WorldWideScience

Sample records for combining vacuum therapy

  1. A new modification of combining vacuum therapy and brachytherapy in large subfascial soft-tissue sarcomas of the extremities

    Energy Technology Data Exchange (ETDEWEB)

    Rudert, Maximilian; Holzapfel, Boris Michael [Dept. of Orthopedics, Univ. of Wuerzburg (Germany); Dept. of Orthopedics and Traumatology, Klinikum Muenchen rechts der Isar, Technical Univ. of Munich (Germany); Winkler, Cornelia; Kneschaurek, Peter; Molls, Michael; Roeper, Barbara [Dept. of Radiation Oncology, Technical Univ. of Munich (Germany); Rechl, Hans; Gradinger, Reiner [Dept. of Orthopedics and Traumatology, Klinikum Muenchen rechts der Isar, Technical Univ. of Munich (Germany)

    2010-04-15

    Purpose: To present a modification of a technique combining the advantages of brachytherapy for local radiation treatment and vacuum therapy for wound conditioning after resection of subfascial soft-tissue sarcomas (STS) of the extremities. Patients and methods: Between January and May 2008, four patients with large (> 10 cm) subfascial STS of the thigh underwent marginal tumor excision followed by early postoperative HDR (high-dose-rate) brachytherapy (iridium-192) and vacuum therapy as part of their interdisciplinary treatment. The sponge of the vacuum system was used to stabilize brachytherapy applicators in parallel positions and to allow for a maximal wound contraction in the early postoperative phase, thus preventing seroma and deterioration of local dose distribution as optimized in computed tomography-(CT-)based three-dimensional conformal treatment planning. In three patients this was followed by external-beam radiotherapy. Acute wound complications and late effects according to LENT-SOMA after 4-8 months of follow-up were recorded. Results: the combination of vacuum and brachytherapy was applicable in all patients. CT scans from the 1st postoperative day showed the shrinkage of the sponge located in the tumor bed with the brachytherapy applicators in the intended position and easily visible. 15-18 Gy in fractions of 3 Gy bid prescribed to 5 mm tissue depth were applied over the next days with removal of the sponge and applicators on days 5-8. No early or late toxicity exceeding grade 2 was observed. The mean Enneking Score for functional outcome was 63% (perfect function = 100%). Conclusion: The combination of vacuum and brachytherapy is applicable and safe in the treatment of large subfascial STS. (orig.)

  2. Vacuum bell therapy

    Science.gov (United States)

    Sesia, Sergio

    2016-01-01

    Background For specific therapy to correct pectus excavatum (PE), conservative treatment with the vacuum bell (VB) was introduced more than 10 years ago in addition to surgical repair. Preliminary results using the VB were encouraging. We report on our 13-year experience with the VB treatment including the intraoperative use during the Nuss procedure and present some technical innovations. Methods A VB with a patient-activated hand pump is used to create a vacuum at the anterior chest wall. Three different sizes of vacuum bells, as well as a model fitted for young women, exist. The appropriate size is selected according to the individual patient’s age and ventral surface. The device should be used at home for a minimum of 30 minutes (twice a day), and may be used up to a maximum of several hours daily. The intensity of the applied negative pressure can be evaluated with an integrated pressure gauge during follow-up visits. A prototype of an electronic model enables us to measure the correlation between the applied negative pressure and the elevation of the anterior chest wall. Results Since 2003, approx. 450 patients between 2 to 61 years of age started the VB therapy. Age and gender specific differences, depth of PE, symmetry or asymmetry, and concomitant malformations such as scoliosis and/or kyphosis influence the clinical course and success of VB therapy. According to our experience, we see three different groups of patients. Immediate elevation of the sternum was confirmed thoracoscopically during the Nuss procedure in every patient. Conclusions The VB therapy has been established as an alternative therapeutic option in selected patients suffering from PE. The initial results up to now are encouraging, but long-term results comprising more than 15 years are so far lacking, and further evaluation and follow-up studies are necessary. PMID:27747177

  3. Combined sildenafil with vacuum erection device therapy in the management of diabetic men with erectile dysfunction after failure of first-line sildenafil monotherapy.

    Science.gov (United States)

    Sun, Lu; Peng, Fang-Li; Yu, Zhi-Ling; Liu, Cai-Ling; Chen, Jun

    2014-12-01

    To evaluate the efficacy and safety of combination therapy of sildenafil plus vacuum erection devices in men with type 2 diabetes mellitus with moderate to severe erectile dysfunction who are dissatisfied with the results of using sildenafil alone. The study included 66 diabetes mellitus patients presenting erectile dysfunction for at least 6 months and dissatisfied with the use of 100 mg sildenafil monotherapy. The patients were randomized in two groups. Those in group A (n = 33) were instructed to use a vacuum erection device only, whereas those in group B (n = 33) were treated with combination therapy, including sildenafil 100 mg and a vacuum erection device. Erectile function was evaluated subjectively using the International Index of Erectile Function, Sexual Encounter Profile questionnaire questions 2 and 3 at visit 1 (baseline; study entry), visit 2 (4 weeks after baseline), and visit 3 (12 weeks after baseline; study end). There were no significant differences in average patient age, duration of diabetes, duration of erectile dysfunction, baseline International Index of Erectile Function scores, hypertension, blood testosterone, smoking and alcohol consumption between two groups. Mean International Index of Erectile Function scores were significantly higher for group B at the 1-month (14.86 ± 2.17 vs 12.41 ± 2.63; P vacuum erection device therapy significantly enhances erectile function, and it is well tolerated by diabetes mellitus patients not responding to first-line sildenafil alone. © 2014 The Japanese Urological Association.

  4. VACUUM THERAPY VERSUS ABDOMINAL EXERCISES ON ABDOMINAL OBESITY

    Directory of Open Access Journals (Sweden)

    Nevein Mohammed Mohammed Gharib

    2016-06-01

    Full Text Available Background: Obesity is a medical condition that may adversely affect wellbeing and leading to increased incidence of many health problems. Abdominal obesity tends to be associated with weight gain and obesity and it is significantly connected with different disorders like coronary heart disease and type II diabetes mellitus.This study was conducted to investigate the efficacy of vacuum therapy as compared to abdominal exercises on abdominal obesity in overweight and obese women. Methods: Thirtyoverweight and obese women participated in this study with body mass index > 25 kg/m2andwaist circumference ≥ 85 cm. Their ages ranged from 28 - 40 years old.The subjects were excluded if they have diabetes, abdominal infection diseases or any physical limitation restricting exercise ability. They were randomly allocated into two equal groups; group I and group II. Group I received vacuum therapy sessions (by the use of LPG device in addition to aerobic exercise training. Group II received abdominal exercises in addition to the same aerobic exercisesgiven to group I. This study was extended for successive 8 weeks (3 sessions/ week. All subjects were assessed for thickness ofnthe abdominal skin fold, waist circumference and body mass index. Results: The results of this study showeda significant difference between group I and group II post-interventionas regarding to the mean values of waist circumference and abdominal skin fold thickness (p<0.05. Conclusion: It can be concluded that aerobic exercises combined with vacuum therapy (for three sessions/week for successive 8 weeks have a positive effect on women with abdominal obesity in terms of reducing waist circumference and abdominal skin fold thickness.

  5. Lefunomide in combination therapy

    NARCIS (Netherlands)

    Kalden, J.R.; Smolen, J.S.; Emery, P.; Riel, P.L.C.M. van; Dougados, M.; Strand, C.V.; Breedveld, F.C.

    2004-01-01

    In most studies of disease modifying antirheumatic drug therapy, in combination with either leflunomide or biological agents, patients are given an additional agent after they have failed treatment with methotrexate (MTX). This review of clinical studies shows that leflunomide is clinically efficaci

  6. Combined infrared-vacuum drying of pumpkin slices.

    Science.gov (United States)

    Ghaboos, Seyyed Hossein Hosseini; Ardabili, Seyed Mahdi Seyedain; Kashaninejad, Mahdi; Asadi, Gholamhassan; Aalami, Mehran

    2016-05-01

    Infrared-vacuum dehydration characteristics of pumpkin (Cucurbita moschata) were evaluated in a combined dryer system. The effects of drying parameters, infrared radiation power (204-272 W), system pressure (5-15 kPa), slice thickness (5 and 7 mm) and time (0-220 min) on the drying kinetics and characteristics of pumpkin slices were investigated. The vacuum pressure, lamp power and slice had significant effect on the drying kinetics and various qualities of the dried pumpkin. Moisture ratios were fitted to 10 different mathematical equations using nonlinear regression analysis. The quadratic equation satisfactorily described the drying behavior of pumpkin slices with the highest r value and the lowest SE values. The effective moisture diffusivity increased with power and ranged between 0.71 and 2.86 × 10(-9) m(2)/s. With increasing in infrared radiation power from 204 to 272 W, β-carotene content of dried pumpkins decreased from 30.04 to 24.55 mg/100 g. The rise in infrared power has a negative effect on the color changes (ΔE). The optimum condition was determined as power, 238W, pressure, 5 kPa and slice thickness, 5mm. These conditions resulted into dried pumpkin slices with maximum B-carotene retention.

  7. Vacuum-assisted closure therapy in reconstructive surgery.

    Science.gov (United States)

    Benech, A; Arcuri, F; Poglio, G; Brucoli, M; Guglielmetti, R; Crespi, M C; Pia, F

    2012-06-01

    In 1997, supported by experimental work, Argenta published a clinical report describing a variety of complicated wounds whose treatment responded successfully to negative pressure dressings using a vacuum-assisted closure system (VAC) (Kinetic Concepts Inc., San Antonio, TX). This system has been successfully used in the fields of orthopaedics and traumatology, general surgery, plastic and reconstructive surgery and gynaecology/obstetrics for a large variety of complicated wounds located in several regions, particularly in the torso and extremities. To the best of our knowledge, the use of the VAC therapy in treating free flaps surgical wounds has not been discussed in the literature. Since 2009 at the Novara Major Hospital, we have been using the VAC therapy in selected cases for difficult and complicated wounds of the maxillofacial region. The purpose of this study is to describe and discuss three cases undergoing VAC therapy followed by loco-regional flaps in the management of exposed bone after fibular free flap. The advantages and disadvantages of VAC therapy in treating complicated wounds have been reported by several studies; compared with conventional wet-to-dry dressings, this system eliminates interstitial oedema, exudates and debrides while increasing blood perfusion leading to a more rapid promotion of wound healing with less bacterial loading. Although surgical debridement, wet-to-dry dressing changes and antibiotic treatment are the mainstay in managing maxillofacial wounds, VAC therapy can be used to obtain primary closure or to prepare the wound bed until definitive reconstruction is carried out. In our opinion, the VAC technique is an innovative therapy, and at our institution represents the standard of care for the majority of complicated wounds.

  8. NONCHEMICAL DEHYDRATION OF FIXED TISSUE COMBINING MICROWAVES AND VACUUM

    NARCIS (Netherlands)

    KOK, LP; BOON, ME

    A novel histoprocessing method for paraffin and plastic sections is presented in which dehydration of fixed tissue blocks is achieved within 5 minutes by microwaving under vacuum. Exploiting the decrease in boiling temperature under vacuum, we succeed in evaporating liquid molecules in the tissues

  9. [Antilipemic agents in combined therapy].

    Science.gov (United States)

    Márk, László; Császár, Albert

    2002-08-25

    In the prevention of coronary heart disease the aim to achieve the target cholesterol and triglyceride levels and the maximal risk reduction leads to the combination of lipid lowering agents. The importance of the combination is supported by the fact that in monotherapy use of the high dose of the drugs, the lipid lowering effect is modest and the side effects are more frequent. The combined therapy is expected to be used more frequently despite the fact, that the improperly applied combination could have serious unfavourable effects. The authors review the advantages and drawbacks of the fibrate-statin combination, which could be used in the most frequent lipid abnormality, the high cholesterol and high triglyceride level, when the combination of micronized fenofibrate and fluvastatin is recommended. Beside the co-administration of other lipid lowering drugs (nicotine acid and resins), it is discussed the combination of statins and fibrates with a new, cholesterol absorption inhibitor, ezetimibe, a well tolerated drug with advantageous safety profile. Considering further metabolic risks the combination of lipid lowering drugs with glitazones, hormone replacement therapy, homocysteine reducing agents is as well highlighted.

  10. Bioslurping: Combined vacuum-enhanced free fuel removal and bioventing

    Energy Technology Data Exchange (ETDEWEB)

    Hoeppel, R.; Goetz, F. [Naval Facilities Engineering Service Center, Port Hueneme, CA (United States); Kittel, J.; Place, M. [Battelle, Columbus, OH (United States); Di Julio, S. [California State Univ., Northridge, CA (United States)

    1996-12-31

    Bioslurping is a new in situ technology that teams bioventing with vacuum-assisted free-phase fuel recovery to promote biodegradation in the vadose zone while simultaneously removing light nonaqueous phase liquid (LNAPL) from the water table and capillary fringe soil pores. Bioslurping differs from dual- or multi-phase extraction primarily in the same manner that bioventing differs from soil venting. The primary purpose of multi-phase extraction is to physically remove more volatile compounds from the groundwater, free product zones and vadose zone through use of high vacuum exerted usually below the water table. Bioslurping typically uses lower vacuum and removal of groundwater is minimized by placing a drop tube in the vacuum well near the free fuel-groundwater interface. Bioslurping is designed to accentuate in situ aerobic biodegradation and vapor extraction is an undesirable component. Thus this technology is ideal for the remediation of soils containing low volatility fuels.

  11. Combination therapy for erectile dysfunction: an update review

    Institute of Scientific and Technical Information of China (English)

    Rohit R Dhir; Hao-Cheng Lin; Steven E Canfield; Run Wang

    2011-01-01

    The introduction of oral phosphodiesterase-5 inhibitors (PDE5ls) in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE5ls are currently first-line monotherapy for erectile dysfunction (ED). However, a significant proportion of patients with complex ED will be therapeutic non-responders to PDE5I monotherapy. Combination therapy has recently been adopted for more refractory cases of ED, but a critical evaluation of current combination therapies is lacking. A thorough PubMed and Cochrane Library search was conducted focusing on the effectiveness of combination therapies for ED in therapeutic non-responders to PDE5I therapy. Journal articles spanning the time period between January 1990 and December 2010 were reviewed. Criteria included all pertinent review articles, randomized controlled trials, cohort studies and retrospective analyses. References from retrieved articles were also manually scanned for additional relevant publications. Published combination therapies include PDE5I plus vacuum erectile device (VED), intraurethral medication, intracavernosal injection (ICI), androgen supplement, a-blocker or miscellaneous combinations. Based on this review, some of these combination treatments appeared to be quite effective in preliminary testing. Caution must be advised, however, as the majority of combination therapy articles in the last decade have numerous limitations including study biases and small subject size. Regardless of limitations, present combination therapy research provides a solid foundation for future studies in complex ED management.

  12. Combination therapies in iron chelation

    Directory of Open Access Journals (Sweden)

    Raffaella Origa

    2014-12-01

    Full Text Available The availability of oral iron chelators and new non-invasive methods for early detection and treatment of iron overload, have significantly improved the life expectancy and quality of life of patients with b thalassemia major. However, monotherapy is not effective in all patients for a variety of reasons. We analyzed the most relevant reports recently published on alternating or combined chelation therapies in thalassemia major with special attention to safety aspects and to their effects in terms of reduction of iron overload in different organs, improvement of complications, and survival. When adverse effects, such as gastrointestinal upset with deferasirox or infusional site reactions with deferoxamine are not tolerable and organ iron is in an acceptable range, alternating use of two chelators (drugs taken sequentially on different days, but not taken on the same day together may be a winning choice. The association deferiprone and deferoxamine should be the first choice in case of heart failure and when dangerously high levels of cardiac iron exist. Further research regarding the safety and efficacy of the most appealing combination treatment, deferiprone and deferasirox, is needed before recommendations for routine clinical practice can be made.

  13. Flexible Furnace Concepts for Vacuum Heat Treatment Combined with High-pressure Gas Quenching

    Institute of Scientific and Technical Information of China (English)

    Karl Ritter; Stefan Wiebach

    2004-01-01

    IN the past five years the process combination of vacuum hardening, respectively vacuum carburizing with high-pressure gas quenching was successfully introduced to the market, especially in the manufacture of gears. In the meantime furnace concepts for various applications are available to the industry. In the following report three plant varieties are introduced, which differ in process flexibility and throughput. This report also explains criteria for the selection of a furnace in view of the existing application requirements. Besides this a short introduction is given into the vacuum carburizing process and the high-pressure gas quenching technology.

  14. Vacuum-compression therapy for ischemic disease of the extremities:experience with 40 patients

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To study the clinical effects of vacuum-compression therapy for ischemic disease of the extremities. Methods A total of 40 cases of peripheral arterial disorders,including 23 thromboangiitis obliterans (31 limbs) and 17 arteriosclerosis obliterans (23 limbs),were treated by a self-made vacuum-compression therapeutic apparatus. Results The effective rate in thromboangiitis obliterans and arteriosclerosis obliterans groups was 96.77% and 92.23%,respectively. The cuffs on the apparatus were improved ...

  15. Effects of vacuum-compression therapy on healing of diabetic foot ulcers: randomized controlled trial.

    Science.gov (United States)

    Akbari, Asghar; Moodi, Hesam; Ghiasi, Fatemeh; Sagheb, Hamidreza Mahmoudzadeh; Rashidi, Homayra

    2007-01-01

    A single-blind, randomized controlled trial was conducted to evaluate vacuum-compression therapy (VCT) for the healing of diabetic foot ulcers. Eighteen diabetic patients with foot ulcers were recruited through simple nonprobability sampling. Subjects were randomly assigned to either an experimental or a control group. Before and after intervention, the foot ulcer surface area was estimated stereologically, based on Cavalieri's principle. The experimental group was treated with VCT in addition to conventional therapy for 10 sessions. The control group received only conventional therapy, including debridement, blood glucose control agents, systemic antibiotics, wound cleaning with normal saline, offloading (pressure relief), and daily wound dressings. The mean foot ulcer surface area decreased from 46.88 +/- 9.28 mm(2) to 35.09 +/- 4.09 mm(2) in the experimental group (p = 0.006) and from 46.62 +/- 10.03 mm(2) to 42.89 +/- 8.1 mm(2) in the control group (p = 0.01). After treatment, the experimental group significantly improved in measures of foot ulcer surface area compared with the control group (p = 0.024). VCT enhances diabetic foot ulcer healing when combined with appropriate wound care.

  16. A New Method of Combination of Electroosmosis, Vacuum and Surcharge Preloading for Soft Ground Improvement

    Institute of Scientific and Technical Information of China (English)

    刘汉龙; 崔允亮; 沈扬; 丁选明

    2014-01-01

    As-a-rapid-and-effective-ground-improvement-method-is-urgently-required-for-the-booming-land-reclamation-in-China’s-coastal-area,-this-study-proposes-a-new-combined-method-of-electroosmosis,-vacuum-preloading-and-surcharge-preloading.-A-new-type-of-electrical-prefabricated-vertical-drain-(ePVD)-and-a-new-electroosmotic-drainage-system-are-suggested-to-allow-the-application-of-the-new-method.-This-combined-method-is-then-field-tested-and-compared-with-the-conventional-vacuum-combined-with-surcharge-preloading-method.-The-monitoring-and-foundation-test-results-show-that-the-new-method-induces-a-settlement-20%larger-than-that-of-the-conventional-vacuum-combined-with-surcharge-preloading-method-in-the-same-treatment-period,-and-saves-approximately-half-of-the-treatment-time-compared-with-the-vacuum-combined-with-surcharge-preloading-method-according-to-the-finite-element-prediction-of-the-settlement.-The-proposed-method-also-increases-the-vane-shear-strength-of-the-soil-significantly.-The-bearing-capacity-of-the-ground-improved-by-use-of-the-new-proposed-method-raises-118%.-In-comparison,-there-is-only-a-75%rise-when-using-the-vacuum-combined-with-surcharge-preloading-method-during-the-same-reinforcement-period.-All-results-indicate-that-the-proposed-combined-method-is-effective-and-suitable-for-reinforcing-the-soft-clay-ground.-Besides,-the-voltage-applied-between-the-anode-and-cathode-increases-exponentially-versus-treatment-time-when-the-output-current-of-power-supplies-is-kept-constant.-Most-of-the-voltage-potential-in-electroosmosis-is-lost-at-electrodes,-leaving-smaller-than-50%-of-the-voltage-to-be-effectively-transmitted-into-the-soil.

  17. Vacuum-assisted closure therapy for infected perineal wounds after abdominoperineal resection. A retrospective cohort study

    NARCIS (Netherlands)

    Walma, M S; Burbach, J P M; Verheijen, P M; Pronk, A; van Grevenstein, W M U

    2016-01-01

    INTRODUCTION: Perineal wound complications are a main problem after abdominoperineal resection (APR). There is little evidence concerning perineal wound management. This study describes and evaluates the role of vacuum-assisted closure (VAC) therapy in wound management strategies of perineal wound i

  18. In patients with post-sternotomy mediastinitis is vacuum-assisted closure superior to conventional therapy?

    OpenAIRE

    Yu, Angela W.; Rippel, Radoslaw A.; Smock, Elliott; Jarral, Omar A.

    2013-01-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether vacuum-assisted closure therapy (VAC) is superior to conventional therapy for treating post-sternotomy mediastinitis. Altogether >261 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results ...

  19. Combined Pharmacologic Therapy in Postmenopausal Osteoporosis.

    Science.gov (United States)

    Shen, Yang; Gray, Dona L; Martinez, Dorothy S

    2017-03-01

    Antiresorptive agents for treating postmenopausal osteoporosis include selective estrogen receptor modulator (SERM), bisphosphonates and denoumab. Teriparatide is the only Food and Drug Administration-approved anabolic agent. Synergistic effects of combining teriparatide with an antiresorptive agent have been proposed and studied. This article reviews the trial designs and the outcomes of combination therapies. Results of the combination therapy for teriparatide and bisphosphonates were mixed; while small increases of bone density were observed in the combination therapy of teriparatide and estrogen/SERM and that of teriparatide and denosumab. Those clinical studies were limited by small sample sizes and lack of fracture outcomes.

  20. [POSSIBILITIES OF VACUUM THERAPY APPLICATION IN DISORDERS OF VENOUS OUTFLOW IN ISLET GRAFTS].

    Science.gov (United States)

    Badyul, P O; Samoylenko, G E; Nor, N M; Slesarenko, K S

    2015-07-01

    The experience of "distressed" (problematic) flaps application in 33 patients with soft tissue defects over 2010-2014 years were analysed. It was proposed to use the local negative pressure for the prevention and treatment of complications associated with venous insufficiency or trombosis in using of plastics with vascularised complexes of tissues. Vacuum-therapy was conducted with the help of negative pressure apparatus "AGATE-Dnepr" (Ukraine) by attaching silver-containing polyurethane sponge on the operating zone, covering the flap with the surrounding skin netting band "Grassolind". The recommended standard of negative pressure of 75-125 mm Hg, both in impulse and in continuous mode was used. The high efficiency of vacuum-therapy for survival of grafts has been demonstrated. Thus, it might be considered as an effective element of prevention and treatment of complications associated with venous insufficiency or trombosis using of vascularised tissue complex plastics of defects.

  1. Successful Treatment of Anterior Tracheal Necrosis after Total Thyroidectomy Using Vacuum-Assisted Closure Therapy

    Directory of Open Access Journals (Sweden)

    Grégory Philippe

    2012-01-01

    Full Text Available Total thyroidectomy involving the adjacent structures of the trachea can cause tracheal damage such as early tracheal necrosis. The authors describe the first case of anterior tracheal necrosis following total thyroidectomy treated using vacuum-assisted closure device. After two weeks of VAC  therapy, there was no evidence of ongoing infection and the trachea was partially closed around a tracheotomy cannula, removed after 3 months. The use of a VAC  therapy to reduce and close the tracheal rent and to create a rapid granulation tissue over tracheal structure appeared as a good opportunity after anterior tracheal necrosis.

  2. Combined interventional therapies of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun Qian; Gan-Sheng Feng; Thomas Vogl

    2003-01-01

    Hepatocellular carcinoma (HCC) is one of the most commonmalignancies in the world, responsible for an estimated one million deaths annually. It has a poor prognosis due to its rapid infiltrating growth and complicating liver cirrhosis.Surgical resection, liver transplantation and cryosurgery are considered the best curative options, achieving a high rate of complete response, especially in patients with small HCC and good residual liver function. In nonsurgery, regional interventional therapies have led to a major breakthrough in the management of unresectable HCC, which include transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave coagulation therapy (MCT), laser-induced thermotherapy (LITT), etc. As a result of the technical development of locoregional approaches for HCC during the recent decades,the range of combined interventional therapies has been continuously extended. Most combined multimodal interventional therapies reveal their enormous advantages as compared with any single therapeutic regimen alone,and play more important roles in treating unresectable HCC.

  3. Combination Therapy for Diabetic Macular Edema

    Directory of Open Access Journals (Sweden)

    Dinah Zur

    2012-01-01

    Full Text Available Diabetic macular edema is a main reason for visual loss in diabetic patients. Until recent years, macular laser photocoagulation was the only available therapy. The awareness that inflammation is an important factor in the pathogenetic process of DME gave reason for intravitreal treatment with corticosteroids. The introduction of anti-VEGF drugs brought a revolutionary change in the treatment of DME. This paper will review the important clinical trials with an emphasis on combination therapies.

  4. Governing stem cell therapy in India: regulatory vacuum or jurisdictional ambiguity?

    Science.gov (United States)

    Tiwari, Shashank S.; Raman, Sujatha

    2014-01-01

    Stem cell treatments are being offered in Indian clinics although preclinical evidence of their efficacy and safety is lacking. This is attributed to a governance vacuum created by the lack of legally binding research guidelines. By contrast, this paper highlights jurisdictional ambiguities arising from trying to regulate stem cell therapy under the auspices of research guidelines when treatments are offered in a private market disconnected from clinical trials. While statutory laws have been strengthened in 2014, prospects for their implementation remain weak, given embedded challenges of putting healthcare laws and professional codes into practice. Finally, attending to the capacities of consumer law and civil society activism to remedy the problem of unregulated treatments, the paper finds that the very definition of a governance vacuum needs to be reframed to clarify whose rights to health care are threatened by the proliferation of commercial treatments and individualized negligence-based remedies for grievances. PMID:25431534

  5. Iatrogenic oesophageal perforation during placement of an endoscopic vacuum therapy device.

    Science.gov (United States)

    Halliday, Edwin; Patel, Anant; Hindmarsh, Andrew; Sujendran, Vijay

    2016-07-28

    Endoscopic vacuum-assisted closure (VAC) is increasingly being used as a means of managing perforations or anastomotic leaks of the upper gastrointestinal (GI) tract. Published outcomes are favourable, with few mentions of complications or morbidity. We present a case in which the management of a gastric perforation with endoscopic vacuum therapy was complicated by cervical oesophageal perforation. The case highlights the risks of such endoscopic therapeutic procedures and is the first report in the literature to describe significant visceral injury during placement of a VAC device for upper GI perforation. Iatrogenic oesophageal perforation is an inherent risk to upper GI endoscopy and the risk increases in therapeutic endoscopic procedures. Complications may be reduced by management under a multidisciplinary team in a centre with specialist upper GI services. There is no doubt that the endoscopic VAC approach is becoming established practice, and training in its use must reflect its increasingly widespread adoption.

  6. Governing stem cell therapy in India: regulatory vacuum or jurisdictional ambiguity?

    Science.gov (United States)

    Tiwari, Shashank S; Raman, Sujatha

    2014-10-02

    Stem cell treatments are being offered in Indian clinics although preclinical evidence of their efficacy and safety is lacking. This is attributed to a governance vacuum created by the lack of legally binding research guidelines. By contrast, this paper highlights jurisdictional ambiguities arising from trying to regulate stem cell therapy under the auspices of research guidelines when treatments are offered in a private market disconnected from clinical trials. While statutory laws have been strengthened in 2014, prospects for their implementation remain weak, given embedded challenges of putting healthcare laws and professional codes into practice. Finally, attending to the capacities of consumer law and civil society activism to remedy the problem of unregulated treatments, the paper finds that the very definition of a governance vacuum needs to be reframed to clarify whose rights to health care are threatened by the proliferation of commercial treatments and individualized negligence-based remedies for grievances.

  7. The Integration of Vacuum Brazing into Heat Treatment - A Progressive Combined Process

    Institute of Scientific and Technical Information of China (English)

    Ingo Reinkensmeier; Henkjan Buursen

    2004-01-01

    The continuous constructive challenge to improve the functionality and efficiency of components always results in higher demands on production engineering, against the background of the generally increasing cost pressure. In many cases, you will just succeed in producing competitive and innovative products by combining and coupling of different procedures to an independent (hybrid) technology. The use of hybrid procedures for metal joining and heat treatment of metallic materials finds more and more industrial fields of application. Modern vacuum lines with integrated pressurized gas quenching are considered high-performance and flexible means of production for brazing and heat treatment tasks as well in the turbine industry as in the mould making and tool manufacturing industry. In doing so, the heat treatment is coupled with the brazing cycle in a combined process so that the brazing temperatures and soak times are adapted to the necessary temperatures and times for solution heat treatment and austeniting. This user-oriented article describes on the one hand examples of brazing of turbine components, but above all the practical experience from the plastics processing industry, where the requirement for a high-efficient cooling of injection moulding dies gains more and more importance.The combined procedure "Vacuum Brazing and Hardening" offers plenty of possibilities to produce mould inserts with an efficient tempering system in an economic way.

  8. In patients with post-sternotomy mediastinitis is vacuum-assisted closure superior to conventional therapy?

    Science.gov (United States)

    Yu, Angela W; Rippel, Radoslaw A; Smock, Elliott; Jarral, Omar A

    2013-11-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether vacuum-assisted closure therapy (VAC) is superior to conventional therapy for treating post-sternotomy mediastinitis. Altogether >261 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Several studies indicate that VAC therapy is associated with shorter lengths of intensive care and in-hospital stay as well as faster rates of wound healing and fewer dressing changes. It has also been shown that VAC therapy is correlated with a statistically significant reduction in reinfection rates, particularly those that occur in the early postoperative period (at the 1-week follow-up). Patients can be discharged with the dressing in situ and managed in the community with a view to delayed closure or reconstruction. However, the studies comparing VAC with conventional therapy are all retrospective in nature and reinforce the need for randomized controlled trials in order to more accurately establish differences in outcomes between VAC and conventional therapy. Additionally, owing tło the variability of treatment protocols within the non-VAC arm, it is more challenging to draw definitive conclusions regarding the superiority of VAC therapy to every modality that is considered conventional treatment. We conclude that VAC therapy is a portable and an increasingly economical option for the treatment of post sternotomy mediastinitis. Although reductions in mortality rates were not reproduced in all studies, evidence suggests that VAC should still be considered as a first-line therapy for post-sternotomy mediastinitis and as a bridge therapy to musculocutaneous reconstruction or primary closure.

  9. Combined photovacuum therapy of copulative dysfunction

    Science.gov (United States)

    Menyaev, Yulian A.; Zharov, Vladimir P.; Mishanin, Evgeniy A.; Kuzmich, Aleksandr P.; Bessonov, Sergey E.

    2006-02-01

    One of the important problems of modern medicine is treatment of urogenital diseases. 1-2 There is a set of the treatment methods for such problems, but any of them does not obey the modern physicians completely. 3-4 Our aim is to present the new combined therapeutic apparatus called "Yarovit" (produced in Russia, in collaboration between Bauman Moscow State University of Technology and Scientific Production Association and Medical Center "Yarovit") which successfully applied in clinics for cure the patients with copulative dysfunction diseases. 5-6 At this apparatus "Yarovit" (description model have abbreviation AMVL-0 1) there is a combination of vacuum decompression (0.1-0.4 kgs/cm2) and light emitting diodes matrix system (660 nm, 1-3 mW/cm2). In treatment procedure apparatus can be applied together with expanded module "Intratherm" (39 °C on average), which has rectal heating elements. The latest clinical studies were made together with volunteer participation of more then one hundred patients, and received results showed the good dynamic of healing. That let to conclude these combinations of physical therapeutic methods supplement each other and in conjunction provides a significant clinical effect. The further developments of such apparatuses are discussed.

  10. Pneumonia in immunocompetent patients: combination antibiotic therapy.

    Science.gov (United States)

    Salva, S; Borgatta, B; Rello, J

    2014-04-01

    Pneumonia's burden is still important worldwide not only because of its high incidence and mortality, but also for the elevated costs related to it. Despite the concerted efforts to reduce the incidence of sepsis-related complications, they continue to represent a major human and economic burden. The cornerstone of sepsis management is early appropriate empiric broad spectrum antibiotics, resuscitation, and source control. The association between inappropriate use of antibiotics and increased mortality is the rationale for the use of empiric antibiotic combination therapy in critically ill patients. The aim of this manuscript was to discuss recent literature regarding the management of severe pneumonia, both community-acquired and hospital-acquired/ventilator-associated, in critically ill patients. Use of combination therapy is warranted in severe infections with shock; considerations should be made on the importance of optimal antibiotic administration and adverse reactions, thus providing guidance for a rational use of antibiotics.

  11. [Combination therapy of chronic bacterial prostatitis].

    Science.gov (United States)

    Khryanin, A A; Reshetnikov, O V

    2016-08-01

    The article discusses the possible etiological factors in the development of chronic bacterial prostatitis. The authors presented a comparative long-term analysis of morbidity from non-viral sexually transmitted infections (STIs) in Russia. Against the background of general decline in STIs incidence, a significant percentage of them is made up by urogenital trichomoniasis. The findings substantiated the advantages of combination therapy (ornidazole and ofloxacin) for bacterial urinary tract infections.

  12. Amodiaquine and Ciprofloxacin Combination in Plasmodiasis Therapy

    Directory of Open Access Journals (Sweden)

    Peace Mayen Edwin Ubulom

    2015-01-01

    Full Text Available Objective. The study was designed to determine the efficacy of combined Amodiaquine and Ciprofloxacin in plasmodiasis therapy. Method. The in vivo antiplasmodial effect of different dosage levels of Amodiaquine, Ciprofloxacin, and their combinations against Plasmodium berghei berghei was evaluated using Swiss albino mice. Results. Amodiaquine (a known antiplasmodial agent had a fairly significant antiplasmodial effect reducing the parasites for every 100 red blood cells (RBC from 66 to 16 (75.75% at the tolerable dosage level of 7.5 mg/kg body weight while Ciprofloxacin (an antibiotic known to have antimalarial effect showed an insignificant antiplasmodial effect reducing the parasites for every 100 RBC from 65 to 64 (1.53% at the tolerable dosage level of 10.7 mg/kg body weight. Conversely, the combination therapy of Amodiaquine and Ciprofloxacin had a significant antiplasmodial effect at all the doses administered. The combination of 7.5 mg/kg of Amodiaquine and 12.8 mg/kg of Ciprofloxacin, however, showed the most significant antiplasmodial effect of the doses used reducing the number of parasites per 100 RBC from 60 to 10 (83.33%. Conclusions. Appropriate Amodiaquine and Ciprofloxacin combination will be effective for the treatment of malaria and better than either Amodiaquine or Ciprofloxacin singly at their recommended dosage levels.

  13. Amodiaquine and Ciprofloxacin Combination in Plasmodiasis Therapy.

    Science.gov (United States)

    Ubulom, Peace Mayen Edwin; Udobi, Chinweizu Ejikeme; Madu, Mark Iheukwumere

    2015-01-01

    Objective. The study was designed to determine the efficacy of combined Amodiaquine and Ciprofloxacin in plasmodiasis therapy. Method. The in vivo antiplasmodial effect of different dosage levels of Amodiaquine, Ciprofloxacin, and their combinations against Plasmodium berghei berghei was evaluated using Swiss albino mice. Results. Amodiaquine (a known antiplasmodial agent) had a fairly significant antiplasmodial effect reducing the parasites for every 100 red blood cells (RBC) from 66 to 16 (75.75%) at the tolerable dosage level of 7.5 mg/kg body weight while Ciprofloxacin (an antibiotic known to have antimalarial effect) showed an insignificant antiplasmodial effect reducing the parasites for every 100 RBC from 65 to 64 (1.53%) at the tolerable dosage level of 10.7 mg/kg body weight. Conversely, the combination therapy of Amodiaquine and Ciprofloxacin had a significant antiplasmodial effect at all the doses administered. The combination of 7.5 mg/kg of Amodiaquine and 12.8 mg/kg of Ciprofloxacin, however, showed the most significant antiplasmodial effect of the doses used reducing the number of parasites per 100 RBC from 60 to 10 (83.33%). Conclusions. Appropriate Amodiaquine and Ciprofloxacin combination will be effective for the treatment of malaria and better than either Amodiaquine or Ciprofloxacin singly at their recommended dosage levels.

  14. Pegvisomant and cabergoline combination therapy in acromegaly.

    Science.gov (United States)

    Bernabeu, I; Alvarez-Escolá, C; Paniagua, A E; Lucas, T; Pavón, I; Cabezas-Agrícola, J M; Casanueva, F F; Marazuela, M

    2013-03-01

    Combination with cabergoline may offer additional benefits to acromegalic patients on pegvisomant monotherapy. We evaluated the safety and efficacy profile of this combination and investigated the determinants of response. An observational, retrospective, cross-sectional study. Fourteen acromegalic patients (9 females), who were partially resistant to somatostatin analogs and on pegvisomant monotherapy. Cabergoline was added because of the presence of persistent mildly increased IGF-I. The mean follow-up time was 18.3 ± 10.4 months. The efficacy and safety profile was assessed. The influence of clinical and biochemical characteristics on treatment efficacy was studied. IGF-I levels returned to normal in 4 patients (28%) at the end of the study. In addition, some decline in IGF-I levels was observed in a further 5 patients. The % IGF-I decreased from 158 ± 64% to 124 ± 44% (p = 0.001). The average change in IGF-I was -18 ± 27% (range -67 to +24%). Lower baseline IGF-I (p = 0.007), female gender (p = 0.013), lower body weight (p = 0.031), and higher prolactin (PRL) levels (p = 0.007) were associated with a better response to combination therapy. There were no significant severe adverse events. Significant tumour shrinkage was observed in 1 patient. Combination therapy with pegvisomant and cabergoline could provide better control of IGF-I in some patients with acromegaly. Baseline IGF-I levels, female gender, body weight, and PRL levels affect the response to this combination therapy.

  15. the first experience of phakoemulsification with vacuum trabeculoplasty ab interno for combined cataract and glaucoma

    Directory of Open Access Journals (Sweden)

    V. N. Trubilin

    2012-01-01

    Full Text Available Purpose: to describe of a new effective method of combined treatment of patients with primary open- angle glaucoma with mod- erately elevated intraocular pressure and cataract.Methods: Studies have been conducted among 30 patients (30 eyes from 46 to 85 years with a combination of cataract of varying degrees of maturity and open-angle glaucoma of different stages. In addition to the standard techniques there were used special clini- cal and functional methods of research: optical cogerent tomography of the anterior segment of the eye Visante OCt (Carl Zeiss, Ger- many, glaucomatous cupping and thickness of nerve fibers study using confocal scanning laser ophthalmoscope HRt II (Heidelberg Engineering, Germany. In accordance with the target patients were divided into 2 groups: the basic group consisted of 15 patients (15 eyes aged 63 to 76 years with primary open angle glaucoma of 1-2 stages and cataracts of varying degrees of maturity. In both groups there was performed the ultrasonic phakoemulsification of the lens on the phakoemulsificator Infinity (Alcon, US.Results: the analysis of intraocular pressure measurements showed that among patients from I and II group eye pressure had a downward trend in the early postoperative period, however, the average dynamics of reduction of the intraocular pressure in the group of patients where phakoemulsification and vacuum trabeculoplasty ab interno performed was higher than in the control group. In the gonioscopy of the corner of the anterior chamber the clinical presentation remained stable throughout the period of observation. In the postoperative period among patients in the main observation group according to OCt it was noted changing the depth of the anterior chamber of eye towards its increase by an average of 1.39 mm, as well as increasing the angle of the anterior chamber at an average of 9.98.Conclusion: Phakoemulsification with IOL implantation combined with vacuum trabeculoplasty ab interno is

  16. the first experience of phakoemulsification with vacuum trabeculoplasty ab interno for combined cataract and glaucoma

    Directory of Open Access Journals (Sweden)

    V. N. Trubilin

    2014-07-01

    Full Text Available Purpose: to describe of a new effective method of combined treatment of patients with primary open- angle glaucoma with mod- erately elevated intraocular pressure and cataract.Methods: Studies have been conducted among 30 patients (30 eyes from 46 to 85 years with a combination of cataract of varying degrees of maturity and open-angle glaucoma of different stages. In addition to the standard techniques there were used special clini- cal and functional methods of research: optical cogerent tomography of the anterior segment of the eye Visante OCt (Carl Zeiss, Ger- many, glaucomatous cupping and thickness of nerve fibers study using confocal scanning laser ophthalmoscope HRt II (Heidelberg Engineering, Germany. In accordance with the target patients were divided into 2 groups: the basic group consisted of 15 patients (15 eyes aged 63 to 76 years with primary open angle glaucoma of 1-2 stages and cataracts of varying degrees of maturity. In both groups there was performed the ultrasonic phakoemulsification of the lens on the phakoemulsificator Infinity (Alcon, US.Results: the analysis of intraocular pressure measurements showed that among patients from I and II group eye pressure had a downward trend in the early postoperative period, however, the average dynamics of reduction of the intraocular pressure in the group of patients where phakoemulsification and vacuum trabeculoplasty ab interno performed was higher than in the control group. In the gonioscopy of the corner of the anterior chamber the clinical presentation remained stable throughout the period of observation. In the postoperative period among patients in the main observation group according to OCt it was noted changing the depth of the anterior chamber of eye towards its increase by an average of 1.39 mm, as well as increasing the angle of the anterior chamber at an average of 9.98.Conclusion: Phakoemulsification with IOL implantation combined with vacuum trabeculoplasty ab interno is

  17. Drying kinetics and characteristics of combined infrared-vacuum drying of button mushroom slices

    Science.gov (United States)

    Salehi, Fakhreddin; Kashaninejad, Mahdi; Jafarianlari, Ali

    2016-10-01

    Infrared-vacuum drying characteristics of button mushroom (Agaricus bisporus) were evaluated in a combined dryer system. The effects of drying parameters, including infrared radiation power (150-375 W), system pressure (5-15 kPa) and time (0-160 min) on the drying kinetics and characteristics of button mushroom slices were investigated. Both the infrared lamp power and vacuum pressure influenced the drying time of button mushroom slices. The rate constants of the nine different kinetic's models for thin layer drying were established by nonlinear regression analysis of the experimental data which were found to be affected mainly by the infrared power level while system pressure had a little effect on the moisture ratios. The regression results showed that the Page model satisfactorily described the drying behavior of button mushroom slices with highest R value and lowest SE values. The effective moisture diffusivity increases as power increases and range between 0.83 and 2.33 × 10-9 m2/s. The rise in infrared power has a negative effect on the ΔE and with increasing in infrared radiation power it was increased.

