental and peri-radicular tissues. In the recent years, research to use natural products for root canal disinfection has gained importance. The aim of this article is to compile various herbal products that have been used as an irrigants and intracanal medicaments in the field of Endodontics to eradicate the biofilm and remove smear layer. PMID:27386007

  12. Therapeutic options in neuromyelitis optica spectrum disorders.

    PubMed

    Kitley, Joanna; Palace, Jackie

    2016-01-01

    Neuromyelitis optica is a relapsing inflammatory disorder of the central nervous system that manifests predominantly with attacks of optic neuritis and longitudinally extensive transverse myelitis; attacks are often severe. In contrast to multiple sclerosis, a secondary progressive phase is rare, and disability in neuromyelitis optica spectrum disorders is related to relapses. Thus, prompt and effective treatment of relapses, and early initiation of long-term immunosuppression to prevent subsequent attacks is required in order to prevent morbidity and mortality. PMID:26840802

  13. Acquired facial lipoatrophy: pathogenesis and therapeutic options

    PubMed Central

    Olszewska, Barbara; Lemańska, Małgorzata; Purzycka-Bohdan, Dorota; Nowicki, Roman

    2015-01-01

    Facial lipoatrophy refers to the loss of subcutaneous fat tissue presenting by flattening or indentation of convex contour of the face. Facial lipoatrophy is a feature of the normal ageing process. It may be also a manifestation of chronic diseases, most frequently it affects HIV-infected individuals treated with highly active antiretroviral therapy (HAART) and may constitute a complication of connective tissue diseases, like lupus erythematosus profundus or morphea. Early recognition and treatment of the active stage of connective tissue diseases is of essential significance in prevention of subsequent scarring and atrophy lesions. In HIV-positive patients undergoing HAART therapy, the attempt to modify thetreatment scheme so it has a less lipemic effect seems to be justified. Esthetic correction of facial lipoatrophy in chronic diseases is a great challenge. Improvement of appearance is very important for affected individuals, because it diminishes their stigmatization and psychosocial dysfunction. Facial volumetric correction includes surgical and dermatological procedures such as adipose transfer and injectable dermal fillers. PMID:26015783

  14. The development and implementation of a patient-centered radiology consultation service: a focus on breast density and additional screening options.

    PubMed

    Sullivan, Courtney L; Pandya, Ankur; Min, Robert J; Drotman, Michele; Hentel, Keith

    2015-01-01

    Increasingly, states are mandating notification to patients if they are found to have dense breast tissue. Information describes the increased risk of cancer and limitations of mammography for this patient group. Such notification often creates anxiety and results in uncertainty as no evidence-based guidelines for additional screening of dense breasts are available. Through an organized consultation service, patients and physicians were provided consultations with radiologists in order to ensure an appropriate screening plan based on individualized histories and preferences. This manuscript describes our dense breast consultation program, examines initial data, and provides lessons for practices interested in providing similar service. PMID:25655643

  15. Novel operative treatment options.

    PubMed

    Ricketts, D N J; Pitts, N B

    2009-01-01

    There are an increasing number of more novel options available for operative intervention. This chapter outlines a series of operative treatment options which are available to the modern clinician to select from once a decision has been made to treat a carious lesion operatively. A series of novel methods of caries removal have been described; including chemomechanical caries removal, air abrasion, sono-abrasion, polymer rotary burs and lasers. There are also novel approaches to ensure complete caries removal and novel approaches for the management of deep caries. A novel question increasingly asked by clinicians is: does all the caries need to be removed? Operative management options here include: therapeutic fissure sealants, ultraconservative caries removal, stepwise excavation and the Hall technique. In conclusion, there is now a growing wealth of evidence that questions the traditional methods of caries removal and restoring the tooth. In parallel, there is a growing movement exploring the merits of therapeutically sealing caries into the tooth. This philosophy is alien to many of today's dentists and, until further randomized controlled trials are carried out in primary care, prudent caution must be exercised with this promising approach. Research is required into techniques which will allow monitoring of sealed caries to detect any rare, but insidious, failures. These novel techniques are an alternative way of managing the later stages of the caries process from a sounder biological basis and have marked potential benefits to patients from treatment, pain and outcome perspectives. PMID:19494685

  16. Katimavik Options.

    ERIC Educational Resources Information Center

    Crelinsten, Michael; And Others

    Designed for students who are just about to complete Katimavik (a nine-month volunteer community service and experiential learning program for 17 to 21-year-old Canadian youth), the bilingual information guide presents facts and considerations about options in lifestyle, academic attainment, and career goals available as a result of Katimavik…

  17. The Additive Inflammatory In Vivo and In Vitro Effects of IL-7 and TSLP in Arthritis Underscore the Therapeutic Rationale for Dual Blockade

    PubMed Central

    Hillen, Maarten R.; Hartgring, Sarita A. Y.; Willis, Cynthia R.; Radstake, Timothy R. D. J.; Hack, Cornelis E.; Lafeber, Floris P. J. G.; van Roon, Joel A. G

    2015-01-01

    Introduction The cytokines interleukin (IL)-7 and thymic stromal lymphopoietin (TSLP) signal through the IL-7R subunit and play proinflammatory roles in experimental arthritis and rheumatoid arthritis (RA). We evaluated the effect of inhibition of IL-7R- and TSLPR-signalling as well as simultaneous inhibition of IL-7R- and TSLPR-signalling in murine experimental arthritis. In addition, the effects of IL-7 and TSLP in human RA dendritic cell (DC)/T-cell co-cultures were studied. Methods Arthritis was induced with proteoglycan in wildtype mice (WT) and in mice deficient for the TSLP receptor subunit (TSLPR-/-). Both mice genotypes were treated with anti-IL-7R or phosphate buffered saline. Arthritis severity was assessed and local and circulating cytokines were measured. Autologous CD1c-positive DCs and CD4 T-cells were isolated from peripheral blood of RA patients and were co-cultured in the presence of IL-7, TSLP or both and proliferation and cytokine production were assessed. Results Arthritis severity and immunopathology were decreased in WT mice treated with anti-IL-7R, in TSLPR-/- mice, and the most robustly in TSLPR-/- mice treated with anti-IL-7R. This was associated with strongly decreased levels of IL-17, IL-6 and CD40L. In human DC/T-cell co-cultures, TSLP and IL-7 additively increased T-cell proliferation and production of Th17-associated cytokines, chemokines and tissue destruction factors. Conclusion TSLP and IL-7 have an additive effect on the production of Th17-cytokines in a human in vitro model, and enhance arthritis in mice linked with enhanced inflammation and immunopathology. As both cytokines signal via the IL-7R, these data urge for IL-7R-targeting to prevent the activity of both cytokines in RA. PMID:26110994

  18. Nevada Transportatoion Options Study

    SciTech Connect

    P. GEHNER; E.M. WEAVER; L. FOSSUM

    2006-05-25

    This study performs a cost and schedule analysis of three Nevada Transportation options that support waste receipt at the repository. Based on the U.S. Department of Energy preference for rail transportation in Nevada (given in the Final Environmental Impact Statement), it has been assumed that a branch rail line would be constructed to support waste receipt at the repository. However, due to potential funding constraints, it is uncertain when rail will be available. The three Nevada Transportation options have been developed to meet a varying degree of requirements for transportation and to provide cost variations used in meeting the funding constraints given in the Technical Direction Letter guidelines for this study. The options include combinations of legal-weight truck, heavy-haul truck, and rail. Option 1 uses a branch rail line that would support initial waste receipt at the repository in 2010. Rail transportation would be the primary mode, supplemented by legal weight trucks. This option provides the highest level of confidence in cost and schedule, lowest public visibility, greatest public acceptability, lowest public dose, and is the recommended option for support of waste receipt. The completion of rail by 2010 will require spending approximately $800 million prior to 2010. Option 2 uses a phased rail approach to address a constrained funding scenario. To meet funding constraints, Option 2 uses a phased approach to delay high cost activities (final design and construction) until after initial waste receipt in 2010. By doing this, approximately 95 percent of the cost associated with completion of a branch rail line is deferred until after 2010. To support waste receipt until a branch rail line is constructed in Nevada, additional legal-weight truck shipments and heavy-haul truck shipments (on a limited basis for naval spent nuclear fuel) would be used to meet the same initial waste receipt rates as in Option 1. Use of heavy-haul shipments in the absence

  19. Exercising options

    NASA Astrophysics Data System (ADS)

    Carlowicz, Michael

    In a recent speech to graduates of the College of Computer, Mathematical, and Physical Sciences at the University of Maryland, Anne Petersen, deputy director of the National Science Foundation, encouraged a new generation of scientists to embrace opportunity and choice, and to use their scientific training as an employment credential, not a limit. In her May 23 commencement address, Petersen exhorted students to view their freshly minted diplomas as tickets to a broad and diverse job market, not just one-way trips to the laboratory.“Looking for the options and alternatives open to us—and creating options for ourselves where they are not apparent—can give us a sense of direction and volition that enriches our lives immensely…

  20. Radiation Therapy in the Management of Head-and-Neck Cancer of Unknown Primary Origin: How Does the Addition of Concurrent Chemotherapy Affect the Therapeutic Ratio?

    SciTech Connect

    Chen, Allen M.; Farwell, D. Gregory; Lau, Derick H.; Li Baoqing; Luu, Quang; Donald, Paul J.

    2011-10-01

    Purpose: To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patients (58%) were treated by intensity-modulated radiotherapy. Results: The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both). Conclusions: Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question.

  1. gp130 receptor ligands as potential therapeutic targets for obesity

    PubMed Central

    Febbraio, Mark A.

    2007-01-01

    Obesity and its related cluster of pathophysiologic conditions including insulin resistance, glucose intolerance, dyslipidemia, and hypertension are recognized as growing threats to world health. It is now estimated that 10% of the world’s population is overweight or obese. As a result, new therapeutic options for the treatment of obesity are clearly warranted. Recent research has focused on the role that gp130 receptor ligands may play as potential therapeutic targets in obesity. One cytokine in particular, ciliary neurotrophic factor (CNTF), acts both centrally and peripherally and mimics the biologic actions of the appetite control hormone leptin, but unlike leptin, CNTF appears to be effective in obesity and as such may have therapeutic potential. In addition, CNTF suppresses inflammatory signaling cascades associated with lipid accumulation in liver and skeletal muscle. This review examines the potential role of gp130 receptor ligands as part of a therapeutic strategy to treat obesity. PMID:17404609

  2. [Additional administration of dutasteride in patients with benign prostatic hyperplasia who did not respond sufficiently to α1-adrenoceptor antagonist : investigation of clinical factors affecting the therapeutic effect of dutasteride].

    PubMed

    Masuda, Mitsunobu; Murai, Tetsuo; Osada, Yutaka; Kawai, Masaki; Kasuga, Jun; Yokomizo, Yumiko; Kuroda, Shinnosuke; Nakamura, Mami; Noguchi, Go

    2014-02-01

    We performed additional administration of dutasteride in patients who did not respond sufficiently to α1-adrenoceptor antagonist treatment for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) (LUTS/BPH). Among 76 registered patients, efficacy was analyzed in 58 patients. International Prostate Symptom Score (IPSS), subscores for voiding and storage symptoms and quality of life (QOL) on the IPSS, and Overactive Bladder Symptom Score (OABSS) were all significantly improved from the third month of administration compared to the time of initiating additional administration of dutasteride. Additional administration of dutasteride also significantly reduced prostate volume, and residual urine with the exception of the sixth month after administration. Age at initiation of administration and voiding symptom subscore on the IPSS were clinical factors affecting the therapeutic effects of dutasteride. The rate of improvement with treatment decreased with increasing age at initiation of dutasteride administration, and increased as voiding symptom subscore on the IPSS increased. Therefore, additional administration of dutasteride appears useful for cases of LUTS/BPH in which a sufficient response is not achieved with α1-adrenoceptor antagonist treatment. Because patients who have severe voiding symptoms or begin dutasteride at an early age may be expected to respond particularly well to dutasteride in terms of clinical efficacy, they were considered to be suitable targets for additional administration. PMID:24755815

  3. FS65 Disposition Option Report

    SciTech Connect

    Wenz, Tracy R.

    2015-09-25

    This report outlines the options for dispositioning the MOX fuel stored in FS65 containers at LANL. Additional discussion regarding the support equipment for loading and unloading the FS65 transport containers is included at the end of the report.

  4. Newer Management Options in Leprosy

    PubMed Central

    Rao, P Narasimha; Jain, Suman

    2013-01-01

    Newer management options are needed for leprosy control even at present, as it is predicted that new cases of leprosy will continue to appear for many more years in future. This article detail newer methods of clinical grading of peripheral nerve involvement (thickening, tenderness and nerve pain which are subjective in nature) and the advances made in the use of Ultrasonography and Colour Doppler as an objective imaging tool for nerves in leprosy. It also briefly discusses the newer drugs and alternative regimens as therapeutic management options which hold promise for leprosy in future. PMID:23372204

  5. Peptide-modified gold nanoparticles for improved cancer therapeutics

    NASA Astrophysics Data System (ADS)

    Yang, Celina; Prooijen, Monique V.; Chithrani, Devika B.

    2014-03-01

    The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options. These nanostructures further provide strategies for improving loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy. Our recent results show enhancement of cell death during radiation therapy when GNPs are targeted to nucleus. In addition, we have seen enhanced therapeutic effects when GNPs are used as anticancer drug carriers. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents will hold the possibility of promising directions in cancer research.

  6. Achalasia: current treatment options.

    PubMed

    Familiari, Pietro; Greco, Santi; Volkanovska, Ance; Gigante, Giovanni; Cali, Anna; Boškoski, Ivo; Costamagna, Guido

    2015-01-01

    Achalasia is a rare esophageal motility disorder, characterized by impaired swallow-induced, lower esophageal sphincter (LES) relaxation and defective esophageal peristalsis. Unfortunately, there are no etiological therapies for achalasia. Patients present with dysphagia, chest pain and regurgitation of undigested food, often leading to weight loss. The currently available treatments have the common aim of relieving symptoms by decreasing the pressure of the LES. This can be achieved with some medications, by inhibiting the cholinergic innervation (botulinum toxin), by stretching (endoscopic dilation) or cutting (surgery) the LES. Recently, other therapeutic options, including per-oral endoscopic myotomy have been developed and are gaining international consensus. The authors report on the benefits and weaknesses of the different therapies and provide an updated approach to the management of achalasia. PMID:26186641

  7. Therapeutics in Huntington's Disease.

    PubMed

    Killoran, Annie; Biglan, Kevin M

    2012-02-01

    OPINION STATEMENT: There is no specific treatment for Huntington's disease (HD). Its many symptoms of motor, psychiatric, and cognitive deterioration are managed with symptomatic relief, rehabilitation, and support. The only drug approved by the US Food and Drug Administration (FDA) for the treatment of HD is an antichoreic agent, tetrabenazine, but this drug is used sparingly because of uneasiness regarding its propensity to cause depression and suicidality in this population, which is already at risk for these complications. Neuroleptics are still first-line treatments for chorea accompanied by comorbid depression and/or behavioral or psychotic symptoms, as is often the case. Psychiatric features, which have a significant impact on a patient's professional and personal life, often become the major focus of management. In addition to neuroleptics, commonly used medications include antidepressants, mood stabilizers, anxiolytics, and psychostimulants. In contrast, few treatment options are available for cognitive impairment in HD; this remains an important and largely unmet therapeutic need. HD patients typically lack insight into their disease manifestations, failing to recognize their need for treatment, and possibly even arguing against it. Multipurpose medications are employed advantageously to simplify the medication regimen, so as to facilitate compliance and not overwhelm the patient. For example, haloperidol can be prescribed for a patient with chorea, agitation, and anorexia, rather than targeting each symptom with a different drug. This approach also limits the potential for adverse effects, which can be difficult to distinguish from the features of the disease itself. With HD's complexity, it is best managed with a multidisciplinary approach that includes a movement disorders specialist, a genetic counselor, a mental health professional, a physical therapist, and a social worker for support and coordination of services. As the disease progresses, there

  8. Biomimetic Particles as Therapeutics

    PubMed Central

    Green, Jordan J.

    2015-01-01

    In recent years, there have been major advances in the development of novel nanoparticle and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health. PMID:26277289

  9. Unmet needs of patients with narcolepsy: perspectives on emerging treatment options

    PubMed Central

    Wozniak, Dariusz R; Quinnell, Timothy G

    2015-01-01

    The treatment options currently available for narcolepsy are often unsatisfactory due to suboptimal efficacy, troublesome side effects, development of drug tolerance, and inconvenience. Our understanding of the neurobiology of narcolepsy has greatly improved over the last decade. This knowledge has not yet translated into additional therapeutic options for patients, but progress is being made. Some compounds, such as histaminergic H3 receptor antagonists, may prove useful in symptom control of narcolepsy. The prospect of finding a cure still seems distant, but hypocretin replacement therapy offers some promise. In this narrative review, we describe these developments and others which may yield more effective narcolepsy treatments in the future. PMID:26045680

  10. Manned Mars mission astronomy options

    NASA Technical Reports Server (NTRS)

    Suess, S. T.

    1986-01-01

    Astronomical observations during the transit phase, in orbit about Mars, and from the surface present important scientific objectives. Primary astronomical objectives are being summarized by J. Burns (University of New Mexico). Additional or alternative options will be introduced here, together with their strengths, weaknesses, viability, and value. It is important to note at the outset that not all possible options are necessarily important or viable.

  11. Standard and Novel Treatment Options for Metabolic Syndrome and Diabetes Mellitus

    PubMed Central

    Groves, Elliott M; Yu, Katherine; Wong, Nathan D.; Malik, Shaista

    2014-01-01

    Type II Diabetes and metabolic syndrome are two intertwined conditions that are critical to the healthcare landscape in the United States and abroad. Patients with either diabetes or metabolic syndrome can have a dramatically increased risk of developing cardiovascular disease. Numerous treatment options have existed for some time, which include non-pharmacologic and pharmacologic therapies. Additionally, within the last decade a multiple of novel treatment options have emerged for the management of hyperglycemia in particular. By targeting novel pathways beyond the secretion and supply of insulin, these new therapeutics provide a valuable adjunctive to the currently available therapies for diabetes and metabolic syndrome. Here we discuss the current guideline driven usage of standard therapies with some novel indications. In addition we discuss the novel therapies for the treatment of hyperglycemia, their mechanisms of action and appropriate therapeutic indications. PMID:24234946

  12. Mesenchymal stem cells (MSCs) as skeletal therapeutics - an update.

    PubMed

    Saeed, Hamid; Ahsan, Muhammad; Saleem, Zikria; Iqtedar, Mehwish; Islam, Muhammad; Danish, Zeeshan; Khan, Asif Manzoor

    2016-01-01

    Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair/regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/serum or by loading onto repair/induction supportive resorb-able scaffolds. Thus, this review is aimed at highlighting a wide range of pertinent clinical therapeutic options of MSCs in the treatment of skeletal diseases and skeletal tissue regeneration. Additionally, in skeletal disease and regenerative sections, only the early and more recent preclinical evidences are discussed followed by all the pertinent clinical studies. Moreover, germane post transplant therapeutic mechanisms afforded by MSCs have also been conversed. Nonetheless, assertive use of MSCs in the clinic for skeletal disorders and repair is far from a mature therapeutic option, therefore, posed challenges and future directions are also discussed. Importantly, for uniformity at all instances, term MSCs is used throughout the review. PMID:27084089

  13. Dark circles: etiology and management options.

    PubMed

    Friedmann, Daniel P; Goldman, Mitchel P

    2015-01-01

    Given their multifactorial nature and the fact that individual patients may have more than a single underlying cause, cosmetic practitioners should be well versed in a number of potential treatment options encompassing all facets of under-eye dark circles. New therapeutic options are also forthcoming. Longer-lasting HA fillers, wavelength tunable laser devices, and topicals speeding up healing and enhancing results after fractionated laser therapy will all serve to make the future of dark circle treatment unabatedly bright. PMID:25440739

  14. Androgenetic Alopecia: An Update of Treatment Options.

    PubMed

    Kelly, Yanna; Blanco, Aline; Tosti, Antonella

    2016-09-01

    Androgenetic alopecia (AGA) is characterized by a non-scarring progressive miniaturization of the hair follicle in predisposed men and women with a pattern distribution. Although AGA is a very prevalent condition, approved therapeutic options are limited. This article discusses the current treatment alternatives including their efficacy, safety profile, and quality of evidence. Finasteride and minoxidil for male androgenetic alopecia and minoxidil for female androgenetic alopecia still are the therapeutic options with the highest level evidence. The role of antiandrogens for female patients, the importance of adjuvant therapies, as well as new drugs and procedures are also addressed. PMID:27554257

  15. Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options--a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference.

    PubMed

    Kirchhof, Paulus; Lip, Gregory Y H; Van Gelder, Isabelle C; Bax, Jeroen; Hylek, Elaine; Kaab, Stefan; Schotten, Ulrich; Wegscheider, Karl; Boriani, Giuseppe; Brandes, Axel; Ezekowitz, Michael; Diener, Hans; Haegeli, Laurent; Heidbuchel, Hein; Lane, Deirdre; Mont, Luis; Willems, Stephan; Dorian, Paul; Aunes-Jansson, Maria; Blomstrom-Lundqvist, Carina; Borentain, Maria; Breitenstein, Stefanie; Brueckmann, Martina; Cater, Nilo; Clemens, Andreas; Dobrev, Dobromir; Dubner, Sergio; Edvardsson, Nils G; Friberg, Leif; Goette, Andreas; Gulizia, Michele; Hatala, Robert; Horwood, Jenny; Szumowski, Lukas; Kappenberger, Lukas; Kautzner, Josef; Leute, Angelika; Lobban, Trudie; Meyer, Ralf; Millerhagen, Jay; Morgan, John; Muenzel, Felix; Nabauer, Michael; Baertels, Christoph; Oeff, Michael; Paar, Dieter; Polifka, Juergen; Ravens, Ursula; Rosin, Ludger; Stegink, W; Steinbeck, Gerhard; Vardas, Panos; Vincent, Alphons; Walter, Maureen; Breithardt, Günter; Camm, A John

    2012-01-01

    While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF. PMID:21791573

  16. Lung cancer: Biology and treatment options.

    PubMed

    Lemjabbar-Alaoui, Hassan; Hassan, Omer Ui; Yang, Yi-Wei; Buchanan, Petra

    2015-12-01

    Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLCs) and non-small cell lung carcinomas (NSCLCs). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation. PMID:26297204

  17. [New treatment options for chronic pruritus].

    PubMed

    Zeidler, C; Pfleiderer, B; Ständer, S

    2016-08-01

    Prevalent in 14-17 % of the population, chronic pruritus is among the most common and stressful symptoms in medicine. In spite of new findings regarding the origin and chronification of the symptom, therapy remains a great challenge. There is a lack of approved therapies that provide rapid and efficient reduction of pruritus. As a result, the affected patients suffer a long time (even months to years), and somatic (scratch lesions, super infections, sleep disorders) and psychosomatic disorders develop. Interdisciplinary cooperation with various specialists is important not just for these reasons, but also due to different etiologies of the symptom and common comorbidities. In addition, there remains a great need for uniformly devised, clinically controlled studies, recommendations and guidelines. New therapeutic approaches are currently being verified in clinical trials. This allows for future prospects of possible new and partially targeted therapies. This article provides a summary of current therapeutic options based on case series, individual randomized controlled trials and the current S2K guideline. PMID:27351559

  18. MACROMOLECULAR THERAPEUTICS

    PubMed Central

    Yang, Jiyuan; Kopeček, Jindřich

    2014-01-01

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines – (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. PMID:24747162

  19. [Melanoma brain metastases : Treatment options].

    PubMed

    Rauschenberg, R; Tabatabai, G; Troost, E G C; Garzarolli, M; Beissert, S; Meier, F

    2016-07-01

    The majority of patients with metastatic melanoma will develop brain metastases, which are the most common cause of death. Until recently, local therapies (e. g., neurosurgery, radiotherapy) were the only options for brain metastases; however, effective systemic treatment options are now available. Upon suspicion of brain metastases, diagnostic staging with brain MRI and a neurological investigation are indicated. Prognostic factors such as number of cerebral metastases and symptoms, serum lactate dehydrogenase and S‑100 levels, extracerebral metastases, and ECOG status are considered during therapeutic planning. Treatment planning and therapeutic interventions should be based on an interdisciplinary and multimodal approach. Established treatments for singular brain metastases are neurosurgical resection and stereotactic radiotherapy, which can prolong survival. In patients with asymptomatic BRAF V600E-mutant brain metastases, the BRAF inhibitors dabrafenib, vemurafenib, and immunotherapy with ipilimumab are used. In the case of multiple symptomatic brain metastases, palliative whole-brain radiotherapy is used for treatment, although it has failed to show an overall survival benefit. Increased intracranial pressure and epileptic seizures are addressed with corticosteroids and anticonvulsants. Current clinical studies for melanoma patients with brain metastases are investigating new treatment options such as PD-1 antibodies, combined ipilimumab and nivolumab, combined BRAF inhibitors and MEK inhibitors, and stereotactic radiation in combination with immunotherapy or targeted therapy. PMID:27206449

  20. Pigeon therapeutics.

    PubMed

    Harlin, R W

    2000-01-01

    This article examines therapeutics for pigeons, discussing their physiology and reproduction, housing, and nutrition. The author also looks at ways to prevent infection, while discussing treatments for various viral diseases, such as paramyxovirus and pigeon herpesvirus, bacterial infections, such as paratyphoid, and parasitic diseases. Drug dosages are listed for antibiotics, antifungals, antiparasitics, and vaccines. PMID:11228828

  1. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  2. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

    Lee, Stephen C.; Ruegsegger, Mark; Barnes, Philip D.; Smith, Bryan R.; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'etre of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multi-step work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  3. Feedlot therapeutics.

    PubMed

    Apley, M D; Fajt, V R

    1998-07-01

    This article discusses therapeutic approaches to conditions commonly encountered in feedlots. Challenges discussed include bovine respiratory complex, tracheal edema, atypical interstitial pneumonia, footrot, toe abscesses, mycoplasma arthritis, cardiovascular disease, lactic acidosis, bloat, coccidiosis, central nervous system diseases, abscesses and cellulitis, pregnancy management and abortion, and ocular disease. PMID:9704416

  4. Gene therapeutic approaches to inhibit hepatitis B virus replication

    PubMed Central

    Gebbing, Maren; Bergmann, Thorsten; Schulz, Eric; Ehrhardt, Anja

    2015-01-01

    Acute and chronic hepatitis B virus (HBV) infections remain to present a major global health problem. The infection can be associated with acute symptomatic or asymptomatic hepatitis which can cause chronic inflammation of the liver and over years this can lead to cirrhosis and the development of hepatocellular carcinomas. Currently available therapeutics for chronically infected individuals aim at reducing viral replication and to slow down or stop the progression of the disease. Therefore, novel treatment options are needed to efficiently combat and eradicate this disease. Here we provide a state of the art overview of gene therapeutic approaches to inhibit HBV replication. We discuss non-viral and viral approaches which were explored to deliver therapeutic nucleic acids aiming at reducing HBV replication. Types of delivered therapeutic nucleic acids which were studied since many years include antisense oligodeoxynucleotides and antisense RNA, ribozymes and DNAzymes, RNA interference, and external guide sequences. More recently designer nucleases gained increased attention and were exploited to destroy the HBV genome. In addition we mention other strategies to reduce HBV replication based on delivery of DNA encoding dominant negative mutants and DNA vaccination. In combination with available cell culture and animal models for HBV infection, in vitro and in vivo studies can be performed to test efficacy of gene therapeutic approaches. Recent progress but also challenges will be specified and future perspectives will be discussed. This is an exciting time to explore such approaches because recent successes of gene therapeutic strategies in the clinic to treat genetic diseases raise hope to find alternative treatment options for patients chronically infected with HBV. PMID:25729471

  5. Pediatric Glaucoma: Pharmacotherapeutic Options.

    PubMed

    Samant, Monica; Medsinge, Anagha; Nischal, Ken K

    2016-06-01

    Childhood glaucoma is a major therapeutic challenge for pediatric ophthalmologists and glaucoma specialists worldwide. Management depends on the etiology and age at presentation. A variety of drugs are available for the control of intraocular pressure in children; however, none of these drugs have been licensed by the regulatory agencies for use in children. Furthermore, evidence gained from randomized controlled trials in the pediatric population is sparse, and little is known regarding the use of newer anti-glaucoma preparations. This evidence-based review aims to discuss the available pharmacotherapeutic options for glaucoma in children. Topical adrenoceptor blockers, topical and systemic carbonic anhydrase inhibitors, prostaglandin (PG) analogs, adrenoceptor agonists, parasympathomimetics, and combined preparations are available for use in children, but usually as an off-label indication. Therefore, it is important to recognize that serious side effects have been reported, even with topical drops, and measures to reduce systemic absorption should be taken. Most drugs have been shown to have comparable ocular hypotensive effects, with the lowest occurrence of systemic side effects with PG analogs. Whereas a newly introduced prostaglandin analog, tafluprost, and some other preservative-free preparations have shown promising results in adult glaucoma patients, no pediatric reports are available as yet. Future studies may describe their role in treating pediatric glaucoma. This review also shares some suggested treatment pathways for primary congenital glaucoma (PCG), juvenile open angle glaucoma (JOAG), developmental glaucoma, aphakic/pseudophakic glaucoma, and uveitic glaucoma. PMID:27093864

  6. A Comprehensive Review of Treatment Options for Premenstrual Syndrome and Premenstrual Dysphoric Disorder.

    PubMed

    Maharaj, Shalini; Trevino, Kenneth

    2015-09-01

    Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome that involves a combination of emotional and physical symptoms that result in significant functional impairment. Because of the debilitating nature of PMDD, multiple treatment options have been considered. This review provides a comprehensive overview of these therapeutic regimens to help health care professionals provide adequate treatment for PMDD and premenstrual syndrome. The treatments that are reviewed are organized into the following categories: psychiatric, anovulatory, supplements, herbal, nonpharmacological, and other. Selective serotonin reuptake inhibitors have been established as the first-line treatment for PMDD. Although luteal phase or continuous dosing can be used, additional research is needed to more thoroughly compare the efficacies and differential symptom response of continuous, semi-intermittent, luteal phase, and symptoms-onset dosing. The psychiatric medications venlafaxine, duloxetine, alprazolam, and buspirone have also been found to be useful treatments for PMDD. Various anovulatory-related treatments have demonstrated efficacy; however, the use of some of these treatments remains limited due to potential side effects and/or the availability of cheaper alternatives. Although a variety of supplement and herbal-related treatments have been proposed, with some warranting further research, at this time only calcium supplementation has demonstrated a consistent therapeutic benefit. In conclusion, serotoninergic antidepressants have been established as the first-line treatment option for PMDD; however, there are a variety of additional treatment options that should be considered if a patient fails to achieve an adequate therapeutic response with a selective serotonin reuptake inhibitor. PMID:26352222

  7. Therapeutic perspectives

    PubMed Central

    Fiore, Carmelo E.; Pennisi, Pietra; Tinè, Marianna

    2008-01-01

    Osteoporosis and atherosclerosis are linked by biological association. This encourages the search for therapeutic strategies having both cardiovascular and skeletal beneficial effects. Among drugs that may concordantly enhance bone density and reduce the progression of atherosclerosis we can include bisphosphonates (BP), statins, β -blockers, and possibly anti-RANKL antibodies. Available data come from experimental animals and human studies. All these treatments however lack controlled clinical studies designed to demonstrate dual-action effects. PMID:22460845

  8. Treatment-resistant depression: therapeutic trends, challenges, and future directions

    PubMed Central

    Al-Harbi, Khalid Saad

    2012-01-01

    Background Patients with major depression respond to antidepressant treatment, but 10%–30% of them do not improve or show a partial response coupled with functional impairment, poor quality of life, suicide ideation and attempts, self-injurious behavior, and a high relapse rate. The aim of this paper is to review the therapeutic options for treating resistant major depressive disorder, as well as evaluating further therapeutic options. Methods In addition to Google Scholar and Quertle searches, a PubMed search using key words was conducted, and relevant articles published in English peer-reviewed journals (1990–2011) were retrieved. Only those papers that directly addressed treatment options for treatment-resistant depression were retained for extensive review. Results Treatment-resistant depression, a complex clinical problem caused by multiple risk factors, is targeted by integrated therapeutic strategies, which include optimization of medications, a combination of antidepressants, switching of antidepressants, and augmentation with non-antidepressants, psychosocial and cultural therapies, and somatic therapies including electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, deep brain stimulation, transcranial direct current stimulation, and vagus nerve stimulation. As a corollary, more than a third of patients with treatment-resistant depression tend to achieve remission and the rest continue to suffer from residual symptoms. The latter group of patients needs further study to identify the most effective therapeutic modalities. Newer biomarker-based antidepressants and other drugs, together with non-drug strategies, are on the horizon to address further the multiple complex issues of treatment-resistant depression. Conclusion Treatment-resistant depression continues to challenge mental health care providers, and further relevant research involving newer drugs is warranted to improve the quality of life of patients

  9. The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects

    PubMed Central

    Hughes, C. L.; Foster, W. G.