  18. Drying kinetics and characteristics of combined infrared-vacuum drying of button mushroom slices

    Science.gov (United States)

    Salehi, Fakhreddin; Kashaninejad, Mahdi; Jafarianlari, Ali

    2017-05-01

    Infrared-vacuum drying characteristics of button mushroom ( Agaricus bisporus) were evaluated in a combined dryer system. The effects of drying parameters, including infrared radiation power (150-375 W), system pressure (5-15 kPa) and time (0-160 min) on the drying kinetics and characteristics of button mushroom slices were investigated. Both the infrared lamp power and vacuum pressure influenced the drying time of button mushroom slices. The rate constants of the nine different kinetic's models for thin layer drying were established by nonlinear regression analysis of the experimental data which were found to be affected mainly by the infrared power level while system pressure had a little effect on the moisture ratios. The regression results showed that the Page model satisfactorily described the drying behavior of button mushroom slices with highest R value and lowest SE values. The effective moisture diffusivity increases as power increases and range between 0.83 and 2.33 × 10-9 m2/s. The rise in infrared power has a negative effect on the ΔE and with increasing in infrared radiation power it was increased.

  19. Optimal combination of antiangiogenic therapy forhepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The success of sorafenib in prolonging survival of patientswith hepatocellular carcinoma (HCC) makes therapeuticinhibition of angiogenesis a component of treatmentfor HCC. To enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, combination ofantiangiogenic agents with chemotherapy,radiotherapyor other targeted agents were evaluated. Nevertheless,the use of antiangiogenic therapy remains suboptimalregarding dosage, schedule and duration of therapy.The issue is further complicated by combinationantiangiogenesis to other cytotoxic or biologic agents.There is no way to determine which patients are mostlikely respond to a given form of antiangiogenic therapy.Activation of alternative pathways associated with diseaseprogression in patients undergoing antiangiogenictherapy has also been recognized. There is increasingimportance in identifying, validating and standardizingpotential response biomarkers for antiangiogenesistherapy for HCC patients. In this review, biomarkers forantiangiogenesis therapy including systemic, circulating,tissue and imaging ones are summarized. The strengthand deficit of circulating and imaging biomarkerswere further demonstrated by a series of studies inHCC patients receiving radiotherapy with or withoutthalidomide.

  20. Combination therapy in hypertension: An update

    Directory of Open Access Journals (Sweden)

    Kalra Sanjay

    2010-06-01

    Full Text Available Abstract Meticulous control of blood pressure is required in patients with hypertension to produce the maximum reduction in clinical cardiovascular end points, especially in patients with comorbidities like diabetes mellitus where more aggressive blood pressure lowering might be beneficial. Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy may be theoretically favored by the fact that multiple factors contribute to hypertension, and achieving control of blood pressure with single agent acting through one particular mechanism may not be possible. Regimens can either be fixed dose combinations or drugs added sequentially one after other. Combining the drugs makes them available in a convenient dosing format, lower the dose of individual component, thus, reducing the side effects and improving compliance. Classes of antihypertensive agents which have been commonly used are angiotensin receptor blockers, thiazide diuretics, beta and alpha blockers, calcium antagonists and angiotensin-converting enzyme inhibitors. Thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensin-aldosterone system blockers, in reducing BP. The majority of currently available fixed-dose combinations are diuretic-based. Combinations may be individualized according to the presence of comorbidities like diabetes mellitus, chronic renal failure, heart failure, thyroid disorders and for special population groups like elderly and pregnant females.

  1. Combination therapy for pain in musculoskeletal diseases

    Directory of Open Access Journals (Sweden)

    Andrei Evgenyevich Karateev

    2012-01-01

    Full Text Available When managing patients with locomotor pathology, serious attention is paid to symptomatic therapy aimed at eliminating the unpleasant manifestations of the disease. At the same time, rational analgesia is of the greatest importance. If acute pain should be arrested, parenteral or tableted formulations of fast-acting analgesics are used for days. Longer analgesic therapy especially for clinically relevant inflammation is based on the use of nonsteroidal anti-inflammatory drugs (NSAID having analgesic and anti-inflammatory effectiveness and good tolerance. The level of analgesia may be increased, by combining NSAID with tramadol and paracetamol. When clinical muscular spasm is implicated in the pathogenesis of chronic pain, it is expedient to prescribe myorelaxants that have an analgesic potential and are able to potentiate the analgesic effect of NSAID.

  2. COMBINATION THERAPY FOR PROSTATE CANCER: CLINICAL OBSERVATIONS

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2014-08-01

    Full Text Available Prostate cancer (PC is one of the urgent problems of modern urological oncology. The incidence of this pathology is steadily growing worldwide. Despite the fact that PSA diagnosis is extensively used and programs for the early detection of this disease are introduced, the rate of dia gnosis of advanced PC forms remains high. Furthermore, a number of aspects of therapy for this disease remain controversial so far. The 7 th Congress of the Russian Society of Urological Oncologists, which dealt with some issues of combination therapy for locally advanced PC, was held in Moscow in October 3 to 5, 2012. The paper covers a number of controversial issues in the management of patients with PC in different clinical situations.

  3. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection....... into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk...

  4. Combined therapy for diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Saba Al Rashaed

    2013-01-01

    Full Text Available Diabetic macular edema (DME is the main cause of visual impairment in diabetic patients. Macular edema within 1 disk diameter of the fovea is present in 9% of the diabetic population. The management of DME is complex and often multiple treatment approaches are needed. This review demonstrates the benefits of intravitreal triamcinolone, bevacizumab and ranibizumab as adjunctive therapy to macular laser treatment in DME. The published results indicate that intravitreal injections of these agents may have a beneficial effect on macular thickness and visual acuity, independent of the type of macular edema that is present. Therefore, pharmacotherapy could complement focal/grid laser photocoagulation in the management of DME. For this review, we performed a literature search and summarized recent findings regarding combined therapy for DME.

  5. Infliximab, azathioprine, or combination therapy for Crohn's disease

    DEFF Research Database (Denmark)

    Colombel, Jean Frédéric; Sandborn, William J; Reinisch, Walter

    2010-01-01

    The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.......The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown....

  6. Small RNA combination therapy for lung cancer

    Science.gov (United States)

    Xue, Wen; Dahlman, James E.; Tammela, Tuomas; Khan, Omar F.; Sood, Sabina; Dave, Apeksha; Cai, Wenxin; Chirino, Leilani M.; Yang, Gillian R.; Bronson, Roderick; Crowley, Denise G.; Sahay, Gaurav; Schroeder, Avi; Langer, Robert; Anderson, Daniel G.; Jacks, Tyler

    2014-01-01

    MicroRNAs (miRNAs) and siRNAs have enormous potential as cancer therapeutics, but their effective delivery to most solid tumors has been difficult. Here, we show that a new lung-targeting nanoparticle is capable of delivering miRNA mimics and siRNAs to lung adenocarcinoma cells in vitro and to tumors in a genetically engineered mouse model of lung cancer based on activation of oncogenic Kirsten rat sarcoma viral oncogene homolog (Kras) and loss of p53 function. Therapeutic delivery of miR-34a, a p53-regulated tumor suppressor miRNA, restored miR-34a levels in lung tumors, specifically down-regulated miR-34a target genes, and slowed tumor growth. The delivery of siRNAs targeting Kras reduced Kras gene expression and MAPK signaling, increased apoptosis, and inhibited tumor growth. The combination of miR-34a and siRNA targeting Kras improved therapeutic responses over those observed with either small RNA alone, leading to tumor regression. Furthermore, nanoparticle-mediated small RNA delivery plus conventional, cisplatin-based chemotherapy prolonged survival in this model compared with chemotherapy alone. These findings demonstrate that RNA combination therapy is possible in an autochthonous model of lung cancer and provide preclinical support for the use of small RNA therapies in patients who have cancer. PMID:25114235

  7. Combination immunotherapy and photodynamic therapy for cancer

    Science.gov (United States)

    Hamblin, Michael R.; Castano, Ana P.; Mroz, Pawel

    2006-02-01

    Cancer is a leading cause of death among modern people largely due to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity towards normal tissue. This is best accomplished by priming the body's immune system to recognize the tumor antigens so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species leading to vascular shutdown and tumor cell death. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, generation of tumor-specific antigens, and induction of heat-shock proteins. Combination regimens using PDT and immunostimulating treatments are likely to even further enhance post-PDT immunity. These immunostimulants are likely to include products derived from pathogenic microorganisms that are effectively recognized by Toll-like receptors and lead to upregulation of transcription factors for cytokines and inflammatory mediators. The following cascade of events causes activation of macrophages, dendritic and natural killer cells. Exogenous cytokine administration can be another way to increase PDT-induced immunity as well as treatment with a low dose of cyclophosphamide that selectively reduces T-regulatory cells. Although so far these combination therapies have only been used in animal models, their use in clinical trials should receive careful consideration.

  8. A novel method of combined phacoemulsification and vacuum trabeculoplasty ab interno

    Directory of Open Access Journals (Sweden)

    V. N. Trubilin

    2014-07-01

    Full Text Available Aim. To improve the efficacy of cataract and primary open-angle glaucoma (POAG surgery using a novel combined surgical technique.Materials and methods. 219 patients were included in the study. According to the design, all subjects weredivided into study group (n = 58 and two control groups (n = 78 and n = 83. Combined phaco and vacuum trabeculoplasty (VTP ab interno was performed in 58 study group patients. Pre-op and post-op, all patents had a complete eye examination including vision and hydrodynamics testing as well as anterior chamber depth (ACD and angle assessmentusing optical coherent tomography.Results. In study group, stable IOP decrease was observed for 2‑yrs follow-up. Phacoemulsification in cataract and POAG patients has an impact on anterior segment anatomy and topography owing to significant increase of ACD by 1.2 mm and anterior chamber angle by 3.3°. VTP ab interno provides additional ACD increase by 1.8 mm and anterior chamber angle by 15.9°. Complication rate was 8.5 % in study group (i.e., following combined phaco and VTP ab interno and 5.1 % and 8.4 % in control groups. Hospitalization days in all groups had no significant differences.Conclusion. A novel method of combined VTP ab interno and cataract phacoemulsification provides significant IOP decrease (by 74 % at 2‑yrs follow-up. Following VTP and phaco, fewer or even no hypotensive eye drops were required. This technique is less traumatic than traditional cataract and glaucoma surgery. Indication for combined VTP and phaco is (im mature cataract with medically (sub compensated POAG.

  9. Delayed endoluminal vacuum therapy for rectal anastomotic leaks after rectal resection in a swine model: a new treatment option.

    Science.gov (United States)

    Rosenberger, Laura H; Shada, Amber; Ritter, Lane A; Mauro, David M; Mentrikoski, Mark J; Feldman, Sanford H; Kleiner, Daniel E

    2014-04-01

    Anastomotic leaks are a dreaded surgical complication following colorectal operations. Creation of a temporary proximal diverting ileostomy is used in high-risk anastomoses, however, additional surgical risk is accumulated with its creation and reversal. Endoluminal vacuum therapy has been shown to seal anastomotic defects in the prophylactic setting in a pig model and we hypothesized it could be utilized in a delayed fashion to rescue subjects with an active anastomotic leak. Yorkshire pigs underwent rectal resection, intentional leak confirmed by fluoroscopy, and endoluminal vacuum therapy device placement to low continuous suction. Following treatment, a contrast enema and necropsy was performed for gross and histopathology. Pigs underwent 2 (or 5) days of free intraperitoneal leak prior to device placement and 5 (or 7) subsequent days of endoluminal vacuum therapy. Six of seven early-treated pigs sealed their anastomotic defect, while two of the four treated pigs in this extended group sealed the defect. Endoluminal vacuum therapy is feasible and well tolerated in a pig model, and it has been shown to seal a significant number of freely leaking anastomoses in the early period (86%). This technology warrants further study as it may provide a noninvasive means to treatment of anastomotic leaks. © 2014 Wiley Periodicals, Inc.

  10. Vacuum therapy in penile rehabilitation after radical prostatectomy: review of hemodynamic and antihypoxic evidence

    Directory of Open Access Journals (Sweden)

    Sheng-Qiang Qian

    2016-01-01

    Full Text Available Generally, hypoxia is a normal physiological condition in the flaccid penis, which is interrupted by regular nocturnal erections in men with normal erectile function. [1] Lack of spontaneous and nocturnal erections after radical prostatectomy due to neuropraxia results in persistent hypoxia of cavernosal tissue, which leads to apoptosis and degeneration of cavernosal smooth muscle fibers. Therefore, overcoming hypoxia is believed to play a crucial role during neuropraxia. The use of a vacuum erectile device (VED in penile rehabilitation is reportedly effective and may prevent loss of penile length. The corporal blood after VED use is increased and consists of both arterial and venous blood, as revealed by color Doppler sonography and blood gas analysis. A similar phenomenon was observed in negative pressure wound therapy (NPWT. However, NPWT employs a lower negative pressure than VED, and a hypoperfused zone, which increases in response to negative pressure adjacent to the wound edge, was observed. Nonetheless, questions regarding ideal subatmospheric pressure levels, modes of action, and therapeutic duration of VED remain unanswered. Moreover, it remains unclear whether a hypoperfused zone or PO 2 gradient appears in the penis during VED therapy. To optimize a clinical VED protocol in penile rehabilitation, further research on the mechanism of VED, especially real-time PO 2 measurements in different parts of the penis, should be performed.

  11. Vacuum therapy in penile rehabilitation after radical prostatectomy: review of hemodynamic and antihypoxic evidence.

    Science.gov (United States)

    Qian, Sheng-Qiang; Gao, Liang; Wei, Qiang; Yuan, Jiuhong

    2016-01-01

    Generally, hypoxia is a normal physiological condition in the flaccid penis, which is interrupted by regular nocturnal erections in men with normal erectile function. [1] Lack of spontaneous and nocturnal erections after radical prostatectomy due to neuropraxia results in persistent hypoxia of cavernosal tissue, which leads to apoptosis and degeneration of cavernosal smooth muscle fibers. Therefore, overcoming hypoxia is believed to play a crucial role during neuropraxia. The use of a vacuum erectile device (VED) in penile rehabilitation is reportedly effective and may prevent loss of penile length. The corporal blood after VED use is increased and consists of both arterial and venous blood, as revealed by color Doppler sonography and blood gas analysis. A similar phenomenon was observed in negative pressure wound therapy (NPWT). However, NPWT employs a lower negative pressure than VED, and a hypoperfused zone, which increases in response to negative pressure adjacent to the wound edge, was observed. Nonetheless, questions regarding ideal subatmospheric pressure levels, modes of action, and therapeutic duration of VED remain unanswered. Moreover, it remains unclear whether a hypoperfused zone or PO 2 gradient appears in the penis during VED therapy. To optimize a clinical VED protocol in penile rehabilitation, further research on the mechanism of VED, especially real-time PO 2 measurements in different parts of the penis, should be performed.

  12. Combination antiretroviral therapy and cancer risk.

    Science.gov (United States)

    Borges, Álvaro H

    2017-01-01

    To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk of Kaposi sarcoma and NHL also during early HIV infection before overt immunosuppression occurs. Long-term effects of cART exposure on cancer risk are not well defined; according to basic and epidemiological research, there might be specific associations of each cART class with distinct patterns of cancer risk. The relationship between cART exposure and cancer risk is complex and nuanced. It is an intriguing fact that, whether initiated during severe immunosuppression or not, cART reduces risk of Kaposi sarcoma and NHL. Further research should identify mediators of the benefit of immediate cART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.

  13. Successful Placement of Penile Prostheses in Men With Severe Corporal Fibrosis Following Vacuum Therapy Protocol.

    Science.gov (United States)

    Tsambarlis, Peter N; Chaus, Fahad; Levine, Laurence A

    2017-01-01

    Penile prosthesis (PP) implantation in men with severe corporal fibrosis presents a significant surgical challenge. For the past 7 years, we have used a novel, preoperative protocol of daily vacuum therapy (VT) using a vacuum erection device for at least 3 months before PP placement for men with severe corporal fibrosis from PP infection or ischemic priapism. To evaluate this standardized preoperative regimen. We retrospectively reviewed all patients who underwent three-piece PP placement at our institution from 2008 through 2015. Of these, 13 men had severe corporal fibrosis from prior PP infection (11 of 13) or prolonged ischemic priapism (2 of 13). Our protocol included VT for 10 to 15 minutes at least two times daily in all patients for at least 3 months (mean = 3.5 months). We report on our surgical experience and post-VT stretched flaccid penile length (SFPL) compared with baseline SFPL. All 13 men underwent successful three-piece PP placement with standard-size cylinders without additional surgical maneuvers. There was one infection and one erosion requiring revision. Daily average use of VT was 32.5 minutes. SFPL increased 0.92 cm (range = 0-2 cm, SD = 0.76 cm) after VT and three-piece PP placement compared with preoperative SFPL. These men also noted improved quality of life and sexuality as measured by postoperative office interviews. The use of VT before surgery appears to result in softening of corporal fibrosis and facilitates placement of a PP regardless of the period from developing corporal fibrosis to starting VT. We strongly recommend preoperative corporal tissue rehabilitation with VT to improve surgical outcomes and to decrease difficulty during PP implantation in men with severe corporal fibrosis. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  14. Combination of aerobic and vacuum packaging to control lipid oxidation and off-odor volatiles of irradiated raw turkey breast.

    Science.gov (United States)

    Nam, K C; Ahn, D U

    2003-03-01

    Effects of the combination of aerobic and anaerobic packaging on color, lipid oxidation, and volatile production were determined to establish a modified packaging method to control quality changes in irradiated raw turkey meat. Lipid oxidation was the major problem with aerobically packaged irradiated turkey breast, while retaining characteristic irradiation off-odor volatiles such as dimethyl sulfide, dimethyl disulfide, and dimethyl trisulfide was the concern for vacuum-packaged breast during the 10-day refrigerated storage. Vacuum packaging of aerobically packaged irradiated turkey breast meat at 1 or 3 days of storage lowered the amounts of S-volatiles and lipid oxidation products compared with vacuum- and aerobically packaged meats, respectively. Irradiation increased the a-value of raw turkey breast, but exposing the irradiated meat to aerobic conditions alleviated the intensity of redness.

  15. [Treatment of septic olecranon and patellar bursitis by excision and vacuum-assisted closure therapy].

    Science.gov (United States)

    Walter, G; Kemmerer, M; Hoffmann, R

    2013-08-01

    Treatment of septic olecranon and patellar bursitis differs considerably and is currently under discussion. We therefore performed a retrospective study of our patients with septic bursitis in the past 5 years. Between March 2007 and February 2012 we treated 79 patients with septic olecranon (n = 43) and patellar (n = 36) bursitis surgically: 61-males, 18 females, age 51 (range: 11-91) years. Four patients had not been treated before, 25 had suffered recurrences after 1-10 previous procedures, and 9 patients had not improved after conservative therapy. 34 patients presented with traumatic rupture or fistula of their bursae. In all cases we performed a radical bursectomy and vacuum-assisted therapy for 4 to 5 days. In addition, patients received systemic antibiotics. We phoned all patients and were successful in 57 cases (72 %). We questioned these patients for range of movement, limitations at work, pain, sensibility disorder, satisfaction with the result and further surgical procedures. In all cases we took tissue specimens for cultures, in 48 preparations histological examination was performed. Microbiological and histological results are discussed in detail. 40 patients were free of complaints, 15 complained of mild pain, 54 of 57 had unlimited range of motion. Minor discomforts at desk work were reported by 5 of 43 patients, 12 out of 36 patient reported discomfort when performing on their knees. There was no recurrence in the period of investigation. We recommend our treatment concept for septic olecranon and patellar bursitis because patient satisfaction is high and recurrences are reliably avoided. The soft tissue is spared, so that plastic covering procedures are seldom necessary. Georg Thieme Verlag KG Stuttgart · New York.

  16. An analytical solution for two-dimensional vacuum preloading combined with electro-osmosis consolidation using EKG electrodes.

    Science.gov (United States)

    Shen, Yang; Qiu, Chenchen; Li, Yande; Shi, Wen; Rui, Xiaoxi

    2017-01-01

    China is a country with vast territory, but economic development and population growth have reduced the usable land resources in recent years. Therefore, reclamation by pumping and filling is carried out in eastern coastal regions of China in order to meet the needs of urbanization. However, large areas of reclaimed land need rapid drainage consolidation treatment. Based on past researches on how to improve the treatment efficiency of soft clay using vacuum preloading combined with electro-osmosis, a two-dimensional drainage plane model was proposed according to the Terzaghi and Esrig consolidation theory. However, the analytical solution using two-dimensional plane model was never involved. Current analytical solutions can't have a thorough theoretical analysis of practical engineering and give relevant guidance. Considering the smearing effect and the rectangle arrangement pattern, an analytical solution is derived to describe the behavior of pore-water and the consolidation process by using EKG (electro-kinetic geo synthetics) materials. The functions of EKG materials include drainage, electric conduction and corrosion resistance. Comparison with test results is carried out to verify the analytical solution. It is found that the measured value is larger than the applied vacuum degree because of the stacking effect of the vacuum preloading and electro-osmosis. The trends of the mean measured value and the mean analytical value processes are comparable. Therefore, the consolidation model can accurately assess the change in pore-water pressure and the consolidation process during vacuum preloading combined with electro-osmosis.

  17. Chinese Consensus on Combination Therapy of Chronic Hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    In May 2011,editorial boards of Chinese Journal of Experimental and Clinical Infectious Diseases (Electronic Edition),Chinese Journal of Liver Diseases (Electronic Edition) and Infection International (Electronic Edition) organized an expert committee to form an expert consensus on antiviral combination therapy of chronic hepatitis B (CHB).The consensus publication promoted and standardized the combination therapy concept of chronic hepatitis B.Clinical evidence of combination therapy for CHB is incomplete.The concept of combination therapy is gradually extended,from combination of antiviral drugs plus antiviral drugs,to antiviral drugs plus hepatoprotective drugs,and antiviral drugs plus immunomodulatory drugs.Therefore,editorial boards once again asked experts to analyze the new clinical evidence,and form the expert consensus on combination therapy of chronic hepatitis B.The formulation of this consensus is according to the principles of evidence-based medicine.Large number of clinical studies of combination therapy is still in progress.This consensus can not fully answer all the problems encountered in the combination therapy of CHB.With the progress of clinical practice of antiviral therapy,and the accumulation of evidence in combination therapy,the expert committee will update the consensus timely.

  18. A STUDY OF NEGATIVE PRESSURE WOUND THERAPY: VACUUM ASSISTED CLOSURE IN CHRONIC NON-HEALING ULCERS

    Directory of Open Access Journals (Sweden)

    Dhamotharan Senraman

    2016-06-01

    Full Text Available BACKGROUND This study evaluates the advantage of Negative Pressure Wound Therapy-Vacuum Assisted Closure over Conventional Dressing in the management of chronic non-healing ulcers. METHODS From June 2014 to June 2015, 50 patients were selected (25 cases and 25 controls. After wound debridement, VAC dressing is applied. Pre VAC and post VAC culture and sensitivity is taken. Dressing is given for 72 hours and intermittent suction is given for 10 mins. in an hour, daily for 12 hours with negative pressure ranging from 100 to 125 mmHg. Rest of the time drain of the VAC dressing is connected to the Romovac suction drain. Doppler study to assess the vascularity of the limb before the procedure and X-ray is taken to rule out osteomyelitis. Control group patients are given conventional dressings. RESULTS The gender, age and ulcer distributions were almost equal in the case and control groups and were found to be statistically insignificant. Duration of hospital stay in days was found to be statistically significant between groups. Majority (52% of cases left hospital within 3 weeks’ time, while a major chunk (88% of control population stayed more than 3 weeks. VAC dressing shows better results in patients with normal Doppler study. VAC dressing have better results in patients with 48% undergoing split skin grafting and less rate (8% of amputation as against none undergoing split skin grafting and 24% needing amputation in the control group. Patients with sterile pre-VAC culture were not turning unsterile after VAC, but 90% unsterile turns sterile after VAC. CONCLUSION NPWT is a novel technique for managing an open wound by submitting the wound either to intermittent or continuous subatmospheric pressure. Here, we did a study to study the advantage of vacuum assisted closure over conventional dressing in the management of chronic non-healing ulcers and concluded that VAC decreases hospital stay, improves pus culture sterility, has better result in

  19. Delayed Endoluminal Vacuum Therapy for Rectal Anastomotic Leaks after Rectal Resection in a Swine Model: A New Treatment Option

    OpenAIRE

    Rosenberger, Laura H; Shada, Amber; Ritter, Lane A.; Mauro, David M.; Mentrikoski, Mark J.; Feldman, Sanford H.; Kleiner, Daniel E.

    2014-01-01

    Anastomotic leaks are a dreaded surgical complication following colorectal operations. Creation of a temporary proximal diverting ileostomy is used in high‐risk anastomoses, however, additional surgical risk is accumulated with its creation and reversal. Endoluminal vacuum therapy has been shown to seal anastomotic defects in the prophylactic setting in a pig model and we hypothesized it could be utilized in a delayed fashion to rescue subjects with an active anastomotic leak. Yorkshire pigs ...

  20. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, N.; Ellebaek, E.

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  1. Therapeutic cancer vaccines in combination with conventional therapy

    DEFF Research Database (Denmark)

    Junker, Niels; Ellebaek, Eva; Svane, Inge Marie

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  2. Combination of supercritical CO2 and vacuum distillation for the fractionation of bergamot oil.

    Science.gov (United States)

    Fang, Tao; Goto, Motonobu; Sasaki, Mitsuru; Hirose, Tsutomu

    2004-08-11

    Supercritical CO2 can be used to separate oxygenated compounds from essential oils. This technique still cannot replace vacuum distillation as an industrial process because of low recoveries and inconsistent results. In the present work, a comparison between the two methods was made in terms of composition, recovery, and color. Vacuum distillation and supercritical CO2 are complementary processes for producing high quality oxygenated compounds with high recovery rates. The former is more suitable for removing monoterpenes at low fraction temperatures ( or =85%) and without other macromolecules, such as pigments and waxes.

  3. Combination therapy for pain in musculoskeletal diseases

    OpenAIRE

    Andrei Evgenyevich Karateev

    2012-01-01

    When managing patients with locomotor pathology, serious attention is paid to symptomatic therapy aimed at eliminating the unpleasant manifestations of the disease. At the same time, rational analgesia is of the greatest importance. If acute pain should be arrested, parenteral or tableted formulations of fast-acting analgesics are used for days. Longer analgesic therapy especially for clinically relevant inflammation is based on the use of nonsteroidal anti-inflammatory drugs (NSAID) having a...

  4. Combination antifungal therapy: a critical review of the evidence.

    Science.gov (United States)

    Ostrosky-Zeichner, L

    2008-05-01

    Invasive fungal infections have extremely high rates of morbidity and mortality, particularly in immunocompromised hosts. Combination antifungal therapy is conceptually attractive as a life-saving measure. However, in-vitro and in-vivo evidence is often conflicting and clinical trials in this area are limited. Most clinical studies show similar outcomes for combination antifungal therapy when compared to monotherapy, although secondary endpoints and sub-analyses often show advantages for the combinations in endpoints such as culture sterilisation. The logistics of large clinical trials of combination therapy are highly complex. Combination of antifungals with immune modulators is an exciting new research area. Until more data are available, clinicians should approach combination antifungal therapy with caution.

  5. Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo-Hyun; Nam, Jae-Kyung; Jang, Junho; Lee, Hae-June, E-mail: hjlee@kcch.re.kr; Lee, Yoon-Jin, E-mail: yjlee8@kcch.re.kr

    2015-06-26

    Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm{sup 3} increased collagen levels, particularly in large tumor vessels. Furthermore, concomitant sunitinib therapy did not show a significant difference in tumor inhibition versus radiation alone. Thus, we evaluated multimodal therapy that combined pirfenidone, an inhibitor of TGF-induced collagen production, with radiation and sunitinib treatment. This trimodal therapy significantly reduced tumor growth, as compared to radiation alone. Immunohistochemical analysis revealed that radiation-induced collagen deposition and tumor microvessel density were significantly reduced with trimodal therapy, as compared to radiation alone. These data suggest that combined therapy using pirfenidone may modulate the radiation-altered tumor microenvironment, thereby enhancing the efficacy of radiation therapy and concurrent chemotherapy. - Highlights: • Radiation changes tumor endothelial cells to fibroblasts. • Radio-resistant tumors contain collagen deposits, especially in tumor vessels. • Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. • Pirfenidone reduces radiation-induced collagen deposits in tumors.

  6. Rationale for combination therapy as initial treatment for hypertension.

    Science.gov (United States)

    Giles, Thomas D

    2003-01-01

    Recent hypertension guidelines recommend initiating antihypertensive therapy with a combination of two or more agents in patients whose blood pressure exceeds their appropriate blood pressure goal by 20/10 mm Hg. This recommendation is based on the knowledge that the majority of patients with blood pressures of this magnitude will not achieve sufficient blood pressure reduction with monotherapy. Further, compared with high-dose monotherapy, combination therapy is often associated with fewer adverse effects and, for this reason, may improve patient adherence. Bringing patients to blood pressure goal quickly is likely to improve clinical outcomes. This article discusses the rationale for using combination antihypertensive therapy as initial therapy for high blood pressure in selected patients and reviews data from a study of 364 high-risk patients with Stage 2 hypertension in which a fixed-dose combination product (amlodipine besylate/benazepril HCl) proved more successful as initial therapy than high-dose monotherapy (amlodipine besylate) in reducing blood pressure.

  7. Combination Therapy for Advanced Kaposi Sarcoma

    Science.gov (United States)

    In this clinical trial, adult patients with any form of advanced Kaposi sarcoma will be treated with liposomal doxorubicin and bevacizumab every 3 weeks for a maximum of six treatments.  Patients who respond to this therapy or have stable disease will rec

  8. An ultrahigh-vacuum chamber for surface X-ray diffraction combined with MBE

    Science.gov (United States)

    Vlieg, E.; Van't Ent, A.; De Jongh, A. P.; Neerings, H.; Van Der Veen, J. F.

    1987-12-01

    An ultrahigh-vacuum chamber has been built which can be coupled to a diffractometer via a rotary feedthrough. X-rays enter and leave the chamber through a large beryllium window. In addition to standard equipment for surface preparation and reflection high-energy electron diffraction, the chamber contains Knudsen evaporation cells for MBE crystal growth. This arrangement allows in situ diffraction experiments to be performed on growing surfaces and thin films.

  9. Current concepts in combination antibiotic therapy for critically ill patients

    Directory of Open Access Journals (Sweden)

    Armin Ahmed

    2014-01-01

    Full Text Available Widespread emergence of multidrug resistant (MDR bacterial pathogens is a problem of global dimension. MDR infections are difficult to treat and frequently associated with high mortality. More than one antibiotic is commonly used to treat such infections, but scientific evidence does not favor use of combination therapy in most cases. However, there are certain subgroups where combination therapy may be beneficial, e.g. sepsis due to carbapenem-resistant Enterobacteriaceae (CRE, bacteremic pneumococcal pneumonia, and patients with multiple organ failure. Well-designed prospective studies are needed to clearly define the role of combination therapy in these subgroups.

  10. Hyperbilirubinemia without Transaminitis during Combined Therapy with Daclatasvir and Asunaprevir

    Directory of Open Access Journals (Sweden)

    Hayato Baba

    2016-07-01

    Full Text Available Daclatasvir (DCV and asunaprevir (ASV are direct-acting antivirals (DAAs used in the treatment of chronic hepatitis C virus (HCV infection. Combined therapy with DCV and ASV shows high efficacy and safety even in patients with cirrhosis. We encountered a patient exhibiting severe hyperbilirubinemia during combined therapy, which is an unreported side effect of DCV and ASV. A 78-year-old woman with cirrhosis developed hyperbilirubinemia >10 mg/dl without transaminitis 3 weeks after starting combined therapy. We suspected DAAs-induced liver disorder and discontinued treatment, which resulted in the improvement of hyperbilirubinemia. Caution is required in the use of DAAs for patients with advanced cirrhosis.

  11. The Vacuum Bell for Treatment of Pectus Excavatum: an Effective Tool for Conservative Therapy

    Directory of Open Access Journals (Sweden)

    Frank Haecker

    2011-01-01

    Full Text Available Aim: Pectus Excavatum (PE is the most common chest wall malformation, and one of the most frequent major congenital anomalies. Surgical repair of PE in childhood is a well-established procedure. Previously used operative techniques to correct PE were largely based on the Ravitch technique. Today, the minimally invasive repair (MIRPE by Nuss is well established. Conservative treatment with the vacuum bell to elevate the funnel in patients with PE, represents a potential alternative. Material and Methods:  A suction cup is used to create a vacuum at the anterior chest wall. 3 different sizes of vacuum bell exist which are selected according to the individual patients age. When creating the vacuum, the lift of the sternum is obvious and remains for a different time period. The device should be used for a minimum of 30 minutes (2/day, and may be used up to a maximum of several hours daily. Results; 93 patients (77 males, 16 females, aged 3 to 61 years (median 17.8 years used the vacuum bell for 1 to maximum 24 months. Computed tomographic scans showed that the device lifted the sternum and ribs immediately. In addition, this was confirmed thoracoscopically during the MIRPE procedure. After 18 months in average, the sternum was lifted to a normal level in 9 patients. Relevant side effects were not noted. Conclusions: The vacuum bell has proved to be an alternative therapeutic option in selected patients with PE. The initial results proved to be dramatic, but longterm results are so far lacking, and further evaluation and follow-up studies are necessary. 

  12. Combination therapy of disseminated coccidioidomycosis with caspofungin and fluconazole

    Directory of Open Access Journals (Sweden)

    Ja Kim Min

    2006-02-01

    Full Text Available Abstract Background The current recommended therapy for diffuse coccidioidal pneumonia involves initial treatment with amphotericin B deoxycholate or high-dose fluconazole, followed by an azole after clinical improvement. Amphotericin B is more frequently used as initial therapy if the patient's deterioration is rapid. Case presentation A 31-year-old Korean male with coccidioidomycosis presented to the hospital with miliary infiltrates on chest X-ray (CXR and skin rash on the face and trunk. Initially, the patient did not respond to amphotericin B deoxycholate therapy. However, following caspofungin and fluconazole combination therapy, the patient showed favourable radiological, serological, and clinical response. Conclusion This appears to be the first case of diffuse coccidioidal pneumonia with skin involvement in an immunocompetent patient who was treated successfully with caspofungin and fluconazole. Combination therapy with caspofungin and fluconazole may, therefore, be an alternative treatment for diffuse coccidioidal pneumonia that does not respond to amphotericin B deoxycholate therapy.

  13. Combined versus monotherapy or concurrent therapy for treatment of thalassaemia.

    Science.gov (United States)

    Song, Ta-Shu; Hsieh, Yow-Wen; Peng, Ching-Tien; Chen, Tai-Lin; Lee, Hong-Zin; Chung, Jing-Gung; Hour, Mann-Jen

    2014-01-01

    A combined deferasirox (DFX) and deferiprone (DFP) treatment protocol for relieving thalassemia patients' iron-overload was designed and the pharmacokinetic study was performed by LC-MS/MS. For this open-label, randomized trial, eight patients were recruited and randomly allocated to different treatment regimens: (A) monotherapy with single oral dose of DFX 30 mg/kg, (B) monotherapy with DFP 80 mg/kg/day, twice daily, (C) combined therapy with DFX and DFP (DFX 30 mg/kg for first dose, DFP 40 mg/kg 7 hours later, and DFP 40 mg/kg after another 7 h) and (D) concurrent therapy with DFX 30 mg/kg and DFP 80 mg/kg. Descriptive statistics evaluated pharmacokinetic parameters, AUC0-t, AUC0-inf, Cmax, Tmax, T1/2 and MRT. A positive pharmacokinetic drug interaction was observed in combined therapy. In case of DFX, combined therapy tallied about 2-fold larger than monotherapy in AUC, 1.5-fold larger in Cmax, 1 h longer in Tmax, but 1 h shorter in T1/2. Regarding DFP, most such parameters of combined therapy concurred with monotherapy. Conversely, negative drug interaction was observed in concurrent therapy. With DFX, concurrent therapy attained 1.2- to 2.2-fold lower than monotherapy in AUC0-t and Cmax, 0.6-h shorter in Tmax, and 3-fold longer in T1/2. With DFP, concurrent therapy proved approximately 2-fold larger than monotherapy in AUC and Cmax, 2.5-fold longer in T1/2, and 1.4-fold longer in MRT. Follow-up of subjects' clinical examinations and subjective symptoms showed no adverse events. Our findings showed the combined therapy had advantages, safe, convenient and painless for patients, over the existing concurrent therapy with deferoxamine (DFO) and DFX. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Effect of Combination Therapy on Joint Destruction in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Graudal, N.; Hubeck-Graudal, T.; Tarp, S.

    2014-01-01

    on progression of radiographic joint erosions in patients with rheumatoid arthritis (RA). Methods and Findings: The following combination drug therapies compared versus single DMARD were investigated: Double DMARD: 2 DMARDs (methotrexate, sulfasalazine, leflunomide, injectable gold, cyclosporine, chloroquine...

  15. Current concepts in combination antibiotic therapy for critically ill patients

    OpenAIRE

    Armin Ahmed; Afzal Azim; Mohan Gurjar; Arvind Kumar Baronia

    2014-01-01

    Widespread emergence of multidrug resistant (MDR) bacterial pathogens is a problem of global dimension. MDR infections are difficult to treat and frequently associated with high mortality. More than one antibiotic is commonly used to treat such infections, but scientific evidence does not favor use of combination therapy in most cases. However, there are certain subgroups where combination therapy may be beneficial, e.g. sepsis due to carbapenem-resistant Enterobacteriaceae (CRE), bacteremic ...

  16. Combined aspirin and anticoagulant therapy in patients with atrial fibrillation.

    Science.gov (United States)

    So, Charlotte H; Eckman, Mark H

    2017-01-01

    The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Of 948 patients receiving OAC, 430 (45 %) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49 and 42 % of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27 % had a diagnosis of CAD and 14 % had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn't discontinued. A surprisingly large proportion of patients (22.8 %) had no obvious indication for dual therapy. Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events.

  17. Combination therapy for carbapenem-resistant Gram-negative bacteria.

    Science.gov (United States)

    Paul, Mical; Carmeli, Yehuda; Durante-Mangoni, Emanuele; Mouton, Johan W; Tacconelli, Evelina; Theuretzbacher, Ursula; Mussini, Cristina; Leibovici, Leonard

    2014-09-01

    Carbapenem-resistant Gram-negative bacteria (CR-GNB) represent an increasing hazard in healthcare settings. A central question concerning the treatment of invasive infections caused by CR-GNB involves the use of combination therapy. Potential advantages of combination therapy include improved efficacy due to synergy, while the disadvantages include adverse events and increased antibiotic use with a potential drive towards resistance. Several observational studies have examined whether combination therapy offers an advantage over colistin/polymyxin monotherapy. We highlight the inherent limitations of these studies related to their observational design and sample size to show why they do not at present provide an answer to the question of combination versus monotherapy. This distinction is important to guide clinical practice until solid evidence has been obtained and to enable the recruitment of patients into randomized controlled trials. A few randomized controlled trials examining specific combinations have recently been completed or are ongoing. Currently, however, there is no evidence-based support for most combination therapies against CR-GNB, including colistin/carbapenem combination therapy.

  18. The comparison between monotherapy and combination therapy in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Khalvat A

    2007-05-01

    Full Text Available Background: Rheumatoid arthritis (RA is a chronic inflammatory condition. The condition can affected many tissues throught out the body, but the joints are usually most severely affected. The high incidence of RA, the conventional treatments and the experimental observation have shown by combination therapy, the disease symptoms of the patients reduce. To compare the efficacy and tolerability of single-agent Hydroxychloroquin (HCQ with combination therapies composed of (HCQ and Methotrexate (MTX and (HCQ, (MTX and Sulfasalazin (SSZ in active rheumatoid arthritis patients with additive arthritis. Methods: One hundred and twenty RA patients with active arthritis (male/female: 30/90 who were treated in rheumatology clinic between 2003 and 2005 were enrolled in this trial. Patients treated with (HCQ alone(200 mg/daywere include in group (I, patients treated with combination of (HCQ (200 mg/dayand (MTX (7.5mg/weekin group (II,and patents treated with combination of (HCQ (200mg/day,(MTX (7.5mg/weekand (SSZ(1 gr/dayin group (III, Forty patients (male/female:10/30 in group (I,(II and (IIIwere eligible for statistical analysis at the end of study. Changes in variable were compared by the T-test. Results: The combination of (MTX, (HCQand (SSZ and the combination of (MTX and (HCQ were more effective regarding the clinical and laboratory parameters than (HCQ alone (P<0.05. Moreover the combination of (MTX, (HCQ and (SSZ was more effective than the combination of (MTX and (HCQ (P<0.05. Combination therapies seem to be more effective and no more toxic than monotherapy in RA patients with additive arthritis. Conclusion: Combination therapy with methotrexate, hydroxychloroquin and sulfasalazin is more effective than hydroxychloroquin alone or a combination of methotrexate and hydroxychloroquin in RA. We suggest starting combination therapy for the patients with early RA, when the diagnosis has been established.