    2015-01-01

    In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women's health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan. PMID:26064879

  10. Breast Cancer: Treatment Options

    MedlinePlus

    ... Cancer - Treatment Options Request Permissions Print to PDF Breast Cancer - Treatment Options Approved by the Cancer.Net Editorial ... recommendations for ovarian ablation . Hormonal therapy for metastatic breast cancer Hormonal therapies are also commonly used to treat ...

  11. TOPEX satellite option study

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The basic design of the fleet satellite communication spacecraft (FLTSATCOM) can easily accommodate any of the three payload options for the ocean dynamic topography experiment (TOPEX). The principal mission requirements as well as the payload accommodations and communications systems needed for launching this payload are reviewed. The existing FLTSATCOM satellite design is identified and the approaches for the proposed propulsion system are described in addition to subsystems for mechanical; power; attitude and velocity control; and telemetry, tracking and control are described. The compatability of FLTSATCOM with the launch vehicle is examined and its capabilities vs TOPEX requirements are summarized. Undetermined changes needed to meet data storage, thermal control, and area to mass ratio requirements are discussed. Cost estimates are included for budgetary and planning purposes. The availability of the described design is assessed based on the continuing production of FLTSATCOM spacecraft during the schedule span planned for TOPEX.

  12. Therapeutic targets of triple-negative breast cancer: a review.

    PubMed

    Jamdade, Vinayak S; Sethi, Nikunj; Mundhe, Nitin A; Kumar, Parveen; Lahkar, Mangala; Sinha, Neeraj

    2015-09-01

    Breast cancer (BC) is the second most common cause of cancer deaths. Triple-negative breast cancer (TNBC) does not show immunohistochemical expression of oestrogen receptors, progesterone receptors or HER2. At present, no suitable treatment option is available for patients with TNBC. This dearth of effective conventional therapies for the treatment of advanced stage breast cancer has provoked the development of novel strategies for the management of patients with TNBC. This review presents recent information associated with different therapeutic options for the treatment of TNBC focusing on promising targets such as the Notch signalling, Wnt/β-catenin and Hedgehog pathways, in addition to EGFR, PARP1, mTOR, TGF-β and angiogenesis inhibitors. PMID:26040571

  13. Therapeutic alliance.

    PubMed

    Fox, Valerie

    2002-01-01

    I have been very fortunate in my journey of mental illness. I respond well to medication, but I don't think that is the complete answer to living successfully with serious, persistent mental illness. I believe a person's environment is also of utmost importance, enabling the person suffering with mental illness to continually grow in life. I found early in my struggle with mental illness a psychiatrist with whom I have always had a very good rapport. Until recently I didn't know that what I have with this psychiatrist is professionally known as a therapeutic alliance. Over the years, when I need someone to talk over anything that is troubling to me, I seek my psychiatrist. A therapeutic alliance is non-judgmental; it is nourishing; and finally it is a relationship of complete trust. Perhaps persons reading this article who have never experienced this alliance will seek it. I believe it can make an insecure person secure; a frightened person less frightened; and allow a person to continue the journey of mental health with a sense of belief in oneself. PMID:12433224

  14. Surgical Removal of Retained Subfoveal Perfluorocarbon Liquid through a Therapeutic Macular Hole with Intravitreal PFCL Injection and Gas Tamponade

    PubMed Central

    Kim, Jae Min; Park, Kyu Hyung; Chung, Hum

    2013-01-01

    We report two cases of surgical removal of a retained subfoveal perfluorocarbon liquid (PFCL) bubble through a therapeutic macular hole combined with intravitreal PFCL injection and gas tamponade. Two patients underwent pars plana vitrectomy with PFCL injection for rhegmatogenous retinal detachment. In both cases, a retained subfoveal PFCL bubble was noticed postoperatively by funduscopy and optical coherence tomography. Both patients underwent surgical removal of the subfoveal PFCL through a therapeutic macular hole and gas tamponade. The therapeutic macular holes were completely closed by gas tamponade and the procedure yielded a good visual outcome (best-corrected visual acuity of 20 / 40 in both cases). In one case, additional intravitreal PFCL injection onto the macula reduced the size of the therapeutic macular hole and preserved the retinal structures in the macula. Surgical removal of a retained subfoveal PFCL bubble through a therapeutic macular hole combined with intravitreal PFCL injection and gas tamponade provides an effective treatment option. PMID:24082781

  15. Lunar Cube Transfer Trajectory Options

    NASA Technical Reports Server (NTRS)

    Folta, David; Dichmann, Donald James; Clark, Pamela E.; Haapala, Amanda; Howell, Kathleen

    2015-01-01

    Numerous Earth-Moon trajectory and lunar orbit options are available for Cubesat missions. Given the limited Cubesat injection infrastructure, transfer trajectories are contingent upon the modification of an initial condition of the injected or deployed orbit. Additionally, these transfers can be restricted by the selection or designs of Cubesat subsystems such as propulsion or communication. Nonetheless, many trajectory options can b e considered which have a wide range of transfer duration, fuel requirements, and final destinations. Our investigation of potential trajectories highlights several options including deployment from low Earth orbit (LEO) geostationary transfer orbits (GTO) and higher energy direct lunar transfer and the use of longer duration Earth-Moon dynamical systems. For missions with an intended lunar orbit, much of the design process is spent optimizing a ballistic capture while other science locations such as Sun-Earth libration or heliocentric orbits may simply require a reduced Delta-V imparted at a convenient location along the trajectory.

  16. Lunar Cube Transfer Trajectory Options

    NASA Technical Reports Server (NTRS)

    Folta, David; Dichmann, Donald J.; Clark, Pamela; Haapala, Amanda; Howell, Kathleen

    2015-01-01

    Numerous Earth-Moon trajectory and lunar orbit options are available for Cubesat missions. Given the limited Cubesat injection infrastructure, transfer trajectories are contingent upon the modification of an initial condition of the injected or deployed orbit. Additionally, these transfers can be restricted by the selection or designs of Cubesat subsystems such as propulsion or communication. Nonetheless, many trajectory options can be considered which have a wide range of transfer durations, fuel requirements, and final destinations. Our investigation of potential trajectories highlights several options including deployment from low Earth orbit (LEO), geostationary transfer orbits (GTO), and higher energy direct lunar transfers and the use of longer duration Earth-Moon dynamical systems. For missions with an intended lunar orbit, much of the design process is spent optimizing a ballistic capture while other science locations such as Sun-Earth libration or heliocentric orbits may simply require a reduced Delta-V imparted at a convenient location along the trajectory.

  17. Ear keloids: a review and update of treatment options

    PubMed Central

    SOBEC, RALUCA; DOBREANU, CODRIN; FODOR, LUCIAN; ŞOMCUTEAN, ANA; ŢICHIL, IOANA; COSGAREA, MARCEL

    2013-01-01

    Ear keloids are among the most challenging plastic surgery conditions and may have significant psychosocial impact for the patient. Their aesthetic considerations are serious and despite a variety of treatment options, they often proved to be recurrent. This paper reviews the management options of ear keloids available in literature up to date. Multiple therapeutic options are discussed, such as: surgical treatment, corticosteroid injections, laser therapy, cryotherapy, radiotherapy, pressure therapy, therapy with antitumor or immunosuppressive agents. PMID:26527968

  18. TANK SPACE OPTIONS REPORT

    SciTech Connect

    WILLIS WL; AHRENDT MR

    2009-08-11

    Since this report was originally issued in 2001, several options proposed for increasing double-shell tank (DST) storage space were implemented or are in the process of implementation. Changes to the single-shell tank (SST) waste retrieval schedule, completion of DST space saving options, and the DST space saving options in progress have delayed the projected shortfall of DST storage space from the 2007-2011 to the 2018-2025 timeframe (ORP-11242, River Protection Project System Plan). This report reevaluates options from Rev. 0 and includes evaluations of new options for alleviating projected restrictions on SST waste retrieval beginning in 2018 because of the lack of DST storage space.

  19. Oligonucleotide conjugates for therapeutic applications

    PubMed Central

    Winkler, Johannes

    2013-01-01

    Insufficient pharmacokinetic properties and poor cellular uptake are the main hurdles for successful therapeutic development of oligonucleotide agents. The covalent attachment of various ligands designed to influence the biodistribution and cellular uptake or for targeting specific tissues is an attractive possibility to advance therapeutic applications and to expand development options. In contrast to advanced formulations, which often consist of multiple reagents and are sensitive to a variety of preparation conditions, oligonucleotide conjugates are defined molecules, enabling structure-based analytics and quality control techniques. This review gives an overview of current developments of oligonucleotide conjugates for therapeutic applications. Attached ligands comprise peptides, proteins, carbohydrates, aptamers and small molecules, including cholesterol, tocopherol and folic acid. Important linkage types and conjugation methods are summarized. The distinct ligands directly influence biochemical parameters, uptake machanisms and pharmacokinetic properties. PMID:23883124

  20. Enhanced durability for high-temperature desulfurization sorbents for moving-bed applications -- Option 3 program: Development and testing of additional zinc titanate sorbents. Final report, September 1992--May 1996

    SciTech Connect

    Ayala, R.E.; Chuck, T.L.

    1996-12-31

    GE is developing a moving-bed, high-temperature desulfurization system for the integrated gasification combined-cycle (IGCC) power cycle in which zinc-based regenerable sorbents are currently being used as desulfurization sorbents. Zinc titanate and other zinc-based oxides are being considered as sorbents for use in the Clean Coal Technology Demonstration Program at Tampa Electric Co.`s Polk Power Station. A key to success in the development of high-temperature desulfurization systems is the matching of sorbent properties for the selected process operating conditions, namely, sustainable desulfurization kinetics, high sulfur capacity, and mechanical durability over multiple cycles. Additionally, the sulfur species produced during regeneration of the sorbent must be in a form compatible with sulfur recovery systems, such as sulfuric acid or elemental sulfur processes. The objective of this contract is to identify and test sorbent fabrication methods and chemical compositions that enhance the long-term chemical reactivity and mechanical strength of zinc titanate and other novel sorbents for moving-bed, high-temperature desulfurization of coal-derived gases. A parametric study on the use of calcium sulfate additives to zinc titanate was conducted for zinc titanates having a 2:1 and 1.5:1 zinc-to-titanium molar ratio, and they showed a beneficial effect on crush strength of fresh 2:1 zinc titanate sorbents. In addition, a test procedure was developed to screen sorbent formulations based on resistance to spalling and pellet breakage induced by zinc sulfate formation in the presence of sulfur dioxide and excess oxygen conditions.

  1. Current therapeutic concepts in peripartum cardiomyopathy.

    PubMed

    Krejci, Jan; Poloczkova, Hana; Nemec, Petr

    2015-01-01

    Peripartum cardiomyopathy (PPCM) is a relatively rare disease characterized by systolic heart failure occuring towards the end of pregnancy or during the months following birth. It is most often seen in women of African descent, and its incidence seems to be slightly increasing in recent years. Other etiologies of heart failure should be excluded to determine the diagnosis of PPCM. The clinical picture corresponds to systolic heart failure. The rapid onset of the symptoms in relation to pregnancy is striking. The essential diagnostic procedures such as echocardiography, cardiac magnetic resonance imaging and endomyocardial biopsy may be beneficial in certain situations. The etiology of the disease remains unclear. Speculated causes include myocarditis, autoimmune disorders, cardiotropic virus infection, and abnormal responses to hemodynamic and hormonal changes during pregnancy. Particular attention is currently given to the concept of increased oxidative stress inducing production of proapoptotic, angiostatic and proinflammatory mediators. Recovery of left ventricular systolic function occurs in about half of the cases. Mortality has been decreasing in recent years, especially in the United States, but is still between 10-15% in less developed countries where therapeutic possibilities are limited. In addition to standard heart failure therapy, specific treatments (pentoxyfilline, bromocriptine, immunomodulatory therapy) have been tested. Mechanical circulatory support is sometimes needed. Heart transplantation is the therapeutic option for the most severe heart failure and is used in about 10% of the cases. Recurrence in subsequent pregnancy is common and therefore, another pregnancy is not recommended in many cases. PMID:25483952

  2. Treatment options for apnoea of prematurity.

    PubMed

    Morton, Sarah U; Smith, Vincent C

    2016-07-01

    Apnoea of prematurity (AOP) affects almost all infants born at <28 weeks gestation or with birth weight <1000 g. When untreated, AOP may be associated with negative outcomes. Because of these negative outcomes, effective treatment for AOP is an important part of optimising care of preterm infants. Standard treatment usually involves xanthine therapy and respiratory support. Cutting-edge work with stochastic vibrotactile stimulation and new pharmaceutical agents continues to expand therapeutic options. In this article, we review the pathophysiology of AOP, associated conditions and treatment options. PMID:27010019

  3. Intrathecal baclofen pump – a viable therapeutic option in pregnancy

    PubMed Central

    Tandon, Saira S; Hoskins, Iffath; Azhar, Salman

    2010-01-01

    Baclofen, a gamma-aminobutyric acid analogue, is used as a muscle relaxant and antispasmodic to relieve symptoms in patients with intractable spasticity arising from cerebral or spinal aetiology such as in traumatic brain injury or multiple sclerosis. As it is often used in women of reproductive age, it is imperative to know the safety and associated maternal and fetal risks. The Food and Drug Administration has assigned the drug to Pregnancy Category C because of the lack of controlled data in humans. Animal studies have revealed an increased incidence of omphalocele if used in doses several times the recommended human dose. Baclofen should only be given during pregnancy when the benefits outweigh the risks. Baclofen is considered compatible with breast feeding by the American Academy of Pediatrics.

  4. Iatrogenic intracranial pseudoaneurysms: neuroradiological and therapeutical considerations, including endovascular options.

    PubMed

    Ciceri, E F M; Regna-Gladin, C; Erbetta, A; Chiapparini, L; Nappini, S; Savoiardo, M; Di Meco, F

    2006-11-01

    Intracranial pseudoaneurysms represent a potentially fatal complication of intracranial surgery. Our purpose is to describe their neuroradiological characteristics, prognostic features and possible treatment. Eight cases of postsurgical intracranial pseudoaneurysms have been observed at our institution since 1988. Four were observed following transsphenoidal (TS) surgery and four after pterional craniotomies. Two types of iatrogenic pseudoaneurysms were observed: "fusiform", probably due to weakening of the adventitia during surgical peeling of the tumour from the artery (three cases) and "saccular", occurring after a more focal or complete laceration of the vessel (five cases), more often after TS surgery. A thorough preoperative neuroradiological examination may identify anatomical conditions at risk for development of this severe complication. Postoperative neuroradiological follow-up is mandatory in cases in which unusual bleeding has occurred during the perioperative period, but absence of bleeding does not exclude the possible development of a pseudoaneurysm. Endovascular treatment of pseudoaneurysms represents a safe and durable procedure, specifically in those cases in which damage to the carotid siphon occurred during TS surgery. PMID:17122940

  5. Diagnosis and therapeutic options for peripheral vasculitic neuropathy.

    PubMed

    Blaes, Franz

    2015-04-01

    Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955

  6. Clostridium difficile Infection: Epidemiology, Pathogenesis, Risk Factors, and Therapeutic Options

    PubMed Central

    Seyedjavadi, Sima Sadat; Goudarzi, Hossein; Mehdizadeh Aghdam, Elnaz; Nazeri, Saeed

    2014-01-01

    The incidence and mortality rate of Clostridium difficile infection have increased remarkably in both hospital and community settings during the last two decades. The growth of infection may be caused by multiple factors including inappropriate antibiotic usage, poor standards of environmental cleanliness, changes in infection control practices, large outbreaks of C. difficile infection in hospitals, alteration of circulating strains of C. difficile, and spread of hypervirulent strains. Detection of high-risk populations could be helpful for prompt diagnosis and consequent treatment of patients suffering from C. difficile infection. Metronidazole and oral vancomycin are recommended antibiotics for the treatment of initial infection. Current treatments for C. difficile infection consist of supportive care, discontinuing the unnecessary antibiotic, and specific antimicrobial therapy. Moreover, novel approaches include fidaxomicin therapy, monoclonal antibodies, and fecal microbiota transplantation mediated therapy. Fecal microbiota transplantation has shown relevant efficacy to overcome C. difficile infection and reduce its recurrence. PMID:24991448

  7. MMPs as therapeutic targets – still a viable option?

    PubMed Central

    Fingleton, Barbara

    2009-01-01

    Matrix metalloproteinases (MMPs) appear to be ideal drug targets – they are disease-associated, extracellular enzymes with a dependence on zinc for activity. This apparently straightforward target, however, is much more complex than initially realized. Although disease associated, the roles for particular enzymes may be healing rather than harmful making broad-spectrum inhibition unwise; targeting the catalytic zinc with specificity is difficult, since other related proteases as well as non-related proteins can be affected by some chelating groups. While the failure of early-generation MMP inhibitors dampened enthusiasm for this type of drug, there has recently been a wealth of studies examining the basic biology of MMPs which will greatly inform new drug trials in this field. PMID:17693104

  8. New Therapeutic Options for Autism Spectrum Disorder: Experimental Evidences

    PubMed Central

    2015-01-01

    Autism spectrum disorder (ASD) is characterized by impairment in two behavioral domains: social interaction/communication together with the presence of stereotyped behaviors and restricted interests. The heterogeneity in the phenotype among patients and the complex etiology of the disorder have long impeded the advancement of the development of successful pharmacotherapies. However, in the recent years, the integration of findings of multiple levels of research, from human genetics to mouse models, have made considerable progress towards the understanding of ASD pathophysiology, allowing the development of more effective targeted drug therapies. The present review discusses the current state of pharmacological research in ASD based on the emerging common pathophysiology signature. PMID:26713078

  9. A less aggressive therapeutic option for electrical storm.

    PubMed

    Bertero, G; Agosti, S; Brunelli, C

    2013-01-01

    Electrical storm (ES) describes the rapidly clustering ventricular fibrillation (VF) that requires multiple cardioversions. Emerging evidence suggests that Purkinje arborization and sympathetic nerve regeneration play a major role in initiating malignant arrhythmias. We report the case of two patients who, after having survived an acute myocardial infarction (MI), developed repetitive episodes of polymorphic ventricular tachycardia and VF one week after percutaneous revascularization, triggered by monomorphic premature ventricular contractions (PVCs). Owing to repetitive and drug-refractory VF episodes, temporary atrial overdrive pacing was attempted with complete suppression of VF. In the following month, recurrence of ventricular arrhythmia was inversely related to the atrial pacing rate. Although antiarrhythmic drugs other than beta-blockers had been discontinued, neither PVCs nor ventricular arrhythmias recurred at one-month follow-up when the lower pacing rate was set at 60 bpm. In conclusion in these patients, ES was likely related to nerve sprouting after ischemic injury. This chaotic phenomenon occurs early after tissue damage and shows a peak seven days after acute MI with degeneration of superfluous axon branches. High pacing rates can reduce early after depolarizations and suppress PVCs, thus preventing ES. On these grounds, ES patients may be treated with temporary overdrive pacing rather than early radiofrequency ablation. PMID:24217829

  10. Treatment strategies for atopic dermatitis: optimizing the available therapeutic options.

    PubMed

    Paller, Amy S; Simpson, Eric L; Eichenfield, Lawrence F; Ellis, Charles N; Mancini, Anthony J

    2012-09-01

    Bathing and moisturization to control dryness, applications of topical anti-inflammatory agents (including corticosteroids and calcineurin inhibitors [TCIs]) to control flares, minimization of the risk for infection, and relief of pruritus are the cornerstones of effective therapy for atopic dermatitis. Education of parents and patients is crucial to enhance adherence. Strategies for reduced Staphylococcus aureus colonization may help control re-emergence of flares following cessation of antimicrobial treatment for infection; these include dilute bleach baths and minimizing the risk for contamination of topical agents. In severe, refractory cases, more aggressive therapy with systemic immunosuppressants may be considered, but appropriate laboratory testing must be included as part of patient monitoring during treatment. The value of adjuvant therapy with wet wraps to "cool down" particularly erythematous and pruritic flares is becoming increasingly recognized. PMID:23021780

  11. Aromatase inhibitors in men: effects and therapeutic options

    PubMed Central

    2011-01-01

    Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic short stature and constitutional delay of puberty. Long-term efficacy and safety of the use of aromatase inhibitors has not yet been established in males, however, and their routine use is therefore not yet recommended. PMID:21693046

  12. Systemic mastocytosis: current classification and novel therapeutic options.

    PubMed

    Barbie, David A; Deangelo, Daniel J

    2006-10-01

    Systemic mast cell disease is characterized by dysregulated mast cell growth and survival, with infiltration into multiple organs and release of systemic mediators. Much has been learned about mast cell biology over the past 20 years, and it has become apparent that activating mutations in the c-KIT receptor tyrosine kinase underlie the aberrant cell signaling and mast cell growth in a majority of patients. Despite this knowledge, targeted therapy with imatinib has been largely unsuccessful due to resistance of the common c-KIT D816V (Asp-->Val) mutation. Novel strategies designed to inhibit the growth of mast cells containing the c-KIT D816V mutations have shown success in vitro and may provide effective targeted therapy for this treatment-refractory disease. PMID:17099633

  13. Functional foods as potential therapeutic options for metabolic syndrome.

    PubMed

    Brown, L; Poudyal, H; Panchal, S K

    2015-11-01

    Obesity as part of metabolic syndrome is a major lifestyle disorder throughout the world. Current drug treatments for obesity produce small and usually unsustainable decreases in body weight with the risk of major adverse effects. Surgery has been the only treatment producing successful long-term weight loss. As a different but complementary approach, lifestyle modification including the use of functional foods could produce a reliable decrease in obesity with decreased comorbidities. Functional foods may include fruits such as berries, vegetables, fibre-enriched grains and beverages such as tea and coffee. Although health improvements continue to be reported for these functional foods in rodent studies, further evidence showing the translation of these results into humans is required. Thus, the concept that these fruits and vegetables will act as functional foods in humans to reduce obesity and thereby improve health remains intuitive and possible rather than proven. PMID:26345360

  14. Management of stress in inflammatory bowel disease: a therapeutic option?

    PubMed

    Goodhand, James R; Wahed, Mahmood; Rampton, David S

    2009-12-01

    There is increasing evidence that psychological stress and associated mood disorders are linked with, and can adversely affect the course of, inflammatory bowel disease (IBD). Unfortunately, owing to methodological difficulties inherent in undertaking appropriately targeted and blinded trials, there are limited high-quality data regarding the effects on IBD of interventions aimed to ameliorate stress and mood disorders. Nevertheless, patients want psychological intervention as well as conventional medical strategies. Emerging trial evidence supports the suggestion that psychologically orientated therapy may ameliorate IBD-associated mood disorders, but there are no strong data as of yet to indicate that stress management has a beneficial effect on the activity or course of IBD. As yet, which, when and how interventions targeted at psychological stress and mood disturbances should be offered to individual patients with IBD is not clear. PMID:19929586

  15. Diagnosis and therapeutic options for peripheral vasculitic neuropathy

    PubMed Central

    2015-01-01

    Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955

  16. ECT as a therapeutic option in severe brain injury.

    PubMed

    Kant, R; Bogyi, A M; Carosella, N W; Fishman, E; Kane, V; Coffey, C E

    1995-03-01

    Electroconvulsive therapy (ECT) is a safe, highly effective, and rapidly acting treatment for certain major psychiatric illnesses, most notably severe mood disorders. Disturbances in mood and behavior as symptoms of delirium may complicate recovery from traumatic brain injury, but virtually no data exist on the role of ECT as a treatment modality in such clinical situations. We describe a patient with severe, unremitting, agitated behavior following a severe closed head injury from a motor vehicle accident. The initial Glasgow Coma Scale score was 3, with computed tomographic evidence of bilateral frontal and left thalamic contusions. After awakening from a 21-day coma, the patient failed to improve beyond a Ranchos Los Amigos level 4 recovery stage. He exhibited persistent severe agitation with vocal outbursts and failed to assist in performing activities of daily living. His difficulties proved unresponsive to combined behavioral therapy and multiple trials of various psychopharmacologic agents. As an intervention of "last resort," he then received six brief-pulse, bilateral ECT treatments that resulted in marked lessening of his agitation and improvement in his ability to express his needs and participate in his self-care. Also, following the ECT, he showed a markedly enhanced response to psychopharmacologic agents. These findings may have important clinical implications for treatment of prolonged delirium after traumatic brain injury. PMID:7796068

  17. Future Lipid-Altering Therapeutic Options Targeting Residual Cardiovascular Risk.

    PubMed

    Farnier, Michel

    2016-07-01

    Low-density lipoproteins (LDL) play a causal role in the development of atherosclerosis, and reduction of LDL cholesterol with a statin is a cornerstone in prevention of cardiovascular disease. However, it remains an unmet need to reduce the residual risk on maximally tolerated statin alone or in combination with other drugs such as ezetimibe. Among the new LDL-lowering therapies, PCSK9 inhibitors appear the most promising class. Genetic studies suggest that triglyceride-rich lipoproteins are associated with cardiovascular risk and several promising triglyceride-lowering therapies are at various stages of development. At the opposite end, high-density lipoprotein (HDL) cholesterol seems to not be causally associated with cardiovascular risk, and thus far, trials designed to reduce cardiovascular risk by mainly raising HDL cholesterol levels have been disappointing. Nevertheless, new drugs targeting HDL are still in development. This review describes the new drugs reducing LDL, apolipoprotein(a), and triglyceride-rich lipoproteins, and the strategies to modulate HDL metabolism. PMID:27216845

  18. Swallow Syncope: Clinical Presentation, Diagnostic Criteria, and Therapeutic Options

    PubMed Central

    Garg, Shashank; Girotra, Mohit; Glasser, Stephen; Dutta, Sudhir K.