  19. Response to combination antiretroviral therapy: variation by age

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2008-01-01

    OBJECTIVE: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. SUBJECTS:: Forty-nine thousand nine hundred and twenty-one antiretroviral......-naive individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2-54.1%) and 59.2% (58.7-59.6%) had experienced a virological and immunological...

  20. Preservation of Steamed Fish (Rastrelliger Sp With Combine Method Using Sodium Acetate, Lactic Acid Bacteria Culture and Vacuum Packaging

    Directory of Open Access Journals (Sweden)

    Betty Sri Laksmi Jenie, . Nuratifa, . Suliantari

    2001-04-01

    Full Text Available This study was carried out to improve the safety and shelf life of cooked kembung fish (Rastrelliger sp, a traditional food called pindang fish. Fresh eviscerated fish was fisrt soaked in 2% NaCl solution for 15 minutes, drained, washed with tap water and drained again. Sodium chloride at 12% concentration (w/w was distributed on the whole surface of the fish. Fish was then laid on a wooden basket inside a clay pot, steamed for 30 minutes, and then cooled. Combine method applied to the steamed fish (pindang was soaking in a mixed culture of Lactobacillus plantarum kik and Lactococcus lactis subsp. cremoris in the ratio of 2 : 1 (v/v containing 4% Na-acetate for 2 hrs and after draining, the product was vacuum packed. The result showed that the combine method using mixed culture of lactic acid bacteria containing 4% Na-acetate could reduce the growth of Staphylococcus aureus by 3-6 log units, decrease the TMA (Trimethylamine content and maintain the organoleptic properties (texture, appearance and odor of pindang fish during 6 days storage at room temperature. Control treatment without 4% Na-acetate could only keep the pindang fish for 4 days. Vacuum and nonvacuum packaging did not show any significant difference.

  1. Combined cannabinoid therapy via an oromucosal spray.

    Science.gov (United States)

    Perez, Jordi

    2006-08-01

    Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1,000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects. Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.

  2. Oxidative stress in malaria and artemisinin combination therapy

    DEFF Research Database (Denmark)

    Kavishe, Reginald A.; Koenderink, Jan B.; Alifrangis, Michael

    2017-01-01

    Artemisinin-based combination therapy (ACT) has been adopted as a strategy to mitigate multidrug resistance to antimalarial monotherapies. ACT combines the rapid and effective but rather short plasma half-life antimalarial action of an artemisinin derivative with a longer acting partner drug...

  3. Combination therapy: the next opportunity and challenge of medicine

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2011-07-01

    Full Text Available Abstract From an historical point of view, combination therapy was the basis for the care of important diseases like infection diseases or cancer. Today the "cocktail drug" of the Highly Active Anti Retroviral Therapy (HAART has reduced the death for HIV infection changing the outcome of such disease. Moreover, the combination of different strategies changed the course of transplants (both in haematology and surgical transplant. Different diseases with high social impact including cardiovascular, metabolic (obesity, hypercholesterolaemia and diabetes and autoimmune diseases, have better results with combinations of different drug classes of drugs. After recent successes in the immunotherapy field (Sepuleucel-T, ipilimumab and the new promising small molecule therapies, cancer should be the next challenge for combination strategies.

  4. Propranolol, doxycycline and combination therapy for the treatment of rosacea.

    Science.gov (United States)

    Park, Jung-Min; Mun, Je-Ho; Song, Margaret; Kim, Hoon-Soo; Kim, Byung-Soo; Kim, Moon-Bum; Ko, Hyun-Chang

    2015-01-01

    Doxycycline is the standard systemic treatment for rosacea. Recently, there have been a few reports on β-adrenergic blockers such as nadolol, carvedilol and propranolol for suppressing flushing reactions in rosacea. To our knowledge, there are no comparative studies of propranolol and doxycycline, and combination therapy using both. The aim of this study was to investigate and compare the efficacy and safety of monotherapy of propranolol, doxycycline and combination therapy. A total of 78 patients who visited Pusan National University Hospital and were diagnosed with rosacea were included in this study. Among them, 28 patients were in the propranolol group, 22 the doxycycline group and 28 the combination group. We investigated the patient global assessment (PGA), investigator global assessment (IGA), assessment of rosacea clinical score (ARCS) and adverse effects. Improvement in PGA and IGA scores from baseline was noted in all groups, and the combination therapy was found to be the most effective during the entire period, but this was statistically insignificant. The reduction rate of ARCS during the treatment period was also highest in the combination group (57.4%), followed by the doxycycline group (52.2%) and the propranolol group (51.0%). Three patients in the combination group had mild and transient gastrointestinal disturbances but there was no significant difference from the other groups. We conclude that the combination therapy of doxycycline and propranolol is effective and safe treatment for rosacea and successful for reducing both flushing and papulation in particular.

  5. INCREASE OF RUNNING ABILITIES OF WOODCUTTING KNIFES BY THE COMBINED METHOD OF APPLICATION VACUUM STRENGTHENING COVERINGS AND MAGNETIC-PULSE PROCESSING

    Directory of Open Access Journals (Sweden)

    A. V. Alifanov

    2014-01-01

    Full Text Available Influence of modes of vacuum spatter of strengthening coverings (in particular titanium nitride on steel samples and magnetic-pulse processing of these coverings on durability of adhesive bindings of the applied covering with bottom layer (steel sample is studied. Results of experimental-industrial tests of the woodcutting knifes strengthened by the combined method of applying of vacuum strengthening coverings and magnetic-pulse processing are presented.

  6. Sono-photodynamic combination therapy: a review on sensitizers.

    Science.gov (United States)

    Sadanala, Krishna Chaitanya; Chaturvedi, Pankaj Kumar; Seo, You Mi; Kim, Jeung Mo; Jo, Yong Sam; Lee, Yang Koo; Ahn, Woong Shick

    2014-09-01

    Cancer is characterized by the dysregulation of cell signaling pathways at several steps. The majority of current anticancer therapies involve the modulation of a single target. A tumor-targeting drug-delivery system consists of a tumor detection moiety and a cytotoxic material joined directly or through a suitable linker to form a conjugate. Photodynamic therapy has been used for more than 100 years to treat tumors. One of the present goals of photodynamic therapy research is to enhance the selective targeting of tumor cells in order to reduce the risk and extension of unwanted side-effects, caused by normal cell damage. Sonodynamic therapy is a promising new treatment for patients with cancer. It treats cancer with ultrasound and sonosensitive agents. Porphyrin compounds often serve as photosensitive and sonosensitive agents. The combination of these two methods makes cancer treatment more effective. The present review provides an overview of photodynamic therapy, sonodynamic therapy, sono-photodynamic therapy and the four sensitizers which are suitable candidates for combined sono-photodynamic therapy. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Combination therapy in A549 cells

    Energy Technology Data Exchange (ETDEWEB)

    Yuan Menghui [Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an 710038 (China); Wang Jing [Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an 710038 (China)], E-mail: wangjing_fmmu@yahoo.com.cn; Deng Jinglan; Wang Zhe; Yang Weidong; Li Guoquan; Ren Bingxiu [Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an 710038 (China)

    2010-04-15

    Background and aim: We investigated the anti-tumor effect induced by the combination of the radiotherapeutic agent {sup 131}I-RC-160 and the prodrug 5-FC in human non-small cell lung cancer (NSCLC) A549 cells that were co-expressing the human somatostatin receptor 2 gene (hSSTR2) and E. coli cytosine deaminase gene (CD). Methods: We cloned both hSSTR2 and CD into a bicistronic mammalian expression plasmid and stably transfected it into A549 cells (pCIS-A549 cells). After antibiotic selection, SSTR expression in stable clones was determined by reverse transcription and polymerase chain reaction (RT-PCR), Western blot, flow cytometry and immunofluorescence analyses. To assess the in vivo targeting efficiency of the 'engineered' A549 cells, the cells were subcutaneously injected into nude mice and the biodistribution of {sup 99m}Tc-RC-160 was assessed at different time points. The tumor inhibitory effects of {sup 131}I-RC-160 and/or 5-FC were evaluated by measurement of tumor growth and immunohistochemical analysis. Results: Multiple analyses demonstrated the successful expression of hSSTR2 in A549 cells. In vivo radioimaging revealed specific targeting of RC-160 to the tumors derived from pCIS-A549 cells when compared to those from control A549 cells. The tumor inhibitory rate of pCIS-A549 tumors in the {sup 131}I-RC-160 plus 5-FC-treated group was significantly higher than that in the single agent-treated group, control group and control tumors. Conclusion: Co-expression of the hSSTR2 and CD genes in tumor cells can selectively sensitize these cells to the infra-additive effects of radioisotope-labeled RC-160 and 5-FC in vivo. This approach offers a potential therapeutic strategy for the treatment of lung cancer.

  8. Combined effects of vacuum packaging and mint extract treatment on the biochemical, sensory and microbial changes of chill stored Indian mackerel.

    Science.gov (United States)

    Viji, P; Panda, S K; Mohan, C O; Bindu, J; Ravishankar, C N; Srinivasa Gopal, T K

    2016-12-01

    The present study was aimed to investigate the combined effects of vacuum packaging and mint extract treatment on the quality changes of gutted Indian mackerel (Rastrelliger kanagurta) during storage at 0-2 °C for 22 days. Biochemical, total viable count and sensory quality of chill stored mackerel were analysed at periodic intervals. Mint extract treated [dipping in 0.5% (w/v) solution of mint extract for 30 min] and vacuum packed fishes (MEVP) had significantly lower total volatile base nitrogen and trimethyl amine nitrogen compared to those packed under vacuum (CVP) and air (CAP) without mint extract treatment. Nucleotide degradation rate was lower in MEVP followed by CVP and CAP. Vacuum packaging in combination with ME treatment significantly inhibited lipid hydrolysis and lipid oxidation in mackerel as observed from its lower free fatty acid, peroxide value and thiobarbituric acid reactive substances values. Synergistic use of mint extract and vacuum packaging has markedly controlled microbial proliferation in the samples. Based on sensory evaluation, shelf life of Indian mackerel stored at 0-2 °C was determined as 13 days for CAP group, 16 days for CVP group and 21 days for MEVP group, respectively. The present study revealed that combination of vacuum packaging and mint extract treatment can be a promising technology to improve the storage quality of chill stored gutted mackerel.

  9. Combined effect of vacuum packaging and refrigerated storage on the chemical quality of paneer tikka.

    Science.gov (United States)

    Ahuja, Kunal K; Goyal, G K

    2013-06-01

    Paneer tikka, a popular dish for vegetarians, is a tongue tingling favourite of Indian gourmets. It is a perishable commodity which requires more than five hours for its preparation. The shelf life of paneer tikka is hardly one day at room temperature which impedes its proper marketing. In order to enhance the shelf life of paneer tikka, the product was vacuum packed in two high barrier packages, viz., LLDPE(*)/BA(†)/Nylon-6/BA/LDPE(‡) (110 μ, (*)linear low density polyethylene, (†)binding agent, (‡)low density polyethylene) and metallized polyester/LDPE (20/75 μ) along with LDPE (100 μ) as control, and stored at 3 ± 1 °C. The stored samples were evaluated at 0, 10, 20, 30 and 40 day(s) for changes in chemical characteristics, namely moisture, pH, titratable acidity, free fatty acids content, tyrosine content and water activity. The analysis of variance of the data revealed that type of packages had significant influence on all the above parameters excluding water activity during storage of paneer tikka.

  10. Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pollom, Erqi L.; Deng, Lei [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Pai, Reetesh K. [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Brown, J. Martin; Giaccia, Amato; Loo, Billy W.; Shultz, David B.; Le, Quynh Thu; Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Chang, Daniel T., E-mail: dtchang@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2015-07-01

    Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action of toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.

  11. Combination antibiotic therapy for community-acquired pneumonia

    OpenAIRE

    Caballero, Jesus; Rello, Jordi

    2011-01-01

    Community-acquired pneumonia (CAP) is a common and potentially serious illness that is associated with morbidity and mortality. Although medical care has improved during the past decades, it is still potentially lethal. Streptococcus pneumoniae is the most frequent microorganism isolated. Treatment includes mandatory antibiotic therapy and organ support as needed. There are several antibiotic therapy regimens that include β-lactams or macrolides or fluoroquinolones alone or in combination. Co...

  12. The role of combination therapy in the treatment of hypertension.

    Science.gov (United States)

    Ruilope, L M; Coca, A

    1998-01-01

    Antihypertensive therapy is indicated for reducing the risk of cardiovascular morbidity and mortality that accompanies arterial hypertension. Usually, pharmacological treatment is started as monotherapy, which, if unsuccessful, is followed by sequential monotherapy, or by combination therapy. Recent data indicate that combination therapy is required in more than 50% of the hypertensive population when the goal is to reduce blood pressure to below 140/90 mm Hg. The choice and doses of drugs used in combination therapy should be such that their synergistic effect on blood pressure is maximized, the tolerability of the drugs is maintained and side-effects are minimized. The combination of a dihydropyridine calcium antagonist with a beta-blocker or an angiotensin-converting enzyme (ACE) inhibitor is one of the most commonly used combination therapies. Two randomized, double-blind, parallel-group studies compared the antihypertensive effects of the dihydropyridine, barnidipine, with the beta-blocker, atenolol (n = 247), and the ACE inhibitor, enalapril (n = 155). The efficacy and tolerability of barnidipine in combination with either atenolol or enalapril was also investigated. Monotherapy with barnidipine was as effective in reducing blood pressure as monotherapy with either atenolol or enalapril. Combining barnidipine with either atenolol or enalapril reduced blood pressure further, and significantly increased the percentage of patients attaining the required reduction in blood pressure. When patients whose blood pressure was not adequately controlled by enalapril monotherapy were switched to barnidipine monotherapy, the majority then achieved the desired reduction in blood pressure. These results indicate that if barnidipine monotherapy fails to lower blood pressure to the desired values, its combination with either a beta-blocker or an ACE inhibitor is effective and well tolerated.

  13. Treating Hypothyroidism with Thyroxine/Triiodothyronine Combination Therapy in Denmark

    DEFF Research Database (Denmark)

    Michaelsson, Luba Freja; Medici, Bjarke Borregaard; la Cour, Jeppe Lerche

    2015-01-01

    BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded as experime......BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded...... after a patient published a book describing her experiences with hypothyroidism and treatment. OBJECTIVE: To investigate current Danish trends in the use of T4/T3 combination therapy. METHODS: We used an Internet-based questionnaire, distributed as a link via two Danish patient fora. Further...

  14. Combined Chelation Therapy with Deferasirox and Deferoxamine in Thalassemia

    OpenAIRE

    Lal, Ashutosh; Porter, John; Sweeters, Nancy; Ng, Vivian; Evans, Patricia; Neumayr, Lynne; Kurio, Gregory; Harmatz, Paul; Vichinsky, Elliott

    2012-01-01

    Iron overload is the primary cause of mortality and morbidity in thalassemia major despite advances in chelation therapy. We performed a pilot clinical trial to evaluate the safety and efficacy of combined therapy with deferasirox (DFX, 20-30 mg/kg daily) and deferoxamine (DFO, 35-50 mg/kg on 3-7 days/week) in 22 patients with persistent iron overload or organ damage. In the 18 subjects completing 12 months of therapy, median liver iron concentration decreased by 31% from 17.4 mg/g (range 3.9...

  15. A multistep approach to manage Fournier’s gangrene in a patient with unknown type II diabetes: surgery, hyperbaric oxygen, and vacuum-assisted closure therapy: a case report

    Directory of Open Access Journals (Sweden)

    Pastore Antonio Luigi

    2013-01-01

    Full Text Available Abstract Introduction Fournier’s gangrene is an infectious necrotizing fasciitis of the perineum and genital regions and has a high mortality rate. It is a synergistic infection caused by a mixture of aerobic and anaerobic organisms and predisposing factors, including diabetes mellitus, alcoholism, malnutrition, and low socioeconomic status. We report a case of Fournier’s gangrene in a patient with unknown type II diabetes submitted to 24-hour catheterization 15 days before gangrene onset. Case presentation The patient, a 60-year-old Caucasian man, presented with a swollen, edematous, emphysematous scrotum with a crepitant skin and a small circle of necrosis. A lack of resistance along the dartos fascia of the scrotum and Scarpa’s lower abdominal wall fascia combined with the presence of gas and pus during the first surgical debridement also supported the diagnosis of Fournier’s gangrene. On the basis of the microbiological culture, the patient was given multiple antibiotic therapy, combined hypoglycemic treatment, hyperbaric oxygen therapy, and several surgical debridements. After five days the infection was not completely controlled and a vacuum-assisted closure device therapy was started. Conclusions This report describes the successful multistep approach of an immediate surgical debridement combined with hyperbaric oxygen and negative pressure wound therapy. The vacuum-assisted closure is a well-known method used to treat complex wounds. In this case study, vacuum-assisted closure treatment was effective and the patient did not require reconstructive surgery. Our report shows that bladder catheterization, a minimally invasive maneuver, may also cause severe infective consequences in high-risk patients, such as patients with diabetes.

  16. Combined statin-fibrate therapy-induced rhabdomyolysis: Case report

    Directory of Open Access Journals (Sweden)

    Jozić Tanja L.

    2014-01-01

    Full Text Available Introduction Rhabdomyolysis is a rare, but serious and potentially fatal adverse reaction of the statin application that may be developed in any time of therapy. It is characterized by massive destruction of muscles associated with the large increase of creatine kinase (CK leading to myoglobinuria and potential acute renal failure. Combined statin-fibrate therapy increases the risk of rhabdomyolysis, especially in elderly and diabetic patients. Case report An 81-year-old male was admitted to Coronary Care Unit of the Emergency Center, Clinical Center of Serbia (CCS with the clinical picture and electrocardiogram of the acute anterior wall myocardial infarction complicated with pulmonary edema. Laboratory tests on admission showed higher elevated values of serum creatinine 179 μmol/L and BUN 9.2 mmol/L (eGFR 32 mL/min/1.73m2, CK 309 U/L (on day 2: 3476 U/L and mixed hyperlipidemia (total cholesterol 10.3 mmol/L, HDL 2.26 mmol/L, TG 4.85 mmol/L. The patient was treated with thrombolysis medication therapy (Alteplase, anticoagulant and dual antiplatelet therapy, diuretics, organic nitrates, angiotensin-converting enzyme (ACE inhibitors, antibiotics, and proton pump inhibitors. During seven days, his therapy included combined pravastatin 20 mg and fenofibrate (160 mg, which was discontinued due to pains and weakness of muscles and significantly elevated CC to 7080 U/L (upper limit 200 U/L, but no significant deterioration of renal function was observed. Discontinuation of therapy resulted in CC level normalization and improvement of clinical condition. Conclusion Combined statin and fibrate therapy requires strict clinical control and monitoring of CK i transaminases. Four-time or higher increase of CK requires discontinuation of therapy. In addition, patients are advised to report immediately any pains in muscles, sensibility, weakness or cramps.

  17. Combined effects of salting, oregano oil and vacuum-packaging on the shelf-life of refrigerated trout fillets.

    Science.gov (United States)

    Frangos, L; Pyrgotou, N; Giatrakou, V; Ntzimani, A; Savvaidis, I N

    2010-02-01

    The present study evaluated the effect of salt, oregano essential oil (EO) and packaging on fresh rainbow trout fillets during storage at 4 degrees C. Treatments included the following: A1 (control samples, unsalted: air packaged), A2 (salted: air packaged), VP1 (salted, vacuum packaged), VP2 (salted, vacuum packaged with added oregano EO 0.2% v/wt), and VP3 salted, vacuum packaged with added oregano EO 0.4% v/wt). Lactic acid bacteria (LAB) (to a greater extent), followed by H(2)S-producing bacteria (including Shewanella putrefaciens), Pseudomonas spp. and Enterobacteriaceae reached higher populations in A1, A2 (as compared to VP1, VP2 and VP3) trout samples. Treatments VP1, VP2 and VP3 produced significantly lower (P TVBN) and trimethylamine nitrogen (TMAN) values as compared to the A1 and A2 samples after day 6 and until end of storage period. Changes in thiobarbituric acid values (TBA) values for A1, A2, VP1, VP2 and VP3 samples were variable, indicative of no specific trend in trout samples, irrespective of packaging in the absence and/or presence of salt and oregano EO. As determined by sensory analysis (overall acceptability attribute) the observed shelf-life of trout fillets was longest for VP2 (16-17 days) followed by VP1 (14 days), A2 (8 days) and control (A1) samples (5 days). The presence of salt and oregano oil (0.2%) in cooked VP1 trout samples produced a distinct but sensorially acceptable pleasant odor, well received by the panellists, in contrast to the combined effect of salt and oregano oil at the higher concentrations (0.4% v/wt) used. Addition of salt (treatment VP1) extended the product's shelf-life by 9 days, whereas the combination of salt, oregano EO (0.2% v/wt) under VP conditions (treatment VP2) resulted in a significant shelf-life extension of trout fillets (11-12 days) according to sensory data, as compared to the control sample, kept under aerobic conditions.

  18. Sonodynamic therapy with photosensitizers and its combination with photodynamic therapy in treatment of malignant tumors

    Directory of Open Access Journals (Sweden)

    D. A. Zerkovskiy

    2014-01-01

    Full Text Available The article reviews mechanisms of sonodynamic therapy with photosensitizers (ultrasound + photosensitizer and combination of sonodynamic with photodynamic therapy (ultrasound + photosensitizer + light exposure for treatment of malignant tumors. Efficacy of these methods with photosensitizers of different chemical structure in experimental study in vitro and in vivo on different tumor models and in clinical trials was assessed. 

  19. The use of endoluminal vacuum (E-Vac) therapy in the management of upper gastrointestinal leaks and perforations.

    Science.gov (United States)

    Smallwood, Nathan R; Fleshman, James W; Leeds, Steven G; Burdick, J S

    2016-06-01

    Upper intestinal leaks and perforations are associated with high morbidity and mortality rates. Despite the growing experience using endoscopically placed stents, the treatment of these leaks and perforations remain a challenge. Endoluminal vacuum (E-Vac) therapy is a novel treatment that has been successfully used in Germany to treat upper gastrointestinal leaks and perforations. There currently are no reports on its use in the USA. E-Vac therapy was used to treat 11 patients with upper gastrointestinal leaks and perforations from September 2013 to September 2014. Five patients with leaks following sleeve gastrectomy were excluded from this study. A total of six patients were treated with E-Vac therapy; these included: (n = 2) iatrogenic esophageal perforations, (n = 1) iatrogenic esophageal and gastric perforations, (n = 1) iatrogenic gastric perforation, (n = 1) gastric staple line leak following a surgical repair of a traumatic gastric perforation, and (n = 1) esophageal perforation due to an invasive fungal infection. Four patients had failed an initial surgical repair prior to starting E-Vac therapy. All six patients (100 %) had complete closure of their perforation or leak after an average of 35.8 days of E-Vac therapy requiring 7.2 different E-Vac changes. No deaths occurred in the 30 days following E-Vac therapy. One patient died following complete closure of his perforation and transfer to an acute care facility due to an unrelated complication. There were no complications directly related to the use of E-Vac therapy. Only one patient had any symptoms of dysphagia. This patient had severe dysphagia from an esophagogastric anastomotic stricture prior to her iatrogenic perforations. Following E-Vac therapy, her dysphagia had actually improved and she could now tolerate a soft diet. E-Vac therapy is a promising new method in the treatment of upper gastrointestinal leaks and perforations. Current successes need to be validated through future

  20. Newer approaches in topical combination therapy for acne.

    Science.gov (United States)

    Fu, Lisa W; Vender, Ronald B

    2011-10-01

    Acne vulgaris is a common chronic inflammatory cutaneous disease involving the pilosebaceous unit. Its pathophysiology is multifactorial and complex, including obstruction of the pilosebaceous unit due to increased sebum production, abnormal keratinization, proliferation of Propionibacterium acnes (P. acnes), and inflammation. Topical agents are the most commonly used therapy for acne. First generation topicals mainly consist of single agent retinoids, benzoyl peroxide (BPO) and antibacterials that target comedones, P. acnes, and inflammation. Novel topical therapies include combination products with advanced vehicle formulations that target multiple acne pathophysiologies and offer simplified treatment regimes. For example, the combination of clindamycin and tretinoin in a unique vehicle formulation allows for progressive follicle penetration and decreased irritation, resulting in increased efficacy. Furthermore, adapalene or clindamycin with BPO combinations target comedones, inflammation, and P. acnes synergistically. These newer combination products have the potential to increase both efficacy and patient adherence when compared with single agent treatment.

  1. Combination DMARD therapy including corticosteroids in early rheumatoid arthritis.

    Science.gov (United States)

    Möttönen, T T; Hannonen, P J; Boers, M

    1999-01-01

    A number of reports indicating the growing acceptance of simultaneous therapy with multiple disease-modifying anti-rheumatic drugs (DMARDs), as well as the use of more aggressive treatment measures in the early phases of disease to combat rheumatoid arthritis (RA), have appeared during the last decade. However, only a few randomized controlled clinical trials have been conducted on the use of DMARD combinations in early RA. We review these trials in this article. In two separate one-year studies combination therapy with sulphasalazine (SSZ) and methotrexate (MTX) seemed to offer no benefits compared to either drug used as monotherapy. On the other hand, the DMARD combinations so far proven to be superior to single DMARDs have initially also included a corticosteroid component. In the COBRA study (Combinatietherapie Bij Reumatoide Artritis) the combination of SSZ (2 gm/day), MTX (7.5 mg/week for 40 weeks), and prednisolone (Prd) (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day and stopped after 28 weeks) compared to SSZ alone (2 gm/day) resulted in significantly better clinical outcomes at week 28. Although the difference in clinical response between the treatment arms was lost at week 58, the progression of joint damage remained statistically significantly slower at week 80 in the patients initially assigned to the combination therapy. Furthermore, in the FIN-RACo trial (Finnish Rheumatoid Arthritis Combination Therapy Trial), therapy using a "tailored-steps" strategy with SSZ (1-2 gm/day), MTX (7.5-1.5 mg/week), hydroxychloroquine (300 mg/day), and Prd (up to 10 mg/day) yielded a significantly increased remission rate and less peripheral joint damage at two years than the single DMARD treatment strategy (initially SSZ 2 gm/day), with or without Prd. Adverse effects in both study arms were comparable. Two additional preliminary reports (in abstract form) suggest that intensive local therapy in the form of intra-articular injections added to single or

  2. A VACUUM ASSISTED CLOSURE (VAC THERAPY IN ORTHOPAEDIC TRAUMA : A PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Suresh

    2015-10-01

    Full Text Available BACKGROUND: Management of open fractures and massive soft tissue injuries around leg ankle, foot and hand requires multi - disciplinary approach. VAC therapy is an innovative approach to the treatment of these wounds. VAC therapy facilitates granulation tissue formation, promotes healing, reduces infection and allows early skin grafting or flap closure. AIM: To describe our experience with VAC therapy for orthopaedics trauma around leg ankle, foot and hand. MATERIALS AND METHODS : 41 patients were included in Prospective Study performed at Preethi hospital, Madurai in years 2011 - 12. Only patients having t raumatic wound of leg, ankle, foot and hand were i ncluded. Patients with bleeding disorders were not included. VAC therapy was used as adjuvant to debridement in wound care. RESULTS: In 39 patients lower limb and in 2 patient hands was involved. The mean age was 39.3 years and 38 pateints were male 3 were female. Mean wound grade after VAC therapy decrease by 1 grade. Average wound area reduction was 10%. The mean duration of VAC therapy was 5.2 days. Plastic surgery was done in mean 6 days after removal of VAC dressing. Local flap was required in only 39% of patients. After VAC therapy all 10 patients having heel injury showed good granulation tissue. Complications like infection, bleeding and skin irritation were not seen in our study. CONCLUSION : VAC therapy is a viable adjuvant in the management of trau matic open wounds. It facilitates the rapid granulation tissue formation and wound healing. It reduces the duration of treatment, hospital stay and need of extensive plastic surgery

  3. Combination therapy: the propitious rationale for drug development.

    Science.gov (United States)

    Phougat, Neetu; Khatri, Savita; Singh, Anu; Dangi, Mrridula; Kumar, Manish; Dabur, Rajesh; Chhillar, Anil Kumar

    2014-01-01

    Therapeutic options for many infections are extremely limited and at crisis point. We run the risk of entering a second pre-antibiotic era. There had been no miracle drug for the patients infected by resistant microbial pathogens. Most of the very few new drugs under development have problems with their toxicity, or pharmacokinetics and pharmacodynamics. We are already decades behind in the discovery, characterization and development of new antimicrobials. In that scenario, we could not imagine surviving without newer and effective antimicrobial agents. Bacteria have been the champions of evolution and are still evolving continuously, where they pose serious challenges for humans. Along with the crisis of evolving resistance, the condition is made worst by the meager drug pipeline for new antimicrobials. Despite ongoing efforts only 2 new antibiotics (Telavancin in 2009 and Ceftaroline fosamil in 2010) have been approved since 2009 pipeline status report of Infectious Disease Society of America (IDSA). Recent approval of new combination based antiviral drugs such as Stribild (combination of four drugs for HIV treatment) and Menhibrix (combination vaccine to prevent meningococcal disease and Haemophilus influenzae type b in children) proves that combination therapy is still the most promising approach to combat the ever evolving pathogens. Combination therapy involves the drug repurposing and regrouping of the existing antimicrobial agents to provide a synergistic approach for management of infectious diseases. This review article is an effort to highlight the challenges in new drug development and potential of combination drug therapy to deal with them.

  4. Combination therapy in hypertension: an Asia-Pacific consensus viewpoint.

    Science.gov (United States)

    Abdul Rahman, Abdul Rashid; Reyes, Eugenio B; Sritara, Piyamitr; Pancholia, Arvind; Van Phuoc, Dang; Tomlinson, Brian

    2015-05-01

    Hypertension incurs a significant healthcare burden in Asia-Pacific countries, which have suboptimal rates of blood pressure (BP) treatment and control. A consensus meeting of hypertension experts from the Asia-Pacific region convened in Hanoi, Vietnam, in April 2013. The principal objectives were to discuss the growing problem of hypertension in the Asia-Pacific region, and to develop consensus recommendations to promote standards of care across the region. A particular focus was recommendations for combination therapy, since it is known that most patients with hypertension will require two or more antihypertensive drugs to achieve BP control, and also that combinations of drugs with complementary mechanisms of action achieve BP targets more effectively than monotherapy. The expert panel reviewed guidelines for hypertension management from the USA and Europe, as well as individual Asia-Pacific countries, and devised a treatment matrix/guide, in which they propose the preferred combination therapy regimens for patients with hypertension, both with and without compelling indications. This report summarizes key recommendations from the group, including recommended antihypertensive combinations for specific patient populations. These strategies generally entail initiating therapy with free drug combinations, starting with the lowest available dosage, followed by treatment with single-pill combinations once the BP target has been achieved. A single reference for the whole Asia-Pacific region may contribute to increased consistency of treatment and greater proportions of patients achieving BP control, and hence reducing hypertension-related morbidity and mortality.

  5. Synergistic nanomedicine by combined gene and photothermal therapy.

    Science.gov (United States)

    Kim, Jinhwan; Kim, Jihoon; Jeong, Cherlhyun; Kim, Won Jong

    2016-03-01

    To date, various nanomaterials with the ability for gene delivery or photothermal effect have been developed in the field of biomedicine. The therapeutic potential of these nanomaterials has raised considerable interests in their use in potential next-generation strategies for effective anticancer therapy. In particular, the advancement of novel nanomedicines utilizing both therapeutic strategies of gene delivery and photothermal effect has generated much optimism regarding the imminent development of effective and successful cancer treatments. In this review, we discuss current research progress with regard to combined gene and photothermal therapy. This review focuses on synergistic therapeutic systems combining gene regulation and photothermal ablation as well as logically designed nano-carriers aimed at enhancing the delivery efficiency of therapeutic genes using the photothermal effect. The examples detailed in this review provide insight to further our understanding of combinatorial gene and photothermal therapy, thus paving the way for the design of promising nanomedicines.

  6. Clinical efficacy of artificial skin combined with vacuum sealing drainage in treating large-area skin defects

    Institute of Scientific and Technical Information of China (English)

    TANG Jin; GUO Wei-chun; YU Ling; ZHAO Sheng-hao

    2010-01-01

    Objective: To observe the clinical efficacy of artificial skin combined with vacuum sealing drainage (VSD) in treating large-area skin defects.Methods: Totally 18 patients with skin defects, treated with artificial skin combined with VSD from September 2008to May 2009 in our hospital, were retrospectively analyzed in this study. There were 15 males and 3 females, aged 7-66years, 34.3 years on average. Among them, 10 cases had skin laceration caused by traffic accidents (7 with open fractures), 1 mangled injury, 1 blast injury, 1 stump infection combined with skin defects after amputation and 5 heel ulcers.Results: All skin grafts in 16 cases survived after being controlled by VSD for one time. For the rest 2 patients,one with skin avulsion on the left foot was given median thickness skin grafts after three times of VSD, the other with open fractures in the left tibia and fibula caused by a traffic accident was given free flap transplantation. Skin grafts of both patients survived, with normal color and rich blood supply.Conclusion: Skin grafting in conjunction with artificial skin and VSD is much more effective than traditional dressing treatment and worth wide application in clinic.

  7. Effect of photodynamic therapy combined with intravitreal injection of Lucentis therapy on choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    Yan-Mei Su

    2016-01-01

    Objective:To analyze the efficacy of photodynamic therapy combined with intravitreal injection of Lucentis therapy for choroidal neovascularization.Methods: A total of 82 cases with choroidal neovascularization receiving inpatient therapy in our hospital from August 2013 to August 2014 were selected as research subjects, and according to random number table method, all enrolled patients were divided into control group (received photodynamic therapy) and observation group (received photodynamic therapy combined with intravitreal injection of Lucentis therapy), each group with 41 cases. Differences in best corrected visual acuity, intraocular pressure and central macular thickness, mean sensitivity of visual field and so on of two groups were compared.Results:After treatment, visual acuity improvement ratio of observation group was significantly higher than that of control group and visual acuity decrease ratio was lower than that of control group (P<0.05); intraocular pressure and central macular thickness were significantly less than those of control group (P<0.05); mean sensitivity of 10o and 30o visual field was higher than that of control group (P<0.05).Conclusions:Photodynamic therapy combined with intravitreal injection of Lucentis therapy can effectively improve vision and visual acuity of patients with choroidal neovascularization and reduce intraocular pressure and central macular thickness; it is an ideal treatment method.

  8. Effectiveness of medication / auricular therapy / phyto-therapy combination in the treatment of hypertensive patients

    Directory of Open Access Journals (Sweden)

    José Ramón Martínez Pérez

    2015-10-01

    Full Text Available Background: hypertension is one of the main cardiovascular risk factors, so its control improves the life expectancy of patients.Objective: to assess the effects of a treatment combining medication with auricular therapy and phyto-therapy in hypertensive patients assisted at the health area of ”Romárico Oro” Polyclinic, in Puerto Padre, Las Tunas province.Methods: an intervention study was carried out in 68 hypertensive patients of the health area of “Romárico Oro” Polyclinic in Puerto Padre from April, 2013 to April, 2014. The patients were distributed at random into two equal groups; the first received medication combined with auricular therapy and phyto-therapy, while the second one received only medication. The statistical analysis was done by means of Statistic system, t-student and Chi-Square tests were used and p< or =0.05 was considered as level of statistical significance.Results: by the end of the intervention, 73, 53% of the patients of the group with the combination of drug treatment and auricular therapy and phyto-therapy were controlled. In this group, the diastolic filling pressure diminished to 2, 2 mm Hg and the systolic gradient to 3, 66 mm, regarding the group treated only with drugs. Only one patient, representing the 2, 94% showed adverse reaction to the natural and traditional treatment.Conclusions: the combination of medication with auricular therapy and phyto-therapy proved to be effective, corroborated by a significant decrease of quantity of crisis, diastolic and systolic filling pressure values and increase of number of patients with their disease controlled; the report of only one complication shows the innocuousness of the auricular therapy and phyto-therapy treatment.

  9. Vacuum-Assisted Closure Combined with a Myocutaneous Flap in the Management of Osteomyelitis in a Dog

    Directory of Open Access Journals (Sweden)

    Jeremy L. Shomper

    2013-01-01

    Full Text Available Case Description. A 2.5-year-old female spayed mixed breed dog presented to the Teaching Hospital for draining tracts on the left medial aspect of the tibia. Two years prior to presentation, the patient sustained a left tibial fracture, which was repaired with an intramedullary (IM pin and two cerclage wires. Multiple antimicrobials were utilized during this time. Clinical Findings. Radiographs were consistent with left tibial osteomyelitis. The implant was removed and the wound was debrided. Treatment and Outcome. A bone window on the medial aspect of the tibia was created in order to facilitate implant removal. The wound and associated bone window were treated with vacuum assisted closure (VAC in preparation for reconstructive surgery. Adjunctive VAC therapy was utilized following the caudal sartorius myocutaneous flap. Complications following this surgery included distal flap necrosis and donor site dehiscence. Clinical Relevance. This presents a difficult case of canine osteomyelitis with subsequent wound care in which VAC and a myocutaneous flap were useful adjunctive treatments for osteomyelitis. This is the first report of VAC in the management of canine osteomyelitis and management with a myocutaneous flap.

  10. Precision medicine and personalized breast cancer: combination pertuzumab therapy

    Directory of Open Access Journals (Sweden)

    Reynolds K

    2014-03-01

    Full Text Available Kerry Reynolds, Sasmit Sarangi, Aditya Bardia, Don S Dizon Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA Abstract: Trastuzumab (Herceptin, a monoclonal antibody directed against the human epidermal growth-factor receptor 2 (HER2, is the poster child for antibody-based targeted therapy in breast cancer. Pertuzumab, another humanized monoclonal antibody, binds to a different domain of HER2 and prevents the formation of HER2:HER3 dimers, which is the most potent heterodimer in the HER family. The combination of trastuzumab and pertuzumab has synergistic activity, and is associated with improved clinical outcomes. The US Food and Drug Administration (FDA approved pertuzumab in combination with trastuzumab-based chemotherapy originally as first-line therapy for metastatic HER2-positive breast cancer in 2012, and more recently as neoadjuvant therapy for localized disease in 2013. Pertuzumab is the first neoadjuvant drug to receive accelerated approval by the FDA based on pathological complete response as the primary end point. In this article, we review the mechanism of action, pharmacokinetics, clinical efficacy, safety, and current role of pertuzumab in the management of breast cancer, as well as ongoing clinical trials and future directions regarding the utility of pertuzumab as a personalized therapeutic option for HER2-positive breast cancer. In the coming years, we anticipate increased utilization of neoadjuvant trials for drug development, biomarker discovery, and validation, and envision conduct of personalized breast cancer clinics in which therapies will be routinely selected based on genetic alterations in the tumor. Regardless of the targeted therapy combinations employed based on tumor genomic profile, trastuzumab and pertuzumab will likely continue to form the backbone of the personalized regimen for HER2-positive breast cancer. Keywords: pertuzumab, HER2 breast cancer, personalized therapy

  11. Amlodipine/benazepril: fixed dose combination therapy for hypertension.

    Science.gov (United States)

    Faulkner, M A; Hilleman, D E

    2001-01-01

    Myocardial infarction, stroke, heart failure and end-stage renal disease have all been linked to inadequate control of blood pressure. Despite overwhelming evidence that uncontrolled hypertension is responsible for a sizeable number of adverse health-related outcomes, control of the disease remains considerably suboptimal. Available data demonstrate that in order to achieve adequate blood pressure control, a large number of patients require therapy with more than one medication. Fixed dose combination antihypertensive therapy has many advantages over other treatment options. Positive effects on blood pressure control, rates of adherence, adverse effects and cost have been identified. Amlodipine/benazepril (Lotrel), Novartis) is a fixed dose combination product indicated for the treatment of hypertension. Although not currently recommended as first-line therapy, studies confirm that this combination of a long-acting calcium antagonist and an angiotensin-converting enzyme (ACE) inhibitor possesses substantial blood pressure lowering capabilities. Whereas adverse events tend to become more frequent with increasing doses of antihypertensive monotherapy, the rate of adverse events attributed to amlodipine/benazepril in clinical trials often correlates with rates ascribed to placebo. Amlodipine/benazepril is capable of sustaining blood pressure control over a 24 h period and appears to be minimally affected by an occasional dose omission. Unlike the older calcium antagonists, amlodipine is unlikely to cause alterations in myocardial contractility. Additionally, the amlodipine/benazepril combination product costs less than the same therapy administered as the individual components. It is, therefore, reasonable to consider therapy with amlodipine/benazepril in appropriate patients after an adequate trial of antihypertensive monotherapy.

  12. Optimizing antimicrobial therapy of sepsis and septic shock: focus on antibiotic combination therapy.

    Science.gov (United States)

    Vazquez-Grande, Gloria; Kumar, Anand

    2015-02-01

    There has been little improvement in septic shock mortality in the past 70 years, despite ever more broad-spectrum and potent antimicrobials. In the past, resuscitative elements have been the primary area of clinical septic shock management and research. The question of the optimal use of antimicrobial therapy was relatively ignored in recent decades. This review explores the pathophysiology of sepsis in an attempt to produce a better understanding and define key determinants of antimicrobial therapy response in septic shock. Optimizing existing antimicrobials delivery can drive significant improvements in the outcome of sepsis and septic shock. Inappropriate antimicrobial selection and dosing or delays in the administration substantially increase mortality and morbidity in life-threatening infections. Definitive combination therapy (where a pathogen known to be susceptible to a given agent is additionally covered by another agent) remains controversial. Although some in vitro studies, animal models, and clinical studies of infection including endocarditis, gram-negative bacteremia, and neutropenic infections have supported combination therapy, the potential clinical benefit in other severe infections has been questioned. Several meta-analyses have failed to demonstrate improvement of outcome with combination therapy in immunocompetent patients with sepsis and/or gram-negative bacteremia. These meta-analyses did not undertake subgroup analyses of the septic shock population. This article reviews the existing evidence supporting combination therapy for severe infections, sepsis, and septic shock.