    2014-01-01

    We recently encountered three patients with episodes of syncope associated with food ingestion. A 31-year-old woman had an episode of syncope in the hospital while drinking soda. Transient asystole was noted on the telemonitor, confirming the diagnosis of swallow syncope. The other two patients were 78- and 80 year old gentlemen, respectively, who presented with recurrent and transient episodes of dizziness during deglutition. Extensive work-up of syncope was negative in both cases and a diagnosis of swallow syncope was made by clinical criteria. These cases illustrate the challenging problem of swallow syncope. The diagnosis can be suspected on the basis of clinical presentation and confirmed with the demonstration of transient brady-arrhythmia during deglutition. Medical management includes avoiding trigger foods, use of anticholinergics, and/or placement of a permanent cardiac pacemaker. PMID:25038205

  19. Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics

    PubMed Central

    Jelveh, Salomeh; Chithrani, Devika B.

    2011-01-01

    The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research. PMID:24212654

  20. Direct renin inhibition: from pharmacological innovation to novel therapeutic opportunities.

    PubMed

    Volpe, Massimo; Pontremoli, Roberto; Borghi, Claudio

    2011-09-01

    Nowadays, social and economic burden related to cardiovascular and renal diseases still remains extremely high, although there has been a dramatic improvement of diagnostic options and therapeutic strategies reported in the last 30 years. The progressively higher attention towards integrated pharmacological strategies, which are able to interfere with different pathophysiological mechanisms, has certainly led to better control of cardiovascular and renal diseases. In view of the large involvement of the renin-angiotensin system (RAS) in the vast majority of pathophysiological mechanisms leading to the development and progression of cardiovascular and renal diseases, it can be easily understood why it has been long viewed as the 'ideal' target for the pharmacological treatment of several clinical conditions. Recently, besides the well known therapeutic approaches for RAS blockade, based on the use of ACE inhibitors, angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) and aldosterone antagonists, both the scientific and medical community have focused their attention on a novel therapeutic option. In 2007, aliskiren, the first compound of a new drug class, the direct renin inhibitors (DRIs), has become available for clinical use, being a novel and innovative therapeutic option. Aliskiren is able to interfere with the enzymatic activity of renin by blocking the catalytic site of the molecule and inducing an 'upstream' RAS blockade. This leads to a modulation of the biological properties of renin, thus resulting in the missed cleavage of angiotensinogen to angiotensin I. Aliskiren has demonstrated antihypertensive efficacy comparable or even superior to that of other classes of antihypertensive drugs, both in monotherapy and in combination therapies. Its safety and tolerability are comparable with those of other antihypertensive drug classes and almost similar to placebo. In addition, it has been demonstrated to reduce progression of

  1. Approximate option pricing

    SciTech Connect

    Chalasani, P.; Saias, I.; Jha, S.

    1996-04-08

    As increasingly large volumes of sophisticated options (called derivative securities) are traded in world financial markets, determining a fair price for these options has become an important and difficult computational problem. Many valuation codes use the binomial pricing model, in which the stock price is driven by a random walk. In this model, the value of an n-period option on a stock is the expected time-discounted value of the future cash flow on an n-period stock price path. Path-dependent options are particularly difficult to value since the future cash flow depends on the entire stock price path rather than on just the final stock price. Currently such options are approximately priced by Monte carlo methods with error bounds that hold only with high probability and which are reduced by increasing the number of simulation runs. In this paper the authors show that pricing an arbitrary path-dependent option is {number_sign}-P hard. They show that certain types f path-dependent options can be valued exactly in polynomial time. Asian options are path-dependent options that are particularly hard to price, and for these they design deterministic polynomial-time approximate algorithms. They show that the value of a perpetual American put option (which can be computed in constant time) is in many cases a good approximation to the value of an otherwise identical n-period American put option. In contrast to Monte Carlo methods, the algorithms have guaranteed error bounds that are polynormally small (and in some cases exponentially small) in the maturity n. For the error analysis they derive large-deviation results for random walks that may be of independent interest.

  2. Therapeutic itineraries and explanations for tuberculosis: an indigenous perspective

    PubMed Central

    Nogueira, Laura Maria Vidal; Teixeira, Elizabeth; Basta, Paulo Cesar; da Motta, Maria Catarina Salvador

    2016-01-01

    ABSTRACT OBJECTIVE To analyze explanations for tuberculosis and therapeutic itineraries of Brazilian indigenous people. METHODS Case study with a qualitative-descriptive approach. We conducted semi-structured interviews with 11 Munduruku indigenous, including direct observation of treatment for tuberculosis in the municipality of Jacareacanga, south-western region of the state of Para, Brazil. To identify explanations for tuberculosis and therapeutic itineraries, we performed thematic content analysis. RESULTS Traditional medicine was the first therapeutic option chosen by the indigenous. However, biomedicine was also employed, which indicates a circulation between different therapeutic contexts and health concepts among the Munduruku. The explanations provided ranged from recognition of the signs and symptoms specific to tuberculosis to the attribution of the disease to a spirit that leaves the body and wanders in the woods, returning ill into the body. Unlike the biomedical model, which links tuberculosis transmission strictly to interpersonal contact, in closed spaces without natural lighting and ventilation (preferably domestic environments), the Munduruku associate the disease to an indirect contact between people socially distant (enemies or adversaries) in public and open places. CONCLUSIONS The explanations made by the indigenous are unique and deserve the attention of those who are responsible for developing health public policies, as well as of the teams who work on the villages. To guarantee an efficient control of tuberculosis in these regions, it is necessary that the developed actions integrate biomedicine knowledge and the traditional medicine of the indigenous people, in addition to respecting and welcoming local culture manifestations. PMID:26815161

  3. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  4. The Origins of Options

    PubMed Central

    Smaldino, Paul E.; Richerson, Peter J.

    2012-01-01

    Most research on decision making has focused on how human or animal decision makers choose between two or more options, posed in advance by the researchers. The mechanisms by which options are generated for most decisions, however, are not well understood. Models of sequential search have examined the trade-off between continued exploration and choosing one’s current best option, but still cannot explain the processes by which new options are generated. We argue that understanding the origins of options is a crucial but untapped area for decision making research. We explore a number of factors which influence the generation of options, which fall broadly into two categories: psycho-biological and socio-cultural. The former category includes factors such as perceptual biases and associative memory networks. The latter category relies on the incredible human capacity for culture and social learning, which doubtless shape not only our choices but the options available for choice. Our intention is to start a discussion that brings us closer toward understanding the origins of options. PMID:22514515

  5. Therapeutic Hypothermia for Neuroprotection

    PubMed Central

    Karnatovskaia, Lioudmila V.; Wartenberg, Katja E.

    2014-01-01

    The earliest recorded application of therapeutic hypothermia in medicine spans about 5000 years; however, its use has become widespread since 2002, following the demonstration of both safety and efficacy of regimens requiring only a mild (32°C-35°C) degree of cooling after cardiac arrest. We review the mechanisms by which hypothermia confers neuroprotection as well as its physiological effects by body system and its associated risks. With regard to clinical applications, we present evidence on the role of hypothermia in traumatic brain injury, intracranial pressure elevation, stroke, subarachnoid hemorrhage, spinal cord injury, hepatic encephalopathy, and neonatal peripartum encephalopathy. Based on the current knowledge and areas undergoing or in need of further exploration, we feel that therapeutic hypothermia holds promise in the treatment of patients with various forms of neurologic injury; however, additional quality studies are needed before its true role is fully known. PMID:24982721

  6. 48 CFR 217.207 - Exercise of options.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Exercise of options. 217.207 Section 217.207 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Exercise of options. (c) In addition to the requirements at FAR 17.207(c), exercise an option only...

  7. 48 CFR 217.207 - Exercise of options.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Exercise of options. 217.207 Section 217.207 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Exercise of options. (c) In addition to the requirements at FAR 17.207(c), exercise an option only...

  8. 48 CFR 217.207 - Exercise of options.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Exercise of options. 217.207 Section 217.207 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Exercise of options. (c) In addition to the requirements at FAR 17.207(c), exercise an option only...

  9. 48 CFR 217.207 - Exercise of options.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Exercise of options. 217.207 Section 217.207 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Exercise of options. (c) In addition to the requirements at FAR 17.207(c), exercise an option only...

  10. 48 CFR 217.207 - Exercise of options.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Exercise of options. 217.207 Section 217.207 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Exercise of options. (c) In addition to the requirements at FAR 17.207(c), exercise an option only...

  11. Expensing options solves nothing.

    PubMed

    Sahlman, William A

    2002-12-01

    The use of stock options for executive compensation has become a lightning rod for public anger, and it's easy to see why. Many top executives grew hugely rich on the back of the gains they made on their options, profits they've been able to keep even as the value they were supposed to create disappeared. The supposed scam works like this: Current accounting regulations let companies ignore the cost of option grants on their income statements, so they can award valuable option packages without affecting reported earnings. Not charging the cost of the grants supposedly leads to overstated earnings, which purportedly translate into unrealistically high share prices, permitting top executives to realize big gains when they exercise their options. If an accounting anomaly is the problem, then the solution seems obvious: Write off executive share options against the current year's revenues. The trouble is, Sahlman writes, expensing option grants won't give us a more accurate view of earnings, won't add any information not already included in the financial statements, and won't even lead to equal treatment of different forms of executive pay. Far worse, expensing evades the real issue, which is whether compensation (options and other-wise) does what it's supposed to do--namely, help a company recruit, retain, and provide the right people with appropriate performance incentives. Any performance-based compensation system has the potential to encourage cheating. Only ethical management, sensible governance, adequate internal control systems, and comprehensive disclosure will save the investor from disaster. If, Sahlman warns, we pass laws that require the expensing of options, thinking that's fixed the fundamental flaws in corporate America's accounting, we will have missed a golden opportunity to focus on the much more extensive defects in the present system. PMID:12510541

  12. Therapeutic Cancer Vaccines: Past, Present and Future

    PubMed Central

    Guo, Chunqing; Manjili, Masoud H.; Subjeck, John R.; Sarkar, Devanand; Fisher, Paul B.; Wang, Xiang-Yang

    2013-01-01

    Therapeutic vaccines represent a viable option for active immunotherapy of cancers that aim to treat late stage disease by using a patient's own immune system. The promising results from clinical trials recently led to the approval of the first therapeutic cancer vaccine by the U.S. Food and Drug Administration. This major breakthrough not only provides a new treatment modality for cancer management, but also paves the way for rationally designing and optimizing future vaccines with improved anticancer efficacy. Numerous vaccine strategies are currently being evaluated both pre-clinically and clinically. This review discusses therapeutic cancer vaccines of diverse platforms or targets as well as the preclinical and clinical studies employing these therapeutic vaccines. We will also consider tumor-induced immune suppression that hinders the potency of therapeutic vaccines, and potential strategies to counteract these mechanisms for generating more robust and durable antitumor immune responses. PMID:23870514

  13. Food additives

    MedlinePlus

    Food additives are substances that become part of a food product when they are added during the processing or making of that food. "Direct" food additives are often added during processing to: Add nutrients ...

  14. A classification system for sinus membrane perforations during augmentation procedures with options for repair.

    PubMed

    Vlassis, J M; Fugazzotto, P A

    1999-06-01

    A classification system for sinus membrane perforations encountered during a sinus augmentation procedure is presented. Five of the perforations are discussed, as are the therapeutic options for their repair. Class I and Class II perforations are most easily repaired, while Class IV is the most difficult to successfully treat. In addition, the effect of the sinus membrane perforation on the course of proposed therapy is discussed. When classified and managed appropriately, sinus membrane perforations are not an absolute indication for aborting the augmentation procedure which is in progress. This paper provides a system of classification that can be used by clinicians to collect data on membrane perforations and repair results. PMID:10397526

  15. Therapeutic cloning and tissue engineering.

    PubMed

    Koh, Chester J; Atala, Anthony

    2004-01-01

    A severe shortage of donor organs available for transplantation in the United States leaves patients suffering from diseased and injured organs with few treatment options. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure. PMID:15094294

  16. Therapeutic Drug Monitoring

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Therapeutic Drug Monitoring Share this page: Was this page ... Monitored Drugs | Common Questions | Related Pages What is therapeutic drug monitoring? Therapeutic drug monitoring is the measurement ...

  17. The Therapeutic Roller Coaster

    PubMed Central

    CHU, JAMES A.

    1992-01-01

    Survivors of severe childhood abuse often encounter profound difficulties. In addition to posttraumatic and dissociative symptomatology, abuse survivors frequently have characterologic problems, particularly regarding self-care and maintaining relationships. Backgrounds of abuse, abandonment, and betrayal are often recapitulated and reenacted in therapy, making the therapeutic experience arduous and confusing for therapists and patients. Efforts must be directed at building an adequate psychotherapeutic foundation before undertaking exploration and abreaction of past traumatic experiences. This discussion sets out a model for treatment of childhood abuse survivors, describing stages of treatment and suggesting interventions. Common treatment dilemmas or "traps" are discussed, with recommendations for their resolution. PMID:22700116

  18. Porphyria Treatment Options

    MedlinePlus

    ... only. For treatment options for Porphyria Cutanea Tarda (PCT) , Congenital Erythropoietic Protoporphyria (CEP) and Hepatoerythropoietic Porphyria (HEP) ... Contact Us About Porphyria AIP VP HCP ADP PCT EPP CEP HEP Diet and Nutrition History of ...

  19. Yale's Tuition Postponement Option

    ERIC Educational Resources Information Center

    Curran, William E.

    1973-01-01

    Discusses Yale's Tuition Postponement Option which bases a student's repayment obligation on the student's future income. Under this system, some students will pay Yale less than the amounts they postponed plus interest and some will pay more. (JF)

  20. Food additives

    PubMed Central

    Spencer, Michael

    1974-01-01

    Food additives are discussed from the food technology point of view. The reasons for their use are summarized: (1) to protect food from chemical and microbiological attack; (2) to even out seasonal supplies; (3) to improve their eating quality; (4) to improve their nutritional value. The various types of food additives are considered, e.g. colours, flavours, emulsifiers, bread and flour additives, preservatives, and nutritional additives. The paper concludes with consideration of those circumstances in which the use of additives is (a) justified and (b) unjustified. PMID:4467857

  1. Options Study - Phase II

    SciTech Connect

    R. Wigeland; T. Taiwo; M. Todosow; W. Halsey; J. Gehin

    2010-09-01

    The Options Study has been conducted for the purpose of evaluating the potential of alternative integrated nuclear fuel cycle options to favorably address the issues associated with a continuing or expanding use of nuclear power in the United States. The study produced information that can be used to inform decisions identifying potential directions for research and development on such fuel cycle options. An integrated nuclear fuel cycle option is defined in this study as including all aspects of the entire nuclear fuel cycle, from obtaining natural resources for fuel to the ultimate disposal of used nuclear fuel (UNF) or radioactive wastes. Issues such as nuclear waste management, especially the increasing inventory of used nuclear fuel, the current uncertainty about used fuel disposal, and the risk of nuclear weapons proliferation have contributed to the reluctance to expand the use of nuclear power, even though it is recognized that nuclear power is a safe and reliable method of producing electricity. In this Options Study, current, evolutionary, and revolutionary nuclear energy options were all considered, including the use of uranium and thorium, and both once-through and recycle approaches. Available information has been collected and reviewed in order to evaluate the ability of an option to clearly address the challenges associated with the current implementation and potential expansion of commercial nuclear power in the United States. This Options Study is a comprehensive consideration and review of fuel cycle and technology options, including those for disposal, and is not constrained by any limitations that may be imposed by economics, technical maturity, past policy, or speculated future conditions. This Phase II report is intended to be used in conjunction with the Phase I report, and much information in that report is not repeated here, although some information has been updated to reflect recent developments. The focus in this Options Study was to

  2. Fertility options in transgender people.

    PubMed

    De Roo, Chloë; Tilleman, Kelly; T'Sjoen, Guy; De Sutter, Petra

    2016-01-01

    Hormonal and surgical treatments for transgender people have a devastating effect on the possibility for these patients to reproduce. Additionally, transgender people tend to start sex reassignment treatment at a young age, when reproductive wishes are not yet clearly defined nor fulfilled. The most recent Standards of Care of the World Professional Association for Transgender Health recommend clearly informing patients regarding their future reproductive options prior to initiation of treatment. This review gives an overview of the current knowledge and state-of-the-art techniques in the field of fertility preservation for transgender people. Where genital reconstructive surgery definitely results in sterility, hormone therapy on the other hand also has an important, but partially reversible impact on fertility. The current fertility preservation options for trans men are embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. For trans women, sperm cryopreservation, surgical sperm extraction and testicular tissue cryopreservation are possible. Although certain fertility preservation techniques could be applicable in a standardized manner based on clear biological criteria, the technique that eventually will be performed should be the preferred choice of the patient after extended explanation of all possible options. PMID:26835612

  3. Pawnee Nation Energy Option Analyses

    SciTech Connect

    Matlock, M.; Kersey, K.; Riding In, C.

    2009-07-31

    introduced two model energy codes Pawnee Nation should consider for adoption. Summary of Current and Expected Future Electricity Usage The research team provided a summary overview of electricity usage patterns in current buildings and included discussion of known plans for new construction. Utility Options Review Pawnee Nation electric utility options were analyzed through a four-phase process, which included: 1) summarizing the relevant utility background information; 2) gathering relevant utility assessment data; 3) developing a set of realistic Pawnee electric utility service options, and 4) analyzing the various Pawnee electric utility service options for the Pawnee Energy Team’s consideration. III. Findings and Recommendations Due to a lack of financial incentives for renewable energy, particularly at the state level, combined mediocre renewable energy resources, renewable energy development opportunities are limited for Pawnee Nation. However, near-term potential exists for development of solar hot water at the gym, and an exterior wood-fired boiler system at the tribe’s main administrative building. Pawnee Nation should also explore options for developing LFGTE resources in collaboration with the City of Pawnee. Significant potential may also exist for development of bio-energy resources within the next decade. Pawnee Nation representatives should closely monitor market developments in the bio-energy industry, establish contacts with research institutions with which the tribe could potentially partner in grant-funded research initiatives. In addition, a substantial effort by the Kaw and Cherokee tribes is underway to pursue wind development at the Chilocco School Site in northern Oklahoma where Pawnee is a joint landowner. Pawnee Nation representatives should become actively involved in these development discussions and should explore the potential for joint investment in wind development at the Chilocco site.

  4. Lunar Cube Transfer Trajectory Options

    NASA Technical Reports Server (NTRS)

    Folta, David C.; Dichman, Don; Clark, Pamela; Haapala, Amanda; Howell, Kathleen

    2014-01-01

    Contingent upon the modification of an initial condition of the injected or deployed orbit. Additionally, these designs can be restricted by the selection of the Cubesat subsystem design such as propulsion or communication. Nonetheless, many trajectory options can be designed with have a wide range of transfer durations, fuel requirements, and final destinations. Our investigation of potential trajectories highlights several design options including deployment into low Earth orbit (LEO), geostationary transfer orbits (GTO), and higher energy direct lunar transfer orbits. In addition to direct transfer options from these initial orbits, we also investigate the use of longer duration Earth-Moon dynamical systems. For missions with an intended lunar orbit, much of the design process is spent optimizing a ballistic capture while other science locations such as Sun-Earth libration or heliocentric orbits may simply require a reduced Delta-V imparted at a convenient location along the trajectory. In this article we examine several design options that meet the above limited deployment and subsystem drivers. We study ways that both impulsive and low-thrust Solar Electric Propulsion (SEP) engines can be used to place the Cubesat first into a highly eccentric Earth orbit, enter the Moon's Sphere of Influence, and finally achieve a highly eccentric lunar orbit. We show that such low-thrust transfers are feasible with a realistic micro-thruster model, assuming that the Cubesat can generate sufficient power for the SEP. Two examples are shown here: (1) A Cubestat injected by Exploration Mission 1 (EM-1) then employing low thrust; and (2) a CubSat deployed in a GTO, then employing impulsive maneuvers. For the EM-1 injected initial design, we increase the EM-1 targeted lunar flyby distance to reduce the energy of the lunar flyby to match that of a typical lMoon system heteroclinic manifold. Figure 1 presents an option that encompasses the similar dynamics as that of the ARTEMIS

  5. Achieving glycemic control in elderly patients with type 2 diabetes: a critical comparison of current options

    PubMed Central

    Du, Ye-Fong; Ou, Horng-Yih; Beverly, Elizabeth A; Chiu, Ching-Ju

    2014-01-01

    The prevalence of type 2 diabetes mellitus (T2DM) is increasing in the elderly. Because of the unique characteristics of elderly people with T2DM, therapeutic strategy and focus should be tailored to suit this population. This article reviews the guidelines and studies related to older people with T2DM worldwide. A few important themes are generalized: 1) the functional and cognitive status is critical for older people with T2DM considering their life expectancy compared to younger counterparts; 2) both severe hypoglycemia and persistent hyperglycemia are deleterious to older adults with T2DM, and both conditions should be avoided when determining therapeutic goals; 3) recently developed guidelines emphasize the avoidance of hypoglycemic episodes in older people, even in the absence of symptoms. In addition, we raise the concern of glycemic variability, and discuss the rationale for the selection of current options in managing this patient population. PMID:25429208

  6. Evaluating and selecting options for oil refit programs

    SciTech Connect

    Hoppe, R.; Graves, W.; Salzano, F.J.

    1980-02-01

    Brookhaven National Laboratory (BNL) Oil Refit Program provides technical support for the US Department of Energy (DOE) Fuel Oil Conservation Marketing Demonstration Program implemented in several states (designed to accelerate the use of fuel saving devices and systems by homeowners). BNL assisted with the planning and implementation of the marketing and grants option phases for the New York State Pilot Marketing Demonstration Program and is monitoring the results. Additionally BNL planned, and is implementing, the Oil Refit Option Qualification Program involving procedures for evaluating refit options for selection, field testing, and quantifying fuel savings for the purpose of qualifying additional options for use in the DOE state and other marketing programs. The BNL approach for the evaluation of options on a comparative basis is shown and the potential for optimizing fuel savings by combining available single-choice refit options is examined. Also shown are the estimated fuel savings for each option installed.

  7. Central Retinal Vein Occlusion: A Review of Current Evidence-based Treatment Options

    PubMed Central

    Patel, Amy; Nguyen, Christine; Lu, Stephanie

    2016-01-01

    A central retinal vein occlusion (CRVO) can induce an ischemic and hypoxic state with resulting sequelae of macular edema and neovascularization. Many treatment options have been studied. Our review aims to investigate the safety and efficacy of the multiple treatment options of CRVO. A PubMed and Cochrane literature search was performed. Well-controlled randomized clinical trials that demonstrated strong level 1 evidence-based on the rating scale developed by the British Centre for Evidence-Based Medicine were included. Seven clinical trials met inclusion criteria to be included in this review. These included studies that investigated the safety and efficacy of retinal photocoagulation (1 study), intravitreal steroid treatment (2 studies), and antivascular endothelial growth factor treatment (4 studies) for the treatment of CRVO. In addition, studies evaluating surgical treatment options for CRVO were also included. Many treatment modalities have been demonstrated to be safe and efficacious in the treatment of CRVO. These treatment options offer therapeutic benefits for patients and clinically superior visual acuity and perhaps the quality of life after suffering from a CRVO. PMID:26957838

  8. Lighting Options for Homes.

    SciTech Connect

    Baker, W.S.

    1991-04-01

    This report covers many aspects of various lighting options for homes. Types of light sources described include natural light, artificial light, incandescent lamps, fluorescent lamps, and high intensity discharge lamps. A light source selection guide gives the physical characteristics of these, design considerations, and common applications. Color, strategies for efficient lighting, and types of lighting are discussed. There is one section giving tips for various situations in specific rooms. Rooms and types of fixtures are shown on a matrix with watts saved by using the recommended type lighting for that room and room location. A major emphasis of this report is saving energy by utilizing the most suitable, recommended lighting option. (BN)

  9. Thermal test options

    SciTech Connect

    Koski, J.A.; Keltner, N.R.; Sobolik, K.B.

    1993-02-01

    Shipping containers for radioactive materials must be qualified to meet a thermal accident environment specified in regulations, such at Title 10, Code of Federal Regulations, Part 71. Aimed primarily at the shipping container design, this report discusses the thermal testing options available for meeting the regulatory requirements, and states the advantages and disadvantages of each approach. The principal options considered are testing with radiant heat, furnaces, and open pool fires. The report also identifies some of the facilities available and current contacts. Finally, the report makes some recommendations on the appropriate use of these different testing methods.

  10. Autoimmune uveitis: clinical, pathogenetic, and therapeutic features.

    PubMed

    Prete, Marcella; Dammacco, Rosanna; Fatone, Maria Celeste; Racanelli, Vito

    2016-05-01

    Autoimmune uveitis (AU), an inflammatory non-infectious process of the vascular layer of the eye, can lead to visual impairment and, in the absence of a timely diagnosis and suitable therapy, can even result in total blindness. The majority of AU cases are idiopathic, whereas fewer than 20 % are associated with systemic diseases. The clinical severity of AU depends on whether the anterior, intermediate, or posterior part of the uvea is involved and may range from almost asymptomatic to rapidly sight-threatening forms. Race, genetic background, and environmental factors can also influence the clinical picture. The pathogenetic mechanism of AU is still poorly defined, given its remarkable heterogeneity and the many discrepancies between experimental and human uveitis. Even so, the onset of AU is thought to be related to an aberrant T cell-mediated immune response, triggered by inflammation and directed against retinal or cross-reactive antigens. B cells may also play a role in uveal antigen presentation and in the subsequent activation of T cells. The management of AU remains a challenge for clinicians, especially because of the paucity of randomized clinical trials that have systematically evaluated the effectiveness of different drugs. In addition to topical treatment, several different therapeutic options are available, although a standardized regimen is thus far lacking. Current guidelines recommend corticosteroids as the first-line therapy for patients with active AU. Immunosuppressive drugs may be subsequently required to treat steroid-resistant AU and for steroid-sparing purposes. The recent introduction of biological agents, such as those targeting tumor necrosis factor-α, is expected to remarkably increase the percentages of responders and to prevent irreversible sight impairment. This paper reviews the clinical features of AU and its crucial pathogenetic targets in relation to the current therapeutic perspectives. Also, the largest clinical trials

  11. 40 CFR 80.163 - Detergent certification options.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 17 2013-07-01 2013-07-01 false Detergent certification options. 80... (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Detergent Gasoline § 80.163 Detergent certification options. To be used to satisfy the detergency requirements under § 80.161(a), a detergent additive must...

  12. 40 CFR 80.163 - Detergent certification options.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 17 2012-07-01 2012-07-01 false Detergent certification options. 80... (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Detergent Gasoline § 80.163 Detergent certification options. To be used to satisfy the detergency requirements under § 80.161(a), a detergent additive must...

  13. 40 CFR 80.163 - Detergent certification options.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 17 2014-07-01 2014-07-01 false Detergent certification options. 80... (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Detergent Gasoline § 80.163 Detergent certification options. To be used to satisfy the detergency requirements under § 80.161(a), a detergent additive must...

  14. Food additives.

    PubMed

    Berglund, F

    1978-01-01

    The use of additives to food fulfils many purposes, as shown by the index issued by the Codex Committee on Food Additives: Acids, bases and salts; Preservatives, Antioxidants and antioxidant synergists; Anticaking agents; Colours; Emulfifiers; Thickening agents; Flour-treatment agents; Extraction solvents; Carrier solvents; Flavours (synthetic); Flavour enhancers; Non-nutritive sweeteners; Processing aids; Enzyme preparations. Many additives occur naturally in foods, but this does not exclude toxicity at higher levels. Some food additives are nutrients, or even essential nutritents, e.g. NaCl. Examples are known of food additives causing toxicity in man even when used according to regulations, e.g. cobalt in beer. In other instances, poisoning has been due to carry-over, e.g. by nitrate in cheese whey - when used for artificial feed for infants. Poisonings also occur as the result of the permitted substance being added at too high levels, by accident or carelessness, e.g. nitrite in fish. Finally, there are examples of hypersensitivity to food additives, e.g. to tartrazine and other food colours. The toxicological evaluation, based on animal feeding studies, may be complicated by impurities, e.g. orthotoluene-sulfonamide in saccharin; by transformation or disappearance of the additive in food processing in storage, e.g. bisulfite in raisins; by reaction products with food constituents, e.g. formation of ethylurethane from diethyl pyrocarbonate; by metabolic transformation products, e.g. formation in the gut of cyclohexylamine from cyclamate. Metabolic end products may differ in experimental animals and in man: guanylic acid and inosinic acid are metabolized to allantoin in the rat but to uric acid in man. The magnitude of the safety margin in man of the Acceptable Daily Intake (ADI) is not identical to the "safety factor" used when calculating the ADI. The symptoms of Chinese Restaurant Syndrome, although not hazardous, furthermore illustrate that the whole ADI

  15. Indications and interventional options for non-resectable tracheal stenosis

    PubMed Central

    Bacon, Jenny Louise; Patterson, Caroline Marie

    2014-01-01

    Non-specific presentation and normal examination findings in early disease often result in tracheal obstruction being overlooked as a diagnosis until patients present acutely. Once diagnosed, surgical options should be considered, but often patient co-morbidity necessitates other interventional options. Non-resectable tracheal stenosis can be successfully managed by interventional bronchoscopy, with therapeutic options including airway dilatation, local tissue destruction and airway stenting. There are common aspects to the management of tracheal obstruction, tracheomalacia and tracheal fistulae. This paper reviews the pathogenesis, presentation, investigation and management of tracheal disease, with a focus on tracheal obstruction and the role of endotracheal intervention in management. PMID:24624290

  16. Frankincense--therapeutic properties.

    PubMed

    Al-Yasiry, Ali Ridha Mustafa; Kiczorowska, Bożena

    2016-01-01

    Recently, increasing interest in natural dietary and therapeutic preparations used as dietary supplements has been observed. One of them is frankincense. This traditional medicine of the East is believed to have anti-inflammatory, expectorant, antiseptic, and even anxiolytic and anti-neurotic effects. The present study aims to verify the reported therapeutic properties of Boswellia resin and describe its chemical composition based on available scientific studies. The main component of frankincense is oil (60%). It contains mono- (13%) and diterpenes (40%) as well as ethyl acetate (21.4%), octyl acetate (13.4%) and methylanisole (7.6%). The highest biological activity among terpenes is characteristic of 11-keto-ß-acetyl-beta-boswellic acid, acetyl-11-keto-ß-boswellic acid and acetyl-α-boswellic acid. Contemporary studies have shown that resin indeed has an analgesic, tranquilising and anti-bacterial effects. From the point of view of therapeutic properties, extracts from Boswellia serrata and Boswellia carterii are reported to be particularly useful. They reduce inflammatory conditions in the course of rheumatism by inhibiting leukocyte elastase and degrading glycosaminoglycans. Boswellia preparations inhibit 5-lipoxygenase and prevent the release of leukotrienes, thus having an anti-inflammatory effect in ulcerative colitis, irritable bowel syndrome, bronchitis and sinusitis. Inhalation and consumption of Boswellia olibanum reduces the risk of asthma. In addition, boswellic acids have an antiproliferative effect on tumours. They inhibit proliferation of tumour cells of the leukaemia and glioblastoma subset. They have an anti-tumour effect since they inhibit topoisomerase I and II-alpha and stimulate programmed cell death (apoptosis). PMID:27117114

  17. Cystic Fibrosis Therapeutics

    PubMed Central

    Ramsey, Bonnie W.