  13. Effects of thermal therapy combining sauna therapy and underwater exercise in patients with fibromyalgia.

    Science.gov (United States)

    Matsumoto, Shuji; Shimodozono, Megumi; Etoh, Seiji; Miyata, Ryuji; Kawahira, Kazumi

    2011-08-01

    Fibromyalgia syndrome (FMS) is a chronic disorder that is characterized by widespread pain with localized tenderness. We aimed to investigate whether thermal therapy combining sauna therapy and underwater exercise improved pain, symptoms, and quality of life (QOL) in FMS patients. Forty-four female FMS patients who fulfilled the American College of Rheumatology (ACR) criteria received 12-week thermal therapy program comprising sauna therapy once daily for 3 days/week and underwater exercise once daily for 2 days/week. Pain, symptoms, and QOL were assessed using a pain visual analog scale (VAS), a fibromyalgia impact questionnaire (FIQ), and a short form 36-item questionnaire (SF-36), respectively. All of the patients reported significant reductions in pain and symptoms of 31-77% after the 12-week thermal therapy program, which remained relatively stable (28-68%) during the 6-month follow-up period (that is, the thermal therapy program improved both the short-term and the long-term VAS and FIQ scores). Improvements were also observed in the SF-36 score. Thermal therapy combining sauna therapy and underwater exercise improved the QOL as well as the pain and symptoms of FMS patients.

  14. Is fixed combination therapy appropriate for initial hypertension treatment?

    Science.gov (United States)

    Elliott, William J

    2002-08-01

    Recent clinical trials in hypertension prove how seldom single drug therapy achieves target blood pressure (BP) and reduces cardiovascular morbidity and mortality. A natural response is the testing and marketing of fixed-dose combination products for hypertension, of which 14 have been approved in the United States since 1993. Currently, only five products are indicated by the Food and Drug Administration for initial therapy of hypertension; all include a diuretic. To achieve such an indication, studies must show not only safety and efficacy of the combination, but also BP lowering that is at least additive compared with the two agents given separately, as well as a "synergy" not present when each agent is given alone. Some advantages to initial combination therapy include greater BP reduction, improved adherence to pill taking, fewer side effects, and lower cost. The most likely candidates for initial combination therapy are patients with initial BP higher than 160/100 mm Hg, or those with a BP goal lower than the customary 140/90 mm Hg. These include patients with target organ damage, clinical cardiovascular disease, proteinuria, renal impairment, or diabetes mellitus. In many of these circumstances, an angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist is frequently recommended; adding a diuretic or calcium antagonist to it is much more likely to result in achievement of the BP goal. More research is being done to explore the combination of not only two representatives from classes of conventional agents, but also other drugs that may help address the multiple manifestations of the "metabolic syndrome" that often accompanies hypertension.

  15. Effect of ganglioside and levodopa combined therapy on Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    Qiong Li; Nan-Nan Li; Jie Zhu

    2016-01-01

    Objective:To investigate the effect of ganglioside and levodopa combined therapy on oxidative stress indexes, serum Parkinson related proteins and inflammatory factors of patients with Parkinson's disease.Methods:A total of 110 patients with Parkinson’s disease treated in our hospital were selected, and randomly divided to be the combination group and the control group, 55 cases for each. Patients in control group were treated with levodopa, patients in combination group were provided with ganglioside and levodopa combined therapy. Oxidative stress indexes, serum Parkinson related proteins and serum inflammatory factors for each group of patients were detected before and after treatment.Results:No statistical difference showed in oxidative stress indexes, serum Parkinson related proteins and serum inflammatory factors between the two groups of patients with Parkinson's disease (P>0.05). Compared with prior treatment, serum Parkinson related proteins (Csy C and S-100B), MDA and inflammatory factors (TNF-α, CRP, IL-6) after relevant treatment were significantly decreased, BDNF, IL-2 and oxidative stress indexes (NO, SOD and GSH) were significantly increased (P<0.05). Oxidative stress indexes (NO, SOD and GSH), BDNF, IL-2 in combination group were significantly higher than which in control group after treatment, serum Parkinson related proteins (Csy C and S-100B), inflammatory factors (TNF-α, CRP, IL-6) and MDA were significantly lower than in control group after treatment (P<0.05).Conclusions:Ganglioside and levodopa combination can significantly improve levels of oxidative stress indexes, serum Parkinson related proteins and serum inflammatory factors in patients with Parkinson’s disease. It has important clinical significance on therapy of patients with Parkinson’s disease.

  16. Optimal lipid modification: the rationale for combination therapy

    Directory of Open Access Journals (Sweden)

    James M Backes

    2005-12-01

    Full Text Available James M Backes1, Cheryl A Gibson2, Patricia A Howard31Department of Pharmacy Practice, Lipid, Atherosclerosis, Metabolic and LDL Apheresis Center, University of Kansas Medical Center, Kansas City, KS, USA; 2Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 3Department of Pharmacy Practice, University of Kansas School of Pharmacy, Kansas City, KS, USABackground: An emphasis on more aggressive lipid-lowering, particularly of low-density lipoprotein cholesterol, to improve patient outcomes has led to an increased use of combination lipid-lowering drugs. This strategy, while potentially beneficial, has triggered concerns regarding fears of adverse effects, harmful drug interactions, and patient nonadherence.Objective: To present key data regarding combination lipid-altering therapy including use, rationale, major trials, benefits, potential adverse effects, compliance issues, and limitations. Method: Literature was obtained from MEDLINE (1966 – June 2005 and references from selected articles.Results: A substantial body of evidence from epidemiological data and clinical trials indicates that aggressive lipid modification, especially low-density lipoprotein reduction, is associated with reduced cardiovascular events. Numerous studies utilizing various combinations of cholesterol-lowering agents including statin/fibrate, statin/niacin, statin/bile acid resin, and statin/ezetimibe have demonstrated significant changes in the lipid profile with acceptable safety. Long-term trials of combination therapy evaluating clinical outcomes or surrogate markers of cardiovascular disease, while limited, are promising.Conclusion: Combining lipid-altering agents results in additional improvements in lipoproteins and has the potential to further reduce cardiovascular events beyond that of monotherapy.Keywords: combination therapy, coronary heart disease, hypercholesterolemia, lipid-lowering, low-density lipoprotein, statins

  17. Orthodontics-surgical combination therapy for Class III skeletal malocclusion

    Science.gov (United States)

    Ravi, M. S.; Shetty, Nillan K.; Prasad, Rajendra B.

    2012-01-01

    The correction of skeletal Class III malocclusion with severe mandibular prognathism in an adult individual requires surgical and Othodontic combination therapy. The inter disciplinary approach is the treatment of choice in most of the skeletal malocclusions. A case report of an adult individual with Class III malocclusion, having mandibular excess in sagittal and vertical plane and treated with orthodontics,, bilateral sagittal split osteotomy and Le – Forte I osteotomy for the correction of skeletal, dental and soft tissue discrepancies is herewith presented. The surgical–orthodontic combination therapy has resulted in near–normal skeletal, dental and soft tissue relationship, with marked improvement in the facial esthetics in turn, has helped the patient to improve the self-confidence level. PMID:22557903

  18. Orthodontics-surgical combination therapy for Class III skeletal malocclusion

    Directory of Open Access Journals (Sweden)

    M S Ravi

    2012-01-01

    Full Text Available The correction of skeletal Class III malocclusion with severe mandibular prognathism in an adult individual requires surgical and Othodontic combination therapy. The inter disciplinary approach is the treatment of choice in most of the skeletal malocclusions. A case report of an adult individual with Class III malocclusion, having mandibular excess in sagittal and vertical plane and treated with orthodontics,, bilateral sagittal split osteotomy and Le - Forte I osteotomy for the correction of skeletal, dental and soft tissue discrepancies is herewith presented. The surgical-orthodontic combination therapy has resulted in near-normal skeletal, dental and soft tissue relationship, with marked improvement in the facial esthetics in turn, has helped the patient to improve the self-confidence level.

  19. Combined Radiation Therapy and Immune Checkpoint Blockade Therapy for Breast Cancer.

    Science.gov (United States)

    Hu, Zishuo I; Ho, Alice Y; McArthur, Heather L

    2017-09-01

    Treatment with checkpoint inhibitors has shown durable responses in a number of solid tumors, including melanoma, lung, and renal cell carcinoma. However, most breast cancers are resistant to monotherapy with checkpoint inhibitors. Radiation therapy (RT) has been shown to have a number of immunostimulatory effects, including priming the immune system, recruiting immune cells to the tumor environment, and altering the immunosuppressive effects of the tumor microenvironment. RT therefore represents a promising adjuvant therapy to checkpoint blockade in breast cancer. We review the data from the checkpoint blockade studies on breast cancer reported to date, the mechanisms by which RT potentiates immune responses, the preclinical and clinical data of checkpoint blockade and RT combinations, and the landscape of current clinical trials of RT and immune checkpoint inhibitor combinations in breast cancer. Clinical trials with checkpoint blockade therapy have demonstrated response rates of up to 19% in breast cancer, and many of the responses are durable. Preclinical data indicate that RT combined with checkpoint inhibition synergizes not only to enhance antitumor efficacy but also to induce responses outside of the radiation field. Thus multiple clinical trials are currently investigating the combination of checkpoint inhibition with RT. The use of combination strategies that incorporate chemotherapy and/or local strategies such as RT may be needed to augment responses to immune therapy in breast cancer. Preclinical and clinical results show that RT in combination with checkpoint blockade may be a promising therapeutic option in breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Combination of Physical and Acupuncture Therapy: Acupoint Stimulation Physical Therapy (ASPT)

    OpenAIRE

    Suzuki, Toshiaki; Tani, Makiko; Onigata, Chieko; Bunno, Yoshibumi; Yoshida, Sohei

    2013-01-01

    We introduced Acupoint Stimulation Physical Therapy (ASPT) as a combination of physical and acupuncture therapy. The characteristics of ASPT were as follows. We pressed acupoints on the meridians running through the affected muscles. The magnitude and duration of acupressure stimulation were maximized to alter muscle tonus and not cause pain to the patient. We demonstrated its effects by scientific research using EMG and clinical evaluation in patients with knee contracture. In the future, we...

  1. Cancer treatment: the combination of vaccination with other therapies

    DEFF Research Database (Denmark)

    Andersen, M.H.; Sorensen, R.B.; Schrama, D.

    2008-01-01

    approach to fight cancer, the combination with additional therapy could create a number of synergistic effects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending...... and endothelial cells. The efficacy of therapeutic vaccination against cancer will over the next few years be studied in settings taking advantage of strategies in which vaccination is combined with other treatment modalities. These combinations should be based on current knowledge not only regarding the biology...... of the cancer cell per se, but also considering how treatment may influence the malignant cell population as well as the immune system Udgivelsesdato: 2008/11...

  2. Low-Energy Solvents For Carbon Dioxide Capture Enabled By A Combination Of Enzymes And Vacuum Regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, Sonja [Novozymes North America, Inc., Franklinton, NC (United States); House, Alan [Novozymes North America, Inc., Franklinton, NC (United States); Liu, Kun [Univ. of Kentucky, Lexington, KY (United States); Frimpong, Reynolds [Univ. of Kentucky, Lexington, KY (United States); Liu, Kunlei [Univ. of Kentucky, Lexington, KY (United States); Freeman, Charles [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Whyatt, Greg [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Slater, Jonathan [Doosan Babcock, Renfew (United Kingdom); Fitzgerald, David [Doosan Babcock, Renfew (United Kingdom)

    2015-08-31

    An integrated bench-scale system combining the attributes of the bio-renewable enzyme carbonic anhydrase (CA) with low-enthalpy CO2 absorption solvents and vacuum regeneration was designed, built and operated for 500 hours using simulated flue gas. The objective was to develop a CO2 capture process with improved efficiency and sustainability when compared to NETL Case 10 monoethanolamine (MEA) scrubbing technology. The use of CA accelerates inter-conversion between dissolved CO2 and bicarbonate ion to enhance CO2 absorption, and the use of low enthalpy CO2 absorption solvents makes it possible to regenerate the solvent at lower temperatures relative to the reference MEA-based solvent. The vacuum regeneration-based integrated bench-scale system operated successfully for an accumulated 500 hours using aqueous 23.5 wt% K2CO3-based solvent containing 2.5 g/L enzyme to deliver an average 84% CO2 capture when operated with a 20% enzyme replenishment rate per ~7 hour steady-state run period. The total inlet gas flow was 30 standard liters per minute with 15% CO2 and 85% N2. The absorber temperature was 40°C and the stripper operated under 35 kPa pressure with an approximate 77°C stripper bottom temperature. Tests with a 30°C absorber temperature delivered >90% capture. On- and off-line operational measurements provided a full process data set, with recirculating enzyme, that allowed for enzyme replenishment and absorption/desorption kinetic parameter calculations. Dissolved enzyme replenishment and conventional process controls were demonstrated as straightforward approaches to maintain system performance. Preliminary evaluation of a novel flow-through ultrasonically enhanced regeneration system was also conducted, yet resulted in CO2 release within the range of temperature-dependent release, and further work would be needed to validate the benefits of ultrasonic enhanced stripping. A full technology assessment was completed in which four techno-economic cases for

  3. Optimising treatment for COPD--new strategies for combination therapy.

    Science.gov (United States)

    Welte, T

    2009-08-01

    Chronic obstructive pulmonary disease (COPD) is a multi-component disease characterised by airflow limitation and airway inflammation. Exacerbations of COPD have a considerable impact on the quality of life, daily activities and general well-being of patients and are a great burden on the health system. Thus, the aims of COPD management include not only relieving symptoms and preventing disease progression but also preventing and treating exacerbations. Attention towards the day-to-day burden of the disease is also required in light of evidence that suggests COPD may be variable throughout the day with morning being the time when symptoms are most severe and patients' ability to perform regular morning activities the most problematic. While available therapies improve clinical symptoms and decrease airway inflammation, they do not unequivocally slow long-term progression or address all disease components. With the burden of COPD continuing to increase, research into new and improved treatment strategies to optimise pharmacotherapy is ongoing - in particular, combination therapies, with a view to their complementary modes of action enabling multiple components of the disease to be addressed. Evidence from recent clinical trials indicates that triple therapy, combining an anticholinergic with an inhaled corticosteroid and a long-acting beta(2)-agonist, may provide clinical benefits additional to those associated with each treatment alone in patients with more severe COPD. This article reviews the evidence for treatment strategies used in COPD with a focus on combination therapies and introduces the 3-month CLIMB study (Evaluation of Efficacy and Safety of Symbicort as an Add-on Treatment to Spiriva in Patients With Severe COPD) which investigated the potential treatment benefits of combining tiotropium with budesonide/formoterol in patients with COPD with regard to lung function, exacerbations, symptoms and morning activities.

  4. Azilsartan/chlorthalidone combination therapy for blood pressure control

    Directory of Open Access Journals (Sweden)

    Cheng JW

    2013-05-01

    Full Text Available Judy WM ChengMassachusetts College of Pharmacy and Health Sciences, Brigham and Women's Hospital, Boston, MA, USABackground: Edarbyclor® is a combined angiotensin receptor blocker (ARB and thiazide-like diuretic (azilsartan and chlorthalidone, and was approved on December 20, 2011 by the US Food and Drug Administration (FDA for hypertension management.Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, tolerability, and role of azilsartan plus chlorthalidone for hypertension management.Methods: Peer-reviewed clinical trials, review articles, and relevant treatment guidelines, were identified from the databases MEDLINE and Current Contents (both 1966 to February 15, 2013, inclusive using search terms “azilsartan”, “chlorthalidone”, “pharmacology”, “pharmacokinetics”, “pharmacodynamics”, “pharmacoeconomics”, and “cost-effectiveness”. The FDA website, as well as manufacturer prescribing information, was also reviewed to identify other relevant information.Results: Azilsartan is a new ARB with high affinity for the angiotensin 1 receptor, approved by the FDA for hypertension management. Unlike other ARBs, azilsartan has no clinical data supporting improvement in cardiovascular outcomes, and is not approved for indications other than hypertension, which a select few other ARBs may be used for (eg, diabetic nephropathy and heart failure. Chlorthalidone is a longer acting thiazide-like diuretic that has been demonstrated to improve cardiovascular outcomes. Combination treatment with azilsartan/chlorthalidone is effective for reducing blood pressure. Compared to olmesartan/hydrochlorothiazide and azilsartan/hydrochlorothiazide combinations, azilsartan/chlorthalidone appears to be more efficacious for reducing blood pressure.Conclusions: Azilsartan/chlorthalidone can be considered an antihypertensive therapy option in patients for whom combination therapy is required (blood pressure >20 mmHg systolic or

  5. A Retrospective Review of the Outcomes of Vacuum-assisted Closure Therapy in a Vascular Surgery Unit.

    Science.gov (United States)

    Ha, Jennifer; Phillips, Michael; Sieunarine, Kishore

    2008-08-01

     Wound problems are common in vascular surgery. They pose a therapeutic dilemma due to multiple etiologies. The use of vacuum-assisted closure (V.A.C.®, KCI, San Antonio, Tex), or negative pressure wound therapy (NPWT) has increased despite conflicting reports regarding its effectiveness. A retrospective review of 74 patients was conducted from 2002 to 2006 to assess the success of NPWT usage. Thirty-four (45.9%) patients were women and 40 (54.1%) men with median age of 65.5. There were 77 wounds in total: 25 foot, 13 toe and groin, 9 leg and thigh, 7 trunk, and 1 neck. Twenty-nine (37.7%) of these wounds were a result of surgical incision breakdown. Majority (n = 42, 54.5%) were infected secondary wounds. Six (7.8%) were infected wounds that broke down after initial closure. Overall surface area was 18.7 cm2: toe (15 cm2), foot (20 cm2), leg (32 cm2), thigh (57.5 cm2), groin (20 cm2), trunk (15 cm2), and neck (1.5 cm2). The median duration of NPWT was 11 days: toe (7.4), foot (12.2), leg (11.4), thigh (19), groin (15.6), trunk (18.4), and neck (1). The median length of stay in hospital was 36 days: toe (29.9), foot (44.5), leg (39.4), thigh (59.8), groin (35.2), trunk (45), and neck (35). The median healing time was 86 days. Overall healing was 75.4% (n ≥ 46). The predictors of poor healing were distal location, higher left dorsalis pedis value, stroke, peripheral vascular disease, retinopathy, dietary input, and supplementation. Weight gain, high dependency area (HDA) admission, combination hypoglycemic therapy, and steroid use were associated with faster healing. The success of vacuum-assisted closure is best above the ankle where the blood supply is usually adequate in vascular patients. .

  6. Fixed-dose combination therapy in hypertension: pros.

    Science.gov (United States)

    Taddei, Stefano

    2012-06-01

    Effective treatment of high blood pressure represents a key strategy for reducing the burden of hypertension-related cardiovascular diseases, mostly myocardial infarction and stroke. Despite these well established concepts, however, hypertension remains poorly controlled, worldwide. In addition, treated hypertensive patients often remain at higher risk compared with the normotensive population, even when a satisfactory blood pressure control is achieved, due to the high or very high added cardiovascular risk profile observed in these patients. An emerging strategy to improve blood pressure control and achieve this unmet target for cardiovascular disease prevention in hypertensive patients is represented by a more extensive use of rational and effective combination therapies with respect to monotherapy. Such an approach has been recently proposed even as first-line strategy in hypertensive patients at high added cardiovascular risk or in those in whom strict blood pressure control is required. Within the possible antihypertensive drug combinations currently available for the clinical management of hypertension, those based on the association of drugs inhibiting the renin-angiotensin system and thiazide diuretics or calcium channel blockers have demonstrated to be effective and safe in lowering both systolic and diastolic blood pressure levels with a good tolerability profile. In addition, these strategies have provided evidence for effective cardiovascular protection compared with conventional antihypertensive therapies. Among the antihypertensive drugs able to counteract the deleterious effects of abnormal activation of the renin-angiotensin system, angiotensin II receptor blockers have demonstrated to provide better tolerability profile and greater cardiovascular protection on hypertension-related organ damage compared with ACE inhibitors in randomized controlled clinical trials, in the presence of similar antihypertensive efficacy and safety. In particular, these

  7. Carfilzomib boosted combination therapy for relapsed multiple myeloma

    Science.gov (United States)

    Steiner, Raphael E; Manasanch, Elisabet E

    2017-01-01

    Carfilzomib is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome, the proteolytic core particle within the 26S proteasome, resulting in the accumulation of proteasome substrates and ultimately growth arrest and apoptosis of tumor cells. The development and ultimate approval of this medication by regulatory agencies has been an important step toward improving clinical outcomes in multiple myeloma. Although initially approved as a single agent for the treatment of multiply relapsed and/or refractory myeloma, in the USA, it is now widely used in the early relapse setting in combination with lenalidomide and dexamethasone. Carfilzomib has also been studied in combination with second-generation immunomodulatory drugs, histone deacetylase inhibitors, alkylating agents and other novel medications. In this review article, we will discuss the efficacy, safety, tolerability and quality of life of carfilzomib-based combination therapies, as well as novel agents, for relapsed multiple myeloma. PMID:28243125

  8. Clinical Opportunities in Combining Immunotherapy with Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Steven Eric Finkelstein

    2012-11-01

    Full Text Available Preclinical work in murine models suggests that local radiotherapy plus intratumoral syngeneic DC injection can mediate immunologic tumor eradication. Radiotherapy affects the immune response to cancer, besides the direct impact on the tumor cells, and other ways to coordinate immune modulation with radiotherapy have been explored. We review here the potential for immune mediated anticancer activity of radiation on tumors. This is mediated by antigen acquisition and presentation by dendritic cells, and through changes of lymphocytes’ activity. Recent work has implemented the combination of external beam radiation (EBRT with intratumoral injection of dendritic cells (DC. This included a pilot study of coordinated intraprostatic, autologous DC injection together with radiation therapy with five HLA-A2(+ subjects with high-risk, localized prostate cancer; the protocol used androgen suppression, external beam radiation therapy (25 fractions, 45 Gy, DC injections after fractions 5, 15, and 25, and then interstitial radioactive implant. Another was a phase II trial using neo-adjuvant cell death-inducing EBRT plus intra-tumoral DC in soft tissue sarcoma, to test if this would increase immune activity toward soft tissue sarcoma associated antigens. Clinical experience using radiation therapies combined with other systemic immune treatments are additionally surveyed, including use of investigational recombinant vaccinia and fowlpox, interleukin-2, toll like receptor 9 (TLR9 agonists and lymphocyte checkpoint inhibitors directed at PD1 and at CTLA4.

  9. A cost-minimization analysis of combination therapy in hypertension: fixed-dose vs extemporary combinations

    Directory of Open Access Journals (Sweden)

    Marco Bellone

    2013-12-01

    Full Text Available BACKGROUND: Cardiovascular disease management and prevention represent the leading cost driver in Italian healthcare expenditure. In order to reach the target blood pressure, a large majority of patients require simultaneous administration of multiple antihypertensive agents.OBJECTIVE: To assess the economic impact of the use of fixed dose combinations of antihypertensive agents, compared to the extemporary combination of the same principles.METHODS: A cost minimization analysis was conducted to determine the pharmaceutical daily cost of five fixed dose combinations (olmesartan 20 mg + amlodipine 5 mg, perindopril 5 mg + amlodipine 5 mg, enalapril 20 mg + lercanidipine 10 mg, felodipine 5 mg + ramipril 5 mg, and delapril 30 mg + manidipine 10 mg compared with extemporary combination of the same principles in the perspective of the Italian NHS. Daily acquisition costs are estimated based on current Italian prices and tariffs.RESULTS: In three cases the use of fixed‑dose combination instead of extemporary combination induces a lower daily cost. Fixed combination treatment with delapril 30 mg + manidipine 10 mg induces greater cost savings for the National Health System (95,47 €/pts/year, as compared to free drugs combination therapy.CONCLUSIONS: Compared with free drug combinations, fixed‑dose combinations of antihypertensive agents are associated with lower daily National Health Service acquisition costs.http://dx.doi.org/10.7175/fe.v14i4.886

  10. Combination therapy versus separate therapy in real-life primary care asthma patients

    NARCIS (Netherlands)

    Metting, Esther I.; Kocks, Janwillem W.H.; Van Der Molen, Thys

    2015-01-01

    In uncontrolled steroid naive asthma patients guidelines recommend separate ICS plus SABA(ST). Many physicians however prescribe combination therapy(CT) in these patients. We retrospectively evaluated the effectiveness of both strategies in an Asthma/COPD(AC)-service for primary care. We included st

  11. Targeted Therapies in Combination With Immune Therapies for the Treatment of Metastatic Melanoma.

    Science.gov (United States)

    Christiansen, Shelly A; Khan, Shaheer; Gibney, Geoffrey T

    In recent years, the field of oncology has witnessed many breakthroughs in the treatment of advanced malignancies, particularly in patients with advanced melanoma. Targeted and immune checkpoint therapies have emerged as the primary treatment strategies for these patients. Molecular profiling of melanoma is incorporated into routine practice to identify potential therapeutic targets, and patients are offered either a targeted or immune checkpoint inhibitor therapy approach. Both strategies have limitations where not all patients experience durable responses. Preclinical data have demonstrated the ability of targeted therapy to enhance activity of effector T cells, reduce immunosuppressive cytokine production, and increase tumor cell antigen presentation, which can augment antitumor immunity. In vivo models have shown synergy with improved tumor control when targeted and immune checkpoint agents are combined. Therefore, combination strategies with targeted and immune checkpoint therapy may improve patient outcomes. Early clinical data with anti-programmed cell-death protein 1/programmed cell-death ligand 1 agents in combination with targeted inhibitors appear to have acceptable toxicity rates and the potential for enhanced antitumor activity. This review explores the current status of preclinical and clinical development for these combination approaches in patients with advanced melanoma.

  12. Cancer nanomedicine: from targeted delivery to combination therapy.

    Science.gov (United States)

    Xu, Xiaoyang; Ho, William; Zhang, Xueqing; Bertrand, Nicolas; Farokhzad, Omid

    2015-04-01

    The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of various diseases, including cancer. The unique properties of nanoparticles (NPs), such as large surface-to-volume ratio, small size, the ability to encapsulate various drugs, and tunable surface chemistry, give them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make NPs a mode of treatment potentially superior to conventional cancer therapies. This review highlights the most recent developments in cancer treatment using NPs as drug delivery vehicles, including promising opportunities in targeted and combination therapy.

  13. Metastatic melanoma treatment: Combining old and new therapies.

    Science.gov (United States)

    Davey, Ryan J; van der Westhuizen, Andre; Bowden, Nikola A

    2016-02-01

    Metastatic melanoma is an aggressive form of cancer characterised by poor prognosis and a complex etiology. Until 2010, the treatment options for metastatic melanoma were very limited. Largely ineffective dacarbazine, temozolamide or fotemustine were the only agents in use for 35 years. In recent years, the development of molecularly targeted inhibitors in parallel with the development of checkpoint inhibition immunotherapies has rapidly improved the outcomes for metastatic melanoma patients. Despite these new therapies showing initial promise; resistance and poor duration of response have limited their effectiveness as monotherapies. Here we provide an overview of the history of melanoma treatment, as well as the current treatments in development. We also discuss the future of melanoma treatment as we go beyond monotherapies to a combinatorial approach. Combining older therapies with the new molecular and immunotherapies will be the most promising way forward for treatment of metastatic melanoma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. PRELIMINARY STUDY OF COMBINED PULSED VACUUM ARC SOURCE PLASMA%组合体脉冲真空电弧源的初步研究

    Institute of Scientific and Technical Information of China (English)

    李璟; 黄杰; 王锴; 张荟星; 彭建华; 邓春凤; 吴先映

    2014-01-01

    为得到高密度的等离子体,设计研制了组合体脉冲真空电弧源,它由4套脉冲真空电弧源组合而成.测量了脉冲真空电弧源弧压与弧流的关系;利用静电探针测量了组合体脉冲真空电弧源和单套脉冲真空电弧源产生的等离子体,得到了探针饱和电流(与等离子体密度成正比)与弧压的关系,以及等离子体密度的轴向分布情况;采用飞行时间方法估测了等离子体的飞行速度.组合脉冲真空电弧源最大等离子体密度达到8×1012 cm-3.%In order to get high density plasma,a combined pulsed vacuum arc source is designed and developed with four pulsed vacuum arc sources.The relationship of arc voltage and arc current is measured;The plasma in combined pulsed vacuum arc source and single pulsed vacuum arc source are measured using electrical probe.The relationship of probe saturation current (in proportion to plasma density)versus arc voltage and axial distribution of plasma are measured;The plasma velocity is estimated using time-of-flight method.The maximal plasma density in combined pulsed vacuum arc source is 8×1012 cm-3 .

  15. Combination of photodynamic therapy and immunotherapy - evolving role in dermatology

    Science.gov (United States)

    Wang, Xiu-Li; Wang, Hong-Wei; Huang, Zheng

    2008-02-01

    Photodynamic therapy (PDT) is a promising treatment modality. It offers alternative options in the treatment of cancer and vascular diseases. In cancer treatment, PDT has been used primarily for localized superficial or endoluminal malignant and premalignant conditions. More recently, its application has also been expanded to solid tumors. However, its antitumor efficacy remains debatable and its acceptance still variable. Pre-clinical studies demonstrate that, in addition to the primary local cytotoxicity, PDT might induce secondary host immune responses, which may further enhance PDT's therapeutic effects on primary tumor as well as metastasis. Therefore, PDT-induced local and systemic antitumor immune response might play an important role in successful control of malignant diseases. Furthermore, PDT's antitumor efficacy might also be enhanced through an effective immunoadjuvant or immunomodulator. Our recent clinical data also indicate that improved clinical outcomes can be obtained by a combination of PDT and immunomodulation therapy for the treatment of pre-malignant skin diseases. For instance, the combination of topical ALA-PDT and Imiquimod is effective for the treatment of genital bowenoid papulosis. This presentation will also report our preliminary data in developing combination approaches of PDT and immunotherapy for actinic keratosis (AK), basal cell carcinomas (BCCs) and Bowen's disease.

  16. Combined aquaretic and diuretic therapy in acute heart failure

    Directory of Open Access Journals (Sweden)

    Goyfman M

    2017-06-01

    Full Text Available Michael Goyfman,1 Paul Zamudio,2 Kristine Jang,3 Jennifer Chee,3 Catherine Miranda,2 Javed Butler,1 Nand K Wadhwa2 1Division of Cardiology, 2Division of Nephrology, 3Department of Medicine, Stony Brook School of Medicine, Stony Brook, NY, USA Introduction: Acute heart failure (AHF is a leading cause of hospitalization and readmission in the US. The present study evaluated maximum diuresis while minimizing electrolyte imbalances, hemodynamic instability, and kidney dysfunction, to achieve a euvolemic state safely in a shorter period of time.Methods and results: A protocol of combined therapy with furosemide, metolazone, and spironolactone, with or without tolvaptan and acetazolamide, was used in 17 hospitalized patients with AHF. The mean number of days on combination diuretic protocol was 3.8 days. The mean daily fluid balance was 3.0±2.1 L negative. The mean daily urine output (UOP was 4.1±2.0 L (range 1.8–10.5 L. There were minimal fluctuations in serum electrolyte levels and serum creatinine over the duration of diuretic therapy. There was no statistically significant change in patients’ creatinine from immediately prior to therapy to the last day of therapy, with a mean increase in creatinine of 0.14 mg/dL (95% CI −0.03, +0.30, p=0.10.Conclusion: Our strategy of treating AHF by achieving high UOP, while maintaining stable electrolytes and creatinine in a short period to euvolemic state, is safe. Keywords: diuretics, aquaretic, acute heart failure, volume overload

  17. Optimization of Vacuum Frying Parameters in Combination with Osmotic Dehydration of Kiwi Slices to Produce Healthy Product

    Directory of Open Access Journals (Sweden)

    Fatemeh Aghabozorg Afjeh Aghabozorg Afjeh

    2014-05-01

    Full Text Available Osmotic dehydration under discontinuous reduced pressure is one of the new methods of preparation fruits and vegetable processing with in view of good health. Processing of foods at high temperatures used to cook them can cause the formation of carcinogenic substances like acrylamide, and this risk remains even if the trans-fat is removed. The low temperatures employed in this method resulted in the products with the desired texture, nutritional, and colour. The purpose of this research was evaluation of the variable effects of osmotic dehydration process (ambient pressure, contact time of product and solution, concentration and temperature of osmotic solution on the quality factors of product (colour changes, texture, moisture, oil uptake, and water loss to solid gain ratio and achieving the optimum process conditions. Studying the quality parameters of the product, the temperature range of osmotic solution, pressure, concentration of the osmotic solution and contact time of product and solution were assumed as 30 to 50°C, 500 to 700 mbar, 30 to 50% and 60 to 180 min, respectively. The test plans involving 31 tests were obtained by using response surface statistical models and central composite design. They were fried at the condition of 108ºC, 8 min and 320 mbar by using statistical correlations, 48.71ºC for the osmotic solution temperature, 592.07 mbar for the pressure, 62.92 min for the time and 34.87% for the osmotic solution. Concentrations were obtained as optimum conditions of osmotic dehydration of kiwi slices under reduced pressure. In summary combination of osmotic dehydration and vacuum frying improved the quality of the final fried kiwi, so this method is recommended for production of healthy products.

  18. Discodermolide analogues as the chemical component of combination bacteriolytic therapy.

    Science.gov (United States)

    Smith, Amos B; Freeze, B Scott; LaMarche, Matthew J; Sager, Jason; Kinzler, Kenneth W; Vogelstein, Bert

    2005-08-01

    The marine natural product (+)-discodermolide (1) and several simplified analogues of this microtubule-stabilizing agent have proven to be potent in vitro cell growth inhibitory agents in several human cancer cell lines. Here, we demonstrate the in vivo efficacy of discodermolide and several simplified congeners, both as stand-alone anti-tumor agents and, in the case of (+)-2,3-anhydrodiscodermolide (3), as a chemical component of the combination bacteriolytic therapy. A single intravenous injection of (+)-3 plus genetically modified Clostridium novyi-NT spores caused rapid and complete regressions of tumors in mice bearing HCT116 colorectal cancer xenografts.

  19. Triple antiviral therapy in HCV positive patients who failed prior combination therapy

    Institute of Scientific and Technical Information of China (English)

    Silvia Fargion; Mauro Borzio; Alessandra Maraschi; Antonietta Cargnel

    2006-01-01

    AIM: To assess the efficacy of triple therapy (peginterferon or high dose standard interferon, plus ribavirin and amantadine) in nonresponders to prior combination therapy.METHODS: A total of 196 patients were enrolled in a multicenter, open, randomized study. Patients were given 180 μg/wk of peginterferon-alpha-2a (40 kD) plus ribavirin (800-1000 mg/d) and amantadine (200 mg/d)for 48 wk (group A) or interferon-alpha-2a (6 MU/d for 4 wk, 3 MU/d for 20 wk, and 3 MU tiw for 24 wk) plus ribavirin (800-1000 mg/d) and amantadine (200 mg/d)for 48 wk (group B).RESULTS: Overall sustained virologic response (SVR)was 26.6% (32.1% and 19.5% in group A and B, P =0.057). Baseline ALT >120 UI/L (OR 2.4; 95% CI:1.11to 5.20; P = 0.026) and HCV RNA negativity after 12 wk (OR 8.7; 95% CI: 3.87 to 19.74; P < 0.0001)were independently associated with SVR. Therapy discontinuation occurred less frequently in patients treated with peginterferon than standard interferon (P =0.036).CONCLUSION: More than 25% of nonresponders to combination therapy can eradicate HCV infection when retreated with triple therapy, especially if they have a high baseline ALT and are treated with pegylated interferon.

  20. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    Directory of Open Access Journals (Sweden)

    René Klysner

    2014-01-01

    Full Text Available The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.

  1. Bioengineered lysozyme in combination therapies for Pseudomonas aeruginosa lung infections

    Science.gov (United States)

    Griswold, Karl E; Bement, Jenna L; Teneback, Charlotte C; Scanlon, Thomas C; Wargo, Matthew J; Leclair, Laurie W

    2014-01-01

    There is increasing urgency in the battle against drug-resistant bacterial pathogens, and this public health crisis has created a desperate need for novel antimicrobial agents. Recombinant human lysozyme represents one interesting candidate for treating pulmonary infections, but the wild type enzyme is subject to electrostatic mediated inhibition by anionic biopolymers that accumulate in the infected lung. We have redesigned lysozyme’s electrostatic potential field, creating a genetically engineered variant that is less susceptible to polyanion inhibition, yet retains potent bactericidal activity. A recent publication demonstrated that the engineered enzyme outperforms wild type lysozyme in a murine model of Pseudomonas aeruginosa lung infection. Here, we expand upon our initial studies and consider dual therapies that combine lysozymes with an antimicrobial peptide. Consistent with our earlier results, the charge modified lysozyme combination outperformed its wild type counterpart, yielding more than an order-of-magnitude reduction in bacterial burden following treatment with a single dose. PMID:24637705

  2. Combining chemotherapy and targeted therapies in metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, cetuximab and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer.

  3. Combination Adriamycin and radiation therapy in gynecologic cancers

    Energy Technology Data Exchange (ETDEWEB)

    Watring, W.G.; Byfield, J.E.; Lagasse, L.D.; Lee, Y.D.; Juillard, G.; Jacobs, M.; Smith, M.L.

    1974-12-01

    Anthracyclic antibiotics, of which adriamycin is representative, have the ability to bind to cellular DNA and thereby interfere with the X ray repair process. When radiation survival curves of tissue cultures were studied, increased cell-killing was noted in those cultures with adriamycin over those without the drug. The mechanism by which this occurs may be related to a reduced rate of DNA strand break rejoining, as demonstrated by use of alkaline sucrose gradient techniques. A preliminary clinical Phase I study, in which patients with advanced gynecologic malignancy were treated by simultaneous adriamycin and X radiation, suggests that combined therapy is well-tolerated, and that such combinations may prove useful in selected patients.

  4. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    DEFF Research Database (Denmark)

    Klysner, René; Bjerg Bendsen, Birgitte; Hansen, Maja Soon

    2014-01-01

    The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.......The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine....

  5. Choosing the right combination therapy in severe community-acquired pneumonia

    OpenAIRE

    Waterer, Grant W.; Rello, Jordi

    2006-01-01

    Recent studies have suggested that combination antibiotic therapy is preferable to monotherapy for severe community-acquired pneumonia (CAP). In this issue Mortensen and colleagues present retrospective data suggesting that combination therapy with a cephalosporin and a fluoroquinolone is inferior to combination therapy with a cephalosporin and a macrolide. Several mechanisms exist by which quinolones could be inferior to macrolides in combination therapy, so if these findings are confirmed b...

  6. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria

    OpenAIRE

    Tängdén, Thomas

    2014-01-01

    Combination antibiotic therapy for Gram-negative sepsis is controversial. The present review provides a brief summary of the existing knowledge on combination therapy for severe infections with multidrug-resistant Pseudomonas spp., Acinetobacter spp., and Enterobacteriaceae. Empirical combination antibiotic therapy is recommended for severe sepsis and septic shock to reduce mortality related to inappropriate antibiotic treatment. Because definitive combination therapy has not been proven supe...

  7. Effects of vacuum or modified atmosphere packaging in combination with irradiation for control of Escherichia coli O157:H7 in ground beef patties.

    Science.gov (United States)

    Kudra, Li L; Sebranek, Joseph G; Dickson, James S; Mendonca, Aubrey F; Larson, Elaine M; Jackson-Davis, Armitra L; Lu, Zheng

    2011-12-01

    The efficacy of controlling Escherichia coli O157:H7 in ground beef patties by combining irradiation with vacuum packaging or modified atmosphere packaging (MAP) was investigated. Fresh ground beef patties were inoculated with a five-strain cocktail of E. coli O157:H7 at 5 log CFU/g. Single patties, packaged with vacuum or high-CO(2) MAP (99.6% CO(2) plus 0.4% CO), were irradiated at 0 (control), 0.5, 1.0, or 1.5 kGy. The D(10)-value for this pathogen was 0.47 ± 0.02 kGy in vacuum and 0.50 ± 0.02 kGy in MAP packaging. Irradiation with 1.5 kGy reduced E. coli O157:H7 by 3.0 to 3.3 log, while 0.5 and 1.0 kGy achieved reductions of 0.7 to 1.0, and 2.0 to 2.2 log, respectively. After irradiation, the numbers of survivors of this pathogen on beef patties in refrigerated storage (4°C) did not change significantly for 6 weeks. Temperature abuse (at 25°C) resulted in growth in vacuum-packaged patties treated with 0.5 and 1.5 kGy, but no growth in MAP packages. This study demonstrated that combining irradiation with MAP was similar in effectiveness to irradiation with vacuum packaging for control of E. coli O157:H7 in ground beef patties during refrigerated storage. However, high-CO(2) MAP appeared to be more effective after temperature abuse.