    2013-01-01

    A great deal of excitement and hope has followed the successful trials and US Food and Drug Administration approval of the drug ivacaftor (Kalydeco), the first therapy available that targets the underlying defect that causes cystic fibrosis (CF). Although this drug has currently demonstrated a clinical benefit for a small minority of the CF population, the developmental pathway established by ivacaftor paves the way for other CF transmembrane conductance regulator (CFTR) modulators that may benefit many more patients. In addition to investigating CFTR modulators, researchers are actively developing numerous other innovative CF therapies. In this review, we use the catalog of treatments currently under evaluation with the support of the Cystic Fibrosis Foundation, known as the Cystic Fibrosis Foundation Therapeutics Pipeline, as a platform to discuss the variety of candidate treatments for CF lung disease that promise to improve CF care. Many of these approaches target the individual components of the relentless cycle of airway obstruction, inflammation, and infection characteristic of lung disease in CF, whereas others are aimed directly at the gene defect, or the resulting dysfunctional protein, that instigates this cycle. We discuss how new findings from the laboratory have informed not only the development of novel therapeutics, but also the rationales for their use and the outcomes used to measure their effects. By reviewing the breadth of candidate treatments currently in development, as well as the recent progress in CF therapies reflected by the evolution of the therapeutics pipeline over the past few years, we hope to build upon the optimism and anticipation generated by the recent success of Kalydeco. PMID:23276843

  18. Sleep physiology, abnormal States, and therapeutic interventions.

    PubMed

    Wickboldt, Alvah T; Bowen, Alex F; Kaye, Aaron J; Kaye, Adam M; Rivera Bueno, Franklin; Kaye, Alan D

    2012-01-01

    Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health-related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process. PMID:22778676

  19. Sleep Physiology, Abnormal States, and Therapeutic Interventions

    PubMed Central

    Wickboldt, Alvah T.; Bowen, Alex F.; Kaye, Aaron J.; Kaye, Adam M.; Rivera Bueno, Franklin; Kaye, Alan D.

    2012-01-01

    Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health-related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process. PMID:22778676

  20. Scenario Writing: A Therapeutic Application.

    ERIC Educational Resources Information Center

    Haddock, Billy D.

    1989-01-01

    Introduces scenario writing as useful therapeutic technique. Presents case study of woman in midst of divorce and custody fight to illustrate context in which technique was applied. Suggests additional applications. Concludes that good response is more likely for clients who possess good writing skills although other clients may use their own…

  1. ARSENIC TREATMENT OPTIONS

    EPA Science Inventory

    The PPT presentation will provide information on the drinking water treatment options for small utilities to remove arsenic from ground water. The discussion will include information on the EPA BAT listed processes and on some of the newer technologies, such as the iron based ad...

  2. Yale Tuition Postponement Option.

    ERIC Educational Resources Information Center

    Yale Univ., New Haven, CT. Office of the President.

    This paper offers a detailed explanation of Yale University's tuition postponement option. The purposes of the Plan are: (1) to enable students to defer part of the expense of education; (2) to enable students to contribute to the support of the University in approximate proportion to their ability to do so and to the economic benefit they have…

  3. Idaho's Energy Options

    SciTech Connect

    Robert M. Neilson

    2006-03-01

    This report, developed by the Idaho National Laboratory, is provided as an introduction to and an update of the status of technologies for the generation and use of energy. Its purpose is to provide information useful for identifying and evaluating Idaho’s energy options, and for developing and implementing Idaho’s energy direction and policies.

  4. CFB repowering options

    SciTech Connect

    Gittinger, J.

    1996-12-31

    Circulating fluidized bed CFB repowering options are summarized. The following topics are discussed: why repower with CFB technology; advantages of repowering; two forms of of repowering; B and N`s internal recirculation CFB; space-saving design features; cost-saving design features; Ukrainian repowering project; and candidates for repowering.

  5. Our Energy Options.

    ERIC Educational Resources Information Center

    Meyers, Paul A.; Witt, Frank C.

    Presented is an analysis of alternatives available to the United States in dealing with energy problems. Options explained and evaluated include coal, solar, hydroelectric, nuclear, geothermal, wind, biomass, and energy conservation. The booklet is part of Project APEC (America's Possible Energy Choices), a nationally validated Title IVc project…

  6. Postsecondary Enrollment Options Programs.

    ERIC Educational Resources Information Center

    Michelau, Demaree K.

    2001-01-01

    Many states are beginning to notice discontinuities in policy between the K-12 and higher education systems. One approach to easing the high school to college transition is to establish postsecondary enrollment options (PSEO) programs. Currently, 32 states have laws or recently have passed legislation to establish and govern PSEO programs. The…

  7. Options in Suicidal Crisis

    ERIC Educational Resources Information Center

    Steenland, Roger

    1973-01-01

    This article briefly outlines possible causes for the prevalence of suicide attempts among college students and then discusses various options for handling such crises: whether to notify the students' closest relatives, whether to obtain medical evaluation and treatment (as opposed to psychological counseling), and whether to allow the student to…

  8. Career Options in Chemistry.

    ERIC Educational Resources Information Center

    Belloli, Robert C.

    1985-01-01

    Describes a credit/no credit course which focuses on career options in chemistry. The course (consisting of 15 one-hour seminar-type sessions) includes guest speakers for several sessions and an emphasis (in introductory sessions) on graduate school in chemistry, the chemical industry, resumes, and interviews. Also briefly describes an internship…

  9. Alternative Education Options.

    ERIC Educational Resources Information Center

    Little (Arthur D.), Inc., Washington, DC.

    This guide deals with various areas of alternative education programs, including current practices and different options available to school and community personnel. Steps are outlined to assess present educational settings, design new programs, select the participants, and implement and evaluate the new program. The first appendix contains…

  10. Current therapeutic procedures in Dravet syndrome.

    PubMed

    Chiron, Catherine

    2011-04-01

    Dravet syndrome is a highly pharmaco-resistant form of epilepsy. Valproate and benzodiazepines are the first-line treatment but are usually insufficient therapeutic options. Lamotrigine, carbamazepine and high doses of intravenous phenobarbital can aggravate seizures and should be avoided. Topiramate, levetiracetam, bromide and ketogenic diet also provide substantial efficacy as adjunctive therapy and procedures. Stiripentol is the only new drug to demonstrate efficacy when combined with valproate and clobazam, as shown in two independent double-blind controlled trials dedicated to Dravet children. In order to avoid side effects (mainly loss of appetite and loss of weight) resulting from the inhibition of cytochromes P450 by stiripentol, the prescribed doses of valproate and clobazam should be reduced. Stiripentol has a proper antiepileptic effect and enhances GABAergic neurotransmission by acting on the alpha-3 subunit of GABA(A) receptors. Stiripentol was approved as an orphan drug in Europe in 2007 for adjunctive therapy in Dravet syndrome. More than 500 Dravet patients have currently been satisfactorily treated and recent experiments in Japan have confirmed stiripentol's benefit. In practice, valproate should be initiated at the first onset of complicated febrile seizure in Dravet patients. Relapses justify the addition of clobazam and stiripentol when available. Topiramate and a ketogenic diet are alternatives in pharmaco-resistant cases. PMID:21504427

  11. Congenital Aniridia: Clinic, Genetics, Therapeutics, and Prognosis

    PubMed Central

    Santos-Silva, R.; Falcão-Reis, F.; Rocha-Sousa, A.

    2014-01-01

    Congenital aniridia is a rare condition related to a deficiency in the PAX6 gene expression, which may occur as a result of a family inheritance or a sporadic occurrence. Additionally, this condition may occur as an isolated ocular phenotype or in association with a systemic syndrome. The most common abnormality is iris hypoplasia; however, a panocular disease which also affects the cornea, anterior chamber of the eye, lens, and the posterior segment with presence of optic nerve and foveal hypoplasia is also evident. The development of keratopathy, glaucoma, and cataract is frequent and its presence has implications in the patient's visual acuity. Managing aniridia is challenging since the focus is on treating the previously mentioned disorders, and the outcomes are often disappointing. In this paper, we shall review the epidemiology, pathophysiology, and clinical characteristics of patients with aniridia. We shall also make a review of the therapeutic options for the several conditions affecting this syndrome and consider the genetics and prognostic factors. PMID:27355034

  12. Avian Diagnostic and Therapeutic Antibodies

    SciTech Connect

    Bradley, David Sherman

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  13. Mechanisms of Plasma Therapeutics

    NASA Astrophysics Data System (ADS)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  14. Therapeutic Devices for Epilepsy

    PubMed Central

    Fisher, Robert S.

    2011-01-01

    Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987

  15. Potlining Additives

    SciTech Connect

    Rudolf Keller

    2004-08-10

    In this project, a concept to improve the performance of aluminum production cells by introducing potlining additives was examined and tested. Boron oxide was added to cathode blocks, and titanium was dissolved in the metal pool; this resulted in the formation of titanium diboride and caused the molten aluminum to wet the carbonaceous cathode surface. Such wetting reportedly leads to operational improvements and extended cell life. In addition, boron oxide suppresses cyanide formation. This final report presents and discusses the results of this project. Substantial economic benefits for the practical implementation of the technology are projected, especially for modern cells with graphitized blocks. For example, with an energy savings of about 5% and an increase in pot life from 1500 to 2500 days, a cost savings of $ 0.023 per pound of aluminum produced is projected for a 200 kA pot.

  16. Phosphazene additives

    SciTech Connect

    Harrup, Mason K; Rollins, Harry W

    2013-11-26

    An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

  17. Cholangiocarcinoma: Molecular Pathways and Therapeutic Opportunities

    PubMed Central

    Rizvi, Sumera; Borad, Mitesh J.; Patel, Tushar; Gores, Gregory J.

    2015-01-01

    Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy with limited treatment options and low survival rates. Currently, there are no curative medical therapies for CCA. Recent advances have enhanced our understanding of the genetic basis of this disease, and elucidated therapeutically relevant targets. Therapeutic efforts in development are directed at several key pathways due to genetic aberrations including receptor tyrosine kinase pathways, mutant IDH enzymes, the PI3K-AKT-mTOR pathway, and chromatin remodeling networks. A highly desmoplastic, hypovascular stroma is characteristic of CCAs and recent work has highlighted the importance of targeting this pathway via stromal myofibroblast depletion. Future efforts should concentrate on combination therapies with action against the cancer cell and the surrounding tumor stroma. As the mutational landscape of CCA is being illuminated, molecular profiling of patient tumors will enable identification of specific mutations and the opportunity to offer directed, personalized treatment options. PMID:25369307

  18. Cholangiocarcinoma: molecular pathways and therapeutic opportunities.

    PubMed

    Rizvi, Sumera; Borad, Mitesh J; Patel, Tushar; Gores, Gregory J

    2014-11-01

    Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy with limited treatment options and low survival rates. Currently, there are no curative medical therapies for CCA. Recent advances have enhanced our understanding of the genetic basis of this disease, and elucidated therapeutically relevant targets. Therapeutic efforts in development are directed at several key pathways due to genetic aberrations including receptor tyrosine kinase pathways, mutant IDH enzymes, the PI3K-AKT-mTOR pathway, and chromatin remodeling networks. A highly desmoplastic, hypovascular stroma is characteristic of CCAs and recent work has highlighted the importance of targeting this pathway via stromal myofibroblast depletion. Future efforts should concentrate on combination therapies with action against the cancer cell and the surrounding tumor stroma. As the mutational landscape of CCA is being illuminated, molecular profiling of patient tumors will enable identification of specific mutations and the opportunity to offer directed, personalized treatment options. PMID:25369307

  19. Emerging treatment options for early mycosis fungoides

    PubMed Central

    Fernandez-Guarino, Montserrat

    2013-01-01

    Mycosis fungoides is a candidate for skin-directed therapies in its initial stages. In recent years, therapeutic options outside of the normal treatment recommendations such as topical imiquimod, topical tazarotene, topical methotrexate, excimer light sources, and photodynamic therapy have been published with variable results. These alternatives have been useful in cases of localized mycosis fungoides that do not respond to routine treatments; nevertheless, more studies on these methods are still needed. This article summarizes the literature and data that are known so far about these treatments. PMID:23450851

  20. Therapeutic drug levels

    MedlinePlus

    ... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

  1. Information technology financing options.

    PubMed

    Rai, D

    1996-01-01

    Healthcare executives facing the challenges of delivering quality care and controlling costs must consider the role information technology systems can play in meeting those challenges. To make the best use of information system expenditures, organizations must carefully plan how to finance system acquisitions. Some options that should be considered are paying cash, financing, financing "soft" costs, leasing, credit warehousing and early acceptance financing, and tax-exempt and conduit financing. PMID:10154097

  2. The safeguards options study

    SciTech Connect

    Hakkila, E.A.; Mullen, M.F.; Olinger, C.T.; Stanbro, W.D.; Olsen, A.P.; Roche, C.T.; Rudolph, R.R.; Bieber, A.M.; Lemley, J.; Filby, E.

    1995-04-01

    The Safeguards Options Study was initiated to aid the International Safeguards Division (ISD) of the DOE Office of Arms Control and Nonproliferation in developing its programs in enhanced international safeguards. The goal was to provide a technical basis for the ISD program in this area. The Safeguards Options Study has been a cooperative effort among ten organizations. These are Argonne National Laboratory, Brookhaven National Laboratory, Idaho National Engineering Laboratory, Lawrence Livermore National Laboratory, Los Alamos National Laboratory, Mound Laboratory, Oak Ridge National Laboratory, Pacific Northwest Laboratories, Sandia National Laboratories, and Special Technologies Laboratory. Much of the Motivation for the Safeguards Options Study is the recognition after the Iraq experience that there are deficiencies in the present approach to international safeguards. While under International Atomic Energy Agency (IAEA) safeguards at their declared facilities, Iraq was able to develop a significant weapons program without being noticed. This is because negotiated safeguards only applied at declared sites. Even so, their nuclear weapons program clearly conflicted with Iraq`s obligations under the Nuclear Nonproliferation Treaty (NPT) as a nonnuclear weapon state.

  3. Laser Ablation as Treatment Strategy for Medically Refractory Dominant Insular Epilepsy – Therapeutic and Functional Considerations

    PubMed Central

    Hawasli, Ammar H.; Bandt, S. Kathleen; Hogan, R. Edward; Werner, Nicole; Leuthardt, Eric C.

    2014-01-01

    Since its introduction to neurosurgery in 2008, laser ablative techniques have been largely confined to the management of unresectable tumors. Application of this technology for the management of focal epilepsy in the adult population has not been fully explored. Given that nearly 1,000,000 Americans live with medically refractory epilepsy and current surgical techniques only address a fraction of epileptic pathologies, additional therapeutic options are needed. We report the successful treatment of dominant insular epilepsy in a 53 year-old male with minimally-invasive laser ablation complicated by mild verbal and memory deficits. We also report neuropsychological test data on this patient before surgery and at 8-months after the ablation procedure. This account represents the first reported successful patient outcome of laser ablation as an effective treatment option for medically refractory post-stroke epilepsy in an adult. PMID:25359500

  4. Identifying therapeutic targets in gastric cancer: the current status and future direction.

    PubMed

    Yu, Beiqin; Xie, Jingwu

    2016-01-01

    Gastric cancer is the third leading cause of cancer-related death worldwide. Our basic understanding of gastric cancer biology falls behind that of many other cancer types. Current standard treatment options for gastric cancer have not changed for the last 20 years. Thus, there is an urgent need to establish novel strategies to treat this deadly cancer. Successful clinical trials with Gleevec in CML and gastrointestinal stromal tumors have set up an example for targeted therapy of cancer. In this review, we will summarize major progress in classification, therapeutic options of gastric cancer. We will also discuss molecular mechanisms for drug resistance in gastric cancer. In addition, we will attempt to propose potential future directions in gastric cancer biology and drug targets. PMID:26373844

  5. Consulting and Training--Career Options.

    ERIC Educational Resources Information Center

    Church, Olive D.

    1986-01-01

    Business teachers have additional career options to consider, namely, joining a consulting-training firm as a junior professional employee; entering a firm as an associate; investing personal resources in an already successful firm; starting one's own firm; and/or applying for part- or full-time work as an internal consultant or trainer and…

  6. The rodent endovascular puncture model of subarachnoid hemorrhage: mechanisms of brain damage and therapeutic strategies

    PubMed Central

    2014-01-01

    Subarachnoid hemorrhage (SAH) represents a considerable health problem. To date, limited therapeutic options are available. In order to develop effective therapeutic strategies for SAH, the mechanisms involved in SAH brain damage should be fully explored. Here we review the mechanisms of SAH brain damage induced by the experimental endovascular puncture model. We have included a description of similarities and distinctions between experimental SAH in animals and human SAH pathology. Moreover, several novel treatment options to diminish SAH brain damage are discussed. SAH is accompanied by cerebral inflammation as demonstrated by an influx of inflammatory cells into the cerebral parenchyma, upregulation of inflammatory transcriptional pathways and increased expression of cytokines and chemokines. Additionally, various cell death pathways including cerebral apoptosis, necrosis, necroptosis and autophagy are involved in neuronal damage caused by SAH. Treatment strategies aiming at inhibition of inflammatory or cell death pathways demonstrate the importance of these mechanisms for survival after experimental SAH. Moreover, neuroregenerative therapies using stem cells are discussed as a possible strategy to repair the brain after SAH since this therapy may extend the window of treatment considerably. We propose the endovascular puncture model as a suitable animal model which resembles the human pathology of SAH and which could be applied to investigate novel therapeutic therapies to combat this debilitating insult. PMID:24386932

  7. Pawnee Nation Energy Option Analyses

    SciTech Connect

    Matlock, M.; Kersey, K.; Riding In, C.

    2009-07-21

    market developments in the bio-energy industry, establish contacts with research institutions with which the tribe could potentially partner in grant-funded research initiatives. In addition, a substantial effort by the Kaw and Cherokee tribes is underway to pursue wind development at the Chilocco School Site in northern Oklahoma where Pawnee is a joint landowner. Pawnee Nation representatives should become actively involved in these development discussions and should explore the potential for joint investment in wind development at the Chilocco site. Financial incentives for project development are generally structured to provide tribes with access to conventional financing mechanisms. Grant funding for project construction is currently difficult to obtain. Substantial new opportunities for bio-fuel development may exist in the next few years with passage of the 2007 Farm Bill, and through opportunities made available through Oklahoma’s new Bio-energy Center. A review of potential alternatives to Pawnee Nation’s current electricity supply scenario revealed that a range of options could be viable. These include the following scenarios: business as usual, alternative supply, negotiate lower rates with City of Pawnee, focus on reducing energy usage, develop electric utility organization. Under any circumstances, Pawnee Nation should purse strategies to reduce energy usage, as this is the simplest means of reducing electric costs and environmental impacts. The research team also recommends that Pawnee Nation initiate some focused discussions with the City of Pawnee, with GRDA, and with IEC to discuss its wholesale supply purchase options. These discussions will better inform the Pawnee Energy Team of the specific pros and cons of its wholesale power supply options, and will assist the Team’s broader decision-making on utility-related issues. The ultimate path chosen by Pawnee Nation will depend on further consideration of priorities and potential barriers by Pawnee

  8. 77 FR 27785 - Request for Information Regarding the NIH-Industry Program To Discover New Therapeutic Uses for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... program will focus on discovering new therapeutic uses of existing molecules (Therapeutics Discovery). The... be submitted electronically to Therapeutics.Discovery@nih.gov . For additional information, please... (Therapeutics Discovery). Many discontinued compounds and biologics that have already been tested in...

  9. Technological options for acid rain control

    SciTech Connect

    Princiotta, F.T.; Sedman, C.B.

    1993-01-01

    The paper discusses technological options for acid rain control. Compliance with Title IV of the Clean Air Act Amendments of 1990 will require careful scrutiny of a number of issues before selecting control options to reduce sulfur dioxide (SO2) and nitrogen oxide (NOx) emissions. One key consideration is the effect of fuel switching or control technology upon the existing dust collector, with additional air toxics legislation looming ahead. A number of likely SO2 and NOx retrofit technologies and estimated costs are presented, along with results of retrofit case studies. New hybrid particulate controls are also being developed to meet future requirements.

  10. How to choose the right capitalization option.

    PubMed

    Vaughan, J; Wise, J

    1996-12-01

    Physician group practices and networks must have ready access to capital to finance their working capital needs, capital equipment acquisitions, and real estate purchases, as well as to fund the acquisition of additional practices. At least three options for capitalization are available to group practices and networks: debt financing, equity financing, or a combination of the two. The best option for physician group practices and networks depends on the costs of capital and the impact the strategy will have on decision making and governance. PMID:10163009

  11. Quantitative Analysis of Therapeutic Drugs in Dried Blood Spot Samples by Paper Spray Mass Spectrometry: An Avenue to Therapeutic Drug Monitoring

    NASA Astrophysics Data System (ADS)

    Manicke, Nicholas Edward; Abu-Rabie, Paul; Spooner, Neil; Ouyang, Zheng; Cooks, R. Graham

    2011-09-01

    A method is presented for the direct quantitative analysis of therapeutic drugs from dried blood spot samples by mass spectrometry. The method, paper spray mass spectrometry, generates gas phase ions directly from the blood card paper used to store dried blood samples without the need for complex sample preparation and separation; the entire time for preparation and analysis of blood samples is around 30 s. Limits of detection were investigated for a chemically diverse set of some 15 therapeutic drugs; hydrophobic and weakly basic drugs, such as sunitinib, citalopram, and verapamil, were found to be routinely detectable at approximately 1 ng/mL. Samples were prepared by addition of the drug to whole blood. Drug concentrations were measured quantitatively over several orders of magnitude, with accuracies within 10% of the expected value and relative standard deviation (RSD) of around 10% by prespotting an internal standard solution onto the paper prior to application of the blood sample. We have demonstrated that paper spray mass spectrometry can be used to quantitatively measure drug concentrations over the entire therapeutic range for a wide variety of drugs. The high quality analytical data obtained indicate that the technique may be a viable option for therapeutic drug monitoring.

  12. Sjögren's syndrome: from pathogenesis to novel therapeutic targets.

    PubMed

    Barone, Francesca; Colafrancesco, Serena

    2016-01-01

    Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease, characterised by a chronic infiltration of exocrine glands, mainly salivary glands, with the histological features of focal lymphocytic sialoadenitis. Disease spectrum is broad and the occurrence of several extra-glandular manifestations, and in rare cases lymphoma development, is well known. A specific approved treatment for pSS is still lacking and the detection of novel therapeutic biologic target is ongoing. The identification of biological fingerprints seems essential in order to stratify patients both in clinical trials and in real life. Discovery of new components of the inflammatory response will be the key in the future for the identification of novel additional therapeutic options. PMID:27586806

  13. Systemic Sclerosis—A systematic review on therapeutic management from 2011–2014

    PubMed Central

    Young, Amber; Khanna, Dinesh

    2016-01-01

    Purpose of review To review pharmacologic and non-pharmacologic therapies in the treatment of systemic sclerosis (SSc) from 2011 to 2014 through a systematic review. Recent Findings Our systematic review identifies randomized controlled trials (RCT), meta-analyses, systematic reviews, case series and observational studies which support organ based therapy with known immunosuppressive agents, novel agents, and hematopoietic stem cell transplantation (HSCT), and also includes non-pharmacologic therapies improving visceral and physical function. Summary SSc is an orphan autoimmune disorder with significant morbidity and mortality. Although there has been significant progress over the years in therapeutic options for SSc, the mainstays of treatment are organ based and primarily symptom management. Our systematic review of the last 4 years of treatment emphasizes known treatment strategies already in practice, but also identifies new therapeutic approaches with additional biologic agents and HSCT. PMID:25775190

  14. Therapeutic algorithm to treat common iliac artery aneurysms by endovascular means.

    PubMed

    Panuccio, Giuseppe; Torsello, Giovanni F; Torsello, Giovanni B; Donas, Konstantinos P

    2016-10-01

    Use of endovascular means is gaining ever greater acceptance in the treatment of aorto-iliac aneurysms. Especially, the treatment of patients with common iliac aneurysms (CIAs) may be very challenging due to the complexity of the underlying disease with often involvement of the hypogastric artery. Additionally, the variety of endovascular therapeutic options such as the use of iliac branch devices, parallel grafts, the bell-bottom technique or coil embolization of the hypogastric artery and overstenting of the origin represents significant limitation regarding the presentation of a clear and robust endovascular therapeutic algorithm. Aim of the present article was the demonstration of the institutional experience with the endovascular management of CIAs in order to provide a clinical recommendation and algorithm. PMID:27406396

  15. Achilles Tendinosis: Treatment Options

    PubMed Central

    Lopez, Roberto Gabriel L.

    2015-01-01

    Athletes usually complain of an ongoing or chronic pain over the Achilles tendon, but recently even non-athletes are experiencing the same kind of pain which affects their daily activities. Achilles tendinosis refers to a degenerative process of the tendon without histologic or clinical signs of intratendinous inflammation. Treatment is based on whether to stimulate or prevent neovascularization. Thus, until now, there is no consensus as to the best treatment for this condition. This paper aims to review the common ways of treating this condition from the conservative to the surgical options. PMID:25729512

  16. Adolescent pregnancy options.

    PubMed

    Resnick, M D

    1992-09-01

    The range of pregnancy options available to adolescents each have significant ramifications for future educational and economic achievement. The changing societal context of adolescent pregnancy decision-making are described, and the characteristics of adolescents who choose to terminate their pregnancy, parent their child, or place for adoption are examined. The role of significant others in decision-making and the implications of mandatory parental involvement in pregnancy decision-making is discussed, as well as the roles of schools in promoting the well-being and potential of adolescents considering pregnancy decisions. PMID:1434557

  17. [Interventional neuroradiology: current options].

    PubMed

    Szikora, István; Marosfői, Miklós; Berentei, Zsolt; Gubucz, István

    2015-04-26

    Modern interventional neuroradiology has a leading role in the treatment of ischemic and hemorrhagic stroke, and it provides more and more important treatment options for degenerative diseases of the vertebral column and the management of correlated pain. During the last decades interventional neuroradiology has played a primary role in the treatment of intracranial berry aneurysms due to the continuous technical improvements. Ongoing studies proved superiority of mechanical stent-thrombectomy in acute proximal occlusion of cerebral arteries. Less invasive neurointerventional methods, such as vertebroplasty, are widely used in osteoporotic and neoplastic pathologic fractures of the vertebral bodies. These treatments should be performed in a specialized center by well trained physicians. PMID:26047151

  18. Options for Mars exploration

    NASA Technical Reports Server (NTRS)

    Pritchard, E. B.; Harrison, E. F.; Moore, J. W.

    1974-01-01

    The many possible post-Viking 1975 Mars mission options are explored. These include small atmospheric probe/landers (adaptations of the Venus Pioneer to Mars), repeat Vikings with and without science changes, long-life orbiters to provide coverage of both hemispheres for a full Martian year, small rovers deployed from the Viking lander with ranges of up to 1 km from it, large autonomous rovers, Mars sample-return missions and, finally, missions to the satellites of Mars, including sample return. The examination includes energy requirements and time frames.

  19. Martingale option pricing

    NASA Astrophysics Data System (ADS)

    McCauley, J. L.; Gunaratne, G. H.; Bassler, K. E.

    2007-07-01

    We show that our earlier generalization of the Black-Scholes partial differential equation (pde) for variable diffusion coefficients is equivalent to a Martingale in the risk neutral discounted stock price. Previously, the equivalence of Black-Scholes to a Martingale was proven for the case of the Gaussian returns model by Harrison and Kreps, but we prove it for a much larger class of returns models where the returns diffusion coefficient depends irreducibly on both returns x and time t. That option prices blow up if fat tails in logarithmic returns x are included in market return is also proven.

  20. Therapeutic Angiogenesis in Critical Limb Ischemia

    PubMed Central

    Ouma, Geoffrey O.; Zafrir, Barak; Mohler, Emile R.; Flugelman, Moshe Y.