  8. A novel temperature-responsive micelle for enhancing combination therapy

    Directory of Open Access Journals (Sweden)

    Peng CL

    2016-07-01

    Full Text Available Cheng-Liang Peng,1,* Yuan-I Chen,2,3,* Hung-Jen Liu,2 Pei-Chi Lee,2 Tsai-Yueh Luo,1 Ming-Jium Shieh2,3 1Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, 2Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, 3Department of Oncology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan *These authors contributed equally to this work Abstract: A novel thermosensitive polymer p(N-isopropylacrylamide-co-poly[ethylene glycol] methyl ether acrylate-block-poly(epsilon-caprolactone, p(NIPAAM-co-PEGMEA-b-PCL, was synthesized and developed as nanomicelles. The hydrophobic heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin and the photosensitizer cyanine dye infrared-780 were loaded into the core of the micelles to achieve both chemotherapy and photothermal therapy simultaneously at the tumor site. The release of the drug could be controlled by varying the temperature due to the thermosensitive nature of the micelles. The micelles were less than 200 nm in size, and the drug encapsulation efficiency was >50%. The critical micelle concentrations were small enough to allow micelle stability upon dilution. Data from cell viability and animal experiments indicate that this combination treatment using photothermal therapy with chemotherapy had synergistic effects while decreasing side effects. Keywords: thermosensitive, photothermal therapy, chemotherapy, nanocarrier, control release, synergistic effect

  9. A Framework for Combining rTMS with Behavioral Therapy.

    Science.gov (United States)

    Tsagaris, K Zoe; Labar, Douglas R; Edwards, Dylan J

    2016-01-01

    Upon its inception, repetitive transcranial magnetic stimulation (rTMS) was delivered at rest, without regard to the potential impact of activity occurring during or around the time of stimulation. rTMS was considered an experimental intervention imposed on the brain; therefore, the myriad features that might suppress or enhance its desired effects had not yet been explored. The field of rTMS has since grown substantially and therapeutic benefits have been reported, albeit with modest and inconsistent improvements. Work in this field accelerated following approval of a psychiatric application (depression), and it is now expanding to other applications and disciplines. In the last decade, experimental enquiry has sought new ways to improve the therapeutic benefits of rTMS, intended to enhance underlying brain reorganization and functional recovery by combining it with behavioral therapy. This concept is appealing, but poorly defined and requires clarity. We provide an overview of how combined rTMS and behavioral therapy has been delineated in the literature, highlighting the diversity of approaches. We outline a framework for study design and reporting such that the effects of this emerging method can be better understood.

  10. A Framework for Combining rTMS with Behavioral Therapy

    Directory of Open Access Journals (Sweden)

    K. Zoe Tsagaris

    2016-11-01

    Full Text Available Upon its inception, repetitive transcranial magnetic stimulation (rTMS was delivered at rest, without regard to the potential impact of activity occurring during or around the time of stimulation. rTMS was considered an experimental intervention imposed on the brain; therefore, the myriad features that might suppress or enhance its desired effects had not yet been explored. The field of rTMS has since grown substantially and therapeutic benefits have been reported, albeit with modest and inconsistent improvements. Work in this field accelerated following approval of a psychiatric application (depression, and it is now expanding to other applications and disciplines. In the last decade, experimental enquiry has sought new ways to improve the therapeutic benefits of rTMS, intended to enhance underlying brain reorganization and functional recovery by combining it with behavioral therapy. This concept is appealing, but poorly defined and requires clarity. We provide a snapshot of how combined rTMS and behavioral therapy has been delineated in the literature, highlighting the diversity of approaches. We outline a framework for study design and reporting such that the effects of this emerging method can be better understood.

  11. Combined preoperative therapy for oral cancer with nedaplatin and radiation

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Masatoshi; Shibata, Akihiko; Hayashi, Munehiro [Nippon Dental Univ., Tokyo (Japan). Hospital] (and others)

    2002-03-01

    We performed preoperative combined therapy using nedaplatin (CDGP) and radiation in 12 patients with squamous cell carcinoma originating from the oral cavity and maxillary sinus, and examined for any adverse events that may have occurred during this therapeutic regimen. Regarding the irradiation, external irradiation utilizing a 6 MV linac (linear accelerator) at a dose of 2.0 Gy/day was performed 5 times a week, with the target total radiation dose set at 40 Gy. In addition, CDGP was intravenously administered 30 minutes before irradiation at a dose of 5 mg/m{sup 2}/day. Mucositis was observed in all 12 subjects, however, the severity was observed to be grade 1-2 with no major differences in comparison to the patients given standard radiation monotherapy. Two subjects developed grade 3 leucopenia and were thus given granulocyte colony stimulating factor (G-CSF). In addition, grade 2 and grade 3 thrombocytopenia were both observed in one subject each. The subject with grade 3 thrombocytopenia required a platelet transfusion during surgery. No marked changes in serum creatinine levels were noted. These findings are therefore considered to provide evidence supporting the safety of this combination therapy. (author)

  12. Pancreatic cancer: systemic combination therapies for a heterogeneous disease.

    Science.gov (United States)

    Melisi, Davide; Calvetti, Lorenzo; Frizziero, Melissa; Tortora, Giampaolo

    2014-01-01

    Pancreatic cancer is the only human malignancy for which patients' survival has not improved substantially during the past 30 years. Despite advances in the comprehension of the molecular mechanisms underlying pancreatic carcinogenesis, current systemic treatments offer only a modest benefit in tumor-related symptoms and survival. Over the past decades, gemcitabine and its combination with other standard cytotoxic agents have been the reference treatments for advanced pancreatic cancer patients. The recent introduction of the three-drug combination regimen FOLFIRINOX or the new taxane nab-paclitaxel represent key advances for a better control of the disease. Novel agents targeting molecular mechanisms involved in cancer development and maintenance are currently under clinical investigation. This review describes the most important findings in the field of systemic combination therapies for the treatment of pancreatic cancer. We discuss the emerging evidences for the clinical activity of combination treatments with standard chemotherapy plus novel agents targeting tumor cell-autonomous and tumor microenvironment signaling pathways. We present some of the most important advances in the comprehension of the molecular mechanisms responsible for the chemoresistance of pancreatic cancer and the emerging therapeutic targets to overcome this resistance.

  13. Epigenetic therapy in gastrointestinal cancer: the right combination

    Science.gov (United States)

    Abdelfatah, Eihab; Kerner, Zachary; Nanda, Nainika; Ahuja, Nita

    2016-01-01

    Epigenetics is a relatively recent field of molecular biology that has arisen over the past 25 years. Cancer is now understood to be a disease of widespread epigenetic dysregulation that interacts extensively with underlying genetic mutations. The development of drugs targeting these processes has rapidly progressed; with several drugs already FDA approved as first-line therapy in hematological malignancies. Gastrointestinal (GI) cancers possess high degrees of epigenetic dysregulation, exemplified by subtypes such as CpG island methylator phenotype (CIMP), and the potential benefit of epigenetic therapy in these cancers is evident. The application of epigenetic drugs in solid tumors, including GI cancers, is just emerging, with increased understanding of the cancer epigenome. In this review, we provide a brief overview of cancer epigenetics and the epigenetic targets of therapy including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. We discuss the epigenetic drugs currently in use, with a focus on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, and explain the pharmacokinetic and mechanistic challenges in their application. We present the strategies employed in incorporating these drugs into the treatment of GI cancers, and explain the concept of the cancer stem cell in epigenetic reprogramming and reversal of chemo resistance. We discuss the most promising combination strategies in GI cancers including: (1) epigenetic sensitization to radiotherapy, (2) epigenetic sensitization to cytotoxic chemotherapy, and (3) epigenetic immune modulation and priming for immune therapy. Finally, we present preclinical and clinical trial data employing these strategies thus far in various GI cancers including colorectal, esophageal, gastric, and pancreatic cancer. PMID:27366224

  14. Aliskiren and valsartan combination therapy for the management of hypertension

    Directory of Open Access Journals (Sweden)

    Benjamin J Epstein

    2010-08-01

    Full Text Available Benjamin J EpsteinDepartments of Pharmacotherapy and Translational Research and Medicine, Colleges of Pharmacy and Medicine, University of Florida, Gainesville, Florida, USA and East Coast Institute for Research, Jacksonville, Florida, USAAbstract: Combination therapy is necessary for most patients with hypertension, and agents that inhibit the renin-angiotensin-aldosterone system (RAAS are mainstays in hypertension management, especially for patients at high cardiovascular and renal risk. Single blockade of the RAAS with an angiotensin-converting enzyme (ACE inhibitor or angiotensin receptor blocker (ARB confers some cardiorenal protection; however, these agents do not extinguish the RAAS as evidenced by a reactive increase in plasma renin activity (PRA, a cardiovascular risk marker, and incomplete cardiorenal protection. Dual blockade with an ACE inhibitor and an ARB offers no additional benefit in patients with hypertension and normal renal and left ventricular function. Indeed, PRA increases synergistically with dual blockade. Aliskiren, the first direct renin inhibitor (DRI to become available has provided an opportunity to study the merit of DRI/ARB combination treatment. By blocking the first and rate-limiting step in the RAAS, aliskiren reduces PRA by at least 70% and buffers the compensatory increase in PRA observed with ACE inhibitors and ARBs. The combination of a DRI and an ARB or an ACE inhibitor is an effective approach for lowering blood pressure; available data indicate that such combinations favorably affect proteinuria, left ventricular mass index, and brain natriuretic peptide in patients with albuminuria, left ventricular hypertrophy, and heart failure, respectively. Ongoing outcome studies will clarify the role of aliskiren and aliskiren-based combination RAAS blockade in patients with hypertension and those at high cardiorenal risk.Keywords: aliskiren, valsartan, single-pill combination, hypertension, renin

  15. Impact of deep sternal wound infection management with vacuum-assisted closure therapy followed by sternal osteosynthesis: a 15-year review of 23,499 sternotomies.

    Science.gov (United States)

    Baillot, Richard; Cloutier, Daniel; Montalin, Livia; Côté, Louise; Lellouche, François; Houde, Chanel; Gaudreau, Geneviève; Voisine, Pierre

    2010-04-01

    This study was undertaken to examine the outcome of patients with deep sternal wound infection (DSWI) now treated with vacuum-assisted closure (VAC) therapy as a bridge to sternal osteosynthesis with horizontal titanium plate fixation. From 1992 to 2007, a consecutive cohort of 23,499 patients underwent open-heart surgery (OHS) in our institution. The period under study was divided in two according to the use of therapeutic modalities: conventional (1992-2001, N=118 DSWI): debridement/drainage with primary closure and irrigation (N=37), debridement/drainage, open packing followed by pectoralis myocutaneous flaps (PMFs) (N=81); contemporary (2002-2007, N=149 DSWI): conventional treatment (N=24) and VAC therapy (N=125/83.8%). VAC was followed by sternal osteosynthesis with horizontal titanium plates in 92 patients (61.7%). DSWI was diagnosed in 267 out of 23 499 (1.1%) patients of our entire series according to Center for Disease Control - Atlanta (CDC) criteria, 118 out of 13 180 (0.9%) in the first and 149 out of 10 319 (1.4%) in the second period (p=0.001). Hospital mortality (N=267/23,499) has been 10.25% for the entire cohort under study without any difference between groups (1992-2001: 11.4%; 2002-2007: 9.1%, p=0.67). More recently, VAC therapy (N=125) was associated with a lower mortality (4.8% vs 14.1%, p=0.01). Stepwise multivariable logistic regression analysis for both periods revealed that prolonged intubation in the intensive care unit (ICU), use of bilateral internal thoracic artery grafting (BIMA), diabetes, re-operation for bleeding and body mass index (BMI) >30 kgm(-2) are the most powerful predictors of DSWI. In the more recently treated patients using VAC therapy, combined procedures (valve and graft) also emerged as a significant predictor. For the entire study, Staphylococcus epidermidis (49.6%) has been the most frequently identified pathogen, followed by Staphylococcus aureus (38.8%). Methicillin-resistant S.aureus (MRSA) was observed in 4

  16. High risk of fistula formation in vacuum-assisted closure therapy in patients with open abdomen due to secondary peritonitis-a retrospective analysis.

    Science.gov (United States)

    Mintziras, Ioannis; Miligkos, Michael; Bartsch, Detlef Klaus

    2016-08-01

    The aim of this study was to evaluate the efficacy of vacuum-assisted closure therapy in patients with open abdomen due to secondary peritonitis and to identify possible risk factors of fistula formation. The hospital OPS-database (time period 2005-2014) was searched to identify patients treated with an open abdomen due to secondary peritonitis, who underwent vacuum-assisted closure therapy. Medical records were retrospectively analyzed for patients' characteristics, cause of peritonitis, duration of vacuum therapy, number of relaparotomies, fascial closure rates, and risk factors of fistula formation. Forty-three patients (19 male, 24 female) with a median age of 65 years (range 24-90 years) were identified. The major cause of secondary peritonitis was anastomotic leakage after intestinal anastomosis or bowel perforation, the median APACHE II score was 11. Median duration of VAC treatment was 12 days (range 3-88 days). Twenty of 43 (47 %) patients died from septic complications. Delayed fascial closure was obtained by suturing in 20 of 43 patients (47 %). Overall 16 of 43 (37 %) patients developed enteroatmospheric fistulas. Re-explorations after starting VAC treatment and duration of VAC therapy were significantly associated with the occurrence of enteroatmospheric fistulas (p analysis determined the optimal duration of VAC therapy to reduce the risk of fistula formation at 13 days. Long-term VAC treatment of patients with an open abdomen due to secondary peritonitis results in a relatively low fascial closure rate and a high risk of fistula formation.

  17. Effects of combined therapy of orbital cobalt Irradiation and oral corticosteroid administration, and pulse therapy for Graves' ophthalmopathy

    Energy Technology Data Exchange (ETDEWEB)

    Shigemasa, Chiaki; Ueta, Yoshihiko; Taniguchi, Shinichi; Mitani, Yasuo; Urabe, Keita; Tanaka, Takashi; Yoshida, Akio; Mashiba, Hiroto

    1989-03-01

    This preliminary study was performed to investigate the efficacy of the combined therapy of orbital cobalt irradiation and oral prednisolone administration, and pulse therapy, for Graves' ophthalmopathy. The combined therapy was undergone according to procedure of Bartalena et al. (1983) in 5 patients. Excellent or good response to combined therapy were shown by 3 patients with short-standing ocular symptoms (3-4 months), but not by 2 patients with long-standing ocular symptoms (12-13 months). Pulse therapy was performed on 2 patients who showed no improvement from combined therapy, and on a patient who had acute onset of opthalmopathy. One gram of methylprednisolone sodium succinate was given intravenously daily for 3 successive days. This infusion procedure was repeated 3 to 4 times at intervals of 1 week. One of 2 patients who showed no improvement from combined therapy also had no response to pulse therapy. The other 2 patients showed a good response to pulse therapy and showed no relapse of ophthalmopathy for 10 and 8 months, respectively. These data emphasize the need for early immuno-suppressive therapy for Graves' ophthalmopathy. Pulse therapy may be employed in patients who show no response to other therapy method.

  18. Automatic Vacuum Flushing Technology for Combined Sewer Solids: Laboratory Testing and Proposed Improvements (WERF Report INFR7SG09)

    Science.gov (United States)

    This research study included an extensive literature review on existing sewer sediment flushing technologies. An innovative vacuum flush system previously developed by the U.S. EPA was tested under laboratory conditions. The tests revealed a strong correlation between the strengt...

  19. Combinational therapy of crizotinib and afatinib for malignant pleural mesothelioma

    Science.gov (United States)

    Huang, Liyan; Cai, Muyan; Zhang, Xu; Wang, Fang; Chen, Likun; Xu, Meng; Yang, Ke; Chen, Zhen; Wang, Xiaokun; Fu, Liwu

    2017-01-01

    Malignant pleural mesothelioma (MPM) is a relative rare but highly aggressive neoplasm which is associated with asbestos exposure in most patients. The majority of patients are diagnosed in advanced stages so patients neither benefit from chemotherapy (e.g. pemetrexed-platinum combination) nor from surgery. It has been reported that cellular-mesenchymal to epithelial transition factor (MET) and epidermal growth factor receptor (EGFR) were critical for MPM cell proliferation. Moreover, targeting MET and EGFR drugs have gained promising results on anti-tumor therapy. Here, a striking difference in overall survival was observed between the MET and EGFR co-expression group (median survival time = 13.5 months) and non-co-expression group (median survival time = 20.5 months). In addition, treatment with combination of crizotinib and afatinib showed stronger inhibition on cell proliferation of MPM than the treatment by either one in vitro and in vivo. In conclusion, our data illustrated that crizotinib combined with afatinib may be a potentially effective strategy for treating MPM patients with over-expression of MET and EGFR.

  20. Carfilzomib boosted combination therapy for relapsed multiple myeloma

    Directory of Open Access Journals (Sweden)

    Steiner RE

    2017-02-01

    Full Text Available Raphael E Steiner, Elisabet E Manasanch Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Carfilzomib is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome, the proteolytic core particle within the 26S proteasome, resulting in the accumulation of proteasome substrates and ultimately growth arrest and apoptosis of tumor cells. The development and ultimate approval of this medication by regulatory agencies has been an important step toward improving clinical outcomes in multiple myeloma. Although initially approved as a single agent for the treatment of multiply relapsed and/or refractory myeloma, in the USA, it is now widely used in the early relapse setting in combination with lenalidomide and dexamethasone. Carfilzomib has also been studied in combination with second-generation immunomodulatory drugs, histone deacetylase inhibitors, alkylating agents and other novel medications. In this review article, we will discuss the efficacy, safety, tolerability and quality of life of carfilzomib-based combination therapies, as well as novel agents, for relapsed multiple myeloma. Keywords: multiple myeloma, relapsed and refractory myeloma, carfilzomib, novel drugs, salvage chemotherapy

  1. Combined therapy with methylprednisolone and ulinastatin in experimental autoimmune encephalomyelitis

    Institute of Scientific and Technical Information of China (English)

    SHU Ya-qing; YANG Yu; WANG Yu-ge; DAI Yong-qiang; XIAO Li; QIU Wei; LU Zheng-qi

    2013-01-01

    Background Our previous study had demonstrated that ulinastatin (UTI) had a neureprotective effect in experimental autoimmune encephalomyelitis (EAE).Methylprednisolone has been recommended to be a standard drug in multiple sclerosis (MS) therapies.The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE.Methods Mice were divided into a UTI treatment group,a methylprednisolone treatment group,a combined treatment group with UTI and methylprednisolone,a normal saline treatment group,and a normal control group.EAE mice were induced in groups receiving different combined treatments,or respective monotherapies.Demyelination was evaluated by Solochrome cyanin staining.2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP)/myelin basic protein (MBP)/the precursor form of nerve growth factor (proNGF)/p75/inducible nitric oxide synthase (iNOS) proteins in cerebral cortex of EAE were detected by Western blotting.Results The combined treatment group had a lower clinical score (0.61±0.06) and demyelinating score (1.33±0.33)than the groups with normal saline (clinical score:1.39±0.08,P <0.001; demyelinating score:2.75±0.49,P <0.05) or monotheraphies.Compared with the saline treated EAE group,UTI combined methylprednisolone significantly increased expressions of CNP (1.14±0.06 vs.0.65±0.04,P <0.001),MBP (1.28±0.14 vs.0.44±0.17,P <0.001),and decreased expressions of proNGF (1.08±0.10 vs.2.32±0.12,P <0.001),p75 (1.13±0.13 vs.2.33±0.17,P <0.001),and iNOS (1.05±0.31 vs.2.17±0.13,P <0.001) proteins in EAE.Furthermore,UTI combined methyiprednisolone could significantly upregulate MBP (1.28±0.14 vs.1.01±0.15,P <0.05) expression and downregulate iNOS (1.05±0.31 vs.1.35±0.14,P <0.05) expression compared to methylprednisolone treatment EAE group.And proNGF expression was significantly lower in combined treatment (1.08±0.10) than that in UTI (1.51±0.24,P <0.05) or methylprednisolone (1.31±0.04,P <0

  2. Early Combination Antiretroviral Therapy Limits HIV-1 Persistence in Children.

    Science.gov (United States)

    Luzuriaga, Katherine

    2016-01-01

    Globally, 240,000 infants are newly infected with HIV-1 each year and 3.2 million children are living with the infection. Combination antiretroviral therapy (cART) has reduced HIV-1-related disease and mortality in children but is not curative owing to the early generation of a latent reservoir of long-lived memory CD4(+) T cells bearing replication-competent HIV-1 provirus integrated into cellular DNA. This review focuses on recent advances in our understanding of the establishment of HIV-1 persistence in children and how early initiation of cART in the setting of the developing infant immune system limits the formation of the long-lived latent CD4(+) cell reservoir that remains a barrier to remission or cure.

  3. Combination bacteriolytic therapy for the treatment of experimental tumors.

    Science.gov (United States)

    Dang, L H; Bettegowda, C; Huso, D L; Kinzler, K W; Vogelstein, B

    2001-12-18

    Current chemotherapeutic approaches for cancer are in part limited by the inability of drugs to destroy neoplastic cells within poorly vascularized compartments of tumors. We have here systematically assessed anaerobic bacteria for their capacity to grow expansively within avascular compartments of transplanted tumors. Among 26 different strains tested, one (Clostridium novyi) appeared particularly promising. We created a strain of C. novyi devoid of its lethal toxin (C. novyi-NT) and showed that intravenously injected C. novyi-NT spores germinated within the avascular regions of tumors in mice and destroyed surrounding viable tumor cells. When C. novyi-NT spores were administered together with conventional chemotherapeutic drugs, extensive hemorrhagic necrosis of tumors often developed within 24 h, resulting in significant and prolonged antitumor effects. This strategy, called combination bacteriolytic therapy (COBALT), has the potential to add a new dimension to the treatment of cancer.

  4. Combined modality preoperative therapy for unresectable rectal cancer.

    Science.gov (United States)

    Percarpio, B; Bitterman, J; Sabbath, K; Alfano, F; Ruszkowski, R; Bowen, J

    1992-01-01

    Locally advanced rectal cancer has been a surgical challenge because of fixation of the primary tumor to the boney pelvis or to other pelvic soft tissues. During a 12-month period seven patients with locally advanced adenocarcinoma of the rectum were treated preoperatively with simultaneous pelvic irradiation (4500-5040 cGy) and infusion chemotherapy (5-fluorouracil 1000 mg per m2 per day over 96 hours and mitomycin 10 mg per m2. Tolerance was reasonable and all patients underwent successful resection of the primary lesion. Two patients had a complete response to preoperative combined modality therapy with no cancer found in the surgical specimen. With a short follow-up period, all patients have experienced satisfactory healing and none have suffered local or distant recurrence. The results of this limited series are encouraging for future clinical trials.

  5. Development of drug delivery systems for radionuclide therapy using a combination therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, On Hee; Choi, Sun Ju [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2005-07-01

    For the development of new controlled drug delivery systems, the application of combination therapy using angiogenesis inhibitor and tumor static agents has drawn great attention. This approach would be very beneficial for cancer treatment especially when a new drug deliver system utilizing biodegradable polymers is developed. Therefore, the present study for the combination therapy of angiogenesis inhibitor and chemotherapeutic agents was to carry out prior to the development of the novel drug delivery. In present study, the ability of inhibition on cell growth was investigated with treatment of anti-angiogenetic agent and anticancer agent. Thalidomide was used as an antivasculatory agents and Doxorubicine was treated as a chemotherapeutic agent. To demonstrate apoptotic process in in-vitro study, TUNEL assay was carried out. Also, the alteration of p53 level was examined by using western blotting. For the cell lines, NIH:OVCAR3, MKN45, SNU719, C6, L929, T98G, Hep3B and Calu6 were applied. Results showed that Thalidomide inhibited cell growth in tumor cell lines in a dose-dependent manner and Doxorubicin as well. A significant synergistic effect on the apoptotic was noticed in the combination treatment of Thalidomide and Doxorubicin compared to a single treatment of either drug. Therefore, it can be concluded that the mechanism of cytotoxicity was due to the enhancement of apoptosis in early cell death with combination treatment in tumor cell lines.

  6. Combined high-pressure cell-ultrahigh vacuum system for fast testing of model metal alloy catalysts using scanning mass spectrometry

    DEFF Research Database (Denmark)

    Johansson, Martin; Jørgensen, Jan Hoffmann; Chorkendorff, Ib

    2004-01-01

    An apparatus for fabrication, surface analysis in ultrahigh vacuum, and testing of the catalytic activity of model metal alloy catalysts is described. Arrays of model catalysts are produced by electron-beam deposition of up to four metals simultaneously onto a substrate. The surface analysis...... techniques available are scanning electron microscopy, x-ray photoemission spectroscopy, ion scattering spectroscopy, Auger electron spectroscopy, sputter profiling, and temperature programmed desorption. The catalytic activity of the model catalysts is tested individually by scanning a combined gas delivery...... be studied on a substrate 10 mm in diameter. A high pressure cell with an all-metal sealed ultrahigh vacuum lock is also described as part of the work. ©2004 American Institute of Physics....

  7. Quantifying the pharmacology of antimalarial drug combination therapy

    Science.gov (United States)

    Hastings, Ian M.; Hodel, Eva Maria; Kay, Katherine

    2016-01-01

    Most current antimalarial drugs are combinations of an artemisinin plus a ‘partner’ drug from another class, and are known as artemisinin-based combination therapies (ACTs). They are the frontline drugs in treating human malaria infections. They also have a public-health role as an essential component of recent, comprehensive scale-ups of malaria interventions and containment efforts conceived as part of longer term malaria elimination efforts. Recent reports that resistance has arisen to artemisinins has caused considerable concern. We investigate the likely impact of artemisinin resistance by quantifying the contribution artemisinins make to the overall therapeutic capacity of ACTs. We achieve this using a simple, easily understood, algebraic approach and by more sophisticated pharmacokinetic/pharmacodynamic analyses of drug action; the two approaches gave consistent results. Surprisingly, the artemisinin component typically makes a negligible contribution (≪0.0001%) to the therapeutic capacity of the most widely used ACTs and only starts to make a significant contribution to therapeutic outcome once resistance has started to evolve to the partner drugs. The main threat to antimalarial drug effectiveness and control comes from resistance evolving to the partner drugs. We therefore argue that public health policies be re-focussed to maximise the likely long-term effectiveness of the partner drugs. PMID:27604175

  8. Combination therapy in the management of atrophic acne scars

    Directory of Open Access Journals (Sweden)

    Shilpa Garg

    2014-01-01

    Full Text Available Background: Atrophic acne scars are difficult to treat. The demand for less invasive but highly effective treatment for scars is growing. Objective: To assess the efficacy of combination therapy using subcision, microneedling and 15% trichloroacetic acid (TCA peel in the management of atrophic scars. Materials and Methods: Fifty patients with atrophic acne scars were graded using Goodman and Baron Qualitative grading. After subcision, dermaroller and 15% TCA peel were performed alternatively at 2-weeks interval for a total of 6 sessions of each. Grading of acne scar photographs was done pretreatment and 1 month after last procedure. Patients own evaluation of improvement was assessed. Results: Out of 16 patients with Grade 4 scars, 10 (62.5% patients improved to Grade 2 and 6 (37.5% patients improved to Grade 3 scars. Out of 22 patients with Grade 3 scars, 5 (22.7% patients were left with no scars, 2 (9.1% patients improved to Grade 1and 15 (68.2% patients improved to Grade 2. All 11 (100% patients with Grade 2 scars were left with no scars. There was high level of patient satisfaction. Conclusion: This combination has shown good results in treating not only Grade 2 but also severe Grade 4 and 3 scars.

  9. Artemisinin-based combination therapies for uncomplicated malaria.

    Science.gov (United States)

    Davis, Timothy M E; Karunajeewa, Harin A; Ilett, Kenneth F

    2005-02-21

    There has been a relentless increase in resistance of malaria parasites to conventional antimalarial drugs, including chloroquine, sulfadoxine-pyrimethamine and mefloquine. In response to this situation, short-course artemisinin-based combination therapies (ACTs) have been developed. The World Health Organization has endorsed ACT as first-line treatment where the potentially life-threatening parasite Plasmodium falciparum is the predominant infecting species. ACTs combine the rapid schizontocidal activity of an artemisinin derivative (artesunate, artemether or dihydroartemisinin) with a longer-half-life partner drug. Although the use of chloroquine and sulfadoxine-pyrimethamine as partners in ACT improves their efficacy, this may only have value as a short-term measure in patients with a degree of immunity to malaria. Alternative currently available partner drugs include mefloquine, lumefantrine and piperaquine. Artesunate-mefloquine is highly effective but is expensive and side effects (mainly neurotoxicity) can be problematic. Artemether-lumefantrine, the only ACT available in Australia, appears less effective than artesunate-mefloquine and needs to be administered with food to ensure adequate bioavailability. Dihydroartemisinin-piperaquine is highly effective, well tolerated and relatively inexpensive. The goal of potent, safe, easy-to-administer and inexpensive ACTs may see trioxolanes in place of artemisinin derivatives, as well as novel partner drugs such as pyronaridine or naphthoquine, in the future.

  10. Apicoplast Biosynthetic Pathways as Possible Targetsfor Combination Therapy of Malaria

    Institute of Scientific and Technical Information of China (English)

    Solomon Tesfaye; Bhanu Prakash; Prati Pal Singh

    2015-01-01

    The emergence of malaria parasite strains resistant to practically all the antimalarial drugs in clinical use is now making itnecessary to discover and develop both new antimalarial drugs and treatments. Recent advances in molecular techniques along withthe availability of genome sequence ofPlasmodiumfalciparum may provide a wide range of novel targets in metabolic pathways likeisoprenoid biosynthesis, fatty acid biosynthesis and heme biosynthesis in the apicoplast of Plasmodiurn. On the other hand, thecombination therapy approach (currently used to retard the selection of parasite strains resistant to individual components of acombination of drugs) has proved to be a success in the combination of sulphadoxine and pyrimethamine, which targets two differentsteps in the folate pathway of malaria parasite. However, after the success of this therapeutic combination, the efficacy of othercombinations of drugs which target different enzymes in a particular metabolic pathway has, apparently, not been reported. Therefore,herein, we review various drug targets so far discovered in apicoplast-related anabolic pathways, especially, with a sharper focus onthe possibility to target more than one enzyme at a time in a particular metabolic pathway of malaria parasites.

  11. Spillover adherence effects of fixed-dose combination HIV therapy

    Directory of Open Access Journals (Sweden)

    Kauf TL

    2012-02-01

    Full Text Available Teresa L Kauf1, Keith L Davis2, Stephanie R Earnshaw2, E Anne Davis31Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, 2RTI Health Solutions, Research Triangle Park, NC, 3Independent consultant, Pittsboro, NC, USAAbstract: The impact of fixed-dose combination (FDC products on adherence to other, non-fixed regimen components has not been examined. We compared adherence to a third antiretroviral (ART component among patients receiving a nucleoside reverse transcriptase inhibitor (NRTI backbone consisting of the FDC Epzicom®, GlaxoSmithKline Inc, Research Triangle Park, NC (abacavir sulfate 600 mg + lamivudine 300 mg; FDC group versus NRTI combinations taken as two separate pills (NRTI Combo group using data from a national sample of 30 health plans covering approximately 38 million lives from 1997 to 2005. Adherence was measured as the medication possession ratio (MPR. Multivariate logistic regression compared treatment groups based on the likelihood of achieving ≥95% adherence, with sensitivity analyses using alternative thresholds. MPR was assessed as a continuous variable using multivariate linear regression. Covariates included age, gender, insurance payer type, year of study drug initiation, presence of mental health and substance abuse disorders, and third agent class. The study sample consisted of 650 FDC and 1947 NRTI Combo patients. Unadjusted mean adherence to the third agent was higher in the FDC group than the NRTI Combo group (0.92 vs 0.85; P < 0.0001. In regression analyses, FDC patients were 48% and 39% more likely to achieve 95% and 90% third agent adherence, respectively (P ≤ 0.03. None of the other MPR specifications achieved comparable results. Among managed care patients, use of an FDC appears to substantially improve adherence to a third regimen component and thus the likelihood of achieving the accepted standard for adherence to HIV therapy of 95%.Keywords

  12. Cognitive behavioral therapy in combination with systemic family therapy improves mild to moderate postpartum depression

    Directory of Open Access Journals (Sweden)

    Yongmei Hou

    2014-03-01

    Full Text Available Objective: To explore the effect of cognitive behavioral therapy (CBT in combination with systemic family therapy (SFT on mild to moderate postpartum depression and sleep quality. Methods: 249 primiparous women with mild to moderate postpartum depression were recruited and randomly assigned to a control group (n=128, which received conventional postpartum care, or to a psychological intervention group (n=121, which received conventional postpartum care combined with psychological intervention. The Edinburgh Postnatal Depression Scale (EPDS and Pittsburgh Sleep Quality Index (PSQI were employed to evaluate depression and sleep quality, respectively. Results: 104 patients in the intervention group and 109 in the control group completed the study. After intervention, the EPDS score, PSQI score, sleep quality score, sleep latency score, sleep duration score, habitual sleep efficiency score, sleep disturbance score, and daytime dysfunction score were significantly lower in the intervention group than in the control group. The EPDS and PSQI scores of each group at different time points after intervention were markedly decreased compared with those before intervention, and the reduction in the intervention group was more evident than that in the control group. Conclusion: CBT in combination with SFT can improve depression and sleep quality in patients with mild to moderate postpartum depression.

  13. Multimodal therapy for painful bladder syndrome / interstitial cystitis: pilot study combining behavioral, pharmacologic, and endoscopic therapies

    Directory of Open Access Journals (Sweden)

    Robert S. Hanley

    2009-08-01

    Full Text Available Purpose: We evaluated the effectiveness of combining behavioral therapy, pharmacologic therapy and endoscopic hydrodistension for treating painful bladder syndrome / interstitial cystitis (PBS/IC. Materials and Methods: Twenty-five patients with PBS/IC were prospectively enrolled in a pilot multimodal behavioral, pharmacologic and endoscopic treatment protocol. Behavioral modification included diet recommendations, fluid restriction to 64 oz. /day, progressive timed voiding and Kegel exercises. Oral pharmacologic therapy consisted of daily doses of macrodantin 100 mg, hydroxyzine 10-20 mg and urised 4 tablets. Patients underwent endoscopic bladder hydrodistention under anesthesia at least 2 weeks after protocol enrollment. Behavioral and pharmacological treatments were continued after the hydrodistention. O'Leary-Sant questionnaire scores were recorded before starting the protocol, after pharmacologic/behavioral therapy, 2 months post-hydrodistension, and at scheduled follow-up. Results: Eighteen patients (72% completed the pilot multimodal treatment protocol and were followed for a mean of 10.2 months. All patients were female with a median age of 36.3 years and had mean bladder capacity under anesthesia of 836 milliliters. Mean O'Leary-Sant symptom index scores for baseline symptoms, after behavioral/pharmacologic treatment, post-hydrodistension and during follow up were 12.5, 8.6, 7.0, and 6.7 (p < 0.05. Mean O'Leary-Sant problem index scores for baseline, after behavioral/pharmacologic treatment, post-hydrodistention and during follow up were 12.7, 8.9, 6.7, and 7.7 (p < 0.05. Conclusion: Our pilot multimodal protocol of behavioral modification, pharmacologic therapy and endoscopic hydrodistention demonstrated a significant progressive improvement in PBS/IC quality of life scores, compared to a pre-treatment baseline. These results should be validated in a larger, placebo controlled trial.

  14. Long-term follow-up of severely symptomatic women with adenomyoma treated with combination therapy

    Directory of Open Access Journals (Sweden)

    Wei-Min Liu

    2013-03-01

    Conclusion: Combination therapy for adenomyoma provides an effective treatment option for long-term symptom control and uterine preservation in severely symptomatic women for whom previous long-term drug therapy has failed or proven to be intolerable.

  15. Combined influence of fluorine doping and vacuum annealing on the electrical properties of ZnO:Ta films

    Science.gov (United States)

    Subha, K.; Ravichandran, K.; Sriram, S.

    2017-07-01

    In this study, our main focus is to investigate the effects of F doping and post deposition annealing (air and vacuum) on the optical and electrical characteristics of tantalum doped zinc oxide films (ZnO:Ta). A cost-effective, automated jet nebulizer spray pyrolysis technique is adopted to deposit the ZnO:Ta:F films. The doping level of Ta is kept constant (1 at.%) and that of F is varied from 5 to 20 at.% in steps of 5 at.%. The electrical resistivity of the as-deposited films decreases for 10 at.% of F concentration. The resistance increases thereafter. The same trend is also observed in annealed films. The reasons for these variations are addressed based on the effective F incorporation into the ZnO lattice and annealing atmosphere with the help of XRD, FESEM, AFM and PL studies. The incorporation of the dopants was confirmed from XPS and EDX analyses and the DFT studies show that the incorporation of the dopants does not affect the stability of the ZnO lattice. Vacuum-annealed films show better electrical properties over the as-deposited and air-annealed counterparts, though their transparency is affected marginally. A minimum resistivity of 0.81 × 10-3 Ω cm and an enhanced quality factor of 2.265 × 10-4 (Ω/sq)-1 are achieved for the vacuum-annealed films having Ta + F doping levels as 1 + 10 at.%. These results make this sample a desirable candidate for transparent electrode applications.

  16. VACUUM TRAP

    Science.gov (United States)

    Gordon, H.S.

    1959-09-15

    An improved adsorption vacuum trap for use in vacuum systems was designed. The distinguishing feature is the placement of a plurality of torsionally deformed metallic fins within a vacuum jacket extending from the walls to the central axis so that substantially all gas molecules pass through the jacket will impinge upon the fin surfaces. T fins are heated by direct metallic conduction, thereby ol taining a uniform temperature at the adeorbing surfaces so that essentially all of the condensible impurities from the evacuating gas are removed from the vacuum system.

  17. p-Si(1 1 1):H/ionic liquid interface investigated through a combination of electrochemical measurements and reflection high energy electron diffraction surface analysis in vacuum

    Science.gov (United States)

    Watanabe, Ko; Maruyama, Shingo; Matsumoto, Yuji

    2016-07-01

    A combination study of electrochemical measurements and reflection high energy electron diffraction (RHEED) surface analysis experiments in a vacuum was first demonstrated to characterize a p-Si(1 1 1):H/ionic liquid interface. Mott-Schottky plot analysis was made to successfully not only evaluate the acceptor density and flat band potential of the p-Si(1 1 1):H, but also get some insight into its surface states. Furthermore, the electric double layer capacitance and specific adsorption properties at the IL/Si(1 1 1):H interface as well as the electrochemical interface stability will be discussed in this paper.

  18. Degradation of Artemisinin-Based Combination Therapies under Tropical Conditions

    Science.gov (United States)

    Hall, Zoe; Allan, Elizabeth Louise; van Schalkwyk, Donelly Andrew; van Wyk, Albert; Kaur, Harparkash

    2016-01-01

    Poor quality antimalarials, including falsified, substandard, and degraded drugs, are a serious health concern in malaria-endemic countries. Guidelines are lacking on how to distinguish between substandard and degraded drugs. “Forced degradation” in an oven was carried out on three common artemisinin-based combination therapy (ACT) brands to detect products of degradation using liquid chromatography mass spectrometry and help facilitate classification of degraded drugs. “Natural aging” of 2,880 tablets each of ACTs artemether/lumefantrine and artesunate/amodiaquine was undertaken to evaluate their long-term stability in tropical climates. Samples were aged in the presence and absence of light on-site in Ghana and in a stability chamber (London), removed at regular intervals, and analyzed to determine loss of the active pharmaceutical ingredients (APIs) over time and detect products of degradation. Loss of APIs in naturally aged tablets (both in Ghana and the pharmaceutical stability chamber) was 0–7% over 3 years (∼12 months beyond expiry) with low levels of degradation products detected. Using this developed methodology, it was found that a quarter of ACTs purchased in Enugu, Nigeria (concurrent study), that would have been classified as substandard, were in fact degraded. Presence of degradation products together with evidence of insufficient APIs can be used to classify drugs as degraded. PMID:26951346

  19. [Acupuncture combined with traction therapy for lumbar disc herniation: a systematic review].

    Science.gov (United States)

    Li, Xiu-zhen; Chen, Hai-yong; Zheng, Xiao; Liu, Nong-yu

    2014-09-01

    To evaluate the efficacy and safety of acupuncture combined with traction therapy for lumbar disc herniation, providing the basis for future research strategies. Randomized control trials. (RCT) of acupuncture combined with traction therapy for lumber disc herniation at home and abroad from 2000 to 2013 were searched, analysis and evaluation of literature and strength of evidence were based on the principles and methods of Evidence-based Medicine. The total effective rate and curative rate were considered as primary outcome measures; pain improvement, quality of life, relapse rate and adverse effects were considered as secondary outcome measures. Seventeen RCTs were identified, Meta-analysis showed that (1) total effective rate and curative rate: acupuncture combined with traction therapy was better than single therapy (acupuncture or traction); (2) pain improvement: acupuncture combined with traction therapy was better than traction therapy; (3) relapse rate: current evidence could not support the conclusion that acupuncture combined with traction therapy was better than traction therapy. Acupuncture combined with traction therapy for lumbar disc herniation was effective. However, the included studies were with high risk of bias, important outcome measures such as quality of life, relapse rate and adverse effects were not found in most of the studies. Current evidence has not yet been able to fully reflect acupuncture combined with traction therapy for lumbar disc herniation is better than single therapy, so more RCTs of higher quality are needed to further confirm its efficacy and safety.

  20. Vacuum Technology

    Energy Technology Data Exchange (ETDEWEB)

    Biltoft, P J

    2004-10-15

    The environmental condition called vacuum is created any time the pressure of a gas is reduced compared to atmospheric pressure. On earth we typically create a vacuum by connecting a pump capable of moving gas to a relatively leak free vessel. Through operation of the gas pump the number of gas molecules per unit volume is decreased within the vessel. As soon as one creates a vacuum natural forces (in this case entropy) work to restore equilibrium pressure; the practical effect of this is that gas molecules attempt to enter the evacuated space by any means possible. It is useful to think of vacuum in terms of a gas at a pressure below atmospheric pressure. In even the best vacuum vessels ever created there are approximately 3,500,000 molecules of gas per cubic meter of volume remaining inside the vessel. The lowest pressure environment known is in interstellar space where there are approximately four molecules of gas per cubic meter. Researchers are currently developing vacuum technology components (pumps, gauges, valves, etc.) using micro electro mechanical systems (MEMS) technology. Miniature vacuum components and systems will open the possibility for significant savings in energy cost and will open the doors to advances in electronics, manufacturing and semiconductor fabrication. In conclusion, an understanding of the basic principles of vacuum technology as presented in this summary is essential for the successful execution of all projects that involve vacuum technology. Using the principles described above, a practitioner of vacuum technology can design a vacuum system that will achieve the project requirements.

  1. Vacuum mechatronics

    Science.gov (United States)

    Hackwood, Susan; Belinski, Steven E.; Beni, Gerardo

    1989-01-01

    The discipline of vacuum mechatronics is defined as the design and development of vacuum-compatible computer-controlled mechanisms for manipulating, sensing and testing in a vacuum environment. The importance of vacuum mechatronics is growing with an increased application of vacuum in space studies and in manufacturing for material processing, medicine, microelectronics, emission studies, lyophylisation, freeze drying and packaging. The quickly developing field of vacuum mechatronics will also be the driving force for the realization of an advanced era of totally enclosed clean manufacturing cells. High technology manufacturing has increasingly demanding requirements for precision manipulation, in situ process monitoring and contamination-free environments. To remove the contamination problems associated with human workers, the tendency in many manufacturing processes is to move towards total automation. This will become a requirement in the near future for e.g., microelectronics manufacturing. Automation in ultra-clean manufacturing environments is evolving into the concept of self-contained and fully enclosed manufacturing. A Self Contained Automated Robotic Factory (SCARF) is being developed as a flexible research facility for totally enclosed manufacturing. The construction and successful operation of a SCARF will provide a novel, flexible, self-contained, clean, vacuum manufacturing environment. SCARF also requires very high reliability and intelligent control. The trends in vacuum mechatronics and some of the key research issues are reviewed.

  2. Vacuum extraction

    DEFF Research Database (Denmark)

    Maagaard, Mathilde; Oestergaard, Jeanett; Johansen, Marianne

    2012-01-01

    Objectives. To develop and validate an Objective Structured Assessment of Technical Skills (OSATS) scale for vacuum extraction. Design. Two part study design: Primarily, development of a procedure-specific checklist for vacuum extraction. Hereafter, validationof the developed OSATS scale for vacuum...... extraction in a prospective observational study. Setting. Rigshospitalet, University Hospital of Copenhagen. Population. For development an obstetric expert from each labor ward in Denmark (28 departments) were invited to participate. For validation nine first-year residents and ten chief physicians...... with daily work in the obstetric field were tested. Methods. The Delphi method was used for development of the scale. In a simulated vacuum extraction scenario first-year residents and obstetric chief physicians were rated using the developed OSATS scale for vacuum extraction to test construct validity...

  3. Vacuum extraction

    DEFF Research Database (Denmark)

    Maagaard, Mathilde; Oestergaard, Jeanett; Johansen, Marianne

    2012-01-01

    Objectives. To develop and validate an Objective Structured Assessment of Technical Skills (OSATS) scale for vacuum extraction. Design. Two part study design: Primarily, development of a procedure-specific checklist for vacuum extraction. Hereafter, validationof the developed OSATS scale for vacuum...... extraction in a prospective observational study. Setting. Rigshospitalet, University Hospital of Copenhagen. Population. For development an obstetric expert from each labor ward in Denmark (28 departments) were invited to participate. For validation nine first-year residents and ten chief physicians...... with daily work in the obstetric field were tested. Methods. The Delphi method was used for development of the scale. In a simulated vacuum extraction scenario first-year residents and obstetric chief physicians were rated using the developed OSATS scale for vacuum extraction to test construct validity...

  4. Gravitational vacuum

    Science.gov (United States)

    Grigoryan, L. S.; Saakyan, G. S.

    1984-09-01

    The existence of a special gravitational vacuum is considered in this paper. A phenomenological method differing from the traditional Einsteinian formalization is utilized. Vacuum, metric and matter form a complex determined by field equations and at great distances from gravitational masses vacuum effects are small but could be large in powerful fields. Singularities and black holes justify the approach as well as the Ambartsmyan theory concerning the existence of supermassive and superdense prestallar bodies that then disintegrate. A theory for these superdense bodies is developed involving gravitational field equations that describe the vacuum by an energy momentum tensor and define the field and mass distribution. Computations based on the theory for gravitational radii with incompressible liquid models adequately reflecting real conditions indicate that a gravitational vacuum could have considerable effects on superdense stars and could have radical effects for very large masses.

  5. Life expectancy after initiation of combination antiretroviral therapy in Thailand.

    Science.gov (United States)

    Teeraananchai, Sirinya; Chaivooth, Suchada; Kerr, Stephen J; Bhakeecheep, Sorakij; Avihingsanon, Anchalee; Teeraratkul, Achara; Sirinirund, Petchsri; Law, Matthew G; Ruxrungtham, Kiat

    2017-01-05

    Access to combination antiretroviral therapy (cART) has decreased mortality in HIV-positive people. We aimed to estimate the expected additional years of life in HIV-positive Thai people after starting cART through the National AIDS Program (NAP), administered by the Thai National Health Security Office (NHSO). The NHSO database collects characteristics of all Thai HIV-infected patients through the National AIDS Program, including linkage with the National Death Registry for vital status. This study included patients aged ≥15 years at cART initiation between 2008 and 2014. The abridged life table method was used to construct life tables stratified by sex and baseline CD4(+) T-cell count. Life expectancy was defined as the additional years of life from age at starting cART. 201,688 eligible patients were included in analyses, contributing 618,837 person-years of follow-up. Median CD4(+) T-cell count was 109 cells/mm(3) and median age 37 years. The overall life expectancy after cART initiation at age 20 was 25.4 (95% CI, 25.3, 25.6) years and 20.6 (95% CI, 20.5, 20.7) at age 35 years. Life expectancy at baseline CD4(+) T-cell count ≥350 cells/mm(3) was 51.9 (95% CI, 51.0, 52.9) years for age 20 years and 43.2 (95% CI, 42.4, 44.1) years for age 35 years, close to life expectancy in the general Thai population. Increasing life expectancy with higher baseline CD4(+) T-cell counts supports the guideline recommendations to start cART irrespective of CD4(+) T-cell count. These results are beneficial to forecast the treatment cost and develop health policies for people living with HIV in Thailand and Asia.

  6. Melanoma: A model for testing new agents in combination therapies

    Directory of Open Access Journals (Sweden)

    Streicher Howard Z

    2010-04-01

    Full Text Available Abstract Treatment for both early and advanced melanoma has changed little since the introduction of interferon and IL-2 in the early 1990s. Recent data from trials testing targeted agents or immune modulators suggest the promise of new strategies to treat patients with advanced melanoma. These include a new generation of B-RAF inhibitors with greater selectivity for the mutant protein, c-Kit inhibitors, anti-angiogenesis agents, the immune modulators anti-CTLA4, anti-PD-1, and anti-CD40, and adoptive cellular therapies. The high success rate of mutant B-RAF and c-Kit inhibitors relies on the selection of patients with corresponding mutations. However, although response rates with small molecule inhibitors are high, most are not durable. Moreover, for a large subset of patients, reliable predictive biomarkers especially for immunologic modulators have not yet been identified. Progress may also depend on identifying additional molecular targets, which in turn depends upon a better understanding of the mechanisms leading to response or resistance. More challenging but equally important will be understanding how to optimize the treatment of individual patients using these active agents sequentially or in combination with each other, with other experimental treatment, or with traditional anticancer modalities such as chemotherapy, radiation, or surgery. Compared to the standard approach of developing new single agents for licensing in advanced disease, the identification and validation of patient specific and multi-modality treatments will require increased involvement by several stakeholders in designing trials aimed at identifying, even in early stages of drug development, the most effective way to use molecularly guided approaches to treat tumors as they evolve over time.

  7. Use of pharmacodynamic indices to predict efficacy of combination therapy in vivo

    NARCIS (Netherlands)

    J.W. Mouton (Johan); M.L. van Ogtrop; D. Andes; W.A. Craig (William)

    1999-01-01

    textabstractAlthough combination therapy with antimicrobial agents is often used, no available method explains or predicts the efficacies of these combinations satisfactorily. Since the efficacies of antimicrobial agents can be described by pharmacodynamic indices (PDIs

  8. Use of pharmacodynamic indices to predict efficacy of combination therapy in vivo

    NARCIS (Netherlands)

    J.W. Mouton (Johan); M.L. van Ogtrop; D. Andes; W.A. Craig (William)

    1999-01-01

    textabstractAlthough combination therapy with antimicrobial agents is often used, no available method explains or predicts the efficacies of these combinations satisfactorily. Since the efficacies of antimicrobial agents can be described by pharmacodynamic indices (PDIs

  9. A Randomized Controlled Trial of Cognitive-Behavioral Therapy, Light Therapy, and Their Combination for Seasonal Affective Disorder

    Science.gov (United States)

    Rohan, Kelly J.; Roecklein, Kathryn A.; Tierney Lindsey, Kathryn; Johnson, Leigh G.; Lippy, Robert D.; Lacy, Timothy J.; Barton, Franca B.

    2007-01-01

    This first controlled psychotherapy trial for seasonal affective disorder (SAD) compared SAD-tailored cognitive-behavioral therapy (CBT), light therapy (LT), and their combination to a concurrent wait-list control. Adults (N = 61) with major depression, recurrent with seasonal pattern, were randomized to one of four 6-week conditions: CBT (1.5-hr…

  10. Calreticulin as cancer treatment adjuvant: combination with photodynamic therapy and photodynamic therapy-generated vaccines

    Directory of Open Access Journals (Sweden)

    Mladen eKorbelik

    2015-02-01

    Full Text Available Calreticulin is recognized as one of pivotal damage-associated molecular pattern (DAMP molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT. The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure-rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4 mg/mouse was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor responses elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.

  11. Combination therapy for pain management in inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis)

    NARCIS (Netherlands)

    S. Ramiro; H. Radner; D. van der Heijde; A. van Tubergen; R. Buchbinder; D. Aletaha; R.B.M. Landewé

    2011-01-01

    Despite optimal therapy with disease-modifying antirheumatic drugs, many people with inflammatory arthritis (IA) continue to have persistent pain that may require additional therapy. To assess the benefits and safety of combination pain therapy for people with IA (rheumatoid arthritis (RA), ankylosi

  12. [Acupuncture combined with catgut embedding therapy for treatment of 158 cases of facial paralysis].

    Science.gov (United States)

    Li, Ling

    2005-03-01

    To observe therapeutic effect of acupuncture combined with catgut embedding therapy on peripheral facial paralysis. Treatment group of 158 cases were treated by acupuncture combined with catgut embedding therapy and control group of 54 cases were treated by acupuncture, and their therapeutic effects were compared. There was no significant difference in the total effective rate (P > 0.05), but the cured rate in the treatment group was significantly higher than that in the control group (P Acupuncture combined with catgut embedding therapy is a better therapy for facial paralysis.

  13. Pancreatitis associated with potassium bromide/phenobarbital combination therapy in epileptic dogs.

    OpenAIRE

    Gaskill, C L; Cribb, A E

    2000-01-01

    In a retrospective study, at least 10% of dogs receiving potassium bromide/phenobarbital combination therapy, compared with 0.3% of dogs receiving phenobarbital monotherapy, had probable pancreatitis. Pancreatitis may be a more frequent and more serious adverse effect of potassium bromide/phenobarbital combination therapy than has been reported previously.

  14. Synergistic combination therapy of antitumor agents, membrane modification agents and irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Watarai, Jiro; Itagaki, Takatomo; Akutsu, Thoru; Yamaguchi, Kouichi; Kato, Isao (Yamagata Univ. (Japan))

    1983-01-01

    Larygeal cancer were treated with synergistic combination therapy of Futraful in suppository, vitamin A, cepharanthin and irradiation from April 1981 to June 1982. This combination therapy resulted in high percentage of the tumor regression in the case of the invading laryngeal cancer and negligible complication.

  15. Vacuum Assisted Closure (VAC) therapyTM as a swiss knife multi-tool for enteric fistula closure: tips and tricks: a pilot study.

    Science.gov (United States)

    Pepe, G; Magalini, S; Callari, C; Persiani, R; Lodoli, C; Gui, D

    2014-01-01

    Enterocutaneous fistulas (ECFs) are an uncommon surgical problem, but they are characterized by a difficult management. Vacuum-assisted closure (VAC) therapy is a method utilized for chronic and traumatic wound healing. At first, VAC therapy had been contraindicated in the treatment of intestinal fistulas, but as time went by, VAC therapy revealed itself to be a "Swiss knife multi-tool". This paper presents some clinical cases of enterocutaneous (ECF) and enteroatmospheric fistulas (EAF) treated with VAC therapy™. The history of 8 patients treated for complex fistulas was revised. Four of them presented with enterocutaneous and four with enteroatmospheric fistulas. All were treated with VAC therapy with variations elaborated to help in accelerated closure of intestinal wall lesions. Four out of four ECFs closed spontaneously. In the EAF group, in three cases the fistula turned slowly into an entero-cutaneous fistula, and in one out of four it closed spontaneously. The mean length of VAC therapy™ was 35.5 days and that of spontaneous closure was 36.4 days. The results of our study encourage the use of VAC therapy™ for the treatment of enterocutaneous fistulas. VAC therapy™ use has a double therapeutic value: (1) it promotes the healing of the skin and allows also the management of EAFs; (2) in selected cases, those in which it is possible to create a deep fistula tract ("well") it is possible to assist to a complete healing with closure of the ECFs.

  16. First report of urinary endoscopic vacuum therapy : For large bladder defect after abdomino-perineal excision of the rectum. Video paper.

    Science.gov (United States)

    Loske, G; Schorsch, T; Kiesow, R U; Müller, C T

    2017-01-01

    The technique of active urinary endoscopic vacuum therapy (uEVT) is described. The surgical technique is demonstrated in detail with the help of a video of the operation, which is available online. Vesical fistulas are a rare complication following rectal surgery. The EVT technique is a novel method for the treatment of gastrointestinal leakage. This endoscopic procedure has been adapted to treat a large bladder defect after abdomino-perineal resection of the rectum with urine flowing out of the perineal wound. A new open-pore film drainage (OFD) catheter with an external diameter of only a few millimeters was developed and constructed from a very thin open-pore double-layered film and a drainage tube. The OFD was inserted into the bladder by means of flexible endoscopy and channeled out through a suprapubic incision. Continuous suction was applied with an electronic vacuum pump to actively drain the urine completely. A passive catheter drainage of urine from the renal pelvis via a transurethral single J stent was carried out simultaneously during the complete duration of treatment. The healing process was monitored during and after therapy via intravesical endoscopy. The application of continuous negative pressure via the OFD resulted in total collapse of the bladder. The urine in the bladder was actively and permanently drained through the OFD. Urine leakage from the perineal wound stopped immediately after induction of suction. The bladder defect healed after 18 days of treatment with uEVT. After therapy and removal of the catheters, the patient had normal micturition. A novel small-bore OFD was developed for EVT. The OFD technique allows for endoscopic application of negative pressure in the bladder. This first successful experience proves uEVT to be a potent interventional alternative in the treatment of bladder defects.

  17. [First report of urinary endoscopic vacuum therapy : For large bladder defect after abdomino-perineal excision of the rectum. Video paper. German version].

    Science.gov (United States)

    Loske, G; Schorsch, T; Kiesow, R U; Müller, C T

    2017-01-01

    The technique of active urinary endoscopic vacuum therapy (uEVT) is described. The surgical technique is demonstrated in detail with the help of a video of the operation and which is available online. Vesical fistulas are a rare complication following rectal surgery. The EVT technique is a novel method for treatment of gastrointestinal leakage. This endoscopic procedure has been adapted to treat a large bladder defect after abdominoperineal resection of the rectum with urine flowing out of the perineal wound. A new open-pore film drainage (OFD) catheter with an external diameter of only a few millimeters has been developed and is constructed from a very thin open-pore double-layered film and a drainage tube. The OFD was inserted into the bladder by means of flexible endoscopy and channeled out through a suprapubic incision. Continuous suction was applied with an electronic vacuum pump to actively drain the urine completely. A passive catheter drainage of urine from the renal pelvis via transurethral single J stent was carried out simultaneously during the complete duration of treatment. The healing process was monitored during and after therapy by intravesical endoscopy. The application of continuous negative pressure via the OFD resulted in total collapse of the bladder. The urine in the bladder was actively and permanently drained through the OFD. Urine leakage from the perineal wound stopped immediately after induction of suction. After 18 days of treatment with the uEVT the bladder defect was healed. After therapy and removal of the catheters the patient had normal micturition. A novel small-bore OFD has been developed for EVT. The OFD technique now allows endoscopic application of negative pressure in the bladder. This first successful experience proves uEVT to be a potent interventional alternative in the treatment of bladder defects.

  18. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

    Science.gov (United States)

    Adding the drug everolimus (Afinitor®) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone.

  19. Is there a decline in cognitive functions after combined electroconvulsive therapy and antipsychotic therapy in treatment-refractory schizophrenia?

    Science.gov (United States)

    Pawełczyk, Agnieszka; Kołodziej-Kowalska, Emilia; Pawełczyk, Tomasz; Rabe-Jabłońska, Jolanta

    2015-03-01

    An analysis of literature shows that there is still little evidence concerning the efficacy of electroconvulsive therapy (ECT) combined with antipsychotic therapy in a group of treatment-resistant schizophrenia patients. More precisely, its influence on cognitive functions is still equivocal. The aim of this study was to assess the influence of ECT combined with antipsychotic therapy on working memory, attention, and executive functions in a group of treatment-refractory schizophrenia patients. Twenty-seven patients completed the study: 14 men and 13 women, aged 21 to 55 years (mean age, 32.8 years), diagnosed with treatment-resistant schizophrenia. Each patient underwent a course of ECT sessions and was treated with antipsychotic medications. Before the ECT and within 3 days after the last ECT session, the participants were assessed with the following neuropsychological tests: Trail Making Test (TMT) and Wisconsin Cart Sorting Test (WCST). There were no significant differences in the TMT and WCST results after combined ECT and antipsychotic therapy in treatment-refractory schizophrenia patients. According to the results of the neuropsychological tests, there was no decline in attention, executive functions, or working memory. The current study shows no significant difference in attention, working memory, or executive functions after treatment with a combination of electroconvulsive and antipsychotic therapy. This suggests that combined electroconvulsive therapy may not have a negative influence on the neuropsychological functioning of patients with treatment resistant schizophrenia.

  20. Acute sensorineural hearing loss associated with peginterferon and ribavirin combination therapy during hepatitis C treatment: Outcome after resumption of therapy

    Institute of Scientific and Technical Information of China (English)

    Victor K Wong; Cindy Cheong-Lee; Jo-Ann E Ford; Eric M Yoshida

    2005-01-01

    Peginterferon and ribavirin combination therapy for the treatment of hepatitis C virus (HCV) is well known to be associated with significant adverse effects. Sensorineural hearing loss, that in most cases is unilateral, has been reported as a consequence of therapy with both non-pegylated and pegylated interferon (pegIFN) but is not a well-known adverse effect. We report a 45-year-old Caucasian woman who developed acute sensorineural hearing loss 2 mo after starting therapy with pegIFN-α 2b and ribavirin for the treatment of chronic HCV, genotype 1a. She did not report the hearing loss to the hepatitis clinic until L mo,later whereupon therapy was promptly discontinued.Although her serum alanine aminotransferase (ALT)normalized and her HCV-RNA became undetectable after 12 wk of pegIFN and ribavirin therapy, after discontinuation,her HCV-RNA became detectable with significant elevations of serum ALT. Four months after initial discontinuation,the patient re-commenced pegIFN and ribavirin combination therapy. After 44 of 48 wk of therapy, the patient's liver biochemistry has normalized and the HCV-RNA is undetectable. She has not developed worsening of her hearing loss and hearing on the left-side is unaffected.Both patients and physicians should be aware that sensorineural hearing loss may occur with pegIFN therapy.Our experience suggests that re-institution of therapy is not always associated with further hearing impairment.

  1. On the Hydrogen Sulfide Removal Method of the Combined Vacuum Flash Tank%组合式负压闪蒸罐脱硫化氢方法

    Institute of Scientific and Technical Information of China (English)

    秦晓光; 陈玉书; 王蓉; 万攀

    2015-01-01

    为降低物流中的硫化氢的浓度,在源头控制硫化氢污染腐蚀,免于下游管线及设备的腐蚀危险,采用负压闪蒸法脱除物流中的硫化氢气体,创新应用组合式负压闪蒸罐,以达到高效脱除硫化氢和减少设备占地面积的目的;敏感性分析表明,影响负压闪蒸脱硫化氢方法的重要影响因素为硫化氢浓度和物流温度及负压闪蒸的压力选择.%In order to reduce the concentration of hydrogen sulfide in the stream, control hydrogen sulfide pollution corrosion at the source, avoid the corrosion hazard of downstream piping and equipment, the method of vacuum flash is used to remove the hydrogen sulfide gas in the stream.The combined vacuum flash tank is applied to achieve efficient removal of hydrogen sulfide and reducing equipment footprint.The sensitivity analysis show that the important factors impacting negative flash removal method of hydrogen sulfide are the hydrogen sulfide concentration, the stream temperature and the negative pressure selection flashed.

  2. Electronic states and optical properties of GaAs/AlAs and GaAs/vacuum superlattices by the linear combination of bulk bands method

    Energy Technology Data Exchange (ETDEWEB)

    Botti, S.; Andreani, L. C.

    2001-06-15

    The linear combination of bulk bands method recently introduced by Wang, Franceschetti, and Zunger [Phys. Rev. Lett. >78, 2819 (1997)] is applied to a calculation of energy bands and optical constants of (GaAs){sub n}/(AlAs){sub n} and (GaAs){sub n}/(vacuum){sub n} (001) superlattices with n ranging from 4 to 20. Empirical pseudopotentials are used for the calculation of the bulk energy bands. Quantum-confinement-induced shifts of critical point energies are calculated and are found to be larger for the GaAs/vacuum system. The E{sub 1} peak in the absorption spectra has a blueshift and splits into two peaks for decreasing superlattice period; the E{sub 2} transition instead is found to be split for large-period GaAs/AlAs superlattices. The band contribution to linear birefringence of GaAs/AlAs superlattices is calculated and compared with recent experimental results of Sirenko [Phys. Rev. B >60, 8253 (1999)]. The frequency-dependent part reproduces the observed increase with decreasing superlattice period, while the calculated zero-frequency birefringence does not account for the experimental results and points to the importance of local-field effects.

  3. Single photon ionization and chemical ionization combined ion source based on a vacuum ultraviolet lamp for orthogonal acceleration time-of-flight mass spectrometry.

    Science.gov (United States)

    Hua, Lei; Wu, Qinghao; Hou, Keyong; Cui, Huapeng; Chen, Ping; Wang, Weiguo; Li, Jinghua; Li, Haiyang

    2011-07-01

    A novel combined ion source based on a vacuum ultraviolet (VUV) lamp with both single photon ionization (SPI) and chemical ionization (CI) capabilities has been developed for an orthogonal acceleration time-of-flight mass spectrometer (oaTOFMS). The SPI was accomplished using a commercial 10.6 eV krypton discharge lamp with a photon flux of about 10(11) photons s(-1), while the CI was achieved through ion-molecule reactions with O(2)(+) reactant ions generated by photoelectron ionization at medium vacuum pressure (MVP). To achieve high ionization efficiency, the ion source pressure was elevated to 0.3 mbar and the photoionization length was extended to 36 mm. As a result, limits of detection (LODs) down to 3, 4, and 6 ppbv were obtained for benzene, toluene, and p-xylene in MVP-SPI mode, and values of 8 and 10 ppbv were obtained for toluene and chloroform, respectively, in SPI-CI mode. As it is feasible to switch between MVP-SPI mode and SPI-CI mode rapidly, this system is capable of monitoring complex organic mixtures with a wide range of ionization energies (IEs). The analytical capacity of this system was demonstrated by measuring dehydrogenation products of long-chain paraffins to olefins through direct capillary sampling and drinking water disinfection byproducts from chlorine through a membrane interface.

  4. Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kavanaugh, James A. [Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, 202 Nicholson Hall, Tower Drive, Baton Rouge, Louisiana 70803-4001 (United States); Hogstrom, Kenneth R.; Fontenot, Jonas P.; Henkelmann, Gregory [Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, 202 Nicholson Hall, Tower Drive, Baton Rouge, Louisiana 70803-4001 and Mary Bird Perkins Cancer Center, 4950 Essen Lane, Baton Rouge, Louisiana 70809 (United States); Chu, Connel; Carver, Robert A. [Mary Bird Perkins Cancer Center, 4950 Essen Lane, Baton Rouge, Louisiana 70809 (United States)

    2013-02-15

    Purpose: The purpose of this study was to demonstrate that a bolus electron conformal therapy (ECT) dose plan and a mixed beam plan, composed of an intensity modulated x-ray therapy (IMXT) dose plan optimized on top of the bolus ECT plan, can be accurately delivered. Methods: Calculated dose distributions were compared with measured dose distributions for parotid and chest wall (CW) bolus ECT and mixed beam plans, each simulated in a cylindrical polystyrene phantom that allowed film dose measurements. Bolus ECT plans were created for both parotid and CW PTVs (planning target volumes) using 20 and 16 MeV beams, respectively, whose 90% dose surface conformed to the PTV. Mixed beam plans consisted of an IMXT dose plan optimized on top of the bolus ECT dose plan. The bolus ECT, IMXT, and mixed beam dose distributions were measured using radiographic films in five transverse and one sagittal planes for a total of 36 measurement conditions. Corrections for film dose response, effects of edge-on photon irradiation, and effects of irregular phantom optical properties on the Cerenkov component of the film signal resulted in high precision measurements. Data set consistency was verified by agreement of depth dose at the intersections of the sagittal plane with the five measured transverse planes. For these same depth doses, results for the mixed beam plan agreed with the sum of the individual depth doses for the bolus ECT and IMXT plans. The six mean measured planar dose distributions were compared with those calculated by the treatment planning system for all modalities. Dose agreement was assessed using the 4% dose difference and 0.2 cm distance to agreement. Results: For the combined high-dose region and low-dose region, pass rates for the parotid and CW plans were 98.7% and 96.2%, respectively, for the bolus ECT plans and 97.9% and 97.4%, respectively, for the mixed beam plans. For the high-dose gradient region, pass rates for the parotid and CW plans were 93.1% and 94

  5. Simulation model for assessing the efficiency of a combined power installation based on a geothermal heat pump and a vacuum solar collector

    Science.gov (United States)

    Vaysman, Ya I.; Surkov, AA; Surkova, Yu I.; Kychkin, AV

    2017-06-01

    The article is devoted to the use of renewable energy sources and the assessment of the feasibility of their use in the climatic conditions of the Western Urals. A simulation model that calculates the efficiency of a combined power installations (CPI) was (RES) developed. The CPI consists of the geothermal heat pump (GHP) and the vacuum solar collector (VCS) and is based on the research model. This model allows solving a wide range of problems in the field of energy and resource efficiency, and can be applied to other objects using RES. Based on the research recommendations for optimizing the management and the application of CPI were given. The optimization system will give a positive effect in the energy and resource consumption of low-rise residential buildings projects.

  6. Changes in non-volatile taste components of button mushroom (Agaricus bisporus) during different stages of freeze drying and freeze drying combined with microwave vacuum drying.

    Science.gov (United States)

    Pei, Fei; Shi, Ying; Gao, Xingyang; Wu, Fangning; Mariga, Alfred Mugambi; Yang, Wenjian; Zhao, Liyan; An, Xinxin; Xin, Zhihong; Yang, Fangmei; Hu, Qiuhui

    2014-12-15

    Button mushroom slices were dehydrated using freeze drying (FD) or FD combined with microwave vacuum drying (FMVD), and the non-volatile component profiles were studied. The results showed that the level of non-volatile components in button mushroom firstly increased during sublimation of FD/FMVD process and then fell during desorption in FD process and MVD in FMVD process. Compared to FD products, the contents of soluble sugars and polyols in FMVD products were relatively low, whereas the contents of total free amino acids were significantly higher, close to the level of fresh mushroom. However, there was no significant difference in the contents of 5'-nucleotides and organic acids between FD and FMVD products. The equivalent umami concentration (EUC) values for FD and FMVD products did not differ from fresh, indicating that both drying methods could effectively preserve MSG (monosodium glutamate)-like components in button mushroom. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Comparative analysis of global gene expression profiles between diabetic rat wounds treated with vacuum-assisted closure therapy, moist wound healing or gauze under suction.

    Science.gov (United States)

    Derrick, Kathleen L; Norbury, Kenneth; Kieswetter, Kris; Skaf, Jihad; McNulty, Amy K

    2008-12-01

    How differential gene expression affects wound healing is not well understood. In this study, Zucker diabetic fatty (fa/fa) male inbred rats were used to investigate gene expression during wound healing in an impaired wound-healing model. Whole genome microarray surveys were used to gain insight into the biological pathways and healing processes in acute excisional wounds treated with vacuum-assisted closure (V.A.C.). Therapy, moist wound healing (MWH) or gauze under suction (GUS). Global gene expression analyses after 2 days of healing indicated major differences with respect to both number of genes showing fold changes and pathway regulation between the three different wound treatments. Statistical analysis of expression profiles indicated that 5072 genes showed a >1.6-fold change with V.A.C. Therapy compared with 3601 genes with MWH and 3952 genes with GUS. Pathways and related genes associated with the early phases of wound healing diverged between treatment groups. For example, pathways involving angiogenesis, cytoskeletal regulation and inflammation were associated with elevated gene expression following V.A.C. Therapy. This study is the first to assess wound healing by whole genome interrogation in a diabetic rat model treated with different healing modalities.

  8. Anti-cancer effects of oncolytic viral therapy combined with photodynamic therapy in human pancreatic cancer cell lines.

    Science.gov (United States)

    Khaled, Yazan S; Wright, Kathleen; Melcher, Alan; Jayne, David

    2015-02-26

    Oncolytic viral therapy and photodynamic therapy are potential therapies for inoperable or advanced pancreatic cancer. Our aim was to investigate the anti-cancer killing effects of reovirus therapy combined with protoporphyrin IX (PpIX)-mediated photodynamic therapy on a variety of human pancreatic cancer cell lines. Pancreatic cancer cell lines (PsPC-1 and BXPC-3) and a non-cancer control cell line (HEK293) were infected with reovirus serotype 3 strain Dearing (T3D) at 0, 0·1, 1, and 10 plaque-forming units (PFU) per cell for 48 h. Cells were incubated with PpIX pro-drug 5-aminolevulinic acid (5-ALA) at 0, 1, 2, 3, and 4 mM for 4 h. Then, cells were photo-irradiated for 15 min with visible red light-emitting diodes with a light-fluence of 0·54 J/cm(2) of 653 nm (PpIX optimal excitation wavelength). The killing effects of reovirus combined with PpIX-mediated photodynamic therapy were analysed in methylthiazoltetrazolium (MTT) and trypan blue assays. The effect of adding reovirus after photodynamic therapy was also assessed. The statistical significance of the difference between groups was assessed with the two-tailed Student's t test. pphotodynamic therapy resulted in a significantly increased cytotoxic effect compared with reovirus monotherapy and photodynamic therapy (p=0·042) with 100% cell death observed across pancreatic cell lines with 10 PFU per cell combined with 1 and 2 mM 5-ALA. There was no difference in cytotoxicity observed between added reovirus before or after photodynamic therapy. To our knowledge, this is the first in-vitro study to combine reovirus oncolytic viral therapy with PpIX-mediated photodynamic therapy to treat pancreatic cancer. These results show a significant additive effect in cell killing and they provide initial evidence for a novel combined therapeutic intervention. National Institute for Health Research. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Hyperbaric oxygen therapy combined with Schwann cell transplantation promotes spinal cord injury recovery

    Directory of Open Access Journals (Sweden)

    Chuan-gang Peng

    2015-01-01

    Full Text Available Schwann cell transplantation and hyperbaric oxygen therapy each promote recovery from spinal cord injury, but it remains unclear whether their combination improves therapeutic results more than monotherapy. To investigate this, we used Schwann cell transplantation via the tail vein, hyperbaric oxygen therapy, or their combination, in rat models of spinal cord contusion injury. The combined treatment was more effective in improving hindlimb motor function than either treatment alone; injured spinal tissue showed a greater number of neurite-like structures in the injured spinal tissue, somatosensory and motor evoked potential latencies were notably shorter, and their amplitudes greater, after combination therapy than after monotherapy. These findings indicate that Schwann cell transplantation combined with hyperbaric oxygen therapy is more effective than either treatment alone in promoting the recovery of spinal cord in rats after injury.

  10. Quality of life and cost-effectiveness of combined therapy for reflux esophagitis

    Institute of Scientific and Technical Information of China (English)

    姒健敏; 王良静; 陈淑洁; 赵岚; 戴宁

    2003-01-01

    Objective : To evaluate clinical, Quality of Life (QoL) and medical cost outcomes in patients with symptomatic reflux esophagitis (RE) receiving different "triple combination therapy". Methods: A muhicenter medical effectiveness trial conducted in 10 hospitals of 5 regions in Zhejiang Province. 248 patient-volunteers were assigned to 8 weeks of " triple combination therapy" with Lansoprazole plus Cisapride and Sucralfate or Ranitidine plus Cisapride and Sucralfate. Main outcomes assessment included symptoms scale scores, RE severity, QoL at baseline and 8 weeks. Medical cost data were collected with cost analysis questionnaire. Resuits: (1)More Lansoprazole group patients noted RE symptoms resolution than Ranitidine group(92.3 % vs 78.4%, P 0.05) . (2)RE significantly impaired QoL of patients( P 0.05 ) . Conclusion : RE significantly impaired QoL of patients. "Triple combination therapies" can significantly improve RE symptoms and QoL. Lansoprazole combination therapy was more cost-effective than Ranitidine combination group.

  11. Successful therapy of progressive rhino-orbital mucormycosis caused by Rhizopus arrhizus with combined and sequential antifungal therapy, surgery and hyperbaric therapy

    Directory of Open Access Journals (Sweden)

    Adrián Imbernón

    2014-10-01

    Full Text Available We present a case of rhino-orbitary mucormycosis which progressed despite liposomal amphotericin and early surgical debridement. Combined echinocandin and high dose liposomal amphotericin, repeated debridement, prolonged therapy with hyperbaric oxygen and continued therapy with posaconazole, along with strict diabetic control, allowed cure without disfigurement.

  12. Possible artemisinin-based combination therapy-resistant malaria in Nigeria: a report of three cases

    Directory of Open Access Journals (Sweden)

    Nnennaya Anthony Ajayi

    2013-07-01

    Full Text Available Artemisinin-based combination therapy-resistant malaria is rare in Sub-Saharan Africa. The World Health Organization identifies monitoring and surveillance using day-3 parasitaemia post-treatment as the standard test for identifying suspected artemisinin resistance. We report three cases of early treatment failure due to possible artemisinin-based combination therapy-resistant Plasmodium falciparum malaria. All cases showed adequate clinical and parasitological responses to quinine. This study reveals a need to re-evaluate the quality and efficacy of artemisinin-based combination therapy agents in Nigeria and Sub-Saharan Africa.

  13. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Postow, Michael A. [Department of Medicine, Melanoma and Sarcoma Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-04-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.

  14. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria.

    Science.gov (United States)

    Tängdén, Thomas

    2014-05-01

    Combination antibiotic therapy for Gram-negative sepsis is controversial. The present review provides a brief summary of the existing knowledge on combination therapy for severe infections with multidrug-resistant Pseudomonas spp., Acinetobacter spp., and Enterobacteriaceae. Empirical combination antibiotic therapy is recommended for severe sepsis and septic shock to reduce mortality related to inappropriate antibiotic treatment. Because definitive combination therapy has not been proven superior to monotherapy in meta-analyses, it is generally advised to de-escalate antibiotic therapy when the antibiotic susceptibility profile is known, although it cannot be excluded that some subgroups of patients might still benefit from continued combination therapy. Definitive combination therapy is recommended for carbapenemase-producing Enterobacteriaceae and should also be considered for severe infections with Pseudomonas and Acinetobacter spp. when beta-lactams cannot be used. Because resistance to broad-spectrum beta-lactams is increasing in Gram-negative bacteria and because no new antibiotics are expected to become available in the near future, the antibacterial potential of combination therapy should be further explored. In vitro data suggest that combinations can be effective even if the bacteria are resistant to the individual antibiotics, although existing evidence is insufficient to support the choice of combinations and explain the synergistic effects observed. In vitro models can be used to screen for effective combinations that can later be validated in animal or clinical studies. Further, in the absence of clinical evidence, in vitro data might be useful in supporting therapeutic decisions for severe infections with multidrug-resistant Gram-negative bacteria.

  15. Sequential combination of robot-assisted therapy and constraint-induced therapy in stroke rehabilitation: a randomized controlled trial.

    Science.gov (United States)

    Hsieh, Yu-Wei; Lin, Keh-Chung; Horng, Yi-Shiung; Wu, Ching-Yi; Wu, Tai-Chieh; Ku, Fang-Ling

    2014-05-01

    Robot-assisted therapy (RT) and constraint-induced therapy (CIT) both show great promise to improve stroke rehabilitation outcomes. Although the respective treatment efficacy of RT and CIT has been validated, the additive effects of RT combined with CIT remain unknown. This study investigated the treatment effects of RT in sequential combination with a distributed form of CIT (RT + dCIT) compared with RT and conventional rehabilitation (CR). Forty-eight patients with stroke were enrolled and randomized to receive one of the three interventions for 4 weeks. Primary outcomes assessed the changes of motor impairment and motor function on the Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT). Secondary outcomes, including the Motor Activity Log (MAL) and accelerometers, examined functional performance during daily activities. The three treatment groups improved significantly on most primary and secondary outcomes over time. The combined RT + dCIT group exhibited significantly greater improvement on the FMA and functional ability subscale of the WMFT than the RT and CR groups. The improvements on the MAL and accelerometers were not significantly different among the three groups. RT in sequential combination with CIT led to additive effects on participants' motor ability and functional ability to perform motor tasks after stroke, which support that combined therapy can be an effective means to intensify outcomes. Further research investigating the potential long-term effects of combination therapy, especially on real-life performance, would be valuable.

  16. ULTRARAPID VACUUM-MICROWAVE HISTOPROCESSING

    NARCIS (Netherlands)

    KOK, LP; BOON, ME

    1995-01-01

    A novel histoprocessing method for paraffin sections is presented in which the combination of vacuum and microwave exposure is the key element. By exploiting the decrease in boiling temperature under vacuum, the liquid molecules in the tissues have been successfully extracted and exchanged at relati

  17. ULTRARAPID VACUUM-MICROWAVE HISTOPROCESSING

    NARCIS (Netherlands)

    KOK, LP; BOON, ME

    A novel histoprocessing method for paraffin sections is presented in which the combination of vacuum and microwave exposure is the key element. By exploiting the decrease in boiling temperature under vacuum, the liquid molecules in the tissues have been successfully extracted and exchanged at

  18. Combined modality therapy for locally advanced penile squamous cell carcinoma.

    Science.gov (United States)

    Pedrick, T J; Wheeler, W; Riemenschneider, H

    1993-12-01

    We report here a patient who presented with locally advanced Jackson Stage IV penile squamous cell carcinoma who was managed with preoperative 5-fluorouracil, mitomycin C chemotherapy, and concurrent radiation therapy. He experienced an excellent partial response which allowed more limited surgery than would otherwise be indicated. He is still alive and well 5 years after completion of his treatment without side effects, local recurrence, or distant metastatic disease.

  19. Vacuum Incalescence

    CERN Document Server

    Intravaia, F

    2016-01-01

    In quantum theory the vacuum is defined as a state of minimum energy that is devoid of particles but still not completely empty. It is perhaps more surprising that its definition depends on the geometry of the system and on the trajectory of an observer through space-time. Along these lines we investigate the case of an atom flying at constant velocity near a planar surface. Using general concepts of statistical mechanics it is shown that the motion-modified interaction with the electromagnetic vacuum is formally equivalent to the interaction with a thermal field having an effective temperature determined by the atom's velocity and distance from the surface. This result suggests new ways to experimentally investigate the properties of the quantum vacuum in non-equilibrium systems and effects such as quantum friction.