    2013-01-01

    Critical limb ischemia (CLI) is a severe form of peripheral artery disease associated with high morbidity and mortality. The primary therapeutic goals in treating CLI are to reduce the risk of adverse cardiovascular events, relieve ischemic pain, heal ulcers, prevent major amputation, and improve quality of life (QoL) and survival. These goals may be achieved by medical therapy, endovascular intervention, open surgery, or amputation and require a multidisciplinary approach including pain management, wound care, risk factors reduction, and treatment of comorbidities. No-option patients are potential candidates for the novel angiogenic therapies. The application of genetic, molecular, and cellular-based modalities, the so-called therapeutic angiogenesis, in the treatment of arterial obstructive diseases has not shown consistent efficacy. This article summarizes the current status related to the management of patients with CLI and discusses the current findings of the emerging modalities for therapeutic angiogenesis. PMID:23129733

  1. 5 CFR 870.506 - Optional insurance: Cancelling a waiver.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Optional insurance: Cancelling a waiver. (a) When there is a change in family circumstances. (1) An employee cannot cancel a waiver of Option A due to a change in family circumstances. (2) An employee who... additional family members (spouse and eligible children) acquired with the marriage; (ii) For acquisition...

  2. 18 CFR 808.4 - Optional joint hearing.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Optional joint hearing... HEARINGS AND ENFORCEMENT ACTIONS Conduct of Hearings § 808.4 Optional joint hearing. (a) The Commission may... agent pursuant to such additional designation and may conduct joint hearings for the Commission and...

  3. 18 CFR 808.4 - Optional joint hearing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 2 2012-04-01 2012-04-01 false Optional joint hearing... HEARINGS AND ENFORCEMENT ACTIONS Conduct of Hearings § 808.4 Optional joint hearing. (a) The Commission may... agent pursuant to such additional designation and may conduct joint hearings for the Commission and...

  4. 18 CFR 808.4 - Optional joint hearing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 2 2013-04-01 2012-04-01 true Optional joint hearing... HEARINGS AND ENFORCEMENT ACTIONS Conduct of Hearings § 808.4 Optional joint hearing. (a) The Commission may... agent pursuant to such additional designation and may conduct joint hearings for the Commission and...

  5. 18 CFR 808.4 - Optional joint hearing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Optional joint hearing... HEARINGS AND ENFORCEMENT ACTIONS Conduct of Hearings § 808.4 Optional joint hearing. (a) The Commission may... agent pursuant to such additional designation and may conduct joint hearings for the Commission and...

  6. College Student Receptiveness to Various Alcohol Treatment Options

    ERIC Educational Resources Information Center

    Epler, Amee J.; Sher, Kenneth J.; Loomis, Tiffany B.; O'Malley, Stephanie S.

    2009-01-01

    Objective: Heavy episodic drinking remains a significant problem on college campuses. Although most interventions for college students are behavioral, pharmacological treatments, such as naltrexone, could provide additional options. Participants: The authors evaluated receptivity to various alcohol treatment options in a general population of…

  7. Mixed waste management options

    SciTech Connect

    Owens, C.B.; Kirner, N.P.

    1991-12-31

    Disposal fees for mixed waste at proposed commercial disposal sites have been estimated to be $15,000 to $40,000 per cubit foot. If such high disposal fees are imposed, generators may be willing to apply extraordinary treatment or regulatory approaches to properly dispose of their mixed waste. This paper explores the feasibility of several waste management scenarios and attempts to answer the question: Can mixed waste be managed out of existence? Existing data on commercially generated mixed waste streams are used to identify the realm of mixed waste known to be generated. Each waste stream is evaluated from both a regulatory and technical perspective in order to convert the waste into a strictly low-level radioactive or a hazardous waste. Alternative regulatory approaches evaluated in this paper include a delisting petition, no migration petition, and a treatability variance. For each waste stream, potentially available treatment options are identified that could lead to these variances. Waste minimization methodology and storage for decay are also considered. Economic feasibility of each option is discussed broadly.

  8. Retrieval options study

    SciTech Connect

    Not Available

    1980-03-01

    This Retrieval Options Study is part of the systems analysis activities of the Office of Nuclear Waste Isolation to develop the scientific and technological bases for radioactive waste repositories in various geologic media. The study considers two waste forms, high level waste and spent fuel, and defines various classes of waste retrieval and recovery. A methodology and data base are developed which allow the relative evaluation of retrieval and recovery costs and the following technical criteria: safety; technical feasibility; ease of retrieval; probable intact retrieval time; safeguards; monitoring; criticality; and licensability. A total of 505 repository options are defined and the cost and technical criteria evaluated utilizing a combination of facts and engineering judgments. The repositories evaluated are selected combinations of the following parameters: Geologic Media (salt, granite, basalt, shale); Retrieval Time after Emplacement (5 and 25 years); Emplacement Design (nominal hole, large hole, carbon steel canister, corrosion resistant canister, backfill in hole, nominal sleeves, thick wall sleeves); Emplacement Configuration (single vertical, multiple vertical, single horizontal, multiple horizontal, vaults; Thermal Considerations; (normal design, reduced density, once-through ventilation, recirculated ventilation); Room Backfill; (none, run-of-mine, early, 5 year delay, 25 year delay, decommissioned); and Rate of Retrieval; (same as emplacement, variably slower depending on repository/canister condition).

  9. NASA's EOSDIS: options for data providers

    NASA Astrophysics Data System (ADS)

    Khalsa, Siri J.; Ujhazy, John E.

    1995-12-01

    EOSDIS, the data and information system being developed by NASA to support interdisciplinary earth science research into the 21st century, will do more than manage and distribute data from EOS-era satellites. It will also promote the exchange of data, tools, and research results across disciplinary, agency, and national boundaries. This paper describes the options that data providers will have for interacting with the EOSDIS Core System (ECS), the infrastructure of EOSDIS. The options include: using the ECS advertising service to announce the availability of data at the provider's site; submitting a candidate data set to one of the Distributed Active Archive Centers (DAACs); establishing a data server that will make the data accessible via ECS and establishing Local Information Manager (LIM) which would make the data available for multi-site searches. One additional option is through custom gateway interfaces which would provide access to existing data archives. The gateway, data server, and LIM options require the implementation of ECS code at the provider site to insure proper protocols. The advertisement and ingest options require no part of ECS design to reside at the provider site.

  10. Treatment options--commentary.

    PubMed

    Arceci, R J

    1994-09-01

    Although effective treatments are available for many children with LCH, there are many others for whom no definitive therapy yet exists. These patients include those with 1) multisystem disease and associated organ dysfunction, 2) chronic, relapsing disease, 3) new onset pituitary involvement associated with diabetes insipidus and 4) long-term complications such as pulmonary fibrosis, liver fibrosis or CNS involvement. This introductory paper discusses these clinical problem areas and then reviews several new therapeutic approaches including novel chemotherapeutic agents, immunosuppressive strategies, bone marrow transplantation and gene therapy. PMID:8075010

  11. Redox Control of Leukemia: From Molecular Mechanisms to Therapeutic Opportunities

    PubMed Central

    Irwin, Mary E.; Rivera-Del Valle, Nilsa

    2013-01-01

    Abstract Reactive oxygen species (ROS) play both positive and negative roles in the proliferation and survival of a cell. This dual nature has been exploited by leukemia cells to promote growth, survival, and genomic instability—some of the hallmarks of the cancer phenotype. In addition to altered ROS levels, many antioxidants are dysregulated in leukemia cells. Together, the production of ROS and the expression and activity of antioxidant enzymes make up the primary redox control of leukemia cells. By manipulating this system, leukemia cells gain proliferative and survival advantages, even in the face of therapeutic insults. Standard treatment options have improved leukemia patient survival rates in recent years, although relapse and the development of resistance are persistent challenges. Therapies targeting the redox environment show promise for these cases. This review highlights the molecular mechanisms that control the redox milieu of leukemia cells. In particular, ROS production by the mitochondrial electron transport chain, NADPH oxidase, xanthine oxidoreductase, and cytochrome P450 will be addressed. Expression and activation of antioxidant enzymes such as superoxide dismutase, catalase, heme oxygenase, glutathione, thioredoxin, and peroxiredoxin are perturbed in leukemia cells, and the functional consequences of these molecular alterations will be described. Lastly, we delve into how these pathways can be potentially exploited therapeutically to improve treatment regimens and promote better outcomes for leukemia patients. Antioxid. Redox Signal. 18, 1349–1383. PMID:22900756

  12. Therapeutic modification of arterial stiffness: An update and comprehensive review.

    PubMed

    Wu, Ching-Fen; Liu, Pang-Yen; Wu, Tsung-Jui; Hung, Yuan; Yang, Shih-Ping; Lin, Gen-Min

    2015-11-26

    Arterial stiffness has been recognized as a marker of cardiovascular disease and associated with long-term worse clinical outcomes in several populations. Age, hypertension, smoking, and dyslipidemia, known as traditional vascular risk factors, as well as diabetes, obesity, and systemic inflammation lead to both atherosclerosis and arterial stiffness. Targeting multiple modifiable risk factors has become the main therapeutic strategy to improve arterial stiffness in patients at high cardiovascular risk. Additionally to life style modifications, long-term ω-3 fatty acids (fish oil) supplementation in diet may improve arterial stiffness in the population with hypertension or metabolic syndrome. Pharmacological treatment such as renin-angiotensin-aldosterone system antagonists, metformin, and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors were useful in individuals with hypertension and diabetes. In obese population with obstructive sleep apnea, weight reduction, aerobic exercise, and continuous positive airway pressure treatment may also improve arterial stiffness. In the populations with chronic inflammatory disease such as rheumatoid arthritis, a use of antibodies against tumor necrosis factor-alpha could work effectively. Other therapeutic options such as renal sympathetic nerve denervation for patients with resistant hypertension are investigated in many ongoing clinical trials. Therefore our comprehensive review provides knowledge in detail regarding many aspects of pathogenesis, measurement, and management of arterial stiffness in several populations, which would be helpful for physicians to make clinical decision. PMID:26635922

  13. Therapeutic modification of arterial stiffness: An update and comprehensive review

    PubMed Central

    Wu, Ching-Fen; Liu, Pang-Yen; Wu, Tsung-Jui; Hung, Yuan; Yang, Shih-Ping; Lin, Gen-Min

    2015-01-01

    Arterial stiffness has been recognized as a marker of cardiovascular disease and associated with long-term worse clinical outcomes in several populations. Age, hypertension, smoking, and dyslipidemia, known as traditional vascular risk factors, as well as diabetes, obesity, and systemic inflammation lead to both atherosclerosis and arterial stiffness. Targeting multiple modifiable risk factors has become the main therapeutic strategy to improve arterial stiffness in patients at high cardiovascular risk. Additionally to life style modifications, long-term ω-3 fatty acids (fish oil) supplementation in diet may improve arterial stiffness in the population with hypertension or metabolic syndrome. Pharmacological treatment such as renin-angiotensin-aldosterone system antagonists, metformin, and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors were useful in individuals with hypertension and diabetes. In obese population with obstructive sleep apnea, weight reduction, aerobic exercise, and continuous positive airway pressure treatment may also improve arterial stiffness. In the populations with chronic inflammatory disease such as rheumatoid arthritis, a use of antibodies against tumor necrosis factor-alpha could work effectively. Other therapeutic options such as renal sympathetic nerve denervation for patients with resistant hypertension are investigated in many ongoing clinical trials. Therefore our comprehensive review provides knowledge in detail regarding many aspects of pathogenesis, measurement, and management of arterial stiffness in several populations, which would be helpful for physicians to make clinical decision. PMID:26635922

  14. Tackling obesity: new therapeutic agents for assisted weight loss

    PubMed Central

    Karam, JG; McFarlane, SI

    2010-01-01

    The pandemic of overweight and obesity continues to rise in an alarming rate in western countries and around the globe representing a major public health challenge in desperate need for new strategies tackling obesity. In the United States nearly two thirds of the population is overweight or obese. Worldwide the number of persons who are overweight or obese exceeded 1.6 billion. These rising figures have been clearly associated with increased morbidity and mortality. For example, in the Framingham study, the risk of death increases with each additional pound of weight gain even in the relatively younger population between 30 and 42 years of age. Overweight and obesity are also associated with increased co-morbid conditions such as diabetes, hypertension and cardiovascular disease as well as certain types of cancer. In this review we discuss the epidemic of obesity, highlighting the pathophysiologic mechanisms of weight gain. We also provide an overview of the assessment of overweight and obese individuals discussing possible secondary causes of obesity. In a detailed section we discuss the currently approved therapeutic interventions for obesity highlighting their mechanisms of action and evidence of their efficacy and safety as provided in clinical trials. Finally, we discuss novel therapeutic interventions that are in various stages of development with a special section on the weight loss effects of anti-diabetic medications. These agents are particularly attractive options for our growing population of obese diabetic individuals. PMID:21437080

  15. Propulsive options for a manned Mars transportation system

    NASA Technical Reports Server (NTRS)

    Braun, Robert D.; Blersch, Donald J.

    1989-01-01

    In this investigation, five potential manned Mars transportation systems are compared. These options include: (1) a single vehicle, chemically propelled (CHEM) option, (2) a single vehicle, nuclear thermal propulsion (NTP) option, (3) a single vehicle solar electric propulsion (SEP) option, (4) a single vehicle hybrid nuclear electric propulsion (NEP)/CHEM option, and (5) a dual vehicle option (NEP cargo spacecraft and CHEM manned vehicle). In addition to utilizing the initial vehicle weight in low-earth orbit as a measure of mission feasibility, this study addresses the major technological barriers each propulsive scenario must surpass. It is shown that instead of a single clearly superior propulsion system, each means of propulsion may be favored depending upon the specified program policy and the extent of the desired manned flight time. Furthermore, the effect which aerobraking and multiple transfer cycles have upon mission feasibility is considered.

  16. Regenerative medicine and hair loss: how hair follicle culture has advanced our understanding of treatment options for androgenetic alopecia.

    PubMed

    Higgins, Claire A; Christiano, Angela M

    2014-01-01

    Many of the current drug therapies for androgenetic alopecia were discovered serendipitously, with hair growth observed as an off-target effect when drugs were used to treat a different disorder. Subsequently, several studies using cultured cells have enabled identification of hair growth modulators with similar properties to the currently available drugs, which may also provide clinical benefit. In situations where the current therapeutics do not work, follicular unit transplantation is an alternative surgical option. More recently, the concept of follicular cell implantation, or hair follicle neogenesis, has been attempted, exploiting the inherent properties of cultured hair follicle cells to induce de novo hair growth in balding scalp. In this review, we discuss both the advances in cell culture techniques that have led to a wider range of potential therapeutics to promote hair growth, in addition to detailing current knowledge on follicular cell implantation, and the challenges in making this approach a reality. PMID:24351010

  17. Mars Surface Habitability Options

    NASA Technical Reports Server (NTRS)

    Howe, A. Scott; Simon, Matthew; Smitherman, David; Howard, Robert; Toups, Larry; Hoffman, Stephen J.

    2015-01-01

    This paper reports on current habitability concepts for an Evolvable Mars Campaign (EMC) prepared by the NASA Human Spaceflight Architecture Team (HAT). For many years NASA has investigated alternative human Mars missions, examining different mission objectives, trajectories, vehicles, and technologies; the combinations of which have been referred to as reference missions or architectures. At the highest levels, decisions regarding the timing and objectives for a human mission to Mars continue to evolve while at the lowest levels, applicable technologies continue to advance. This results in an on-going need for assessments of alternative system designs such as the habitat, a significant element in any human Mars mission scenario, to provide meaningful design sensitivity characterizations to assist decision-makers regarding timing, objectives, and technologies. As a subset of the Evolvable Mars Campaign activities, the habitability team builds upon results from past studies and recommends options for Mars surface habitability compatible with updated technologies.

  18. 17 CFR 48.10 - Additional contracts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Additional contracts. 48.10... FOREIGN BOARDS OF TRADE § 48.10 Additional contracts. (a) Generally. A registered foreign board of trade that wishes to make an additional futures, option or swap contract available for trading by...

  19. 17 CFR 48.10 - Additional contracts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 2 2014-04-01 2014-04-01 false Additional contracts. 48.10...) REGISTRATION OF FOREIGN BOARDS OF TRADE § 48.10 Additional contracts. (a) Generally. A registered foreign board of trade that wishes to make an additional futures, option or swap contract available for trading...

  20. 17 CFR 48.10 - Additional contracts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Additional contracts. 48.10... FOREIGN BOARDS OF TRADE § 48.10 Additional contracts. (a) Generally. A registered foreign board of trade that wishes to make an additional futures, option or swap contract available for trading by...

  1. Early amplification options.

    PubMed

    Gabbard, Sandra Abbott; Schryer, Jennifer

    2003-01-01

    Children with permanent hearing loss have been remediated with hearing amplification devices for decades. The influx of young infants identified with hearing loss through successful newborn hearing screening programs has established a need for amplification resources for infants within the first six months of life. For the approximately two of every 1000 infants born who are identified with bilateral hearing loss [Mehl and Thomson, 1998, Pediatrics 101, p. e4], the use of amplification is commonly the first step in treating the sequella of their loss. The use of hearing aids, combined with early intervention, has been shown to significantly improve the speech and language skills of young children with hearing loss [Yoshinaga-Itano, 2000, Seminars in Hearing 21, p. 309]. Speech and language delays have contributed to compromised academic performance of school aged children with hearing loss [Johnson et al., 1997, Educational Audiology Handbook, Singular Publishing, San Diego]. Most hard-of-hearing and deaf children use hearing aids and other assistive listening devices every day throughout their lifetime and the life expectancy of a hearing aid is only five to eight years. The current challenge for pediatric audiologists is selecting and evaluating the available amplification to provide the best options for children and their families. Amplification technology has seen an explosion in growth the past few years and the options continue to expand rapidly. This article examines currently available amplification technology and reviews the selection criteria that may be used for infants and young children. Issues such as style, type, amplification features, signal processing strategies, and verification and validation tools are also discussed. PMID:14648816

  2. Strategic Options Development and Analysis

    NASA Astrophysics Data System (ADS)

    Ackermann, Fran; Eden, Colin

    Strategic Options Development and Analysis (SODA) enables a group or individual to construct a graphical representation of a problematic situation, and thus explore options and their ramifications with respect to a complex system of goals or objectives. In addition the method aims to help groups arrive at a negotiated agreement about how to act to resolve the situation. It is based upon the use of causal mapping - a formally constructed means-ends network - as representation form. Because the picture has been constructed using the natural language of the problem owners it becomes a model of the situation that is ‘owned' by those who define the problem. The use of formalities for the construction of the model makes it amenable to a range of analyses as well as encouraging reflection and a deeper understanding. These analyses can be used in a ‘rough and ready' manner by visual inspection or through the use of specialist causal mapping software (Decision Explorer). Each of the analyses helps a group or individual discover important features of the problem situation, and these features facilitate agreeing agood solution. The SODA process is aimed at helping a group learn about the situation they face before they reach agreements. Most significantly the exploration through the causal map leads to a higher probability of more creative solutions and promotes solutions that are more likely to be implemented because the problem construction process is wider and more likely to include richer social dimensions about the blockages to action and organizational change. The basic theories that inform SODA derive from cognitive psychology and social negotiation, where the model acts as a continuously changing representation of the problematic situation - changing as the views of a person or group shift through learning and exploration. This chapter, jointly written by two leading practitioner academics and the original developers of SODA, Colin Eden and Fran Ackermann

  3. Peak load management: Potential options

    SciTech Connect

    Englin, J.E.; De Steese, J.G.; Schultz, R.W.; Kellogg, M.A.

    1989-10-01

    This report reviews options that may be alternatives to transmission construction (ATT) applicable both generally and at specific locations in the service area of the Bonneville Power Administration (BPA). Some of these options have potential as specific alternatives to the Shelton-Fairmount 230-kV Reinforcement Project, which is the focus of this study. A listing of 31 peak load management (PLM) options is included. Estimated costs and normalized hourly load shapes, corresponding to the respective base load and controlled load cases, are considered for 15 of the above options. A summary page is presented for each of these options, grouped with respect to its applicability in the residential, commercial, industrial, and agricultural sectors. The report contains comments on PLM measures for which load shape management characteristics are not yet available. These comments address the potential relevance of the options and the possible difficulty that may be encountered in characterizing their value should be of interest in this investigation. The report also identifies options that could improve the efficiency of the three customer utility distribution systems supplied by the Shelton-Fairmount Reinforcement Project. Potential cogeneration options in the Olympic Peninsula are also discussed. These discussions focus on the options that appear to be most promising on the Olympic Peninsula. Finally, a short list of options is recommended for investigation in the next phase of this study. 9 refs., 24 tabs.

  4. Therapy options in pulmonary alveolar proteinosis.

    PubMed

    Luisetti, Maurizio; Kadija, Zamir; Mariani, Francesca; Rodi, Giuseppe; Campo, Ilaria; Trapnell, Bruce C

    2010-08-01

    Pulmonary alveolar proteinosis is a rare condition characterized by the accumulation of lipoproteinaceous material within the airspaces, resulting in impaired gas transfer, and clinical manifestations ranging from asymptomatic to severe respiratory failure. To the best of the authors' knowledge, there are only a few conditions whose natural history has been so dramatically changed by the influence of advances in basic science, clinical medicine, and translational research in therapeutic approaches. Whole-lung lavage is the current standard of care and it plays a critical role as a modifier factor of the natural history of proteinosis. That notwithstanding, the identification of autoantibodies neutralizing granulocyte-macrophage colony-stimulating factor in serum and lung of patients affected by the form of proteinosis previously referred to as idiopathic, has opened the way to novel therapeutic options, such as supplementation of exogenous granulocyte-macrophage colony-stimulating factor, or strategies aimed at reducing the levels of the autoantibodies. The aim of this paper is to provide an updated review of the current therapeutic approach to proteinosis. PMID:20647242

  5. Therapeutic Recreation Practicum Manual.

    ERIC Educational Resources Information Center

    Schneegas, Kay

    This manual provides information on the practicum program offered by Moraine Valley Community College (MVCC) for students in its therapeutic recreation program. Sections I and II outline the rationale and goals for providing practical, on-the-job work experiences for therapeutic recreation students. Section III specifies MVCC's responsibilities…

  6. Chicanoizing the Therapeutic Community

    ERIC Educational Resources Information Center

    Aron, William S.; And Others

    1974-01-01

    Focusing on the drug addiction problem and its antecedent conditions in a Chicano population, the article examines several therapeutic interventions suggested by these conditions and indicates how they might be incorporated into a drug addiction Therapeutic Community treatment program designed to meet the needs of Chicano drug addicts. (Author/NQ)

  7. Cytokines and therapeutic oligonucleotides.

    PubMed

    Hartmann, G; Bidlingmaier, M; Eigler, A; Hacker, U; Endres, S

    1997-12-01

    Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies. PMID:9740353

  8. Trans-Differentiation of Neural Stem Cells: A Therapeutic Mechanism Against the Radiation Induced Brain Damage

    PubMed Central

    Kang, Bong Gu; Lee, Se Jeong; Kim, Kang Ho; Yang, Heekyoung; Lee, Young-Ae; Cho, Yu Jin; Im, Yong-Seok; Lee, Dong-Sup; Lim, Do-Hoon; Kim, Dong Hyun; Um, Hong-Duck; Lee, Sang-Hun; Lee, Jung-II; Nam, Do-Hyun

    2012-01-01

    Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases. PMID:22347993

  9. Scaling and long range dependence in option pricing, IV: Pricing European options with transaction costs under the multifractional Black-Scholes model

    NASA Astrophysics Data System (ADS)

    Wang, Xiao-Tian

    2010-02-01

    This paper deals with the problem of discrete time option pricing using the multifractional Black-Scholes model with transaction costs. Using a mean self-financing delta hedging argument in a discrete time setting, a European call option pricing formula is obtained. The minimal price of an option under transaction costs is obtained. In addition, we show that scaling and long range dependence have a significant impact on option pricing.

  10. Reporting therapeutic discourse in a therapeutic community.

    PubMed

    Chapman, G E

    1988-03-01

    Research in nurses' communications has concentrated on nurse to patient interactions. Those few studies which focus on nurse to nurse communications seem to be generated by a pragmatic and normative concern with effective information sharing. In this paper, which describes one aspect of a larger case study of a hospital-based therapeutic community, the description and analysis of nurses' reports flows not from a normative model of professional practice, but rather an exploration of how professional practice is articulated as discourse in nurses' written accounts. Foucault's ideas about therapeutic discourse inform the theoretical framework of the research. Ethnomethodological concerns with the importance of documentary analysis provide the methodological rationale for examining nurses' 24-hour report documents, as official discourse, reflecting therapeutic practice in this setting. A content analysis of nurses' reports, collected over a period of 4 months, demonstrated the importance of domesticity and ordinary everyday activities in nurses' accounts of hospital life. Disruption to the 'life as usual' domesticity in the community seemed to be associated with admission to and discharge from the hospital when interpersonal and interactional changes between patients occur. It is suggested that nurses in general hospital wards and more orthodox psychiatric settings might usefully consider the impact of admissions and discharges on the group of patients they manage, and make this a discursive focus of their work. PMID:3372900

  11. [Implementation of therapeutic hypothermia into clinical practice].

    PubMed

    Himmel, Friederike; Desch, Steffen; Wolfrum, Sebastian

    2015-08-01

    Implementation of mild therapeutic hypothermia after cardiac arrest into clinical practice is a continuing process. Although ILCOR recommendation was given in 2003, only 24% of the German hospitals reported the use of hypothermia in this setting in 2005. Growing evidence and most importantly the implementation of hypothermia into the guidelines led to a significant increase of acceptance of this therapeutic option leading to a user rate of 69% in 2009. Encouraged by the new guidelines from 2010 86% of German hospitals finally reported to use hypothermia after cardiac arrest routinely in 2012, a decade after publication of the mile stone studies. The phenomenon of a delayed implementation of hypothermia into clinical practice can be seen throughout the world as many surveys from different countries at different time points have shown. When hypothermia is used, hospitals go with the guidelines quite strictly with respect to indication, duration of treatment and target temperature. This strengthens the importance of guidelines in the process to implement new therapeutic options. However, although a recent study still promotes a strict target temperature management it questions the need for a markedly reduced target temperature of 33°C. It remains to be elucidated how this study will affect the daily routine in the hospitals and most interestingly how this study will change the coming guidelines in 2015. PMID:26261928

  12. Oral Therapeutics for Rhinosinusitis with Nasal Polyposis.

    PubMed

    Thomas, Andrew J; Alt, Jeremiah A

    2016-01-01

    Oral therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP) include oral corticosteroids (OCS), antibiotics, antifungals and anti-leukotrienes. Of these treatments, the strongest evidence exists to support the use of a short course of OCS for treatment of CRSwNP, and OCS are the most consistently recommended oral therapy in practice guidelines. Antibiotics have demonstrated some utility, which appears more likely related to an anti-inflammatory rather than antimicrobial effect. The non-macrolide antibiotics lack sufficient evidence to support their use, though among this class doxycycline has some limited evidence of benefit in CRSwNP. Greater evidence exists for the use of macrolide antibiotics which have shown reduction of subjective and objective measures of CRSwNP severity. A short course of a macrolide should be considered as an option. Oral antifungals are not recommended in the treatment of CRSwNP given disappointing results and known potential adverse effects, except in allergic fungal rhinosinusitis where they may play a role. Leukotriene antagonists have demonstrated some promise in the treatment of CRSwNP, though studies are limited, but should be considered a potentially useful oral therapeutic. The current level of evidence for these oral therapeutic options for CRSwNP is reviewed in this chapter. PMID:27466856

  13. Selected Energy Conservation Options for Homeowners: Options, Expenses and Payoffs.

    ERIC Educational Resources Information Center

    Lengyel, Dorothy L.; And Others

    This publication is a check list for homeowners and renters to help them reduce energy costs. The list consists of 126 energy conservation options. These options range from "change clothes instead of adjusting thermostat" and "air conditioners turned off when not home" to "use sink stopper" and "weatherstripping and caulking applied." For each…

  14. Myc proteins as therapeutic targets

    PubMed Central

    Gustafson, WC; Weiss, WA

    2010-01-01

    Myc proteins (c-myc, Mycn and Mycl) target proliferative and apoptotic pathways vital for progression in cancer. Amplification of the MYCN gene has emerged as one of the clearest indicators of aggressive and chemotherapy-refractory disease in children with neuroblastoma, the most common extracranial solid tumor of childhood. Phosphorylation and ubiquitin-mediated modulation of Myc protein influence stability and represent potential targets for therapeutic intervention. Phosphorylation of Myc proteins is controlled in-part by the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt/mTOR signaling, with additional contributions from Aurora A kinase. Myc proteins regulate apoptosis in part through interactions with the p53/Mdm2/Arf signaling pathway. Mutation in p53 is commonly observed in patients with relapsed neuroblastoma, contributing to both biology and therapeutic resistance. This review examines Myc function and regulation in neuroblastoma, and discusses emerging therapies that target Mycn. PMID:20101214

  15. Synroc processing options

    SciTech Connect

    Rozsa, R.B.; Hoenig, C.L.

    1981-09-01

    Synroc is a titanate-based ceramic material currently being developed for immobilizing high-level nuclear reactor wastes in solid form. Synroc D is a unique variation of Synroc. It can contain the high-level defense wastes, particularly those in storage at the Savannah River Plant. In this report, we review the early development of the initial Synroc process, discuss modification and other options that simplify it overall, and recommend the future direction of research and development in the processing area. A reference Synroc process is described briefly and contrasted with the Savannah River Laboratory glass-based reference case. Preliminary engineering layouts show Synroc to be a more complex processing operation and, thus, more expensive than the glass-based process. However, we believe that simplifications, which will significantly reduce the cost difference, are possible. Further research and development will continue in the areas of slurry processing, fluidized bed calcination, and mineralization. This last will use sintering, hot uniaxial pressing, or hot isostatic pressing.

  16. Maintenance and supply options

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The object of the Maintenance and Supply Option was to develop a high level operational philosophy related to maintenance and supply operations and incorporate these concepts into the Lunar Base Study. Specific products to be generated during this task were three trade studies and a conceptual design of the Logistic Supply Module. The crew size study was performed to evaluate crew sizes from the baseline size of four to a crew size of eight and determine the preferred crew size. The second trade study was to determine the impact of extending surface stay times and recommend a preferred duration of stay time as a function of crew, consumables, and equipment support capabilities. The third trade study was an evaluation of packaging and storage methods to determine the preferred logistics approach to support the lunar base. A modified scenario was developed and served as the basis of the individual trade studies. Assumptions and guidelines were also developed from experience with Apollo programs, Space Shuttle operations, and Space Station studies. With this information, the trade studies were performed and a conceptual design for the Logistic Supply Module was developed.

  17. Treatment Options for Narcolepsy.

    PubMed

    Barateau, Lucie; Lopez, Régis; Dauvilliers, Yves

    2016-05-01

    Narcolepsy type 1 and narcolepsy type 2 are central disorders of hypersomnolence. Narcolepsy type 1 is characterized by excessive daytime sleepiness and cataplexy and is associated with hypocretin-1 deficiency. On the other hand, in narcolepsy type 2, cerebrospinal fluid hypocretin-1 levels are normal and cataplexy absent. Despite major advances in our understanding of narcolepsy mechanisms, its current management is only symptomatic. Treatment options may vary from a single drug that targets several symptoms, or multiple medications that each treats a specific symptom. In recent years, narcolepsy treatment has changed with the widespread use of modafinil/armodafinil for daytime sleepiness, antidepressants (selective serotonin and dual serotonin and noradrenalin reuptake inhibitors) for cataplexy, and sodium oxybate for both symptoms. Other psychostimulants can also be used, such as methylphenidate, pitolisant and rarely amphetamines, as third-line therapy. Importantly, clinically relevant subjective and objective measures of daytime sleepiness are required to monitor the treatment efficacy and to provide guidance on whether the treatment goals are met. Associated symptoms and comorbid conditions, such as hypnagogic/hypnopompic hallucinations, sleep paralysis, disturbed nighttime sleep, unpleasant dreams, REM- and non REM-related parasomnias, depressive symptoms, overweight/obesity, and obstructive sleep apnea, should also be taken into account and managed, if required. In the near future, the efficacy of new wake-promoting drugs, anticataplectic agents, hypocretin replacement therapy and immunotherapy at the early stages of the disease should also be evaluated. PMID:27155860

  18. AFCI Options Study

    SciTech Connect

    R. Wigeland; T. Taiwo; M. Todosow; W. Halsey; J. Gehin

    2009-09-01

    This report describes the background and framework for both organizing the discussion and providing information on the potential for nuclear energy R&D to develop alternative nuclear fuel cycles that would address the issues with the current implementations of nuclear power, including nuclear waste disposal, proliferation risk, safety, security, economics, and sustainability. The disposition of used fuel is the cause of many of the concerns, and the possible approaches to used fuel management identify a number of basic technology areas that need to be considered. The basic science in each of the technology areas is discussed, emphasizing what science is currently available, where scientific knowledge may be insufficient, and especially to identify specific areas where transformational discoveries may allow achievement of performance goals not currently attainable. These discussions lead to the wide range of technical options that have been the basis for past and current research and development on advanced nuclear fuel cycles in the United States. The results of this work are then briefly reviewed to show the extent to which such approaches are capable of addressing the issues with nuclear power, the potential for moving further, and the inherent limitations.

  19. [Therapeutic Effects of Multipotent Mesenchymal Stromal Cells after Irradiation].

    PubMed

    Kalmykova, N V; Alexandrova, S A

    2016-01-01

    Multipotent mesenchymal stromal cells (MSC) are now considered to be a perspective multifunctional treatment option for radiation side effects. At present.a great number of sufficient evidence has been collected in favor of therapeutic effects of MSCs in acute radiation reactions. It has been shown that MSC-based products injected locally or systemically have therapeutic effects on irradiated organs and tissues. This review presents summarized experimental and clinical data about protective and regenerative effects of MSCs on different radiation-injured organs and tissues; the main probable therapeutic mechanisms of their action are also discussed. PMID:27534063

  20. Therapeutic potential of mesenchymal stem cells for pulmonary complications associated with preterm birth.

    PubMed

    Laube, Mandy; Stolzing, Alexandra; Thome, Ulrich H; Fabian, Claire

    2016-05-01

    Preterm infants frequently suffer from pulmonary complications resulting in significant morbidity and mortality. Physiological and structural lung immaturity impairs perinatal lung transition to air breathing resulting in respiratory distress. Mechanical ventilation and oxygen supplementation ensure sufficient oxygen supply but enhance inflammatory processes which might lead to the establishment of a chronic lung disease called bronchopulmonary dysplasia (BPD). Current therapeutic options to prevent or treat BPD are limited and have salient side effects, highlighting the need for new therapeutic approaches. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential in animal models of BPD. This review focuses on MSC-based therapeutic approaches to treat pulmonary complications and critically compares results obtained in BPD models. Thereby bottlenecks in the translational systems are identified that are preventing progress in combating BPD. Notably, current animal models closely resemble the so-called "old" BPD with profound inflammation and injury, whereas clinical improvements shifted disease pathology towards a "new" BPD in which arrest of lung maturation predominates. Future studies need to evaluate the utility of MSC-based therapies in animal models resembling the "new" BPD though promising in vitro evidence suggests that MSCs do possess the potential to stimulate lung maturation. Furthermore, we address the mode-of-action of MSC-based therapies with regard to lung development and inflammation/fibrosis. Their therapeutic efficacy is mainly attributed to an enhancement of regeneration and immunomodulation due to paracrine effects. In addition, we discuss current improvement strategies by genetic modifications or precondition of MSCs to enhance their therapeutic efficacy which could also prove beneficial for BPD therapies. PMID:26928452

  1. Real options reasoning in healthcare: an integrative approach and synopsis.

    PubMed

    Williams, David R; Hammes, Paul H

    2007-01-01

    For the past 40 years, practitioners and researchers alike have been grappling with the natural shortcomings associated with the net present value approach to strategic decision making and capital budgeting. Work by scholars in option pricing theory has evolved into an alternative perspective on strategic capital investments, called "real options." Proponents of real options argue that this is a superior way of approaching decision making and capital budgeting, compared with other approaches, as it allows for greater strategic flexibility and encourages exploration, experimentation, and innovation. Within the healthcare literature, articles on real options have focused on pricing these options. This article is unique to the healthcare literature as it emphasizes the cognitive or strategic aspects of real options. Additionally, this article integrates two techniques for applying the real options approach for interested practitioners using a hospital's imaging department as an example, while providing scholars with additional applications and questions for future research. For practitioners, the implications are that thinking of and planning for capital investments as real options may create greater strategic and operating flexibility than other, more traditional approaches. PMID:17552354

  2. Recent additions in the treatment of cough

    PubMed Central

    Gibson, Peter G.

    2014-01-01

    Background Worldwide, cough is regarded as a challenging clinical problem due to its frequency and often limited therapeutic options. Chronic cough that remains refractory to usual medical treatment causes significant quality of life impairment in people with this problem. Methods We have examined current evidence on recent additions in the treatment of cough, specifically treatment of refractory chronic cough with speech pathology and gabapentin. Relevant randomised control trials, reviews and case reports were identified through a PubMed and SCOPUS search of English-language literature referring to these concepts over the last eight years. Summary Of the one hundred and two articles comprising this review the majority investigated the role of the transient receptor potential (TRP) receptors TRP Vanilloid 1 (TRPV1) and TRPA1 in cough and the potential of TRP antagonists as effective anti-tussives. However, these have only been tested in the laboratory and therefore their clinical effectiveness is unknown. Behavioural treatments such as speech pathology have gained momentum and this was evident in the increasing number of articles investigating its positive effect on cough. Investigation on the effectiveness of neuromodulating medications in the treatment of cough have been supported primarily through case series reports and prospective reviews however; their use (particularly gabapentin) has been significantly advanced through recently conducted randomised controlled trials. Conclusions Recent additions in the treatment of chronic cough have been significant as they consider cough to have a unifying diagnosis of cough hypersensitivity with or without the presence of a neuropathic basis. Primarily, effective treatments for chronic cough target these areas and include behavioural treatment such as speech pathology and pharmaceutical treatment with neuromodulating medications such as gabapentin. PMID:25383209

  3. Cryoglobulinaemic vasculitis: classification and clinical and therapeutic aspects

    PubMed Central

    Braun, Gerald S; Horster, Sophia; Wagner, Katrin S; Ihrler, Stephan; Schmid, Holger

    2007-01-01

    Cryoglobulinaemia may cause cutaneous vasculitis and glomerulonephritis, potentially leading to end stage renal failure. An important proportion of cryoglobulinaemias are secondary to hepatitis C virus infection. Emerging antiviral treatment options offer a chance for causal therapy of these cases of cryoglobulinaemia. This review summarises the classification and clinical and therapeutic aspects of cryoglobulinaemic vasculitis and glomerulonephritis. PMID:17308210

  4. Optional Extended Year Program. FEEDBACK.

    ERIC Educational Resources Information Center

    Washington, Wanda

    The Optional Extended Year (OEY) program was initiated in Texas in 1995 and was first implemented in the Austin Independent School District (AISD) in 1996. The OEY is designed to add an extended school year and reduce student retention through four school-day options: (1) extended day; (2) extended week; (3) intersessions for year-round schools;…

  5. Bounds for Asian basket options

    NASA Astrophysics Data System (ADS)

    Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

    2008-09-01

    In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

  6. A Smorgasbord of Assessment Options

    ERIC Educational Resources Information Center

    Bacon, Kathy A.

    2010-01-01

    The wealth of assessment options that exists offers teachers and students a "menu" of selections. Just as matching appetite needs with appropriate food selection is fundamental to a successful dining experience, matching assessment options to targeted achievement needs is crucial to an effective assessment experience. The author uses a geometry…

  7. Designer blood vessels and therapeutic revascularization

    PubMed Central

    Berglund, Joseph D; Galis, Zorina S

    2003-01-01

    Inadequate vascular perfusion leads to fatal heart attacks, chronic ulcers, and other serious clinical conditions. The body's capacity to restore vascular perfusion through angiogenesis and arteriogenesis is often impaired by pre-existing disease, and availability of native replacements for nonfunctional arteries is limited in many patients. Thus, recreating blood vessels of various calibres through novel engineering technologies has emerged as a radical option among therapeutic strategies for revascularization. Ranging from artificial, recycled or reassembled natural conduits to sophisticated microdevices, we refer to these as ‘designer blood vessels'. Our common efforts to continuously improve vascular replacement design have provided many clues about our own blood vessels, but nature's ability to create nonthrombogenic, immunocompatible, strong, yet biologically responsive blood vessels remains unparalleled. Just as art reproductions never equal the original masterpiece, designer blood vessels may never attain nature's perfection. Nevertheless, they will provide a valuable option as long as they come close enough and are available to many. PMID:14534146

  8. Engineering antibody therapeutics.

    PubMed

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  9. Pectus excavatum: history, hypotheses and treatment options

    PubMed Central

    Brochhausen, Christoph; Turial, Salmai; Müller, Felix K.P.; Schmitt, Volker H.; Coerdt, Wiltrud; Wihlm, Jean-Marie; Schier, Felix; Kirkpatrick, C. James

    2012-01-01

    Pectus excavatum and pectus carinatum represent the most frequent chest wall deformations. However, the pathogenesis is still poorly understood and research results remain inconsistent. To focus on the recent state of knowledge, we summarize and critically discuss the pathological concepts based on the history of these entities, beginning with the first description in the sixteenth century. Based on the early clinical descriptions, we review and discuss the different pathogenetic hypotheses. To open new perspectives for the potential pathomechanisms, the embryonic and foetal development of the ribs and the sternum is highlighted following the understanding that the origin of these deformities is given by the disruption in the maturation of the parasternal region. In the second, different therapeutical techniques are highlighted and based on the pathogenetic hypotheses and the embryological knowledge potential new biomaterial-based perspectives with interesting insights for tissue engineering-based treatment options are presented. PMID:22394989

  10. [Chronic obstructive pulmonary disease : new pharmacotherapeutic options].

    PubMed

    Greulich, T; Koczulla, A R; Vogelmeier, C

    2012-11-01

    Data about the clinical presentation of chronic obstructive pulmonary disease (COPD) have resulted in a new classification of the disease. The degree of airflow limitation has been amended by symptoms and exacerbation rate. The standard pharmacotherapy of stable COPD is in transition, as fixed combinations of long acting beta agonists and long acting anticholinergics are in the late stages of clinical development. On this background inhaled corticosteroids will need to be re-evaluated. Roflumilast is a recently approved therapeutic option that primarily diminishes exacerbation frequency in patients with chronic bronchitis and severe airflow obstruction (FEV(1) < 50%). In COPD patients with acute exacerbations procalcitonin levels can be used to guide antibiotic therapy. Comparable clinical outcomes can be achieved while using significantly less amounts of antibiotics. PMID:22955248

  11. Current Treatment Options in Vestibular Migraine

    PubMed Central

    Obermann, Mark; Strupp, Michael

    2014-01-01

    Approximately 1% of the general population in western industrialized countries suffers from vestibular migraine. However, it remains widely unknown and often under diagnosed despite the recently published diagnostic criteria for vestibular migraine. Treatment trials that specialize on vestibular migraine are scarce and systematic randomized controlled clinical trials are now only emerging. This review summarizes the knowledge on the currently available treatment options that were tested specifically for vestibular migraine and gives an evidence-based, informed treatment recommendation with all its limitations. To date only two randomized controlled treatment trials provide limited evidence for the use of rizatriptan and zolmitriptan for the treatment of vestibular migraine attacks because of methodological shortcomings. There is an ongoing multicenter randomized placebo-controlled trial testing metoprolol 95 mg vs. placebo (PROVEMIG-trial). Therefore, the therapeutic recommendations for the prophylactic treatment of vestibular migraine are currently widely based on the guidelines of migraine with and without aura as well as expert opinion. PMID:25538676

  12. Are therapeutic communities therapeutic for women?

    PubMed Central

    Eliason, Michele J

    2006-01-01

    This paper addresses the growing phenomena of therapeutic community (TC) treatment approaches for women in correctional settings. Although rapidly increasing in number across the country, there is very little empirical research to support the effectiveness of TC treatment for women. Therefore, the literature on the efficacy and effectiveness of TC treatment for women is reviewed in relation to the literature on women's treatment issues. The literature review highlights the gaps where TC treatment ignores or exacerbates issues that are common to addicted women, or uses methods that may be contradictory to women's recovery. PMID:16722560

  13. Investigation of Neptunium Precipitator Cleanout Options

    SciTech Connect

    Hill, B.C.

    2003-09-08

    Oxalate precipitation followed by filtration is used to prepare plutonium oxalate. Historically, plutonium oxalate has tended to accumulate in the precipitation tanks. These solids are periodically removed by flushing with concentrated (64 percent) nitric acid. The same precipitation tanks will now be used in the processing of neptunium. Literature values indicate that neptunium oxalate may not be as soluble as plutonium oxalate in nitric acid. Although a wide variety of options is available to improve neptunium oxalate solubility for precipitator flushing, most of these options are not practical for use. Many of these options require the use of incompatible or difficult to handle chemicals. Other options would require expensive equipment modifications or are likely to lead to product contamination. Based on review of literature and experimental results, the two best options for flushing the precipitator are (1) 64 percent nitric acid and (2) addition of sodium permanganate follow ed by sodium nitrite. Nitric acid is the easiest option to implement. It is already used in the facility and will not lead to product contamination. Experimental results indicate that neptunium oxalate can be dissolved in concentrated nitric acid (64 percent) at 60 degree C to a concentration of 2.6 to 5.6 grams of Np/liter after at least three hours of heating. A lower concentration (1.1 grams of Np/liter) was measured at 60 degree C after less than two hours of heating. These concentrations are acceptable for flushing if precipitator holdup is low (approximately 100-250 grams), but a second method is required for effective flushing if precipitator holdup is high (approximately 2 kilograms). The most effective method for obtaining higher neptunium concentrations is the use of sodium permanganate followed by the addition of sodium nitrite. There is concern that residual manganese from these flushes could impact product purity. Gas generation during permanganate addition is also a concern

  14. Non-coding RNAs Enabling Prognostic Stratification and Prediction of Therapeutic Response in Colorectal Cancer Patients.

    PubMed

    Perakis, Samantha O; Thomas, Joseph E; Pichler, Martin

    2016-01-01

    Colorectal cancer (CRC) is a heterogeneous disease and current treatment options for patients are associated with a wide range of outcomes and tumor responses. Although the traditional TNM staging system continues to serve as a crucial tool for estimating CRC prognosis and for stratification of treatment choices and long-term survival, it remains limited as it relies on macroscopic features and cases of surgical resection, fails to incorporate new molecular data and information, and cannot perfectly predict the variety of outcomes and responses to treatment associated with tumors of the same stage. Although additional histopathologic features have recently been applied in order to better classify individual tumors, the future might incorporate the use of novel molecular and genetic markers in order to maximize therapeutic outcome and to provide accurate prognosis. Such novel biomarkers, in addition to individual patient tumor phenotyping and other validated genetic markers, could facilitate the prediction of risk of progression in CRC patients and help assess overall survival. Recent findings point to the emerging role of non-protein-coding regions of the genome in their contribution to the progression of cancer and tumor formation. Two major subclasses of non-coding RNAs (ncRNAs), microRNAs and long non-coding RNAs, are often dysregulated in CRC and have demonstrated their diagnostic and prognostic potential as biomarkers. These ncRNAs are promising molecular classifiers and could assist in the stratification of patients into appropriate risk groups to guide therapeutic decisions and their expression patterns could help determine prognosis and predict therapeutic options in CRC. PMID:27573901

  15. Treatment options in the young patient with Graves' disease.

    PubMed

    Cheetham, Tim; Bliss, Richard

    2016-08-01

    The treatment options in the young patient with Graves' disease are the same as in adults, namely antithyroid drug (ATD), surgery (partial or total thyroidectomy) and radioiodine. However, the emphasis and expectation is different in the young person, reflecting a range of considerations including age, pubertal status, disease natural history, likely impact of ATD on disease course and the implications of radiation exposure. New therapeutic strategies that could increase the likelihood of long-term remission are being explored. PMID:26252256

  16. An overview of treatment options for urinary stones

    PubMed Central

    Shafi, Hamid; Moazzami, Bobak; Pourghasem, Mohsen; Kasaeian, Aliakbar

    2016-01-01

    Urolithiasis has become a worldwide problem with the prevalence of the disease increasing over the past few decades. While various treatment modalities have evolved over the years, discrepancies exist regarding the clinical indications and the efficacy of each of these treatment options. In the present review, we aim to review the current treatment modalities for urinary tract stones to provide a better understanding on the therapeutic approaches as well as their clinical indications. PMID:26958325

  17. Options for Technology Transfer.

    ERIC Educational Resources Information Center

    Anderson, Richard E.; Sugarman, Barry

    1989-01-01

    Structural means by which institutions of higher education can tap technology are explored with an examination of the licensing of technological discoveries as well as the creation of start-up companies based upon university-developed technology. Additionally, the corporate structures that are being formed so that institutions can more easily hold…

  18. Autoimmune hemolytic anemia: classification and therapeutic approaches.

    PubMed

    Sève, Pascal; Philippe, Pierre; Dufour, Jean-François; Broussolle, Christiane; Michel, Marc

    2008-12-01

    Autoimmune hemolytic anemia (AIHA) is a relatively uncommon cause of anemia. Classifications of AIHA include warm AIHA, cold AIHA (including mainly chronic cold agglutinin disease and paroxysmal cold hemoglobinuria), mixed-type AIHA and drug-induced AIHA. AIHA may also be further subdivided on the basis of etiology. Management of AIHA is based mainly on empirical data and on small, retrospective, uncontrolled studies. The therapeutic options for treating AIHA are increasing with monoclonal antibodies and, potentially, complement inhibitory drugs. Based on data available in the literature and our experience, we propose algorithms for the treatment of warm AIHA and cold agglutinin disease in adults. Therapeutic trials are needed in order to better stratify treatment, taking into account the promising efficacy of rituximab. PMID:21082924

  19. Tissue engineering applications of therapeutic cloning.

    PubMed

    Atala, Anthony; Koh, Chester J

    2004-01-01

    Few treatment options are available for patients suffering from diseased and injured organs because of a severe shortage of donor organs available for transplantation. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for replacement therapy. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure. PMID:15255761

  20. The potential therapeutic effects of THC on Alzheimer's disease.

    PubMed

    Cao, Chuanhai; Li, Yaqiong; Liu, Hui; Bai, Ge; Mayl, Jonathan; Lin, Xiaoyang; Sutherland, Kyle; Nabar, Neel; Cai, Jianfeng

    2014-01-01

    The purpose of this study was to investigate the potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer's disease. N2a-variant amyloid-β protein precursor (AβPP) cells were incubated with THC and assayed for amyloid-β (Aβ) levels at the 6-, 24-, and 48-hour time marks. THC was also tested for synergy with caffeine, in respect to the reduction of the Aβ level in N2a/AβPPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-Aβ aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3β (GSK-3β) and related signaling pathways. From the results, we have discovered THC to be effective at lowering Aβ levels in N2a/AβPPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together. We did discover that THC directly interacts with Aβ peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3β levels and phosphorylated GSK-3β in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin's enhancement of mitochondria function. These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer's disease through multiple functions and pathways. PMID:25024327

  1. Fibromyalgia syndrome: novel therapeutic targets.

    PubMed

    Ablin, Jacob N; Häuser, Winfried

    2016-05-01

    Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread pain and tenderness, accompanied by disturbed sleep, chronic fatigue and multiple additional functional symptoms. FMS continues to pose an unmet need regarding pharmacological treatment and many patients fail to achieve sufficient relief from existing treatments. As FMS is considered to be a condition in which pain amplification occurs within the CNS, therapeutic interventions, both pharmacological and otherwise, have revolved around attempts to influence pain processing in the CNS. In the current review, we present an update on novel targets in the search for effective treatment of FMS. PMID:27296699

  2. Bioengineering Lantibiotics for Therapeutic Success

    PubMed Central

    Field, Des; Cotter, Paul D.; Hill, Colin; Ross, R. P.

    2015-01-01

    Several examples of highly modified antimicrobial peptides have been described. While many such peptides are non-ribosomally synthesized, ribosomally synthesized equivalents are being discovered with increased frequency. Of the latter group, the lantibiotics continue to attract most attention. In the present review, we discuss the implementation of in vivo and in vitro engineering systems to alter, and even enhance, the antimicrobial activity, antibacterial spectrum and physico-chemical properties, including heat stability, solubility, diffusion and protease resistance, of these compounds. Additionally, we discuss the potential applications of these lantibiotics for use as therapeutics. PMID:26640466

  3. New treatment options for alcoholic hepatitis

    PubMed Central

    Shasthry, Saggere Muralikrishna; Sarin, Shiv Kumar

    2016-01-01

    The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, continues to have high morbidity and mortality, with significant financial and healthcare burden with limited treatment options. Steroids remain the current standard of care in severe alcoholic hepatitis in carefully selected patients. No specific treatments are available for those patients who are steroid ineligible, intolerant or unresponsive. Liver transplant has shown good short-term outcome; however, feasibility, ethical and economic concerns remain. Modification of gut microbiota composition and their products, such as lipopolysaccharide, nutritional interventions, immune modulation, increasing steroid sensitivity, genetic polymorphism and epigenetic modification of alcohol induced liver damage, augmenting hepatic regeneration using GCSF are potential therapeutic avenues in steroid non-responsive/ineligible patients. With better understanding of the pathophysiology, using “Omics” platforms, newer options for patients with alcoholic hepatitis are expected soon. PMID:27099434

  4. Making real options really work.

    PubMed

    van Putten, Alexander B; MacMillan, Ian C

    2004-12-01

    As a way to value growth opportunities, real options have had a difficult time catching on with managers. Many CFOs believe the method ensures the overvaluation of risky projects. This concern is legitimate, but abandoning real options as a valuation model isn't the solution. Companies that rely solely on discounted cash flow (DCF) analysis underestimate the value of their projects and may fail to invest enough in uncertain but highly promising opportunities. CFOs need not--and should not--choose one approach over the other. Far from being a replacement for DCF analysis, real options are an essential complement, and a project's total value should encompass both. DCF captures a base estimate of value; real options take into account the potential for big gains. This is not to say that there aren't problems with real options. As currently applied, they focus almost exclusively on the risks associated with revenues, ignoring the risks associated with a project's costs. It's also true that option valuations almost always ignore assets that an initial investment in a subsequently abandoned project will often leave the company. In this article, the authors present a simple formula for combining DCF and option valuations that addresses these two problems. Using an integrated approach, managers will, in the long run, select better projects than their more timid competitors while keeping risk under control. Thus, they will outperform their rivals in both the product and the capital markets. PMID:15605572

  5. Imaging enabled platforms for development of therapeutics

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan; Rizvi, Imran; Blanden, Adam R.; Evans, Conor L.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Muzikansky, Alona; Pogue, Brian W.; Finkelstein, Dianne M.; Hasan, Tayyaba

    2011-03-01

    Advances in imaging and spectroscopic technologies have enabled the optimization of many therapeutic modalities in cancer and noncancer pathologies either by earlier disease detection or by allowing therapy monitoring. Amongst the therapeutic options benefiting from developments in imaging technologies, photodynamic therapy (PDT) is exceptional. PDT is a photochemistry-based therapeutic approach where a light-sensitive molecule (photosensitizer) is activated with light of appropriate energy (wavelength) to produce reactive molecular species such as free radicals and singlet oxygen. These molecular entities then react with biological targets such as DNA, membranes and other cellular components to impair their function and lead to eventual cell and tissue death. Development of PDT-based imaging also provides a platform for rapid screening of new therapeutics in novel in vitro models prior to expensive and labor-intensive animal studies. In this study we demonstrate how an imaging platform can be used for strategizing a novel combination treatment strategy for multifocal ovarian cancer. Using an in vitro 3D model for micrometastatic ovarian cancer in conjunction with quantitative imaging we examine dose and scheduling strategies for PDT in combination with carboplatin, a chemotherapeutic agent presently in clinical use for management of this deadly form of cancer.

  6. New therapeutic approaches in PV

    PubMed Central

    Falchi, Lorenzo; Newberry, Kate J.; Verstovsek, Srdan

    2015-01-01

    Polycytemia vera (PV) is one of the three Philadelphia-negative myeloproliferative neoplasms. Clinically, PV is an indolent disease but its course can be complicated by arterial and venous vascular accidents, evolution to myelofibrosis or leukemic transformation. Treatment of PV is, therefore, aimed at preventing such acute complications. The cornerstone of therapy of low-risk patients remains strict control of cardiovascular risk factors, the use of phlebotomy and low dose aspirin. Higher risk patients should also receive cytoreductive treatments. Hydroxyurea and interferon-α represent standard first-line options for newly diagnosed high-risk PV patients. Recommendations for patients who fail these therapies are less clearly defined. The discovery of a mutation in the Janus kinase 2 gene (V617F) in almost all cases of PV has prompted the development of molecularly targeted agents for the treatment of these patients. In this review we will discuss key clinical aspects, the current therapeutic armamentarium and data on the use of novel agents in patients with PV. PMID:26297275

  7. Shiga Toxins as Multi-Functional Proteins: Induction of Host Cellular Stress Responses, Role in Pathogenesis and Therapeutic Applications.

    PubMed

    Lee, Moo-Seung; Koo, Sunwoo; Jeong, Dae Gwin; Tesh, Vernon L

    2016-01-01

    Shiga toxins (Stxs) produced by Shiga toxin-producing bacteria Shigella dysenteriae serotype 1 and select serotypes of Escherichia coli are primary virulence factors in the pathogenesis of hemorrhagic colitis progressing to potentially fatal systemic complications, such as hemolytic uremic syndrome and central nervous system abnormalities. Current therapeutic options to treat patients infected with toxin-producing bacteria are limited. The structures of Stxs, toxin-receptor binding, intracellular transport and the mode of action of the toxins have been well defined. However, in the last decade, numerous studies have demonstrated that in addition to being potent protein synthesis inhibitors, Stxs are also multifunctional proteins capable of activating multiple cell stress signaling pathways, which may result in apoptosis, autophagy or activation of the innate immune response. Here, we briefly present the current understanding of Stx-activated signaling pathways and provide a concise review of therapeutic applications to target tumors by engineering the toxins. PMID:26999205

  8. Shiga Toxins as Multi-Functional Proteins: Induction of Host Cellular Stress Responses, Role in Pathogenesis and Therapeutic Applications

    PubMed Central

    Lee, Moo-Seung; Koo, Sunwoo; Jeong, Dae Gwin; Tesh, Vernon L.