  20. Combination antiretroviral therapy and the risk of myocardial infarction

    NARCIS (Netherlands)

    Friis-Moller, N; Sabin, CA; Weber, R; Monforte, AD; El-Sadr, WM; Reiss, P; Thiebaut, R; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Lundgren, JD; Lundgren, JD; Weber, R; Monteforte, AD; Bartsch, G; Reiss, P; Dabis, F; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Houyez, F; Loeliger, E; Tressler, R; Weller, I.; Friis-Moller, N; Sabin, CA; Sjol, A; Lundgren, JD; Sawitz, A; Rickenbach, M; Pezzotti, P; Krum, E; Meester, R; Lavignolle, V.; Sundstrom, A; Poll, B; Fontas, E; Torres, F; Petoumenos, K; Kjaer, J; Hammer, S; Neaton, J; Sjol, A; de Wolf, F; van der Ven, E; Zaheri, S; Van Valkengoed, L; Meester, R; Bronsveld, W; Weigel, H; Brinkman, K; Frissen, P; ten Veen, J; Hillbrand, M; Schieveld, S; Mulder, J; van Gorp, E; Meenhorst, P; Danner, S; Claessen, F; Perenboom, R; Schattenkerk, JKE; Godfried, M; Lange, J; Lowe, S; van der Meer, J; Nellen, F; Pogany, K; van der Poll, T; Reiss, R; Ruys, T; Wit, F; Richter, C; van Leusen, R; Vriesendorp, R; Jeurissen, F; Kauffmann, R; Koger, E; Brevenboer, B; Sprenger, HG; Law, G; ten Kate, RW; Leemhuis, M; Schippers, E; Schrey, G; van der Geest, S; Verbon, A; Koopmans, P; Keuter, M; Telgt, D; van der Ven, A; van der Ende, Marchina E.; Gyssens, I.; de Marie, S; Juttmann, J; van der Heul, C; Schneider, M; Borleffs, J; Hoepelman, I.; Jaspers, C; Matute, A; Schurink, C; Blok, W; Salamon, R; Beylot, J; Dupon, M; Le Bras, M; Pellegrin, JL; Ragnaud, JM; Dabis, F; Chene, G; Jacqmin-Gadda, H; Rhiebaut, R; Lawson-Ayayi, S; Lavignolle, V.; Balestre, E; Blaizeau, MJ; Decoin, M; Formaggio, AM; Delveaux, S; Labarerre, S; Uwamaliya, B; Vimard, E; Merchadou, L; Palmer, G; Touchard, D; Dutoit, D; Pereira, F; Boulant, B; Beylot, J; Morlat, P; Bonarek, M; Bonnet, F; Coadou, B; Gelie, P; Jaubert, D; Nouts, C; Lacoste, D; Dupon, M; Dutronc, H; Cipriano, G; Lafarie, S; Chossat, I.; Lacut, JY; Leng, B; Pellegrin, JL; Mercie, P; Viallard, JF; Faure, I.; Rispal, P; Cipriano, C; Tchamgoue, S; Le Bras, M; Djossou, F; Malvy, D; Pivetaud, JP; Ragnaud, JM; Chambon, D; De La Taille, C; Galperine, T; Lafarie, S; Neau, D; Ochoa, A; Beylot, C; Doutre, MS; Bezian, JH; Moreau, JF; Taupin, JL; Conri, C; Constans, J; Couzigou, P; Castera, L; Fleury, H; Lafon, ME; Masquelier, B; Pellegrin, I.; Trimoulet, P; Moreau, F; Mestre, C; Series, C; Taytard, A; Law, M; Petoumenos, K; Bal, J; Mijch, A; Watson, K; Roth, N; Wood, H; Austin, D; Gowers, A; Baker, B; McFarlane, R; Carr, A; Cooper, D; Chuah, J; Fankhauser, W; Mallal, S; Skett, J; Calvo, G; Torres, F; Mateau, S; Domingo, P; Sambeat, MA; Gatell, J; Del Cacho, E; Cadafalch, J; Fuster, M; Codina, C; Sirera, G; Vaque, A; Clumeck, N; De Wit, S; Gerard, M; Hildebrand, M; Kabeya, K; Konopnicki, D; Payen, MC; Poll, B; Van Laethem, Y; Neaton, J; Bartsch, G; El-Sadr, WM; Krum, E; Thompson, G; Wentworth, D; Luskin-Hawk, R; Telzak, E; El-Sadr, WM; Abrams, DI; Cohn, D; Markowitz, N; Arduino, R; Mushatt, D; Friedland, G; Perez, G; Tedaldi, E; Fisher, E; Gordin, F; Crane, LR; Sampson, J; Baxter, J; Kirk, O; Mocroft, A; Phillips, AN; Lundgren, JD; Vetter, N; Clumeck, N; Hermans, P; Colebunders, R; Machala, L; Nielsen, J; Benfield, T; Gerstoft, J; Katzenstein, T; Roge, B; Skinhoj, P; Pedersen, C; Katlama, C; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Miller, V.; Staszewski, S; Bieckel, M; Goebel, FD; Salzberger, B; Rockstroh, J; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Karydis, I.; Filandras, A; Banhegyi, D; Mulcahy, F; Yust, I.; Turner, D; Pollack, S; Ben-Ishai, Z; Bentwich, Z; Maayan, S; Vella, S; Chiesi, A; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Esposito, R; Bedini, A; Chirianni, A; Montesarchio, E; Vullo, V.; Santopadre, P; Narciso, P; Antinori, A; Franci, P; Zaccarelli, M; Lazzarin, A; Finazzi, R; Monforte, VO; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, V.; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Boron-Kaczmarska, A; Pnyka, M; Beniowski, M; Trocha, H; Antunes, F; Mansinho, K; Proenca, R; Gonzalez-Lahoz, J; Diaz, B; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, V.; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Blaxhult, A; Heidemann, B; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Telenti, A; Hirschel, B; Soravia-Dunand, V.; Furrer, H; Fisher, M; Brettle, R; Barton, S; Johnson, AM; Mercey, D; Loveday, C; Johnson, MA; Pinching, A; Parkin, J; Weber, J; Scullard, G; Morfeldt, L; Thulin, G; Sunstrom, A; Akerlund, B; Koppel, K; Karlsson, A; Flamholc, L; Hakangard, C; Monforte, AD; Pezzotti, P; Moroni, M; Monforte, AD; Cargnel, A; Merli, S; Vigevani, GM; Pastecchia, C; Lazzarin, A; Novati, R; Caggese, L; Moioli, C; Mura, MS; Mannazzu, M; Suter, F; Arici, C; Manconi, PE; Piano, P; Mazzotta, F; Lo Caputo, S; Poggio, A; Bottari, G; Pagano, G; Alessandrini, A; Scasso, A; Vincenti, A; Abbadesse, V.; Mancuso, S; Alberici, F; Ruggieri, A; Arlotti, M; Ortolani, P; De Lalla, F; Tositti, G; Piersantelli, N; Piscopo, R; Raise, E; Pasquinucci, S; Soscia, F; Tacconi, L; Tirelli, U; Nasti, G; Santoro, D; Pusterla, L; Carosi, G; Castelli, F; Cadeo, G; Vangi, D; Carnevale, G; Galloni, D; Filice, G; Bruno, R; Sinicco, A; Sciandra, M; Caramello, P; Gennero, L; Soranzo, ML; Bonasso, M; Rizzardini, G; Migliorino, G; Chiodo, F; Colangeli, V.; Magnani, G; Ursitti, M; Menichetti, F; Martinelli, C; Esposito, R; Mussini, C; Ghinelli, F; Sighinolfi, L; Coronado, O; Zauli, T; Ballardini, G; Montroni, M; Zoli, A; Petrelli, E; Cioppi, A; Ortona, L; De Luca, A; Petrosillo, N; Noto, P; Narciso, P; Salcuni, P; Antinori, A; De Longis, P; Vullo, V.; Lichtner, M; Pastore, G; Minafra, G; Chiriann, A; Loiacono, L; Piazza, M; Nappa, S; Abrescia, N; De Marco, M; Colomba, A; Prestileo, T; De Stefano, C; La Gala, A; Ferraro, T; Scerbo, A; Grima, P; Tundo, P; Pizzigallo, E; D'Alessandro, M; Grisorio, B; Ferrara, S; Pradier, C; Fontas, E; Caissotti, C; Dellamonica, P; Bentz, L; Bernard, E; Chaillou, S; De Salvador-Guillouet, F; Durant, J; Guttman, R; Heripret, L; Mondain-Miton, V.; Perbost, I.; Prouvost-Keller, B; Pugliese, P; Rahelinirina, V.; Roger, PM; Vandenbos, F; Bernasconi, E; Bucher, H; Burgisser, P; Cattacin, S; Egger, M; Erb, P; Fierz, W; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, HJ; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Ledergerber, B; Lauper, U; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schupbach, J; Speck, R; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; Ten Napel, C.

    2003-01-01

    Background: It remains controversial whether exposure to combination antiretroviral treatment increases the risk of myocardial infarction. Methods: In this prospective observational study, we enrolled 23,468 patients from 11 previously established cohorts from December 1999 to April 2001 and

  1. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors

    Directory of Open Access Journals (Sweden)

    Alberto F Rubio-Guerra

    2009-11-01

    Full Text Available Alberto F Rubio-Guerra1, David Castro-Serna2, Cesar I Elizalde Barrera2, Luz M Ramos-Brizuela21Metabolic and Research Clinic, 2Internal Medicine Department, Hospital General de Ticomán SS DF, MéxicoAbstract: Recent guidelines for the management of hypertension recommend target blood pressures <140/90 mmHg in hypertensive patients, or <130/80 mmHg in subjects with diabetes, chronic kidney disease, or coronary artery disease. Despite the availability and efficacy of antihypertensive drugs, most hypertensive patients do not reach the recommended treatment targets with monotherapy, making combination therapy necessary to achieve the therapeutic goal. Combination therapy with 2 or more agents is the most effective method for achieving strict blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs, and improves adherence. There are many drug choices for combination therapy, but few data are available about the efficacy and safety of some specific combinations. Combination therapy of calcium antagonists and inhibitors of the renin-angiotensin-aldosterone system (RAAS are efficacious and safe, and have been considered rational by both the JNC 7 and the 2007 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. The aim of this review is to discuss some relevant issues about the use of combinations with calcium channel blockers and RAAS inhibitors in the treatment of hypertension.Keywords: hypertension, calcium channel blockers, renin-angiotensin-aldosterone system inhibitors, fixed-dose combination, adherence

  2. Combining Voice Therapy and Physical Therapy: A Novel Approach to Treating Muscle Tension Dysphonia

    Science.gov (United States)

    Craig, Jennifer; Tomlinson, Carey; Stevens, Kristin; Kotagal, Kiran; Fornadley, Judith; Jacobson, Barbara; Garrett, C. Gaelyn; Francis, David O.

    2015-01-01

    Objective This study investigated the role of a specialized physical therapy program for muscle tension dysphonia patients as an adjunct to standard of care voice therapy. Study Design Retrospective Cohort Study Methods Adult MTD patients seen between 2007 and 2012 were identified from the clinical database. They were prescribed voice therapy and, if concomitant neck pain, adjunctive physical therapy. In a pragmatic observational cohort design, patients underwent one of four potential treatment approaches: voice therapy alone (VT), voice therapy and physical therapy (VT+PT), physical therapy alone (PT), or incomplete/no treatment. Voice handicap outcomes were compared between treatment approaches. Results Of 153 patients meeting criteria (Median age 48 years, 68% female, and 30% had fibromyalgia, chronic pain, chronic fatigue, depression, and/or anxiety), there was a similar distribution of patients with moderate or severe pre-treatment VHI scores across treatment groups (VT 45.5%, VT+PT 43.8%, PT 50%, no treatment 59.1%; p=0.45). Patients treated with VT alone had significantly greater median improvement in VHI than those not treated: 10-point vs. 2-point (p=0.02). Interestingly, median VHI improvement in patients with baseline moderate-severe VHI scores was no different between VT (10), VT+PT (8) and PT alone (10; p=0.99). Conclusions Findings show voice therapy to be an effective approach to treating MTD. Importantly, other treatment modalities incorporating physical therapy had a similar, albeit not significant, improvement in VHI. This preliminary study suggests that physical therapy techniques may have a role in the treatment of a subset of MTD patients. Larger, comparative studies are needed to better characterize the role of physical therapy in this population. PMID:26012419

  3. Treatment for recurrent medulloblastoma with intrathecal liposomal cytarabine and systemic metronomic combination therapy.

    Science.gov (United States)

    Nygaard, Randi; Kivivuori, Sanna-Maria

    2012-03-01

    The prognosis of recurrent medulloblastoma is dismal, with a median survival of less than 1 year. Our patient was initially diagnosed with high-risk medulloblastoma when he was 14 years old. He had a recurrence 18 months after the end of therapy. Recurrence treatment consisted of 13 intrathecal applications of liposomal cytarabine over an 18-month period, and oral metronomic antiangiogenic therapy with thalidomide, celecoxib, and etoposide. Side effects from the intrathecal treatment were most likely related to arachnoiditis despite prolonged prophylaxis with steroids. He also developed partial hearing loss. Neutropenia was the main side effect of the metronomic therapy. He remains alive, with a good quality of life and without evidence of disease 34 months from the start of recurrence therapy. This combination of local antineoplastic and systemic antiangiogenic therapy seems to be promising for recurrent medulloblastoma. However, more patients and standardized protocols are needed to verify the benefit of this combination therapy and to define the correct duration of treatment.

  4. Combination therapy of murine mucormycosis or aspergillosis with iron chelation, polyenes, and echinocandins.

    Science.gov (United States)

    Ibrahim, Ashraf S; Gebremariam, Teclegiorgis; Luo, Guanpingsheng; Fu, Yue; French, Samuel W; Edwards, John E; Spellberg, Brad

    2011-04-01

    Liposomal amphotericin B (LAmB) combined wither either micafungin or deferasirox was synergistic in previous murine studies with mucormycosis or aspergillosis. We hypothesized that triple therapy using LAmB, micafungin, and deferasirox could further improve outcomes of mucormycosis or aspergillosis. Triple therapy improved survival and reduced tissue fungal burden of mice with mucormycosis and to a lesser extent with aspergillosis. Continued investigation into the use of triple therapy against mucormycosis and aspergillosis is warranted.

  5. Effect analysis of a soft ground reinforced by a combined vacuum preloading and pneumatic fracturing method%劈裂真空法加固软土地基的效果分析

    Institute of Scientific and Technical Information of China (English)

    章定文; 韩文君; 刘松玉; 杜广印

    2012-01-01

    To overcome the problems of traditional vacuum preloading method, vacuum preloading and pneumatic fracturing are combined to reinforce the performance of ground improvement. The mechanism and construction procedures of the combined method are introduced firstly. The reinforcement effect of the combined method is validated through a pilot highway embankment on soft clay in Jiangsu, China. Comparing to the traditional vacuum preloading method, the combined vacuum preloading and pneumatic fracturing method would enhance the transfer efficiency of vacuum into deep soil layers and accelerate the dissipation of excess pore water pressure. Therefore, the strength increase of soft soil layers improved by the combined method is much larger than that of ground reinforced by the traditional vacuum preloading method. The combined method also can reduce the construction period than the traditional vacuum preloading method. The test results of cone penetration tests and engineering properties tests of soft soils also indicate the superior of the combined vacuum preloading and pneumatic fracturing method.%针对常规真空预压法加固软土地基中存在的问题,介绍了最新研制开发的气压劈裂真空预压法及其施工工艺,并通过现场试验段测试结果分析了劈裂真空法加固软土地基的效果.测试结果表明,较常规真空预压法而言,劈裂真空法可以提高真空荷载向深层土体中的传递效率和加速超静孔隙水压力的消散,既可改善深层软土的加固效果又可加速地基固结,缩短工程工期;劈裂真空法加固地基的沉降效率大于常规真空预压法处理地基,沉降易于收敛,有利于工后沉降的控制.通过加固前后孔压静力触探试验测试结果对比和取样室内试验土性参数变化分析,论证了劈裂真空法加固深层软土地基的有效性和优越性.

  6. Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy

    DEFF Research Database (Denmark)

    Abdulla, Salim; Achan, Jane; Adam, Ishag

    2016-01-01

    Background: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are importa...

  7. Use of pharmacodynamic parameters to predict efficacy of combination therapy by using fractional inhibitory concentration kinetics

    NARCIS (Netherlands)

    J.G. den Hollander (Jan); J.W. Mouton (Johan); H.A. Verbrugh (Henri)

    1998-01-01

    textabstractCombination therapy with antimicrobial agents can be used against bacteria that have reduced susceptibilities to single agents. We studied various tobramycin and ceftazidime dosing regimens against four resistant Pseudomonas aeruginosa strains in an in vitro

  8. Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum.

    NARCIS (Netherlands)

    Bousema, J.T.; Schneider, P.; Gouagna, L.C.; Drakeley, C.; Tostmann, A.; Houben, R.; Githure, J.I.; Ord, R.; Sutherland, C.J.; Omar, S.A.; Sauerwein, R.W.

    2006-01-01

    Background. Artemisinin-based combination therapy (ACT) reduces microscopically confirmed gametocytemia and mosquito infection. However, molecular techniques have recently revealed high prevalences of submicroscopic gametocytemia. Our objective here was to determine the effect of sulfadoxine-pyrimet

  9. Effectiveness of a positive psychology intervention combined with cognitive behavioral therapy in university students

    National Research Council Canada - National Science Library

    Rosario Josefa Marrero; Mónica Carballeira; Sabrina Martín; Miriam Mejías

    2016-01-01

      The aim of this study was to design and implement a positive intervention combined with cognitive-behavioral therapy to enhance subjective and psychological well-being and other positive functioning...

  10. Combination therapy with leflunomide and genetic engineering biological agents

    Directory of Open Access Journals (Sweden)

    Nataliya Vladimirovna Chichasova

    2011-06-01

    Full Text Available The paper gives data on the use of a combination of genetic engineering biological agents (GEBAs and leflunomide in patients with rheumatoid arthritis (RA. In accordance with the international guidelines, the majority of GEBAs should be given in a combination with methotrexate (MTX, which increases the efficacy of a number of GEBAs (tumor necrosis factor-α inhibitors, rituximab and affects tolerability (remikeid, humira. However, MTX cannot be always used in real practice. The data given in the paper on the efficiency and safety of the coadministration of leflunomide and a GEBA in patients with active RA, which are based on the results of randomized studies and national registers, including the Russian one, point to the compatibility of the results of treatment with this and GEBA-MTX combinations.

  11. Ultrasmall Biocompatible WO3- x Nanodots for Multi-Modality Imaging and Combined Therapy of Cancers.

    Science.gov (United States)

    Wen, Ling; Chen, Ling; Zheng, Shimin; Zeng, Jianfeng; Duan, Guangxin; Wang, Yong; Wang, Guanglin; Chai, Zhifang; Li, Zhen; Gao, Mingyuan

    2016-07-01

    Ultrasmall biocompatible WO3 - x nanodots with an outstanding X-ray radiation sensitization effect are prepared, and demonstrated to be applicable for multi-modality tumor imaging through computed tomography and photoacoustic imaging (PAI), and effective cancer treatment combining both photothermal therapy and radiation therapy.

  12. Preservation of Steamed Fish (Rastrelliger Sp) With Combine Method Using Sodium Acetate, Lactic Acid Bacteria Culture and Vacuum Packaging

    OpenAIRE

    Betty Sri Laksmi Jenie, . Nuratifa, . Suliantari

    2001-01-01

    This study was carried out to improve the safety and shelf life of cooked kembung fish (Rastrelliger sp), a traditional food called pindang fish. Fresh eviscerated fish was fisrt soaked in 2% NaCl solution for 15 minutes, drained, washed with tap water and drained again. Sodium chloride at 12% concentration (w/w) was distributed on the whole surface of the fish. Fish was then laid on a wooden basket inside a clay pot, steamed for 30 minutes, and then cooled. Combine method applied to the stea...

  13. Photothermal combined gene therapy achieved by polyethyleneimine-grafted oxidized mesoporous carbon nanospheres.

    Science.gov (United States)

    Meng, Ying; Wang, Shanshan; Li, Chengyi; Qian, Min; Yan, Xueying; Yao, Shuangchao; Peng, Xiyue; Wang, Yi; Huang, Rongqin

    2016-09-01

    Combining controllable photothermal therapy and efficacious gene therapy in a single platform holds great promise in cancer therapy due to the enhanced combined therapeutic effects. Herein, polyethyleneimine-grafted oxidized mesoporous carbon nanospheres (OP) were developed for combined photothermal combined gene therapy in vitro and in vivo. The synthesized OP was characterized to have three dimensional spherical structure with uniformed diameter, ordered mesopores with graphitic domains, high water dispersion with zeta potential of +22 mV, and good biocompatibility. Consequently, OP was exploited as the photothermal convertor with strong NIR absorption and the gene vector via electrostatic interaction, which therefore cannot only deliver the therapeutic gene (pING4) to tumors for gene therapy, but also can eliminate the tumors by photothermal ablation. Moreover, the improved gene therapy accompanied by the NIR photothermally enhanced gene release was also well achieved based on OP. The excellent combined therapeutic effects demonstrated in vitro and in vivo suggested the OP's potential for cancer therapy.

  14. Vacuum Valve

    CERN Multimedia

    1974-01-01

    This valve was used in the Intersecting Storage Rings (ISR) to protect against the shock waves that would be caused if air were to enter the vacuum tube. Some of the ISR chambers were very fragile, with very thin walls - a design required by physicists on the lookout for new particles.

  15. Adjuvant combined ozone therapy for extensive wound over tibia.

    Science.gov (United States)

    Shah, Prasham; Shyam, Ashok K; Shah, Sambhav

    2011-07-01

    Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15(th) day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability.

  16. Adjuvant combined ozone therapy for extensive wound over tibia

    Directory of Open Access Journals (Sweden)

    Prasham Shah

    2011-01-01

    Full Text Available Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15th day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability.

  17. Expanding the therapeutic index of radiation therapy by combining in situ gene therapy in the treatment of prostate cancer.

    Science.gov (United States)

    Tetzlaff, Michael T; Teh, Bin S; Timme, Terry L; Fujita, Tetsuo; Satoh, Takefumi; Tabata, Ken-Ichi; Mai, Wei-Yuan; Vlachaki, Maria T; Amato, Robert J; Kadmon, Dov; Miles, Brian J; Ayala, Gustavo; Wheeler, Thomas M; Aguilar-Cordova, Estuardo; Thompson, Timothy C; Butler, E Brian

    2006-02-01

    The advances in radiotherapy (3D-CRT, IMRT) have enabled high doses of radiation to be delivered with the least possible associated toxicity. However, the persistence of cancer (local recurrence after radiotherapy) despite these increased doses as well as distant failure suggesting the existence of micro-metastases, especially in the case of higher risk disease, have underscored the need for continued improvement in treatment strategies to manage local and micro-metastatic disease as definitively as possible. This has prompted the idea that an increase in the therapeutic index of radiotherapy might be achieved by combining it with in situ gene therapy. The goal of these combinatorial therapies is to maximize the selective pressure against cancer cell growth while minimizing treatment-associated toxicity. Major efforts utilizing different gene therapy strategies have been employed in conjunction with radiotherapy. We reviewed our and other published clinical trials utilizing this combined radio-genetherapy approach including their associated pre-clinical in vitro and in vivo models. The use of in situ gene therapy as an adjuvant to radiation therapy dramatically reduced cell viability in vitro and tumor growth in vivo. No significant worsening of the toxicities normally observed in single-modality approaches were identified in Phase I/II clinical studies. Enhancement of both local and systemic T-cell activation was noted with this combined approach suggesting anti-tumor immunity. Early clinical outcome including biochemical and biopsy data was very promising. These results demonstrate the increased therapeutic efficacy achieved by combining in situ gene therapy with radiotherapy in the management of local prostate cancer. The combined approach maximizes tumor control, both local-regional and systemic through radio-genetherapy induced cytotoxicity and anti-tumor immunity.

  18. Gene Therapy for RAG-deficient Severe Combined Immunodeficiency

    NARCIS (Netherlands)

    K. Pike (Karin)

    2007-01-01

    textabstractSevere combined immunodeficiency (SCID) is a rare class of primary, inherited, immunodeficiency causing infants to suffer from persistent diarrhea, opportunistic infections and a failure to thrive. RAG proteins play a crucial role in the initiation of V(D)J recombination of immun

  19. Gene Therapy for RAG-deficient Severe Combined Immunodeficiency

    NARCIS (Netherlands)

    K. Pike (Karin)

    2007-01-01

    textabstractSevere combined immunodeficiency (SCID) is a rare class of primary, inherited, immunodeficiency causing infants to suffer from persistent diarrhea, opportunistic infections and a failure to thrive. RAG proteins play a crucial role in the initiation of V(D)J recombination of immun

  20. Combination antiretroviral therapy and the risk of myocardial infarction

    NARCIS (Netherlands)

    Friis-Moller, N; Sabin, CA; Weber, R; Monforte, AD; El-Sadr, WM; Reiss, P; Thiebaut, R; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Lundgren, JD; Lundgren, JD; Weber, R; Monteforte, AD; Bartsch, G; Reiss, P; Dabis, F; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Houyez, F; Loeliger, E; Tressler, R; Weller, I.; Friis-Moller, N; Sabin, CA; Sjol, A; Lundgren, JD; Sawitz, A; Rickenbach, M; Pezzotti, P; Krum, E; Meester, R; Lavignolle, V.; Sundstrom, A; Poll, B; Fontas, E; Torres, F; Petoumenos, K; Kjaer, J; Hammer, S; Neaton, J; Sjol, A; de Wolf, F; van der Ven, E; Zaheri, S; Van Valkengoed, L; Meester, R; Bronsveld, W; Weigel, H; Brinkman, K; Frissen, P; ten Veen, J; Hillbrand, M; Schieveld, S; Mulder, J; van Gorp, E; Meenhorst, P; Danner, S; Claessen, F; Perenboom, R; Schattenkerk, JKE; Godfried, M; Lange, J; Lowe, S; van der Meer, J; Nellen, F; Pogany, K; van der Poll, T; Reiss, R; Ruys, T; Wit, F; Richter, C; van Leusen, R; Vriesendorp, R; Jeurissen, F; Kauffmann, R; Koger, E; Brevenboer, B; Sprenger, HG; Law, G; ten Kate, RW; Leemhuis, M; Schippers, E; Schrey, G; van der Geest, S; Verbon, A; Koopmans, P; Keuter, M; Telgt, D; van der Ven, A; van der Ende, Marchina E.; Gyssens, I.; de Marie, S; Juttmann, J; van der Heul, C; Schneider, M; Borleffs, J; Hoepelman, I.; Jaspers, C; Matute, A; Schurink, C; Blok, W; Salamon, R; Beylot, J; Dupon, M; Le Bras, M; Pellegrin, JL; Ragnaud, JM; Dabis, F; Chene, G; Jacqmin-Gadda, H; Rhiebaut, R; Lawson-Ayayi, S; Lavignolle, V.; Balestre, E; Blaizeau, MJ; Decoin, M; Formaggio, AM; Delveaux, S; Labarerre, S; Uwamaliya, B; Vimard, E; Merchadou, L; Palmer, G; Touchard, D; Dutoit, D; Pereira, F; Boulant, B; Beylot, J; Morlat, P; Bonarek, M; Bonnet, F; Coadou, B; Gelie, P; Jaubert, D; Nouts, C; Lacoste, D; Dupon, M; Dutronc, H; Cipriano, G; Lafarie, S; Chossat, I.; Lacut, JY; Leng, B; Pellegrin, JL; Mercie, P; Viallard, JF; Faure, I.; Rispal, P; Cipriano, C; Tchamgoue, S; Le Bras, M; Djossou, F; Malvy, D; Pivetaud, JP; Ragnaud, JM; Chambon, D; De La Taille, C; Galperine, T; Lafarie, S; Neau, D; Ochoa, A; Beylot, C; Doutre, MS; Bezian, JH; Moreau, JF; Taupin, JL; Conri, C; Constans, J; Couzigou, P; Castera, L; Fleury, H; Lafon, ME; Masquelier, B; Pellegrin, I.; Trimoulet, P; Moreau, F; Mestre, C; Series, C; Taytard, A; Law, M; Petoumenos, K; Bal, J; Mijch, A; Watson, K; Roth, N; Wood, H; Austin, D; Gowers, A; Baker, B; McFarlane, R; Carr, A; Cooper, D; Chuah, J; Fankhauser, W; Mallal, S; Skett, J; Calvo, G; Torres, F; Mateau, S; Domingo, P; Sambeat, MA; Gatell, J; Del Cacho, E; Cadafalch, J; Fuster, M; Codina, C; Sirera, G; Vaque, A; Clumeck, N; De Wit, S; Gerard, M; Hildebrand, M; Kabeya, K; Konopnicki, D; Payen, MC; Poll, B; Van Laethem, Y; Neaton, J; Bartsch, G; El-Sadr, WM; Krum, E; Thompson, G; Wentworth, D; Luskin-Hawk, R; Telzak, E; El-Sadr, WM; Abrams, DI; Cohn, D; Markowitz, N; Arduino, R; Mushatt, D; Friedland, G; Perez, G; Tedaldi, E; Fisher, E; Gordin, F; Crane, LR; Sampson, J; Baxter, J; Kirk, O; Mocroft, A; Phillips, AN; Lundgren, JD; Vetter, N; Clumeck, N; Hermans, P; Colebunders, R; Machala, L; Nielsen, J; Benfield, T; Gerstoft, J; Katzenstein, T; Roge, B; Skinhoj, P; Pedersen, C; Katlama, C; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Miller, V.; Staszewski, S; Bieckel, M; Goebel, FD; Salzberger, B; Rockstroh, J; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Karydis, I.; Filandras, A; Banhegyi, D; Mulcahy, F; Yust, I.; Turner, D; Pollack, S; Ben-Ishai, Z; Bentwich, Z; Maayan, S; Vella, S; Chiesi, A; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Esposito, R; Bedini, A; Chirianni, A; Montesarchio, E; Vullo, V.; Santopadre, P; Narciso, P; Antinori, A; Franci, P; Zaccarelli, M; Lazzarin, A; Finazzi, R; Monforte, VO; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, V.; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Boron-Kaczmarska, A; Pnyka, M; Beniowski, M; Trocha, H; Antunes, F; Mansinho, K; Proenca, R; Gonzalez-Lahoz, J; Diaz, B; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, V.; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Blaxhult, A; Heidemann, B; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Telenti, A; Hirschel, B; Soravia-Dunand, V.; Furrer, H; Fisher, M; Brettle, R; Barton, S; Johnson, AM; Mercey, D; Loveday, C; Johnson, MA; Pinching, A; Parkin, J; Weber, J; Scullard, G; Morfeldt, L; Thulin, G; Sunstrom, A; Akerlund, B; Koppel, K; Karlsson, A; Flamholc, L; Hakangard, C; Monforte, AD; Pezzotti, P; Moroni, M; Monforte, AD; Cargnel, A; Merli, S; Vigevani, GM; Pastecchia, C; Lazzarin, A; Novati, R; Caggese, L; Moioli, C; Mura, MS; Mannazzu, M; Suter, F; Arici, C; Manconi, PE; Piano, P; Mazzotta, F; Lo Caputo, S; Poggio, A; Bottari, G; Pagano, G; Alessandrini, A; Scasso, A; Vincenti, A; Abbadesse, V.; Mancuso, S; Alberici, F; Ruggieri, A; Arlotti, M; Ortolani, P; De Lalla, F; Tositti, G; Piersantelli, N; Piscopo, R; Raise, E; Pasquinucci, S; Soscia, F; Tacconi, L; Tirelli, U; Nasti, G; Santoro, D; Pusterla, L; Carosi, G; Castelli, F; Cadeo, G; Vangi, D; Carnevale, G; Galloni, D; Filice, G; Bruno, R; Sinicco, A; Sciandra, M; Caramello, P; Gennero, L; Soranzo, ML; Bonasso, M; Rizzardini, G; Migliorino, G; Chiodo, F; Colangeli, V.; Magnani, G; Ursitti, M; Menichetti, F; Martinelli, C; Esposito, R; Mussini, C; Ghinelli, F; Sighinolfi, L; Coronado, O; Zauli, T; Ballardini, G; Montroni, M; Zoli, A; Petrelli, E; Cioppi, A; Ortona, L; De Luca, A; Petrosillo, N; Noto, P; Narciso, P; Salcuni, P; Antinori, A; De Longis, P; Vullo, V.; Lichtner, M; Pastore, G; Minafra, G; Chiriann, A; Loiacono, L; Piazza, M; Nappa, S; Abrescia, N; De Marco, M; Colomba, A; Prestileo, T; De Stefano, C; La Gala, A; Ferraro, T; Scerbo, A; Grima, P; Tundo, P; Pizzigallo, E; D'Alessandro, M; Grisorio, B; Ferrara, S; Pradier, C; Fontas, E; Caissotti, C; Dellamonica, P; Bentz, L; Bernard, E; Chaillou, S; De Salvador-Guillouet, F; Durant, J; Guttman, R; Heripret, L; Mondain-Miton, V.; Perbost, I.; Prouvost-Keller, B; Pugliese, P; Rahelinirina, V.; Roger, PM; Vandenbos, F; Bernasconi, E; Bucher, H; Burgisser, P; Cattacin, S; Egger, M; Erb, P; Fierz, W; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, HJ; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Ledergerber, B; Lauper, U; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schupbach, J; Speck, R; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; Ten Napel, C.

    2003-01-01

    Background: It remains controversial whether exposure to combination antiretroviral treatment increases the risk of myocardial infarction. Methods: In this prospective observational study, we enrolled 23,468 patients from 11 previously established cohorts from December 1999 to April 2001 and collect

  1. Effect of combination antiretroviral therapy on cytomegalovirus retinitis

    Directory of Open Access Journals (Sweden)

    Banker Alay

    2002-01-01

    Full Text Available Purpose: To study the various changes in the course of cytomegalovirus (CMV retinitis following combination antiretroviral treatment. Methods: Combination antiretroviral treatment was given to 12 patients with active CMV retinitis following which all anti-CMV medications were discontinued once the CD4 cell counts were> 100/mm3 for 3 months. Results: The median CD4 cell count increased from 36.5/mm3 (range, 3-74/mm3 at baseline to 175.5/mm3 (range, 97-410/mm3 at 3 months. No patient had reactivation of CMV retinitis or developed extraocular CMV infection during median follow-up of 16.7 months. In one patient with peripheral active CMV retinitis, the retinitis resolved completely and remained so throughout the follow-up period without specific anti-CMV treatment. Five (41.7% patients had immune recovery vitritis. Conclusion: Patients receiving combination antiretroviral treatment following treatment for CMV retinitis have better control of CMV retinitis but immune recovery vitritis is a common sequelae. Reactivation of CMV retinitis is common in patients who discontinue combination antiretroviral treatment

  2. Combination antiretroviral therapy and the risk of myocardial infarction

    NARCIS (Netherlands)

    Friis-Moller, N; Sabin, CA; Weber, R; Monforte, AD; El-Sadr, WM; Reiss, P; Thiebaut, R; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Lundgren, JD; Lundgren, JD; Weber, R; Monteforte, AD; Bartsch, G; Reiss, P; Dabis, F; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Houyez, F; Loeliger, E; Tressler, R; Weller, I.; Friis-Moller, N; Sabin, CA; Sjol, A; Lundgren, JD; Sawitz, A; Rickenbach, M; Pezzotti, P; Krum, E; Meester, R; Lavignolle, V.; Sundstrom, A; Poll, B; Fontas, E; Torres, F; Petoumenos, K; Kjaer, J; Hammer, S; Neaton, J; Sjol, A; de Wolf, F; van der Ven, E; Zaheri, S; Van Valkengoed, L; Meester, R; Bronsveld, W; Weigel, H; Brinkman, K; Frissen, P; ten Veen, J; Hillbrand, M; Schieveld, S; Mulder, J; van Gorp, E; Meenhorst, P; Danner, S; Claessen, F; Perenboom, R; Schattenkerk, JKE; Godfried, M; Lange, J; Lowe, S; van der Meer, J; Nellen, F; Pogany, K; van der Poll, T; Reiss, R; Ruys, T; Wit, F; Richter, C; van Leusen, R; Vriesendorp, R; Jeurissen, F; Kauffmann, R; Koger, E; Brevenboer, B; Sprenger, HG; Law, G; ten Kate, RW; Leemhuis, M; Schippers, E; Schrey, G; van der Geest, S; Verbon, A; Koopmans, P; Keuter, M; Telgt, D; van der Ven, A; van der Ende, Marchina E.; Gyssens, I.; de Marie, S; Juttmann, J; van der Heul, C; Schneider, M; Borleffs, J; Hoepelman, I.; Jaspers, C; Matute, A; Schurink, C; Blok, W; Salamon, R; Beylot, J; Dupon, M; Le Bras, M; Pellegrin, JL; Ragnaud, JM; Dabis, F; Chene, G; Jacqmin-Gadda, H; Rhiebaut, R; Lawson-Ayayi, S; Lavignolle, V.; Balestre, E; Blaizeau, MJ; Decoin, M; Formaggio, AM; Delveaux, S; Labarerre, S; Uwamaliya, B; Vimard, E; Merchadou, L; Palmer, G; Touchard, D; Dutoit, D; Pereira, F; Boulant, B; Beylot, J; Morlat, P; Bonarek, M; Bonnet, F; Coadou, B; Gelie, P; Jaubert, D; Nouts, C; Lacoste, D; Dupon, M; Dutronc, H; Cipriano, G; Lafarie, S; Chossat, I.; Lacut, JY; Leng, B; Pellegrin, JL; Mercie, P; Viallard, JF; Faure, I.; Rispal, P; Cipriano, C; Tchamgoue, S; Le Bras, M; Djossou, F; Malvy, D; Pivetaud, JP; Ragnaud, JM; Chambon, D; De La Taille, C; Galperine, T; Lafarie, S; Neau, D; Ochoa, A; Beylot, C; Doutre, MS; Bezian, JH; Moreau, JF; Taupin, JL; Conri, C; Constans, J; Couzigou, P; Castera, L; Fleury, H; Lafon, ME; Masquelier, B; Pellegrin, I.; Trimoulet, P; Moreau, F; Mestre, C; Series, C; Taytard, A; Law, M; Petoumenos, K; Bal, J; Mijch, A; Watson, K; Roth, N; Wood, H; Austin, D; Gowers, A; Baker, B; McFarlane, R; Carr, A; Cooper, D; Chuah, J; Fankhauser, W; Mallal, S; Skett, J; Calvo, G; Torres, F; Mateau, S; Domingo, P; Sambeat, MA; Gatell, J; Del Cacho, E; Cadafalch, J; Fuster, M; Codina, C; Sirera, G; Vaque, A; Clumeck, N; De Wit, S; Gerard, M; Hildebrand, M; Kabeya, K; Konopnicki, D; Payen, MC; Poll, B; Van Laethem, Y; Neaton, J; Bartsch, G; El-Sadr, WM; Krum, E; Thompson, G; Wentworth, D; Luskin-Hawk, R; Telzak, E; El-Sadr, WM; Abrams, DI; Cohn, D; Markowitz, N; Arduino, R; Mushatt, D; Friedland, G; Perez, G; Tedaldi, E; Fisher, E; Gordin, F; Crane, LR; Sampson, J; Baxter, J; Kirk, O; Mocroft, A; Phillips, AN; Lundgren, JD; Vetter, N; Clumeck, N; Hermans, P; Colebunders, R; Machala, L; Nielsen, J; Benfield, T; Gerstoft, J; Katzenstein, T; Roge, B; Skinhoj, P; Pedersen, C; Katlama, C; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Miller, V.; Staszewski, S; Bieckel, M; Goebel, FD; Salzberger, B; Rockstroh, J; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Karydis, I.; Filandras, A; Banhegyi, D; Mulcahy, F; Yust, I.; Turner, D; Pollack, S; Ben-Ishai, Z; Bentwich, Z; Maayan, S; Vella, S; Chiesi, A; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Esposito, R; Bedini, A; Chirianni, A; Montesarchio, E; Vullo, V.; Santopadre, P; Narciso, P; Antinori, A; Franci, P; Zaccarelli, M; Lazzarin, A; Finazzi, R; Monforte, VO; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, V.; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Boron-Kaczmarska, A; Pnyka, M; Beniowski, M; Trocha, H; Antunes, F; Mansinho, K; Proenca, R; Gonzalez-Lahoz, J; Diaz, B; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, V.; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Blaxhult, A; Heidemann, B; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Telenti, A; Hirschel, B; Soravia-Dunand, V.; Furrer, H; Fisher, M; Brettle, R; Barton, S; Johnson, AM; Mercey, D; Loveday, C; Johnson, MA; Pinching, A; Parkin, J; Weber, J; Scullard, G; Morfeldt, L; Thulin, G; Sunstrom, A; Akerlund, B; Koppel, K; Karlsson, A; Flamholc, L; Hakangard, C; Monforte, AD; Pezzotti, P; Moroni, M; Monforte, AD; Cargnel, A; Merli, S; Vigevani, GM; Pastecchia, C; Lazzarin, A; Novati, R; Caggese, L; Moioli, C; Mura, MS; Mannazzu, M; Suter, F; Arici, C; Manconi, PE; Piano, P; Mazzotta, F; Lo Caputo, S; Poggio, A; Bottari, G; Pagano, G; Alessandrini, A; Scasso, A; Vincenti, A; Abbadesse, V.; Mancuso, S; Alberici, F; Ruggieri, A; Arlotti, M; Ortolani, P; De Lalla, F; Tositti, G; Piersantelli, N; Piscopo, R; Raise, E; Pasquinucci, S; Soscia, F; Tacconi, L; Tirelli, U; Nasti, G; Santoro, D; Pusterla, L; Carosi, G; Castelli, F; Cadeo, G; Vangi, D; Carnevale, G; Galloni, D; Filice, G; Bruno, R; Sinicco, A; Sciandra, M; Caramello, P; Gennero, L; Soranzo, ML; Bonasso, M; Rizzardini, G; Migliorino, G; Chiodo, F; Colangeli, V.; Magnani, G; Ursitti, M; Menichetti, F; Martinelli, C; Esposito, R; Mussini, C; Ghinelli, F; Sighinolfi, L; Coronado, O; Zauli, T; Ballardini, G; Montroni, M; Zoli, A; Petrelli, E; Cioppi, A; Ortona, L; De Luca, A; Petrosillo, N; Noto, P; Narciso, P; Salcuni, P; Antinori, A; De Longis, P; Vullo, V.; Lichtner, M; Pastore, G; Minafra, G; Chiriann, A; Loiacono, L; Piazza, M; Nappa, S; Abrescia, N; De Marco, M; Colomba, A; Prestileo, T; De Stefano, C; La Gala, A; Ferraro, T; Scerbo, A; Grima, P; Tundo, P; Pizzigallo, E; D'Alessandro, M; Grisorio, B; Ferrara, S; Pradier, C; Fontas, E; Caissotti, C; Dellamonica, P; Bentz, L; Bernard, E; Chaillou, S; De Salvador-Guillouet, F; Durant, J; Guttman, R; Heripret, L; Mondain-Miton, V.; Perbost, I.; Prouvost-Keller, B; Pugliese, P; Rahelinirina, V.; Roger, PM; Vandenbos, F; Bernasconi, E; Bucher, H; Burgisser, P; Cattacin, S; Egger, M; Erb, P; Fierz, W; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, HJ; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Ledergerber, B; Lauper, U; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schupbach, J; Speck, R; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; Ten Napel, C.

    2003-01-01

    Background: It remains controversial whether exposure to combination antiretroviral treatment increases the risk of myocardial infarction. Methods: In this prospective observational study, we enrolled 23,468 patients from 11 previously established cohorts from December 1999 to April 2001 and collect

  3. [Combination therapy of prostatitis-associated copulative dysfunction].