    2016-01-01

    Shiga toxins (Stxs) produced by Shiga toxin-producing bacteria Shigella dysenteriae serotype 1 and select serotypes of Escherichia coli are primary virulence factors in the pathogenesis of hemorrhagic colitis progressing to potentially fatal systemic complications, such as hemolytic uremic syndrome and central nervous system abnormalities. Current therapeutic options to treat patients infected with toxin-producing bacteria are limited. The structures of Stxs, toxin-receptor binding, intracellular transport and the mode of action of the toxins have been well defined. However, in the last decade, numerous studies have demonstrated that in addition to being potent protein synthesis inhibitors, Stxs are also multifunctional proteins capable of activating multiple cell stress signaling pathways, which may result in apoptosis, autophagy or activation of the innate immune response. Here, we briefly present the current understanding of Stx-activated signaling pathways and provide a concise review of therapeutic applications to target tumors by engineering the toxins. PMID:26999205

  9. Advanced Nuclear Fuel Cycle Options

    SciTech Connect

    Roald Wigeland; Temitope Taiwo; Michael Todosow; William Halsey; Jess Gehin

    2010-06-01

    A systematic evaluation has been conducted of the potential for advanced nuclear fuel cycle strategies and options to address the issues ascribed to the use of nuclear power. Issues included nuclear waste management, proliferation risk, safety, security, economics and affordability, and sustainability. The two basic strategies, once-through and recycle, and the range of possibilities within each strategy, are considered for all aspects of the fuel cycle including options for nuclear material irradiation, separations if needed, and disposal. Options range from incremental changes to today’s implementation to revolutionary concepts that would require the development of advanced nuclear technologies.

  10. Pelvic radiation disease: Updates on treatment options.

    PubMed

    Frazzoni, Leonardo; La Marca, Marina; Guido, Alessandra; Morganti, Alessio Giuseppe; Bazzoli, Franco; Fuccio, Lorenzo

    2015-12-10

    Pelvic cancers are among the most frequently diagnosed neoplasms and radiotherapy represents one of the main treatment options. The irradiation field usually encompasses healthy intestinal tissue, especially of distal large bowel, thus inducing gastrointestinal (GI) radiation-induced toxicity. Indeed, up to half of radiation-treated patients say that their quality of life is affected by GI symptoms (e.g., rectal bleeding, diarrhoea). The constellation of GI symptoms - from transient to long-term, from mild to very severe - experienced by patients who underwent radiation treatment for a pelvic tumor have been comprised in the definition of pelvic radiation disease (PRD). A correct and evidence-based therapeutic approach of patients experiencing GI radiation-induced toxicity is mandatory. Therapeutic non-surgical strategies for PRD can be summarized in two broad categories, i.e., medical and endoscopic. Of note, most of the studies have investigated the management of radiation-induced rectal bleeding. Patients with clinically significant bleeding (i.e., causing chronic anemia) should firstly be considered for medical management (i.e., sucralfate enemas, metronidazole and hyperbaric oxygen); in case of failure, endoscopic treatment should be implemented. This latter should be considered the first choice in case of acute, transfusion requiring, bleeding. More well-performed, high quality studies should be performed, especially the role of medical treatments should be better investigated as well as the comparative studies between endoscopic and hyperbaric oxygen treatments. PMID:26677440

  11. Pelvic radiation disease: Updates on treatment options

    PubMed Central

    Frazzoni, Leonardo; La Marca, Marina; Guido, Alessandra; Morganti, Alessio Giuseppe; Bazzoli, Franco; Fuccio, Lorenzo

    2015-01-01

    Pelvic cancers are among the most frequently diagnosed neoplasms and radiotherapy represents one of the main treatment options. The irradiation field usually encompasses healthy intestinal tissue, especially of distal large bowel, thus inducing gastrointestinal (GI) radiation-induced toxicity. Indeed, up to half of radiation-treated patients say that their quality of life is affected by GI symptoms (e.g., rectal bleeding, diarrhoea). The constellation of GI symptoms - from transient to long-term, from mild to very severe - experienced by patients who underwent radiation treatment for a pelvic tumor have been comprised in the definition of pelvic radiation disease (PRD). A correct and evidence-based therapeutic approach of patients experiencing GI radiation-induced toxicity is mandatory. Therapeutic non-surgical strategies for PRD can be summarized in two broad categories, i.e., medical and endoscopic. Of note, most of the studies have investigated the management of radiation-induced rectal bleeding. Patients with clinically significant bleeding (i.e., causing chronic anemia) should firstly be considered for medical management (i.e., sucralfate enemas, metronidazole and hyperbaric oxygen); in case of failure, endoscopic treatment should be implemented. This latter should be considered the first choice in case of acute, transfusion requiring, bleeding. More well-performed, high quality studies should be performed, especially the role of medical treatments should be better investigated as well as the comparative studies between endoscopic and hyperbaric oxygen treatments. PMID:26677440

  12. Option pricing: Stock price, stock velocity and the acceleration Lagrangian

    NASA Astrophysics Data System (ADS)

    Baaquie, Belal E.; Du, Xin; Bhanap, Jitendra

    2014-12-01

    The industry standard Black-Scholes option pricing formula is based on the current value of the underlying security and other fixed parameters of the model. The Black-Scholes formula, with a fixed volatility, cannot match the market's option price; instead, it has come to be used as a formula for generating the option price, once the so called implied volatility of the option is provided as additional input. The implied volatility not only is an entire surface, depending on the strike price and maturity of the option, but also depends on calendar time, changing from day to day. The point of view adopted in this paper is that the instantaneous rate of return of the security carries part of the information that is provided by implied volatility, and with a few (time-independent) parameters required for a complete pricing formula. An option pricing formula is developed that is based on knowing the value of both the current price and rate of return of the underlying security which in physics is called velocity. Using an acceleration Lagrangian model based on the formalism of quantum mathematics, we derive the pricing formula for European call options. The implied volatility of the market can be generated by our pricing formula. Our option price is applied to foreign exchange rates and equities and the accuracy is compared with Black-Scholes pricing formula and with the market price.

  13. NYMEX electricity futures and options

    SciTech Connect

    Burke, L.

    1996-12-31

    Electricity futures and options are discussed under the following topics: a futures contract, primary economic role of commodity exchanges, characteristics of an effective exchange, natural gas and electricity similarities, hedging, and coal futures contracts.

  14. Hyperphosphataemia: treatment options.

    PubMed

    Malberti, Fabio

    2013-05-01

    Hyperphosphataemia can be induced by three main conditions: a massive acute phosphate load, a primary increase in renal phosphate reabsorption, and an impaired renal phosphate excretion due to acute or chronic renal insufficiency. Renal excretion is so efficient in normal subjects that balance can be maintained with only a minimal rise in serum phosphorus concentration even for a large phosphorus load. Therefore, acute hyperphosphataemia usually resolves within few hours if renal function is intact. The most frequent cause of chronic hyperphosphataemia is chronic renal failure. Hyperphosphataemia in chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Lowering the phosphate load and maintaining serum phosphorus levels within the normal range are considered important therapeutic goals to improve clinical outcomes in CKD patients. Treatment consists of diminishing intestinal phosphate absorption by a low phosphate diet and phosphate binders. In CKD patients on dialysis an efficient dialysis removal of phosphate should be ensured. Dietary restriction of phosphorus while maintaining adequate protein intake is not sufficient to control serum phosphate levels in most CKD patients; therefore, the prescription of a phosphate binder is required. Aluminium-containing agents are efficient but no longer widely used because of their toxicity. Calcium-based salts are inexpensive, effective and most widely used, but there is now concern about their association with hypercalcaemia, parathyroid gland suppression, adynamic bone disease, and vascular and extraosseous calcification. The average daily dose of calcium acetate or carbonate prescribed in the randomised controlled trials to control hyperphosphataemia in dialysis patients ranges between 1.2 and 2.3 g of elemental calcium. Such doses are greater than the recommended dietary calcium intake and can lead to a positive calcium balance. Although large amounts of calcium salts should

  15. Development and novel therapeutics in hepatocellular carcinoma: a review.

    PubMed

    Ingle, Pravinkumar Vishwanath; Samsudin, Sarah Zakiah; Chan, Pei Qi; Ng, Mei Kei; Heng, Li Xuan; Yap, Siu Ching; Chai, Amy Siaw Hui; Wong, Audrey San Ying

    2016-01-01

    This review summarizes the epidemiological trend, risk factors, prevention strategies such as vaccination, staging, current novel therapeutics, including the drugs under clinical trials, and future therapeutic trends for hepatocellular carcinoma (HCC). As HCC is the third most common cause of cancer-related death worldwide, its overall incidence remains alarmingly high in the developing world and is steadily rising across most of the developed and developing world. Over the past 15 years, the incidence of HCC has more than doubled and it increases with advancing age. Chronic infection with hepatitis B virus is the leading cause of HCC, closely followed by infection with hepatitis C virus. Other factors contributing to the development of HCC include alcohol abuse, tobacco smoking, and metabolic syndrome (including obesity, diabetes, and fatty liver disease). Treatment options have improved in the past few years, particularly with the approval of several molecular-targeted therapies. The researchers are actively pursuing novel therapeutic targets as well as predictive biomarker for treatment of HCC. Advances are being made in understanding the mechanisms underlying HCC, which in turn could lead to novel therapeutics. Nevertheless, there are many emerging agents still under clinical trials and yet to show promising results. Hence, future therapeutic options may include different combination of novel therapeutic interventions. PMID:27042086

  16. Development and novel therapeutics in hepatocellular carcinoma: a review

    PubMed Central

    Ingle, Pravinkumar Vishwanath; Samsudin, Sarah Zakiah; Chan, Pei Qi; Ng, Mei Kei; Heng, Li Xuan; Yap, Siu Ching; Chai, Amy Siaw Hui; Wong, Audrey San Ying

    2016-01-01

    This review summarizes the epidemiological trend, risk factors, prevention strategies such as vaccination, staging, current novel therapeutics, including the drugs under clinical trials, and future therapeutic trends for hepatocellular carcinoma (HCC). As HCC is the third most common cause of cancer-related death worldwide, its overall incidence remains alarmingly high in the developing world and is steadily rising across most of the developed and developing world. Over the past 15 years, the incidence of HCC has more than doubled and it increases with advancing age. Chronic infection with hepatitis B virus is the leading cause of HCC, closely followed by infection with hepatitis C virus. Other factors contributing to the development of HCC include alcohol abuse, tobacco smoking, and metabolic syndrome (including obesity, diabetes, and fatty liver disease). Treatment options have improved in the past few years, particularly with the approval of several molecular-targeted therapies. The researchers are actively pursuing novel therapeutic targets as well as predictive biomarker for treatment of HCC. Advances are being made in understanding the mechanisms underlying HCC, which in turn could lead to novel therapeutics. Nevertheless, there are many emerging agents still under clinical trials and yet to show promising results. Hence, future therapeutic options may include different combination of novel therapeutic interventions. PMID:27042086

  17. Therapeutic Antioxidant Medical Gas

    PubMed Central

    Nakao, Atsunori; Sugimoto, Ryujiro; Billiar, Timothy R; McCurry, Kenneth R

    2009-01-01

    Medical gases are pharmaceutical gaseous molecules which offer solutions to medical needs and include traditional gases, such as oxygen and nitrous oxide, as well as gases with recently discovered roles as biological messenger molecules, such as carbon monoxide, nitric oxide and hydrogen sulphide. Medical gas therapy is a relatively unexplored field of medicine; however, a recent increasing in the number of publications on medical gas therapies clearly indicate that there are significant opportunities for use of gases as therapeutic tools for a variety of disease conditions. In this article, we review the recent advances in research on medical gases with antioxidant properties and discuss their clinical applications and therapeutic properties. PMID:19177183

  18. Therapeutics for cognitive aging

    PubMed Central

    Shineman, Diana W.; Salthouse, Timothy A.; Launer, Lenore J.; Hof, Patrick R.; Bartzokis, George; Kleiman, Robin; Luine, Victoria; Buccafusco, Jerry J.; Small, Gary W.; Aisen, Paul S.; Lowe, David A.; Fillit, Howard M.

    2011-01-01

    This review summarizes the scientific talks presented at the conference “Therapeutics for Cognitive Aging,” hosted by the New York Academy of Sciences and the Alzheimer’s Drug Discovery Foundation on May 15, 2009. Attended by scientists from industry and academia, as well as by a number of lay people—approximately 200 in all—the conference specifically tackled the many aspects of developing therapeutic interventions for cognitive impairment. Discussion also focused on how to define cognitive aging and whether it should be considered a treatable, tractable disease. PMID:20392284

  19. Advances in Therapeutic Cholangioscopy

    PubMed Central

    Moura, Renata Nobre; de Moura, Eduardo Guimarães Hourneaux

    2016-01-01

    Nowadays, cholangioscopy is an established modality in diagnostic and treatment of pancreaticobiliary diseases. The more widespread use and the recent development of new technologies and accessories had renewed the interest of endoscopic visualization of the biliary tract, increasing the range of indications and therapeutic procedures, such as diagnostic of indeterminate biliary strictures, lithotripsy of difficult bile duct stones, ablative techniques for intraductal malignancies, removal of foreign bodies and gallbladder drainage. These endoscopic interventions will probably be the last frontier in the near future. This paper presents the new advances in therapeutic cholangioscopy, focusing on the current clinical applications and on research areas. PMID:27403156

  20. DELIVERY OF THERAPEUTIC PROTEINS

    PubMed Central

    Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

    2009-01-01

    The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. PMID:20049941

  1. Antibody Therapeutics in Oncology

    PubMed Central

    Wold, Erik D; Smider, Vaughn V; Felding, Brunhilde H

    2016-01-01

    One of the newer classes of targeted cancer therapeutics is monoclonal antibodies. Monoclonal antibody therapeutics are a successful and rapidly expanding drug class due to their high specificity, activity, favourable pharmacokinetics, and standardized manufacturing processes. Antibodies are capable of recruiting the immune system to attack cancer cells through complement-dependent cytotoxicity or antibody dependent cellular cytotoxicity. In an ideal scenario the initial tumor cell destruction induced by administration of a therapeutic antibody can result in uptake of tumor associated antigens by antigen-presenting cells, establishing a prolonged memory effect. Mechanisms of direct tumor cell killing by antibodies include antibody recognition of cell surface bound enzymes to neutralize enzyme activity and signaling, or induction of receptor agonist or antagonist activity. Both approaches result in cellular apoptosis. In another and very direct approach, antibodies are used to deliver drugs to target cells and cause cell death. Such antibody drug conjugates (ADCs) direct cytotoxic compounds to tumor cells, after selective binding to cell surface antigens, internalization, and intracellular drug release. Efficacy and safety of ADCs for cancer therapy has recently been greatly advanced based on innovative approaches for site-specific drug conjugation to the antibody structure. This technology enabled rational optimization of function and pharmacokinetics of the resulting conjugates, and is now beginning to yield therapeutics with defined, uniform molecular characteristics, and unprecedented promise to advance cancer treatment. PMID:27081677

  2. Therapeutic Recombinant Monoclonal Antibodies

    ERIC Educational Resources Information Center

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  3. Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis.

    PubMed

    Blakeley, Jaishri O; Plotkin, Scott R

    2016-05-01

    Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1andLZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations inNF1(ie, glioblastoma, breast cancer, melanoma),NF2(ie, meningioma, mesothelioma) andSMARCB1(ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations. PMID:26851632

  4. International veterinary epilepsy task force consensus proposal: outcome of therapeutic interventions in canine and feline epilepsy.

    PubMed

    Potschka, Heidrun; Fischer, Andrea; Löscher, Wolfgang; Patterson, Ned; Bhatti, Sofie; Berendt, Mette; De Risio, Luisa; Farquhar, Robyn; Long, Sam; Mandigers, Paul; Matiasek, Kaspar; Muñana, Karen; Pakozdy, Akos; Penderis, Jacques; Platt, Simon; Podell, Michael; Rusbridge, Clare; Stein, Veronika; Tipold, Andrea; Volk, Holger A

    2015-01-01

    Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered. PMID:26314300

  5. [New features in the recommendations of the Second Hungarian Therapeutic Consensus Conference].

    PubMed

    Pados, Gyula; Karádi, István; Paragh, György; Halmy, László; Jermendy, György; Zámolyi, Károly; Kiss, István

    2006-07-16

    The First Hungarian Therapeutic Consensus Conference took place on 3rd Nov. 2003 with the participation of 9 medical societies. Over the past 2 years the results of new major studies have been published and the American ATP III has also updated its guidelines issued in 2004. Based on the above proposals, the Second Hungarian Therapeutic Consensus Conference held on 3rd Nov. 2005 partly confirmed its earlier suggestions, but made some changes as well. Within the high risk category the Conference optionally created a very high risk group from those patients who - in addition to their cardiovascular disease--have either diabetes or metabolic syndrome or acut coronaria syndrome or who are chain smokers. We have included - as a complement - into the asymptomatic high risk category such newly emerging risk factors, one of which already in itself means high risk: ankle/arm index < or = 0.9, GFR <60 ml/min, microalbuminuria (30-300 mg), preclinical atherosclerosis (plaque). Besides, 4 other risk factors were also categorised such as Lp/a (> or = 30 mg/dl), CRP (> or = 3mg/l), homocysteine (> or = 12 micromol), familiarity--atherogenic gene constellation, but only the presence of at least two of these verify high risk. In very high risk group the goals of 3.5 mmol/l and 1.8 mmol/l were determined as therapeutic option. The goal in obese patients--expressed earlier only in BMI--can now be equally determined by the abdominal circumference (94 cm for men, 80 cm for women respectively). ACE inhibitors were recommended earlier as a preventive therapy in case of dysfunction of the left ventricle, while at present they are suggested for all patients with cardiovascular disease. In the recent recommendations guidelines related to nutrition, smoking, exercise have also been included. PMID:16999015

  6. Amino Acid PET – An Imaging Option to Identify Treatment Response, Posttherapeutic Effects, and Tumor Recurrence?

    PubMed Central

    Galldiks, Norbert; Langen, Karl-Josef

    2016-01-01

    Routine diagnostics and treatment monitoring in patients with primary and secondary brain tumors is usually based on contrast-enhanced standard MRI. However, the capacity of standard MRI to differentiate neoplastic tissue from non-specific posttreatment effects may be limited particularly after therapeutic interventions such as radio- and/or chemotherapy or newer treatment options, e.g., immune therapy. Metabolic imaging using PET may provide relevant additional information on tumor metabolism, which allows a more accurate diagnosis especially in clinically equivocal situations, particularly when radiolabeled amino acids are used. Amino acid PET allows a sensitive monitoring of a response to various treatment options, the early detection of tumor recurrence, and an improved differentiation of tumor recurrence from posttherapeutic effects. In the past, this method had only limited availability due to the use of PET tracers with a short half-life, e.g., C-11. In recent years, however, novel amino acid PET tracers labeled with positron emitters with a longer half-life (F-18) have been developed and clinically validated, which allow a more efficient and cost-effective application. These developments and the well-documented diagnostic performance of PET using radiolabeled amino acids suggest that its application continues to spread and that this technique may be available as a routine diagnostic tool for several indications in the field of neuro-oncology. PMID:27516754

  7. Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma

    PubMed Central

    Li, Qi; Wang, Wei; Machino, Yusuke; Yamada, Tadaaki; Kita, Kenji; Oshima, Masanobu; Sekido, Yoshitaka; Tsuchiya, Mami; Suzuki, Yui; Nan-ya, Ken-ichiro; Iida, Shigeru; Nakamura, Kazuyasu; Iwakiri, Shotaro; Itoi, Kazumi; Yano, Seiji

    2015-01-01

    Malignant pleural mesothelioma (MPM) is a rare and highly aggressive neoplasm that arises from the pleural, pericardial, or peritoneal lining. Although surgery, chemotherapy, radiotherapy, and combinations of these therapies are used to treat MPM, the median survival of such patients is dismal. Therefore, there is a compelling need to develop novel therapeutics with different modes of action. Ganglioside GM2 is a glycolipid that has been shown to be overexpressed in various types of cancer. However, there are no published reports regarding the use of GM2 as a potential therapeutic target in cases of MPM. In this study, we evaluated the efficacy of the anti-GM2 antibody BIW-8962 as an anti-MPM therapeutic using in vitro and in vivo assays. Consequently, the GM2 expression in the MPM cell lines was confirmed using flow cytometry. In addition, eight of 11 cell lines were GM2-positive (73%), although the GM2 expression was variable. BIW-8962 showed a significant antibody-dependent cellular cytotoxicity activity against the GM2-expressing MPM cell line MSTO-211H, the effect of which depended on the antibody concentration and effector/target ratio. In an in vivo orthotropic mouse model using MSTO-211H cells, BIW-8962 significantly decreased the incidence and size of tumors. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. Fifty-eight percent of the MPM tumors were positive for GM2, with individual variation in the intensity and frequency of staining. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients. PMID:25421609

  8. Current and Potential Therapeutic Strategies for Hemodynamic Cardiorenal Syndrome

    PubMed Central

    Obi, Yoshitsugu; Kim, Taehee; Kovesdy, Csaba P.; Amin, Alpesh N.; Kalantar-Zadeh, Kamyar

    2016-01-01

    Background Cardiorenal syndrome (CRS) encompasses conditions in which cardiac and renal disorders co-exist and are pathophysiologically related. The newest classification of CRS into seven etiologically and clinically distinct types for direct patient management purposes includes hemodynamic, uremic, vascular, neurohumoral, anemia- and/or iron metabolism-related, mineral metabolism-related and protein-energy wasting-related CRS. This classification also emphasizes the pathophysiologic pathways. The leading CRS category remains hemodynamic CRS, which is the most commonly encountered type in patient care settings and in which acute or chronic heart failure leads to renal impairment. Summary This review focuses on selected therapeutic strategies for the clinical management of hemodynamic CRS. This is often characterized by an exceptionally high ratio of serum urea to creatinine concentrations. Loop diuretics, positive inotropic agents including dopamine and dobutamine, vasopressin antagonists including vasopressin receptor antagonists such as tolvaptan, nesiritide and angiotensin-neprilysin inhibitors are among the pharmacologic agents used. Additional therapies include ultrafiltration (UF) via hemofiltration or dialysis. The beneficial versus unfavorable effects of these therapies on cardiac decongestion versus renal blood flow may act in opposite directions. Some of the most interesting options for the outpatient setting that deserve revisiting include portable continuous dobutamine infusion, peritoneal dialysis and outpatient UF via hemodialysis or hemofiltration. Key Messages The new clinically oriented CRS classification system is helpful in identifying therapeutic targets and offers a systematic approach to an optimal management algorithm with better understanding of etiologies. Most interventions including UF have not shown a favorable impact on outcomes. Outpatient portable dobutamine infusion is underutilized and not well studied. Revisiting traditional and

  9. Treatment Options in Cushing’s Disease

    PubMed Central

    Rizk, Ahmed; Honegger, Juergen; Milian, Monika; Psaras, Tsambika

    2012-01-01

    Endogenous Cushing’s syndrome is a grave disease that requires a multidisciplinary and individualized treatment approach for each patient. Approximately 80% of all patients harbour a corticotroph pituitary adenoma (Cushing’s disease) with excessive secretion of adrenocorticotropin-hormone (ACTH) and, consecutively, cortisol. The goals of treatment include normalization of hormone excess, long-term disease control and the reversal of comorbidities caused by the underlying pathology. The treatment of choice is neurosurgical tumour removal of the pituitary adenoma. Second-line treatments include medical therapy, bilateral adrenalectomy and radiation therapy. Drug treatment modalities target at the hypothalamic/pituitary level, the adrenal gland and at the glucocorticoid receptor level and are commonly used in patients in whom surgery has failed. Bilateral adrenalectomy is the second-line treatment for persistent hypercortisolism that offers immediate control of hypercortisolism. However, this treatment option requires a careful individualized evaluation, since it has the disadvantage of permanent hypoadrenalism which requires lifelong glucocorticoid and mineralocorticoid replacement therapy and bears the risk of developing Nelson’s syndrome. Although there are some very promising medical therapy options it clearly remains a second-line treatment option. However, there are numerous circumstances where medical management of CD is indicated. Medical therapy is frequently used in cases with severe hypercortisolism before surgery in order to control the metabolic effects and help reduce the anestesiological risk. Additionally, it can help to bridge the time gap until radiotherapy takes effect. The aim of this review is to analyze and present current treatment options in Cushing’s disease. PMID:22346367

  10. Asteroid Redirect Robotic Mission: Robotic Boulder Capture Option Overview

    NASA Technical Reports Server (NTRS)

    Mazanek, Daniel D.; Merrill, Raymond G.; Belbin, Scott P.; Reeves, David M.; Earle, Kevin D.; Naasz, Bo J.; Abell, Paul A.

    2014-01-01

    The National Aeronautics and Space Administration (NASA) is currently studying an option for the Asteroid Redirect Robotic Mission (ARRM) that would capture a multi-ton boulder (typically 2-4 meters in size) from the surface of a large (is approximately 100+ meter) Near-Earth Asteroid (NEA) and return it to cislunar space for subsequent human and robotic exploration. This alternative mission approach, designated the Robotic Boulder Capture Option (Option B), has been investigated to determine the mission feasibility and identify potential differences from the initial ARRM concept of capturing an entire small NEA (4-10 meters in size), which has been designated the Small Asteroid Capture Option (Option A). Compared to the initial ARRM concept, Option B allows for centimeter-level characterization over an entire large NEA, the certainty of target NEA composition type, the ability to select the boulder that is captured, numerous opportunities for mission enhancements to support science objectives, additional experience operating at a low-gravity planetary body including extended surface contact, and the ability to demonstrate future planetary defense strategies on a hazardous-size NEA. Option B can leverage precursor missions and existing Agency capabilities to help ensure mission success by targeting wellcharacterized asteroids and can accommodate uncertain programmatic schedules by tailoring the return mass.

  11. Platelet-delivered therapeutics.

    PubMed

    Lyde, R; Sabatino, D; Sullivan, S K; Poncz, M

    2015-06-01

    We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to sights of vascular injury. Ectopic expression of proteins within α-granules prior to platelet activation has been achieved for several proteins, including urokinase, factor (F) VIII, and partially for FIX. Potential uses of platelet-directed therapeutics will be discussed, focusing on targeted delivery of urokinase as a thromboprophylactic agent and FVIII for the treatment of hemophilia A patients with intractable inhibitors. This presentation will discuss new strategies that may be useful in the care of patients with vascular injury as well as remaining challenges and limitations of these approaches. PMID:26149015

  12. Therapeutic antibodies against cancer

    PubMed Central

    Adler, Mark J.; Dimitrov, Dimiter S.

    2012-01-01

    Antibody-based therapeutics against cancer are highly successful in clinic and currently enjoy unprecedented recognition of their potential; 13 monoclonal antibodies (mAbs) have been approved for clinical use in the European Union and in the United States (one, mylotarg, was withdrawn from market in 2010). Three of the mAbs (bevacizumab, rituximab, trastuzumab) are in the top six selling protein therapeutics with sales in 2010 of more than $5 bln each. Hundreds of mAbs including bispecific mAbs and multispecific fusion proteins, mAbs conjugated with small molecule drugs and mAbs with optimized pharmacokinetics are in clinical trials. However, challenges remain and it appears that deeper understanding of mechanisms is needed to overcome major problems including resistance to therapy, access to targets, complexity of biological systems and individual variations. PMID:22520975

  13. Multistage vector (MSV) therapeutics.

    PubMed

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-12-10

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers. PMID:26264836

  14. Strategies for therapeutic hypometabothermia

    PubMed Central

    Liu, Shimin; Chen, Jiang-Fan

    2013-01-01

    Although therapeutic hypothermia and metabolic suppression have shown robust neuroprotection in experimental brain ischemia, systemic complications have limited their use in treating acute stroke patients. The core temperature and basic metabolic rate are tightly regulated and maintained in a very stable level in mammals. Simply lowering body temperature or metabolic rate is actually a brutal therapy that may cause more systemic as well as regional problems other than providing protection. These problems are commonly seen in hypothermia and barbiturate coma. The main innovative concept of this review is to propose thermogenically optimal and synergistic reduction of core temperature and metabolic rate in therapeutic hypometabothermia using novel and clinically practical approaches. When metabolism and body temperature are reduced in a systematically synergistic manner, the outcome will be maximal protection and safe recovery, which happen in natural process, such as in hibernation, daily torpor and estivation. PMID:24179563

  15. Endoscopy and polyps-diagnostic and therapeutic advances in management

    PubMed Central

    Steele, Scott R; Johnson, Eric K; Champagne, Bradley; Davis, Brad; Lee, Sang; Rivadeneira, David; Ross, Howard; Hayden, Dana A; Maykel, Justin A

    2013-01-01

    Despite multiple efforts aimed at early detection through screening, colon cancer remains the third leading cause of cancer-related deaths in the United States, with an estimated 51000 deaths during 2013 alone. The goal remains to identify and remove benign neoplastic polyps prior to becoming invasive cancers. Polypoid lesions of the colon vary widely from hyperplastic, hamartomatous and inflammatory to neoplastic adenomatous growths. Although these lesions are all benign, they are common, with up to one-quarter of patients over 60 years old will develop pre-malignant adenomatous polyps. Colonoscopy is the most effective screening tool to detect polyps and colon cancer, although several studies have demonstrated missed polyp rates from 6%-29%, largely due to variations in polyp size. This number can be as high as 40%, even with advanced (> 1 cm) adenomas. Other factors including sub-optimal bowel preparation, experience of the endoscopist, and patient anatomical variations all affect the detection rate. Additional challenges in decision-making exist when dealing with more advanced, and typically larger, polyps that have traditionally required formal resection. In this brief review, we will explore the recent advances in polyp detection and therapeutic options. PMID:23885138

  16. Cannabidiol and epilepsy: Rationale and therapeutic potential.

    PubMed

    Leo, Antonio; Russo, Emilio; Elia, Maurizio

    2016-05-01

    Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remains still poor. Unfortunately, besides several advantages, these new AEDs have not satisfactorily reduced the number of refractory patients. Therefore, the need for different other therapeutic options to manage epilepsy is still a current issue. To this purpose, emphasis has been given to phytocannabinoids, which have been medicinally used since ancient time in the treatment of neurological disorders including epilepsy. In particular, the nonpsychoactive compound cannabidiol (CBD) has shown anticonvulsant properties, both in preclinical and clinical studies, with a yet not completely clarified mechanism of action. However, it should be made clear that most phytocannabinoids do not act on the endocannabinoid system as in the case of CBD. In in vivo preclinical studies, CBD has shown significant anticonvulsant effects mainly in acute animal models of seizures, whereas restricted data exist in chronic models of epilepsy as well as in animal models of epileptogenesis. Likewise, clinical evidence seems to indicate that CBD is able to manage epilepsy both in adults and children affected by refractory seizures, with a favourable side effect profile. However, to date, clinical trials are both qualitatively and numerically limited, thus yet inconsistent. Therefore, further preclinical and clinical studies are undoubtedly needed to better evaluate the potential therapeutic profile of CBD in epilepsy, although the actually available data is promising. PMID:26976797

  17. Therapeutic Strategies in HCC: Radiation Modalities

    PubMed Central

    Gallicchio, R.; Nardelli, A.; Mainenti, P.; Nappi, A.; Capacchione, D.; Simeon, V.; Sirignano, C.; Abbruzzi, F.; Barbato, F.; Landriscina, M.

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with 131I Lipiodol or 90Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment. PMID:27563661

  18. Recombinant therapeutic proteins: production platforms and challenges.

    PubMed

    Dingermann, Theo

    2008-01-01

    Since the approval of insulin in 1982, more than 120 recombinant drug substances have been approved and become available as extremely valuable therapeutic options. Exact copying of the most common human form is no longer a value per se, as challenges, primarily related to the pharmacokinetics of artificial recombinant drugs, can be overcome by diverging from the original. However, relatively minor changes in manufacturing or packaging may impact safety of therapeutic proteins. A major achievement is the development of recombinant proteins capable of entering a cell. Such drugs open up completely new opportunities by targeting intracellular mechanisms or by substituting intracellularly operating enzymes. Concerns that protein variants would cause an intolerable immune response turned out to be exaggerated. Although most recombinant drugs provoke some immune response, they are still well tolerated. This knowledge might result in a change in attitude towards antibody formation, i.e., neutralizing antibody activity (in vitro) may be overcome by dosing consistently on the basis of antibody titers and not only on body weight. As with other drugs, efficacy and safety of therapeutic proteins have to be demonstrated in clinical studies, and superiority over available products has to be proven instead of just claimed. PMID:18041103

  19. Therapeutic Strategies in HCC: Radiation Modalities.

    PubMed

    Gallicchio, R; Nardelli, A; Mainenti, P; Nappi, A; Capacchione, D; Simeon, V; Sirignano, C; Abbruzzi, F; Barbato, F; Landriscina, M; Storto, G

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with (131)I Lipiodol or (90)Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment. PMID:27563661

  20. Personnel Preparation Options: Ideas from a Policy Options Conference.

    ERIC Educational Resources Information Center

    Gallagher, James J.; And Others

    This report summarizes discussions from a policy options conference devoted to the needs for personnel preparation related to the implementation of Public Law 99-457, Part H, which provides services to infants and toddlers with handicapping conditions and their families. The three policy questions identified as the most significant were: (1) what…

  1. Therapeutic targets for premature ejaculation.

    PubMed

    Andersson, Karl-Erik; Abdel-Hamid, Ibrahim A

    2011-09-01

    Premature ejaculation (PE) is the most common male sexual complaint, and may exert a profound negative impact on the man's life and partnership. Using currently available treatment alternatives (e.g., selective serotonin uptake inhibitor, agents acting locally on the penis), PE can be treated in most, but not all patients. However, since long term success rates have been disappointing, and the only approved treatment so far is the short-acting selective serotonin re-uptake inhibitor dapoxetine, there is currently an intensive search for new treatment modalities. Selection of the most promising therapeutic targets from a host of current and potential candidates depends heavily on their roles in the pathophysiology of PE. Possible central nervous targets that will be discussed are serotonin transporters, and CNS receptors for 5-HT(IA) and 5-HT(1B), dopamine, oxytocin, opioids, neurokinin-1, and glutamate. Putative peripheral targets include α(1)-adrenoceptors, phosphodiestrase enzymes, Rho kinases, purinergic (P2X) receptors, and penile sensory nerves. It is clear that exploiting the full therapeutic potential of these targets will require additional basic and clinical research. PMID:21816550

  2. Therapeutic Robotics: A Technology Push

    PubMed Central

    Krebs, Hermano Igo; Hogan, Neville

    2009-01-01

    In this paper, we present a retrospective and chronological review of our efforts to revolutionize the way physical medicine is practiced by developing and deploying therapeutic robots. We present a sample of our clinical results with well over 300 stroke patients, both inpatients and outpatients, proving that movement therapy has a measurable and significant impact on recovery following brain injury. Bolstered by this result, we embarked on a two-pronged approach: 1) to determine what constitutes best therapy practice and 2) to develop additional therapeutic robots. We review our robots developed over the past 15 years and their unique characteristics. All are configured both to deliver reproducible therapy but also to measure outcomes with minimal encumbrance, thus providing critical measurement tools to help unravel the key question posed under the first prong: what constitutes “best practice”? We believe that a “gym” of robots like these will become a central feature of physical medicine and the rehabilitation clinic within the next ten years. PMID:19779587

  3. Polycyclic peptide therapeutics.

    PubMed

    Baeriswyl, Vanessa; Heinis, Christian

    2013-03-01

    Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases. PMID:23355488

  4. Design Evolution Study - Aging Options

    SciTech Connect

    P. McDaniel

    2002-04-05

    The purpose of this study is to identify options and issues for aging commercial spent nuclear fuel received for disposal at the Yucca Mountain Mined Geologic Repository. Some early shipments of commercial spent nuclear fuel to the repository may be received with high-heat-output (younger) fuel assemblies that will need to be managed to meet thermal goals for emplacement. The capability to age as much as 40,000 metric tons of heavy metal of commercial spent nuclear he1 would provide more flexibility in the design to manage this younger fuel and to decouple waste receipt and waste emplacement. The following potential aging location options are evaluated: (1) Surface aging at four locations near the North Portal; (2) Subsurface aging in the permanent emplacement drifts; and (3) Subsurface aging in a new subsurface area. The following aging container options are evaluated: (1) Complete Waste Package; (2) Stainless Steel inner liner of the waste package; (3) Dual Purpose Canisters; (4) Multi-Purpose Canisters; and (5) New disposable canister for uncanistered commercial spent nuclear fuel. Each option is compared to a ''Base Case,'' which is the expected normal waste packaging process without aging. A Value Engineering approach is used to score each option against nine technical criteria and rank the options. Open issues with each of the options and suggested future actions are also presented. Costs for aging containers and aging locations are evaluated separately. Capital costs are developed for direct costs and distributable field costs. To the extent practical, unit costs are presented. Indirect costs, operating costs, and total system life cycle costs will be evaluated outside of this study. Three recommendations for aging commercial spent nuclear fuel--subsurface, surface, and combined surface and subsurface are presented for further review in the overall design re-evaluation effort. Options that were evaluated but not recommended are: subsurface aging in a new

  5. Technetium removal: preliminary flowsheet options

    SciTech Connect

    Eager, K.M.

    1995-10-24

    This document presents the results of a preliminary investigation into options for preliminary flowsheets for 99Tc removal from Hanford Site tank waste. A model is created to show the path of 99Tc through pretreatment to disposal. The Tank Waste Remediation (TWRS) flowsheet (Orme 1995) is used as a baseline. Ranges of important inputs to the model are developed, such as 99Tc inventory in the tanks and important splits through the TWRS flowsheet. Several technetium removal options are discussed along with sensitivities of the removal schemes to important model parameters

  6. 75 FR 67419 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-02

    ...), 75 FR 64773 (October 20, 2010) (SR-ISE-2010-91) (order approving Additional Expiration Months Pilot... Expiration Months for Each Class of Options Opened for Trading on the Exchange October 27, 2010. Pursuant to... to adopt a pilot program to list additional expiration months for each class of options opened...

  7. 48 CFR 2917.207 - Exercising options.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Exercising options. 2917... AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 2917.207 Exercising options. The contracting officer must use a standardized determination and finding before exercising an option in accordance...

  8. 48 CFR 2917.207 - Exercising options.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Exercising options. 2917... AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 2917.207 Exercising options. The contracting officer must use a standardized determination and finding before exercising an option in accordance...

  9. 17 CFR 32.3 - Trade options.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Trade options. 32.3 Section 32... OPTION TRANSACTIONS § 32.3 Trade options. (a) Subject to paragraphs (b), (c), and (d) of this section... period preceding the date on which the trade option is entered into, (iv) In connection with any...

  10. 17 CFR 32.3 - Trade options.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Trade options. 32.3 Section 32... OPTION TRANSACTIONS § 32.3 Trade options. (a) Subject to paragraphs (b), (c), and (d) of this section... period preceding the date on which the trade option is entered into, (iv) In connection with any...

  11. Therapeutic drug monitoring in neonates.

    PubMed

    Pauwels, Steven; Allegaert, Karel

    2016-04-01

    Therapeutic drug monitoring (TDM) aims to integrate drug measurement results into clinical decision making. The basic rules apply when using TDM in neonates (aminoglycosides, vancomycin, phenobarbital, digoxin), but additional factors should also be taken into account. First, due to both pharmacokinetic variability and non-pharmacokinetic factors, the correlation between dosage and concentration is poor in neonates, but can be overcome with the use of more complex, validated dosing regimens. Second, the time to reach steady state is prolonged, especially when no loading dose is used. Consequently, the timing of TDM sampling is important in this population. Third, the target concentration may be uncertain (vancomycin) or depend on specific factors (phenobarbital during whole body cooling). Finally, because of differences in matrix composition (eg, protein, bilirubin), assay-related inaccuracies may be different in neonates. We anticipate that complex validated dosing regimens, with subsequent TDM sampling and Bayesian forecasting, are the next step in tailoring pharmacotherapy to individual neonates. PMID:26803050

  12. Options for English Language Learners

    ERIC Educational Resources Information Center

    Minaya-Rowe, Liliana

    2008-01-01

    Between 69 percent and 90 percent of English language learners (ELLs) in middle and high schools were born in the United States and have been in U.S. schools since kindergarten still have not achieved the academic proficiency to succeed in an all-English mainstream program. Various ELL program options are available for school districts to…

  13. Exploring Higher Education Financing Options

    ERIC Educational Resources Information Center

    Nkrumah-Young, Kofi K.; Powell, Philip

    2011-01-01

    Higher education can be financed privately, financed by governments, or shared. Given that the benefits of education accrue to the individual and the state, many governments opt for shared financing. This article examines the underpinnings of different options for financing higher education and develops a model to compare conditions to choices and…

  14. Minnesota's Public School Choice Options.

    ERIC Educational Resources Information Center

    Colopy, Kelly W.; Tarr, Hope C.

    This document presents findings of a study that identified patterns of use among a broad array of open-enrollment options available to elementary and secondary students in Minnesota. During the period 1985-91, the Minnesota legislature passed several pieces of new legislation designed to: (1) increase the educational choices available to students,…

  15. 77 FR 25319 - Commodity Options

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... Recordkeeping, 76 FR 29818, May 23, 2011 (``Product Definitions NPRM''). The final rule and interpretations that... not applicable. \\7\\ Commodity Options and Agricultural Swaps, 76 FR 6095, Feb. 3, 2011. Note that in... 10, 2011 and are not addressed herein. See Agricultural Swaps, 76 FR 49291, Aug. 10, 2011...

  16. Tool for Ranking Research Options

    NASA Technical Reports Server (NTRS)

    Ortiz, James N.; Scott, Kelly; Smith, Harold

    2005-01-01

    Tool for Research Enhancement Decision Support (TREDS) is a computer program developed to assist managers in ranking options for research aboard the International Space Station (ISS). It could likely also be adapted to perform similar decision-support functions in industrial and academic settings. TREDS provides a ranking of the options, based on a quantifiable assessment of all the relevant programmatic decision factors of benefit, cost, and risk. The computation of the benefit for each option is based on a figure of merit (FOM) for ISS research capacity that incorporates both quantitative and qualitative inputs. Qualitative inputs are gathered and partly quantified by use of the time-tested analytical hierarchical process and used to set weighting factors in the FOM corresponding to priorities determined by the cognizant decision maker(s). Then by use of algorithms developed specifically for this application, TREDS adjusts the projected benefit for each option on the basis of levels of technical implementation, cost, and schedule risk. Based partly on Excel spreadsheets, TREDS provides screens for entering cost, benefit, and risk information. Drop-down boxes are provided for entry of qualitative information. TREDS produces graphical output in multiple formats that can be tailored by users.

  17. Option trading and oil futures markets

    SciTech Connect

    Chassard, C.; Halliwell, M.

    1986-01-01

    This book describes mechanics of options trading, particularly their use to complement trading in oil futures and forward markets to increase agents' flexibility in hedging against price risks. The main determinants of option premiums and a number of option pricing models are discussed as are the Black and Scholes Model, issues of options and oil-indexed bonds: The Philbro Proposal, NYMEX Crude Oil Option Contract and Standard Oil Issue.

  18. Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics.

    PubMed

    Sparrow, Janet R

    2016-04-26

    Although currently available treatment options for age-related macular degeneration (AMD) are limited, particularly for atrophic AMD, the identification of predisposing genetic variations has informed clinical studies addressing therapeutic options such as complement inhibitors and anti-inflammatory agents. To lower risk of early AMD, recommended lifestyle interventions such as the avoidance of smoking and the intake of low glycemic antioxidant-rich diets have largely followed from the identification of nongenetic modifiable factors. On the other hand, the challenge of understanding the complex relationship between aging and cumulative damage leading to AMD has fueled investigations of the visual cycle adducts that accumulate in retinal pigment epithelial (RPE) cells and are a hallmark of aging retina. These studies have revealed properties of these compounds that provide insights into processes that may compromise RPE and could contribute to disease mechanisms in AMD. This work has also led to the design of targeted therapeutics that are currently under investigation. PMID:27071115

  19. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    PubMed Central

    2011-01-01

    Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

  20. Psychodynamic Perspective on Therapeutic Boundaries

    PubMed Central

    Bridges, Nancy A.

    1999-01-01

    Discussion of boundaries in therapeutic work most often focuses on boundary maintenance, risk management factors, and boundary violations. The psychodynamic meaning and clinical management of boundaries in therapeutic relationships remains a neglected area of discourse. Clinical vignettes will illustrate a psychodynamic, developmental-relational perspective using boundary dilemmas to deepen and advance the therapeutic process. This article contributes to the dialogue about the process of making meaning and constructing therapeutically useful and creative boundaries that further the psychotherapeutic process. PMID:10523432

  1. Telomerase and cancer therapeutics.

    PubMed

    Harley, Calvin B

    2008-03-01

    Telomerase is an attractive cancer target as it appears to be required in essentially all tumours for immortalization of a subset of cells, including cancer stem cells. Moreover, differences in telomerase expression, telomere length and cell kinetics between normal and tumour tissues suggest that targeting telomerase would be relatively safe. Clinical trials are ongoing with a potent and specific telomerase inhibitor, GRN163L, and with several versions of telomerase therapeutic vaccines. The prospect of adding telomerase-based therapies to the growing list of new anticancer products is promising, but what are the advantages and limitations of different approaches, and which patients are the most likely to respond? PMID:18256617

  2. [Achievement of therapeutic objectives].

    PubMed

    Mantilla, Teresa

    2014-07-01

    Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk. PMID:25043543

  3. Revitalizing Psychiatric Therapeutics

    PubMed Central

    Hyman, Steven E

    2014-01-01

    Despite high prevalence and enormous unmet medical need, the pharmaceutical industry has recently de-emphasized neuropsychiatric disorders as ‘too difficult' a challenge to warrant major investment. Here I describe major obstacles to drug discovery and development including a lack of new molecular targets, shortcomings of current animal models, and the lack of biomarkers for clinical trials. My major focus, however, is on new technologies and scientific approaches to neuropsychiatric disorders that give promise for revitalizing therapeutics and may thus answer industry's concerns. PMID:24317307

  4. [Is therapeutic deadlock inevitable?].

    PubMed

    Vignat, Jean-Pierre

    2016-01-01

    Many long-term treatments appear to be an expression of therapeutic deadlock. The situation leads to a questioning of the concept of chronicity and the identification of the determining factors of situations which are apparently blocked, marked by the search for solutions taking a back seat to the taking of action. The interaction between patients' mental apparatus and the care apparatus lies at the heart of the question, interpreted from an institutional, collective and individual perspective, supported by the clinical and psychopathological approach, and the return to the prioritisation of the thought. PMID:27389427

  5. Therapeutic Endoscopic Ultrasound

    PubMed Central

    Cheriyan, Danny

    2015-01-01

    Endoscopic ultrasound (EUS) technology has evolved dramatically over the past 20 years, from being a supplementary diagnostic aid available only in large medical centers to being a core diagnostic and therapeutic tool that is widely available. Although formal recommendations and practice guidelines have not been developed, there are considerable data supporting the use of EUS for its technical accuracy in diagnosing pancreaticobiliary and gastrointestinal pathology. Endosonography is now routine practice not only for pathologic diagnosis and tumor staging but also for drainage of cystic lesions and celiac plexus neurolysis. In this article, we cover the use of EUS in biliary and pancreatic intervention, ablative therapy, enterostomy, and vascular intervention. PMID:27118942

  6. Natural history of hepatocellular carcinoma and current treatment options.

    PubMed

    Raoul, Jean-Luc

    2008-03-01

    Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the most severe complication of chronic liver disease. The annual number of new cases worldwide is approximately 550,000, representing more than 5% of human cancers and is the third leading cause of cancer-related deaths. The stages of the malignancy as well as the severity of the underlying liver disease are essential factors in planning the therapeutic approach. Curative treatment options are represented mainly by surgery (ie, resection or transplantation), but most patients are not candidates for a curative option, and only palliative treatment could be given to these patients. Among palliative treatments, only chemoembolization has been proven to be effective, but other options are currently being investigated. Major risk factors for HCC are well known and are dependent on the geographic area. In Europe, the United States, and Japan, the main risk factors are liver cirrhosis, hepatitis B and C virus, alcohol, and tobacco; in contrast, in Africa and Asia, these factors are hepatitis B and C virus, tobacco use, and aflatoxin exposure. Cirrhosis from any cause is a predisposing factor for HCC and could be considered as a premalignant condition. The present concept of carcinogenesis in HCC is a multistage process. This article describes the natural history of HCC and discusses the various treatment options available at present. PMID:18243838

  7. Current options for the treatment of pathological scarring.

    PubMed

    Poetschke, Julian; Gauglitz, Gerd G

    2016-05-01

    Scarring is the consequence of surgery, trauma or different skin diseases. Apart from fresh, immature scars,that transform into mature scars over the course of would healing and that do not require further treatment,linear hypertrophic scars, widespread hypertrophic scars, keloids and atrophic scars exist. Symptoms like pruritusand pain, stigmatization as well as functional and aesthetic impairments that are very disturbing for the affected patients can bethe basis for the desire for treatment. Today, a multitude of options for the treatment and prevention of scars exists. Topical agents based on silicone or onion extract, intralesional injections of cristalline glucocorticoids (oftentimes in combinationwith cryotherapy) or 5-Fluorouracil as well as ablative and nonablative laser treatment are used. Current guidelines summarize the multitude of available treatment options and the currently available datafor the treating physicians, allowing them to make clear therapy recommendations for every single scar type. Relieving patients of their discomfort and doing their aesthetic demands justice is thus possible. Apart from scar prevention becoming more and more important, the increased use of modernlaser treatment options constitutes a key point in clinical scar treatment. At the same time the attention is turned to evaluating current therapeutic options with the help of contemporary study designs so as to graduallyimprove the level of evidence in scar treatment. PMID:27119465

  8. Treatment of Mycobacterium marinum with lymecycline: new therapeutic alternative?

    PubMed

    Neugebauer, Maria Gertrudes Fernandes Pereira; Neugebauer, Samuel Antônio; Almeida Junior, Hiram Larangeira; Mota, Laís Marques

    2015-01-01

    Skin infections by Mycobacterium marinum are quite rare in our environment and, therefore, little studied. The majority of the lesions appear three weeks after traumas in aquariums, beaches and fish tanks. Lymph node drainage and systematization of the disease are rare and most lesions disappear in about three years. This case aims to show the effectiveness of the treatment used (lymecycline 150 mg/orally/day). This medication may be a new therapeutic option for the treatment of Mycobacterium marinum. PMID:25672310

  9. [Therapeutic abortion, unjustified absence in health policy].

    PubMed

    Chávez-Alvarado, Susana

    2013-07-01

    Although abortion for health reasons is not considered a crime in Peru, the State does not allow its inclusion in public policy, thus violating women's right to terminate a pregnancy when it affects their health. When examining the article in the Criminal Code which decriminalizes this type of abortion, provisions are identified which protect women and set the conditions to offer this type of service. This document sets the debate about the arguments used by the Peruvian State for not approving a therapeutic abortion protocol which would regulate the provision and financing of therapeutic abortion in public services, and explains why this obligation should be complied with, based on the conceptual framework of "health exception" In addition, it presents two cases brought before the judicial court in which the Peruvian State was found guilty of violating the human rights of two adolescents to whom a therapeutic abortion was denied. PMID:24100828

  10. The effect of therapeutic horseback riding on social functioning in children with autism.

    PubMed

    Bass, Margaret M; Duchowny, Catherine A; Llabre, Maria M

    2009-09-01

    This study evaluated the effects of therapeutic horseback riding on social functioning in children with autism. We hypothesized that participants in the experimental condition (n = 19), compared to those on the wait-list control (n = 15), would demonstrate significant improvement in social functioning following a 12-weeks horseback riding intervention. Autistic children exposed to therapeutic horseback riding exhibited greater sensory seeking, sensory sensitivity, social motivation, and less inattention, distractibility, and sedentary behaviors. The results provide evidence that therapeutic horseback riding may be a viable therapeutic option in treating children with autism spectrum disorders. PMID:19350376

  11. Current treatment options for latent tuberculosis infection.

    PubMed

    Bocchino, Marialuisa; Matarese, Alessandro; Sanduzzi, Alessandro

    2014-05-01

    Treatment of latent tuberculosis infection (LTBI) is a key component in TB control strategies worldwide. However, as people with LTBI are neither symptomatic nor contagious, any screening decision should be weighed carefully against the potential benefit of preventing active disease in those who are known to be at higher risk and are willing to accept therapy for LTBI. This means that a targeted approach is desirable to maximize cost effectiveness and to guarantee patient adherence. We focus on LTBI treatment strategies in patient populations at increased risk of developing active TB, including candidates for treatment with tumor necrosis factor-α blockers. In the last 40 years, isoniazid (INH) has represented the keystone of LTBI therapy across the world. Although INH remains the first therapeutic option, alternative treatments that are effective and associated with increased adherence and economic savings are available. Current recommendations, toxicity, compliance, and cost issues are discussed in detail in this review. A balanced relationship between the patient and healthcare provider could increase adherence, while cost-saving treatment strategies with higher effectiveness, fewer side effects, and of shorter duration should be offered as preferred. PMID:24789003

  12. Epigenomes as therapeutic targets.

    PubMed

    Hamm, Christopher A; Costa, Fabricio F

    2015-07-01

    Epigenetics is a molecular phenomenon that pertains to heritable changes in gene expression that do not involve changes in the DNA sequence. Epigenetic modifications in a whole genome, known as the epigenome, play an essential role in the regulation of gene expression in both normal development and disease. Traditional epigenetic changes include DNA methylation and histone modifications. Recent evidence reveals that other players, such as non-coding RNAs, may have an epigenetic regulatory role. Aberrant epigenetic signaling is becoming to be known as a central component of human disease, and the reversible nature of the epigenetic modifications provides an exciting opportunity for the development of clinically relevant therapeutics. Current epigenetic therapies provide a clinical benefit through disrupting DNA methyltransferases or histone deacetylases. However, the emergence of next-generation epigenetic therapies provides an opportunity to more effectively disrupt epigenetic disease states. Novel epigenetic therapies may improve drug targeting and drug delivery, optimize dosing schedules, and improve the efficacy of preexisting treatment modalities (chemotherapy, radiation, and immunotherapy). This review discusses the epigenetic mechanisms that contribute to the disease, available epigenetic therapies, epigenetic therapies currently in development, and the potential future use of epigenetic therapeutics in a clinical setting. PMID:25797698

  13. AMUM LECTURE: Therapeutic ultrasound

    NASA Astrophysics Data System (ADS)

    Crum, Lawrence A.

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques.

  14. Winnicott's therapeutic consultations revisited.

    PubMed

    Brafman, A H

    1997-08-01

    Winnicott described in his book 'Therapeutic Consultations' (1971) how a diagnostic assessment of a referred child developed into a fruitful therapeutic intervention when he was able to discover the unconscious fantasy that underlay the child's symptoms. Because these were children who were, essentially, developing normally, he used the word 'knot' to depict the obstacle the child had met. Any conflicts the parents might have were not explored in that context. This work present cases in which child and parents are seen together for the diagnostic assessment. The child's feelings about his world and his difficulties are explored through a variety of techniques including drawings. In the same interview, an analytic enquiry into the parents' history and also their views of the child reveals how the child's fantasies and the parents' past experiences interact and create a mutually reinforcing vicious circle. In other words, the 'knot' involves all of them. If the child's unconscious fantasy can be verbalised and if the parents are able to approach the child in a manner that acknowledges the child's real needs, the 'knot' disappears and normal development can be resumed. PMID:9306188

  15. Engineering therapeutic protein disaggregases.

    PubMed

    Shorter, James

    2016-05-15

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID:27255695

  16. Engineering therapeutic protein disaggregases

    PubMed Central

    Shorter, James

    2016-01-01

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID:27255695

  17. Pharmacogenetics approach to therapeutics.

    PubMed

    Koo, Seok Hwee; Lee, Edmund Jon Deoon

    2006-01-01

    1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care. PMID:16700889

  18. Person-centered Therapeutics

    PubMed Central

    Cloninger, C. Robert; Cloninger, Kevin M.

    2015-01-01

    A clinician’s effectiveness in treatment depends substantially on his or her attitude toward -- and understanding of -- the patient as a person endowed with self-awareness and the will to direct his or her own future. The assessment of personality in the therapeutic encounter is a crucial foundation for forming an effective working alliance with shared goals. Helping a person to reflect on their personality provides a mirror image of their strengths and weaknesses in adapting to life’s many challenges. The Temperament and Character Inventory (TCI) provides an effective way to describe personality thoroughly and to predict both the positive and negative aspects of health. Strengths and weaknesses in TCI personality traits allow strong predictions of individual differences of all aspects of well-being. Diverse therapeutic techniques, such as diet, exercise, mood self-regulation, meditation, or acts of kindness, influence health and personality development in ways that are largely indistinguishable from one another or from effective allopathic treatments. Hence the development of well-being appears to be the result of activating a synergistic set of mechanisms of well-being, which are expressed as fuller functioning, plasticity, and virtue in adapting to life’s challenges PMID:26052429

  19. Clinical evaluation of therapeutic cancer vaccines

    PubMed Central

    Ogi, Chizuru; Aruga, Atsushi

    2013-01-01

    Therapeutic cancer vaccines are an immunotherapy that targets tumor antigens to induce an active immune response. To date, Provenge® is the only therapeutic cancer vaccine approved by the United States Food and Drug Administration. Although therapeutic cancer vaccines have not been approved by the European Medicines Agency (EMA), they have been approved in several countries other than the United States (US) and the European Union (EU). Provenge® is the only approved cancer vaccine that showed significant primary endpoint efficacy in a phase III study at the time of approval. Retrospective analysis of 23 completed or terminated phase III studies showed that 74% (17/23) failed to demonstrate significant efficacy in the primary endpoint. The reasons for failure were surveyed in 13 of the 17 studies. Despite efforts to minimize tumor burden, including surgery and induction chemotherapy before therapeutic cancer vaccine therapy, 69% (9/13) of the phase III studies failed. These findings indicate that tumor burden may not be the only prognostic factor. Immunological response has often been used as a predictive factor, and a small number of sub-group analyses have succeeded in showing that immunological response is associated with the efficacy of therapeutic cancer vaccines. Being a prognostic factor, inclusion of immunological response in addition to tumor stage in the eligibility criteria or sub-group analysis may minimize study population heterogeneity, a key factor in the success of phase III studies. PMID:23454867

  20. Pricing of swing options: A Monte Carlo simulation approach

    NASA Astrophysics Data System (ADS)

    Leow, Kai-Siong

    We study the problem of pricing swing options, a class of multiple early exercise options that are traded in energy market, particularly in the electricity and natural gas markets. These contracts permit the option holder to periodically exercise the right to trade a variable amount of energy with a counterparty, subject to local volumetric constraints. In addition, the total amount of energy traded from settlement to expiration with the counterparty is restricted by a global volumetric constraint. Violation of this global volumetric constraint is allowed but would lead to penalty settled at expiration. The pricing problem is formulated as a stochastic optimal control problem in discrete time and state space. We present a stochastic dynamic programming algorithm which is based on piecewise linear concave approximation of value functions. This algorithm yields the value of the swing option under the assumption that the optimal exercise policy is applied by the option holder. We present a proof of an almost sure convergence that the algorithm generates the optimal exercise strategy as the number of iterations approaches to infinity. Finally, we provide a numerical example for pricing a natural gas swing call option.