    Science.gov (United States)

    Bliumberg, B I; Shatylko, T V; Tverdokhleb, S A; Fomkin, R N; Voskoboĭnikova, I V

    2014-01-01

    Chronic prostatitis is characterized by clinical polymorphism, that may include pain, dysuria, asthenovegetative syndrome, and others. Symptoms associated with impaired copulatory cycle in chronic prostatitis have a significant impact on the quality of life of patient. Sexual dysfunction and sexuality cessation can exacerbate the inflammation of the prostate gland and worsen the underlying disease. The study included 60 patients diagnosed with chronic bacterial prostatitis, complicated by sexual disorders. Patients were divided into two comparable groups of 30 persons. Control group ofpatients received standard antibacterial therapy; study group ofpatients in addition received phytodrug prostanorm. At the end of treatment, higher IIEF-5 scores, increasing number of lecithin granules in the prostate secretion, as well as reducing the severity of irritative symptoms were registered in the study group.

  4. Healing the wounded self: combining hypnotherapy with ego state therapy.

    Science.gov (United States)

    Alladin, Assen

    2013-07-01

    The purpose of this article is to formulate a theoretical conceptualization for utilizing ego state therapy (EST) as an adjunct with cognitive hypnotherapy (CH) for depression. As the relationship between life events and onset of depression is very complex, it is not clear from current literature how stressors cause depressive symptoms. The notion of "wounded self," derived from the work of Wolfe (2005, 2006), is examined as a potential unifying concept for binding the role of risk factors in the precipitation of depression. By incorporating wounded self, the circular feedback model of depression, on which CH for depression is based, is expanded. This revised version provides conceptual and empirical underpinnings for integrating EST with CH in the management of depression.

  5. Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy.

    Science.gov (United States)

    Swart, Maarten; Verbrugge, Inge; Beltman, Joost B

    2016-01-01

    In healthy individuals, immune-checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune-checkpoint blockade of cytotoxic T lymphocyte antigen-4 and programed death-1 emerged as promising strategies to activate antitumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune-checkpoint blockade in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing.

  6. Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

    Science.gov (United States)

    Swart, Maarten; Verbrugge, Inge; Beltman, Joost B.

    2016-01-01

    In healthy individuals, immune-checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune-checkpoint blockade of cytotoxic T lymphocyte antigen-4 and programed death-1 emerged as promising strategies to activate antitumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune-checkpoint blockade in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing. PMID:27847783

  7. Cellular Levels of HIV Unspliced RNA from Patients on Combination Antiretroviral Therapy with Undetectable Plasma Viremia Predict the Therapy Outcome

    NARCIS (Netherlands)

    Pasternak, A.O.; Jurriaans, S.; Bakker, M.; Prins, J.M.; Berkhout, B.; Lukashov, V.V.

    2009-01-01

    Background: Combination antiretroviral therapy (cART), the standard of care for HIV-1 infection, is considered to be successful when plasma viremia remains below the detection limit of commercial assays. Yet, cART fails in a substantial proportion of patients after the apparent success. No laborator

  8. Preoperative combination therapy of 5-fluorouracil suppository and radiation for carcinoma of the rectum

    Energy Technology Data Exchange (ETDEWEB)

    Mizusawa, Hirokazu; Takahashi, Toshio (Akita Univ. (Japan))

    1983-10-01

    Twelve cases of carcinoma of the rectum were treated preoperatively by combination therapy with 5-fluorouracil (5-FU) suppository (100 mg twice a day consecutively, a total dose of more than 4,000 mg) and irradiation (300 rad x 3/week, a total dose of 3,000 rad). This group was compared with 34 cases given single preoperative 5-FU therapy and 24 control cases given no preoperative adjuvant modality. The group treated by preoperative combination therapy showed marked antitumor effects macroscopically and histologically. In addition, decrease in local recurrence was expected for this group, compared with the other two groups.

  9. Mirror therapy combined with functional electrical stimulation for rehabilitation of stroke survivors' ankle dorsiflexion.

    Science.gov (United States)

    Salhab, Ghadir; Sarraj, Ahmad Rifaii; Saleh, Soha

    2016-08-01

    This study investigates the effect of combining both mirror therapy with Electrical Stimulation (ES) on improvement of the function of lower extremity compared to conventional therapy. 18 stroke survivors (sub acute stage) were recruited, 9 of them were randomly assigned to receive conventional treatment and another 9 started the mirror therapy combined with ES treatment. Duration of each session in both interventions was 50 minutes, done 4 times per week over two weeks. After 2 weeks, subjects took one week rest before switching they type of treatment; those started with conventional therapy continued with mirror therapy combined with ES, and vice versa. The duration of this phase was 2 weeks with same schedule as the 1st one. Ankle dorsi-flexion range of motion, lower extremity sensory-motor function, and walking duration were measured at baseline, after 1st 2 weeks, and immediately after the last two weeks, and 4 weeks after end of training (retention test). Repeated Measures ANCOVA was done to compare outcome measures scores in both groups and between all testing days, and paired T-test was used measure the difference between groups. Significant increase in all outcome measures was found after the (MT+ES) training, which is higher than conventional therapy training (pmirror therapy and ES is more effective than conventional therapy in improving lower limb motor function after stroke.

  10. Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

    Science.gov (United States)

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-05-01

    Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

  11. The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

    Energy Technology Data Exchange (ETDEWEB)

    Ataman, Ozlem U., E-mail: ouataman@hotmail.com [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Sambrook, Sally J. [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Wilks, Chris [Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Lloyd, Andrew [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Taylor, Amanda E. [Yellow Delaney Communications Ltd, Wilmslow, Cheshire (United Kingdom); Wedge, Stephen R. [Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom)

    2012-11-15

    Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, and PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that

  12. Effect of combination antiretroviral therapy on the frequency of oral candidiasis in HIV/AIDS patient

    Directory of Open Access Journals (Sweden)

    Sayuti Hasibuan

    2007-03-01

    Full Text Available Oral candidiasis is one of the most common opportunistic infections in HIV/AIDS patients. It serves as important markers of HIV infection, viral load, and CD4 cells count in the blood and predict disease progression to AIDS. The development of oral candidiasis in HIV/AIDS patients associated by imbalances between Candida and impaired host immune defenses that caused by decreased of CD4 cell counts and the increased of plasma HIV-viral load. Since the introduction of antiretroviral therapy combination, commonly known as Highly Active Antiretroviral Therapy (HAART, it has been observed that certain oral lesions, such as oral candidiasis as declined. The aim of this paper is to review the mechanism of combination antiretroviral therapy influenced the frequency of oral candidiasis in HIV/AIDS patient. We conclude that combination antiretroviral therapy generally reduced the frequency and severity of oral candidiasis in HIV/AIDS patient.

  13. Single versus combination antibiotic therapy in adults hospitalised with community acquired pneumonia.

    Science.gov (United States)

    Rodrigo, Chamira; Mckeever, Tricia M; Woodhead, Mark; Lim, Wei Shen

    2013-05-01

    The benefits of β-lactam/macrolide combination therapy over β-lactam therapy alone for the treatment of hospitalised community-acquired pneumonia (CAP) in relation to pneumonia severity are uncertain. We studied 5240 adults hospitalised with CAP from 72 secondary care trusts across England and Wales. The overall 30-day inpatient (IP) death rate was 24.4%. Combination therapy was prescribed in 3239 (61.8%) patients. In a multivariable model, combination therapy was significantly associated with lower 30-day IP death rate in patients with moderate-severity CAP (adjusted OR 0.54, 95% CI 0.41 to 0.72) and high-severity CAP (adjusted OR 0.76, 95% CI 0.60 to 0.96) but not low-severity CAP.

  14. Albendazole alone vs. albendazole and diethylcarbamazine combination therapy for trichuriasis

    Directory of Open Access Journals (Sweden)

    Windya Sari Nasution

    2014-03-01

    Full Text Available Background Trichuris trichiura is one of the most common soil-transmitted helminths, estimated to infect 1 billion people worldwide. Several studies have compared the efficacies of albendazole and diethylcarbamazine, but the efficacy of a combination of these two drugs has been inconclusive. Objective To assess the effectiveness of a single dose of albendazole compared to a combination of albendazole and diethylcarbamazine for trichuriasis treatment. Methods A randomized, clinical open trial was conducted from June to September 2009 on elementary school children with trichuriasis from two villages in the North Sumatera Province. Stool specimens were collected at baseline and at days 7, 14, 21, and 28 after treatment, and examined by the Kato Katz method. Subjects were randomized into two groups. Group I received a single dose of albendazole (400 mg and group II received albendazole (400 mg plus diethylcarbamazine (6 mg/kg. Statistical analyses used were Chi square test for cure rates and Wilcoxon rank test for egg reduction rates. Results One hundred eight children were enrolled and randomized into group 1 (53 children and group II (55 children. The prevalence of T. trichiura infection was 54.7%. There were no significant differences (P=0.52 in the cure rate between groups I and II (66% and 60%, respectively or in egg reduction rates at day 28 (54.5% and 60.07%, respectively, P= 0.10. Conclusion Albendazole alone and abendazole combined with diethylcarbamazine have similar efficacies for trichuriasis treatment, in terms of cure rates and egg reduction rates.

  15. Use of biologic agents in combination with other therapies for the treatment of psoriasis.

    Science.gov (United States)

    Cather, Jennifer C; Crowley, Jeffrey J

    2014-12-01

    Psoriasis is a chronic inflammatory skin disorder, which is associated with a significant negative impact on a patient's quality of life. Traditional therapies for psoriasis are often not able to meet desired treatment goals, and high-dose and/or long-term use is associated with toxicities that can result in end-organ damage. An improved understanding of the involvement of cytokines in the etiology of psoriasis has led to the development of biologic agents targeting tumor necrosis factor (TNF)-α and interleukins (ILs)-12/23. While biologic agents have improved treatment outcomes, they are not effective in all individuals with psoriasis. The combination of biologic agents with traditional therapies may provide improved therapeutic options for patients who inadequately respond to a single drug or when efficacy may be increased with supplementation of another treatment. In addition, combination therapy may reduce safety concerns and cumulative toxicity, as lower doses of individual agents may be efficacious when used together. This article reviews the current evidence available on the efficacy and safety of combining biologic agents with systemic therapies (methotrexate, cyclosporine, or retinoids) or with phototherapy, and the combination of biologic agents themselves. Guidance is provided to help physicians identify situations and the characteristics of patients who would benefit from combination therapy with a biologic agent. Finally, the potential clinical impact of biologic therapies in development (e.g., those targeting IL-17A, IL-17RA, or IL-23 alone) is analyzed.

  16. Combination approaches with immune checkpoint blockade in cancer therapy

    Directory of Open Access Journals (Sweden)

    Maarten Swart

    2016-11-01

    Full Text Available In healthy individuals, immune checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune checkpoint blockade of cytotoxic T lymphocyte antigen-4 (CTLA-4 and programmed death-1 (PD-1 emerged as promising strategies to activate anti-tumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune checkpoint blockade, aimed at increasing response-rates to the single treatments.

  17. Vacuum measurement on vacuum packaged MEMS devices

    Energy Technology Data Exchange (ETDEWEB)

    Gan Zhiyin; Lin Dong; Wang Xuefang; Chenggang; Zhang Honghai; Liu Sheng [Institute of Microsystems and Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China, 430074 (China)

    2007-07-15

    This paper investigates the relationship between the resonance impedance of a tuning fork quartz oscillator and the small size cavity vacuum pressure and develops an on-line vacuum measurement system to track real-time vacuum pressure in MEMS devices. Furthermore, authors completely analyze all facts that affect the resonance impedance. A set of metal vacuum packaged devices have been monitored for more than 10 months using this on-line vacuum measurement system. The results indicate that it is very critical to investigate vacuum packaging processes, reliability and durability of the vacuum devices by using this on-line vacuum measurement system.

  18. Combination therapy of statin and ezetimibe for the treatment of familial hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Ian Hamilton-Craig

    2010-11-01

    Full Text Available Ian Hamilton-Craig1, Karam Kostner2, David Colquhoun2, Stan Woodhouse21Griffith University School of Medicine, Southport, Queensland, Australia; 2University of Queensland, Brisbane, Queensland, AustraliaAbstract: High-dose potent statin therapy in combination with ezetimibe is now standard practice for the treatment of adult patients with heterozygous familial hypercholesterolemia (heFH, as the result of numerous studies in patients with primary hypercholesterolemia or heFH. These studies have shown the combination to be both effective and safe in the short to medium term. Recently, short-term ezetimibe therapy has also been shown to be effective and safe in combination with statin therapy for children and adolescents with heFH. Effective statin–ezetimibe combination therapy is capable of achieving near-normal lipid profiles in heFH patients, with expected improvement in risk for cardiovascular disease (CVD and improved life expectancy resulting predominantly from reduction in levels of low-density lipoprotein cholesterol. There are few data to support a pleiotropic action of ezetimibe with regard to CVD benefit, unlike therapy with statins. No serious and unexpected clinical adverse effects of combination statin–ezetimibe therapy have emerged till date, although data are limited in children and adolescents, for whom longer-term studies are required. Recent data suggesting possible proatherogenic effects of ezetimibe require confirmation. One large long-term randomized controlled clinical outcomes trial is in progress in non-FH patients to determine the efficacy and safety of ezetimibe therapy; it is unlikely that such a trial will ever be performed in patients with FH.Keywords: familial hypercholesterolemia, ezetimibe, statin, combination therapy, low-density lipoprotein cholesterol

  19. Combination antihypertensive therapy in clinical practice. The analysis of 1254 consecutive patients with uncontrolled hypertension.

    Science.gov (United States)

    Petrák, O; Zelinka, T; Štrauch, B; Rosa, J; Šomlóová, Z; Indra, T; Turková, H; Holaj, R; Widimský, J

    2016-01-01

    The aim of the study was to analyze the clinical use of different types of combination therapy in a large sample of consecutive patients with uncontrolled hypertension referred to Hypertension Centre. We performed a retrospective analysis of combination antihypertensive therapy in 1254 consecutive patients with uncontrolled hypertension receiving at least triple-combination antihypertensive therapy. Among the most prescribed antihypertensive classes were renin-angiotensin blockers (96.8%), calcium channel blockers (82.5%), diuretics (82.0%), beta-blockers (73.0%), centrally acting drugs (56.0%) and urapidil (24.1%). Least prescribed were spironolactone (22.2%) and alpha-1-blockers (17.1%). Thiazide/thiazide-like diuretics were underdosed in more than two-thirds of patients. Furosemide was prescribed in 14.3% of patients treated with diuretics, while only indicated in 3.9%. Inappropriate combination therapy was found in 40.4% of patients. Controversial dual and higher blockade of renin-angiotensin system occurred in 25.2%. Incorrect use of a combination of two antihypertensive drugs with the similar mechanism of action was found in 28.1%, most commonly a combination of two drugs with central mechanism (13.5%). In conclusion, use of controversial or incorrect combinations of drugs in uncontrolled hypertension is common. Diuretics are frequently underdosed and spironolactone remains neglected in general practice. The improper combination of antihypertensive drugs may contribute to uncontrolled hypertension.

  20. FIRST EXPERIENCE OF CYMEVEN IN THE COMBINED THERAPY OF RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    R M Balabanova

    2001-01-01

    Full Text Available Ummary Objective. To reveal J'reguency of accompaning virus infection and possibility to use antivirus therapy together in therapy RA. Material. 40 patients with RA at the age of 17-45 were studied. The duration of disease was not more than 6 months; patients had 2-3 degrees of activity. Every one had a positive rheumatoid factor. Results. 78,2% of the examined patients connected the beginning of the illness with virus infection they have had. The most difficalt variant of RA course and uneffectiveness of basic therapy were registerd among the patients with combination HSV and CMV infection. Inclusion of Cymevene in complex therapy RA has exerted positive influence on clinical-laboratory, signs stregthened effect of basic therapy. Conclusion. The most difficult variant of RA course was registered among the patients with virus infection. Inclusion of antivirus drugs had a positive influence on effectiveness of basic therapy.

  1. Combination therapy in severe Acinetobacter baumannii infections: an update on the evidence to date.

    Science.gov (United States)

    Durante-Mangoni, Emanuele; Utili, Riccardo; Zarrilli, Raffaele

    2014-01-01

    Acinetobacter baumannii is a drug-resistant Gram-negative pathogen increasingly causing hospital-acquired infections in critically ill patients. In this review, we summarize the current mechanisms of antimicrobial resistance in A. baumannii and describe in detail recent in vitro and in vivo experimental data on the activity of antimicrobial combinations against this microorganism. We then introduce the rationale for the use of combination antibiotic therapy in resistant A. baumannii infections. Finally, we present and critically discuss both uncontrolled clinical studies and the few randomized clinical trials of combination antimicrobial therapy for these infections, with a special focus on ongoing multinational trials and optimal approach to future research in this field.

  2. Intermittent preventive therapy for malaria: arguments in favour of artesunate and sulphamethoxypyrazine - pyrimethamine combination

    Directory of Open Access Journals (Sweden)

    Jansen Frans

    2011-03-01

    Full Text Available Abstract Recent publications put a serious warning regarding the inefficacy of sulphadoxine-pyrimethamine (SP for the intermittent preventive treatment of malaria in young children (IPTi. Recommendations for other therapies are being made. By using a different and better sulphonamide (sulphamethoxypyrazine, it is possible to manufacture fixed dose combination pills with artesunate and pyrimethamine. This combination permits a full therapy over 24 hours (dosing interval being 12 hours. It is recommended that this combination should be tested in future field studies of IPTi.

  3. Combined systemic therapy and radiotherapy for bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, C.; Weiss, C. [Dept. of Radiotherapy and Oncology, Univ. of Frankfurt (Germany); Sauer, R. [Dept. of Radiotherapy, Univ. of Erlangen (Germany)

    2007-12-15

    The standard of care for transitional-cell carcinoma of the bladder with invasion to the muscularis propria is radical cystectomy. Sophisticated techniques for urinary diversion have been developed to improve patients' quality of life. Even the construction of a neobladder with continent urinary diversion, however, cannot substitute for the patient's original bladder. Attempts to obtain organ preservation are only justified when they have a high likelihood of achieving local cure with no compromise in survival rates. Adequate local control cannot be achieved with transurethral resection of the bladder tumor (TURBT), chemotherapy, or radiotherapy, when used alone. Several groups have reported the value of combining all three modalities, with salvage cystectomy being reserved for patients with incomplete response or local relapse. (orig.)

  4. [Current optimization of combined therapy for chronic obstructive pulmonary disease].

    Science.gov (United States)

    Popova, E N

    2015-01-01

    Testing the new combined bronchodilator Anoro Ellipta in different clinical trials gives to its high clinical efficacy and safety in chronic obstructive pulmonary disease. The drug contains the molecules of sustained-release selective β2-adrenergic receptor agonist (vilanterol) and a muscarinic cholinergic receptor antagonist (umeclidinium bromide). The bronchodilating mechanisms of umeclidinium bromide are in the competitive inhibition of the binding of acetylcholine with muscarinic acetylcholine receptors of airway smooth muscles whereas in those of vilanterol are in that with the stimulation of intracellular adenylate cyclase. On days 1 and 24 after inhalation of the first dose of vilanterol and umeclidinium bromide, there was a significant increase in the forced expiratory volume in one second as compared to placebo. No clinical effects on QT interval on an electrocardiogram and cardiac rhythm were found. The benefits of an inhalation device (Ellipta) are its innovation design ensuring the effective delivery of an aerosol dose into the airway, convenience, and simplicity.

  5. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis

    Science.gov (United States)

    Bunn, Patrick T.; Singh, Neetu; Chauhan, Shashi Bhushan; Sheel, Meru; Amante, Fiona H.; Montes de Oca, Marcela; Edwards, Chelsea L.; Ng, Susanna S.; Best, Shannon E.; Haque, Ashraful; Beattie, Lynette; Hafner, Louise M.; Sacks, David; Nylen, Susanne; Sundar, Shyam; Engwerda, Christian R.

    2016-01-01

    Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR) on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL) patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNγ production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of combining different

  6. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Rebecca J Faleiro

    2016-02-01

    Full Text Available Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNγ production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of

  7. Epigenetic polypharmacology: from combination therapy to multitargeted drugs.

    Science.gov (United States)

    de Lera, Angel R; Ganesan, A

    The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed.

  8. Use of combination antihypertensive therapy initiation in older Americans without prevalent cardiovascular disease.

    Science.gov (United States)

    Li, Xiaojuan; Camelo Castillo, Wendy; Stürmer, Til; Pate, Virginia; Gray, Christine L; Simpson, Ross J; Setoguchi, Soko; Hanson, Laura C; Jonsson Funk, Michele

    2014-09-01

    To describe new users of antihypertensive medications and identify predictors of combination therapy initiation in older Americans. Retrospective observational cohort study. Population-based study using U.S. Medicare fee-for-service healthcare claims (2007-2010). Medicare beneficiaries aged 65 and older with no recent diagnoses, procedures, or medications for cardiovascular disease who newly initiated an antihypertensive therapy (n = 275,493; 210,605 initiated monotherapy, 64,888 initiated combination therapy). Multivariable Poisson regression was used to assess factors associated with initiation of combination therapy versus monotherapy, including participant characteristics, prescriber characteristics, and participant encounters with the healthcare system. Initiation of combination therapy increased from 21.9% in 2007 to 24.7% in 2010. The most frequently initiated combinations were angiotensin-converting enzyme inhibitors with thiazide (29.7%) and angiotensin II receptor antagonists with thiazide (18.7%). Blacks (prevalence ratio (PR) = 1.48, 95% confidence interval (CI) = 1.45-1.51 vs. whites), individuals seeing a generalist (PR = 1.10, 95% CI = 1.07-1.14), individuals seeing more than one doctor (PR = 3.38, 95% CI = 3.33-3.44), and participants with no pharmacy claims in the previous 6 months (PR = 1.34, 95% CI = 1.30-1.37 vs. ≥3 unique drug classes) were more likely to initiate combination therapy, whereas those who had more outpatient visits in the previous 12 months were less likely to initiate combination therapy (per five visits, PR = 0.82, 95% CI = 0.80-0.83). Nearly one in four new users of antihypertensive medications aged 65 and older started treatment with combination therapy. Blacks, individuals living in the south, and those with fewer outpatient physician office visits were more likely to initiate combination therapy. Further research is needed to determine whether this approach to managing hypertension is being well targeted to individuals who

  9. Combined anti-tumor necrosis factor-α therapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone

    Directory of Open Access Journals (Sweden)

    Carl K Edwards

    2012-12-01

    Full Text Available Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs or anti-TNF-α therapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable" RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a DMARD and an anti-TNF-α agent (infliximab or etanercept to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N=122, unstable DMARD patients (N=18, stable DMARD patients (N=26, and stable patients on combination therapy (N=20. Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-TNF-α therapy. Furthermore, combination DMARD and anti-TNF-α therapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.

  10. Clinical effects of intensive insulin therapy treating traumatic shock combined with multiple organ dysfunction syndrome.

    Science.gov (United States)

    Du, Jundong; Liu, Hongming; Liu, Rong; Yao, Yongming; Jiao, Huabo; Zhao, Xiaodong; Yin, Huinan; Li, Zhanliang

    2011-04-01

    The therapeutic effects of intensive insulin therapy in treatment of traumatic shock combined with multiple organ dysfunction syndrome (MODS) were investigated. A total of 114 patients with traumatic shock combined with MODS were randomly divided into two groups: control group (n=56) treated with conventional therapy, and intensive insulin therapy group (n=58) treated with conventional therapy plus continuous insulin pumping to control the blood glucose level at range of 4.4-6.1 mmol/L. White blood cells (WBC) counts, prothrombin time (PT), serum creatinine (SCr), alanine aminotransferase (ALT), serum albumin and PaO(2) were measured before and at the day 1, 3, 5, 7 and 14 after treatment. The incidence of gastrointestinal dysfunction, the incidence of MODS, hospital stay and the mortality were also observed and compared. After intensive insulin therapy, the WBC counts, SCr, ALT and PT were significantly reduced (Pinsulin therapy. The incidence of gastrointestinal dysfunction, the incidence of MODS, the length of hospital stay and the mortality were markedly decreased (Pinsulin therapy is effective for traumatic shock combined with MODS and can decrease the length of hospital stay and the mortality.

  11. Nanostructured lipid carriers of artemether-lumefantrine combination for intravenous therapy of cerebral malaria.

    Science.gov (United States)

    Prabhu, Priyanka; Suryavanshi, Shital; Pathak, Sulabha; Patra, Aditya; Sharma, Shobhona; Patravale, Vandana

    2016-11-20

    Patients with cerebral malaria (CM) are unable to take oral medication due to impaired consciousness and vomiting thus necessitating parenteral therapy. Quinine, artemether, and artesunate which are currently used for parenteral malaria therapy have their own drawbacks. The World Health Organization (WHO) has now banned monotherapy and recommends artemisinin-based combination therapy for malaria treatment. However, presently there is no intravenous formulation available for combination therapy of malaria. Artemether-Lumefantrine (ARM-LFN) is a WHO approved combination for oral malaria therapy. However, the low aqueous solubility of ARM and LFN hinders their intravenous delivery. The objective of this study was to formulate ARM-LFN nanostructured lipid carriers (NLC) for intravenous therapy of CM. ARM-LFN NLC were prepared by microemulsion template technique and characterized for size, drug content, entrapment efficiency, drug release, crystallinity, morphology, amenability to autoclaving, compatibility with infusion fluids, stability, antimalarial efficacy in mice, and toxicity in rats. The ARM-LFN NLC showed sustained drug release, amenability to autoclaving, compatibility with infusion fluids, good stability, complete parasite clearance and reversal of CM symptoms with 100% survival in Plasmodium berghei-infected mice, and safety in rats. The biocompatible ARM-LFN NLC fabricated by an industrially feasible technique offer a promising solution for intravenous therapy of CM. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. A versatile elevated-pressure reactor combined with an ultrahigh vacuum surface setup for efficient testing of model and powder catalysts under clean gas-phase conditions

    Energy Technology Data Exchange (ETDEWEB)

    Morfin, Franck; Piccolo, Laurent [Institut de recherches sur la catalyse et l' environnement de Lyon (IRCELYON), UMR 5256 CNRS and Université Lyon 1, 2 avenue Albert Einstein, F-69626 Villeurbanne (France)

    2013-09-15

    A small-volume reaction cell for catalytic or photocatalytic testing of solid materials at pressures up to 1000 Torr has been coupled to a surface-science setup used for standard sample preparation and characterization under ultrahigh vacuum (UHV). The reactor and sample holder designs allow easy sample transfer from/to the UHV chamber, and investigation of both planar and small amounts of powder catalysts under the same conditions. The sample is heated with an infrared laser beam and its temperature is measured with a compact pyrometer. Combined in a regulation loop, this system ensures fast and accurate temperature control as well as clean heating. The reaction products are automatically sampled and analyzed by mass spectrometry and/or gas chromatography (GC). Unlike previous systems, our GC apparatus does not use a recirculation loop and allows working in clean conditions at pressures as low as 1 Torr while detecting partial pressures smaller than 10{sup −4} Torr. The efficiency and versatility of the reactor are demonstrated in the study of two catalytic systems: butadiene hydrogenation on Pd(100) and CO oxidation over an AuRh/TiO{sub 2} powder catalyst.

  13. Single-Inhaler Combination Therapy for Asthma: A Review of Cost Effectiveness

    OpenAIRE

    Manabu Akazawa; Stempel, David A.

    2006-01-01

    Clinical studies have shown that the combination of an inhaled corticosteroid (ICS) and a long-acting beta2-adrenoceptor agonist (LABA) for patients with asthma is more effective than the use of ICS alone in equivalent or higher doses, as well as the use of other combinations. However, the relatively higher acquisition costs for the combination therapy require assessment of the value of the incremental costs, especially from a societal perspective. This review provides an overall assessment o...

  14. [Recurrence of esophageal cancer treated by combination TS-1/CDDP therapy].

    Science.gov (United States)

    Hiraki, Masatsugu; Yunotani, Seiji; Noguchi, Ryo; Shinozaki, Yukari; Tani, Hiroki; Sakai, Masashi; Ishimitsu, Toshiyuki; Tabuchi, Masanobu

    2005-02-01

    A 68-year-old man underwent subtotal esophagectomy with two fields lymphadenectomy and postoperative chemotherapy so called low dose FP therapy for advanced esophageal cancer (Stage IIIa, pT 3, pN 1, M 0) in October 1999. As he was diagnosed with a recurrence of esophageal cancer as metastatic lymph node tumors which were placed in the right anterocervical and supraclavicular region in March 2001, he underwent enucleation of metastatic lymph node tumors and postoperative chemoradiation therapy, so-called low-dose FP-R therapy. Recently, since other metastatic lymph node tumors in the neck appeared again in August 2001, he underwent radical neck lymph node dissection and postoperative chemoradiation treatment, so-called FAP-R therapy. In October 2003, a chest CT showed multiple lung tumors. He was diagnosed with multiple metastatic lung tumors originating from esophageal cancer. Then, two courses of a combined chemotherapy consisting of TS-1 and CDDP were administered at an interval of one month. We judged the effect of this chemotherapy to be a partial response (PR), because the largest metastatic lung tumor 18 mm in diameter showed a reduction rate of 81.9%, and other tumors had almost disappeared in the chest CT after the combined therapy. No severe adverse effects of more than grade 3 were observed during this combined therapy. This combined chemotherapy consisting of TS-1 and CDDP may prove effective for treating recurrent cases of esophageal cancer.

  15. Comparison of zinc-probiotic combination therapy to zinc therapy alone in reducing the severity of acute diarrhea

    Directory of Open Access Journals (Sweden)

    Muhammad Hatta

    2011-02-01

    Full Text Available Background Although the incidence of diarrhea in Indonesia has declined in the last five years, the mortality rate in children under five years old is still high. Therefore, appropriate and comprehensive management of diarrhea is essential. There have been many studies on the role of zinc therapy and probiotic therapy in reducing the severity of acute diarrhea, but not many studies have compared the use of a combination of the two therapies to zinc therapy alone. Objective To compare the efficacy of zinc-probiotic combination therapy to zinc alone in reducing the severity of acute diarrhea. Methods We conducted a randomized, open-label, controlled trial from July 2009 to January 2010 in Adam Malik Hospital and Pirngadi Hospital, Medan. Children aged between 1 month and 5 years who met the criteria were divided into two groups. Group I received zinc sulphate (aged <6 months: 10 mg/day; aged 2:6 months: 20 mg/day combined with heat-killed Lactobacillus acidophilus (3x101O CFU/day for 10 days. Group II received only zinc sulphate at the same dosage as group I. Measurement of disease severity was based on the frequency of diarrhea (times/day and the duration of diarrhea (hours after initial drug consumption. Results Eighty subjects were enrolled, randomised, and divided equally into two groups. 40 children received zinc-probiotic in combination (group I and the remainder (group II received zinc alone. We observed significant differences in frequency of diarrhea (2.1 vs 3.1 times/day, P=0.001, 95%CI -1.62 to -0.49, and duration of diarrhea (52.1 vs. 72.6 hours, P=0.00l, 95%CI -30.91 to -10.18 in the two groups. Conclusion Combination of zinc-probiotic therapy was more effective in reducing the severity of acute diarrhea than zinc therapy alone in children under five years of age.

  16. Initial monotherapy and combination therapy and hypertension control the first year.

    Science.gov (United States)

    Egan, Brent M; Bandyopadhyay, Dipankar; Shaftman, Stephanie R; Wagner, C Shaun; Zhao, Yumin; Yu-Isenberg, Kristina S

    2012-06-01

    Initial antihypertensive therapy with single-pill combinations produced more rapid blood pressure control than initial monotherapy in clinical trials. Other studies reported better cardiovascular outcomes in patients achieving lower blood pressure during the first treatment year. We assessed the effectiveness of initial antihypertensive monotherapy, free combinations, and single-pill combinations in controlling untreated, uncontrolled hypertensives during their first treatment year. Electronic record data were obtained from 180 practice sites; 106 621 hypertensive patients seen from January 2004 to June 2009 had uncontrolled blood pressure, were untreated for ≥ 6 months before therapy, and had ≥ 1 one-year follow-up blood pressure data. Control was determined by the first follow-up visit with blood pressure blood pressure, body mass index, diabetes mellitus, chronic kidney disease, cardiovascular disease, initial therapy, final blood pressure medication number, and therapeutic inertia. Patients on initial single-pill combinations (N = 9194) were more likely to have stage 2 hypertension than those on free combinations (N = 18 328) or monotherapy (N = 79 099; all Phypertension control in the first year than free combinations (HR, 1.34; [95% CI, 1.31-1.37]) or monotherapy (reference) with benefits in black and white patients. Greater use of single-pill combinations as initial therapy may improve hypertension control and cardiovascular outcomes in the first treatment year.

  17. Tailored Antibiotic Combination Powders for Inhaled Rotational Antibiotic Therapy.

    Science.gov (United States)

    Lee, Sie Huey; Teo, Jeanette; Heng, Desmond; Ng, Wai Kiong; Zhao, Yanli; Tan, Reginald B H

    2016-04-01

    Respiratory lung infections due to multidrug-resistant (MDR) superbugs are on a global upsurge and have very grim clinical outcomes. Their MDR profile makes therapeutic options extremely limited. Although a highly toxic antibiotic, colistin, is favored today as a "last-line" therapeutic against these hard-to-treat MDR pathogens, it is fast losing its effectiveness. This work therefore seeks to identify and tailor-make useful combination regimens (that are potentially rotatable and synergistic) as attractive alternative strategies to address the rising rates of drug resistance. Three potentially rotatable ternary dry powder inhaler constructs (each involving colistin and 2 other different-classed antibiotics chosen from rifampicin, meropenem, and tigecycline) were identified (with distinct complementary killing mechanisms), coformulated via spray drying, evaluated on their aerosol performance using a Next-Generation Impactor and tested for their efficacies against a number of MDR pathogens. The powder particles were of respirable size (d50, 3.1 ± 0.3 μm-3.4 ± 0.1 μm) and predominantly crumpled in morphology. When dispersed via a model dry powder inhaler (Aerolizer(®)) at 60 L/min, the powders showed concomitant in vitro deposition with fine particle fractions of ∼53%-70%. All formulations were successfully tested in the laboratory to be highly effective against the MDR pathogens. In addition, a favorable synergistic interaction was detected across all 3 formulations when tested against MDR Pseudomonas aeruginosa.

  18. [Hemodynamics during long-term combination therapy of arterial hypertension].

    Science.gov (United States)

    Wiechmann, H W; Schuster, P; Sturm, A

    1985-04-12

    In 20 patients with essential arterial hypertension, grade II or III, the haemodynamic effect of a fixed combination of antihypertensive drugs (bemetizide, triamteren, bupranolol and dihydralazine) was studied by percutaneously-introduced flow-guided catheter in the pulmonary artery before, after three weeks and at the end of a six-month period of treatment; systemic arterial blood pressures were measured by the cuff method. Mean pressures, both at rest and on exercise were significantly and persistently lowered. Mean blood pressure at rest fell from 184/110 mmHg before treatment to 167/98 mmHg after three weeks, and to 158/93 mmHg after six months. The initial blood pressure on exercise was 226/129 mmHg, which fell after three weeks to 199/113 mmHg and after six months to 190/106 mmHg. At the same time, pulmonary artery pressure (as a measure of preload) fell by 23% at rest and 30% on exercise. Exercise tolerance of the patients rose by 28%. Pressure-heartrate product fell by 18%, as a pointer to an additional favourable effect on left ventricular oxygen consumption.

  19. Optimization of combined radiation therapy of the cervix cancer

    Directory of Open Access Journals (Sweden)

    Vladimir Philippenko

    2010-04-01

    Full Text Available Use of a new combination of known medical products - inhibitorsenzyme of cyclooxigenase-2 (diclofenac, ketoprofen with smalldoses cytostatics (methotrexate, 5-fluorouracil as“nonconventional” radiosensibilizators for optimization of combinedradial treatment of cervical cancer is offered. One hundred andtwenty patients with cervix cancer were involved into research(average age - 52.5±3.3, mainly II stage of process (50.8±4.6%,morphologically - nonkeratinizing squamous cell carcinoma(65.0±4.4%. Frequency of full regress of a tumor in the basicgroups has reached in 77.5±6.6% (1-basic group and 82.5±6.0% (2-basic group in comparison with a control group 70.0±7.2%(р<0.05. By results of the cytological research in cells thepathomorphosis of IV degree was recorded in 1-basic group - 60.0%(superficial smears and 57.5% (a puncture biopsy, in 2-basic group- 85.0% (superficial smears and 82.5% (a puncture biopsy incomparison with the control - 55.0% (superficial smears and apuncture biopsy, р<0.05.

  20. The Power of Combination Topical Therapy for Psoriasis.

    Science.gov (United States)

    Kircik, Leon H; Zografos, Panagiotis

    2015-10-01

    Psoriasis is a chronic inflammatory skin disease where the use of topical corticosteroids is a mainstream treatment. However, the continuous use of high potency topical corticosteroids is limited by a variety of well known adverse events which include, atrophy, and telangiectasia. Also, inhibition of lipid synthesis by steroids can cause impairment of the epidermal barrier, which is already disrupted in most of the inflammatory cutaneous disorders such as psoriasis. This will further lead to increase transepidermal water loss (TEWL), decreased hydration, dry skin, and irritation. On the other hand, topical vitamin D analogs directly affect keratinocyte proliferation and differentiation as well as modulation of epidermal lipids and antimicrobial peptides. Although the exact mechanism of action of topical vitamin D analogs is not well understood in the treatment of psoriasis, their efficacy and safety has been shown in several clinical trials over the years and they are widely used for psoriasis. Therefore, combination of topical steroids and vitamin D analogs may be a logical option for the treatment of psoriasis.

  1. Facile preparation of hybrid core-shell nanorods for photothermal and radiation combined therapy

    Science.gov (United States)

    Deng, Yaoyao; Li, Erdong; Cheng, Xiaju; Zhu, Jing; Lu, Shuanglong; Ge, Cuicui; Gu, Hongwei; Pan, Yue

    2016-02-01

    The hybrid platinum@iron oxide core-shell nanorods with high biocompatibility were synthesized and applied for combined therapy. These hybrid nanorods exhibit a good photothermal effect on cancer cells upon irradiation with a NIR laser. Furthermore, due to the presence of a high atomic number element (platinum core), the hybrid nanorods show a synergistic effect between photothermal and radiation therapy. Therefore, the as-prepared core-shell nanorods could play an important role in facilitating synergistic therapy between photothermal and radiation therapy to achieve better therapeutic efficacy.The hybrid platinum@iron oxide core-shell nanorods with high biocompatibility were synthesized and applied for combined therapy. These hybrid nanorods exhibit a good photothermal effect on cancer cells upon irradiation with a NIR laser. Furthermore, due to the presence of a high atomic number element (platinum core), the hybrid nanorods show a synergistic effect between photothermal and radiation therapy. Therefore, the as-prepared core-shell nanorods could play an important role in facilitating synergistic therapy between photothermal and radiation therapy to achieve better therapeutic efficacy. Electronic supplementary information (ESI) available: Details of general experimental procedures. See DOI: 10.1039/c5nr09102k

  2. Combined Antirelapse Therapy in Patients with Schizoaffective Disorder: A Prospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Zhanna R. Gardanova

    2016-06-01

    Full Text Available Background: In most studies, patients with schizoaffective disorder (SAD are often combined into one group along with schizophrenia patients or less commonly with those suffering from affective disorders, which makes it difficult to obtain data about the peculiarities of SAD treatment. Articles dedicated to SAD treatment in the interictal period are rare. Methods and Results: The prospective cohort study was conducted from 2011 to 2015. The study involved 86 patients diagnosed with SAD according to ICD-10. Patients received neuroleptics (NLs as antirelapse therapy for 2 years (NL therapy; then mood stabilizers (MSs were added to the antirelapse treatment (NL+MS therapy. The results of this combined therapy with MSs were evaluated after 2 years of treatment. Our results suggest that the use of combination therapy that includes antipsychotics and MSs leads to maintenance of a higher quality remission. Remission becomes more prolonged and affective swings less pronounced, resulting in improved quality of life in SAD patients. Improving the quality of remission can be attributed to the following characteristics of the combined therapy: a the use of lower doses of neuroleptics; b a reduction in the frequency and severity of mood swings; and c an increase in patient compliance. Conclusion: The use of combined pharmacotherapy including antipsychotics and MSs produces a longer, high-quality remission. The inclusion of MSs in the scheme of treatment increases the patient adherence to a medication regimen. The use of MSs in combination therapy reduces affective fluctuations, thereby increasing the probability of maintaining remission with complete symptom relief.

  3. 冰温结合真空包装牛肉的品质变化%Study on freezing points combined with vacuum packaging of beef quality

    Institute of Scientific and Technical Information of China (English)

    岳喜庆; 张秀梅; 孙天利; 张平; 李江阔

    2013-01-01

    In order to study the small vacuum packaging beef quality changes during storage in freezing point,beef's pH,water lost rate,color difference,the total bacteria count and tenderness at 0,4,8,12,16,20,24,28 days storage at 4 ℃,0 ℃ freezing point temperatures were measured.The difference and correlation between storage temperature index and the storage time was determined.The results showed that:the freezing point storage can effectively extend the storage time,and meat quality were better than the traditional storage method.On the 28th day of freezing point storage,plate count of lgCFU was 5.02 g-1.The shear stress was 3.065 kg.Therefore,freezing point combined with vacuum packing is feasible,and can better maintain the quality of beef.%为研究真空小块包装牛内在冰温贮藏期间的品质变化,测定了4、0℃、冰点温度贮藏的牛肉在0、4、8、12、16、20、24、28 d的pH值、失水率、色差值、细菌总数、嫩度,确定了各贮藏温度下指标随贮藏时间的变化规律及差异性和相关性.结果表明:冰温可有效延长牛肉的贮藏期,且贮藏后期各指标变化皆优于传统冷鲜肉,冰温条件下贮藏到第28天,细菌总数为5.02 lgCFU/g,剪切力值为3.065kg.由此判断冰温结合真空小块包装是可行的,且能较好的保持牛肉的品质.

  4. Chirped pulse inverse free-electron laser vacuum accelerator

    Science.gov (United States)

    Hartemann, Frederic V.; Baldis, Hector A.; Landahl, Eric C.

    2002-01-01

    A chirped pulse inverse free-electron laser (IFEL) vacuum accelerator for high gradient laser acceleration in vacuum. By the use of an ultrashort (femtosecond), ultrahigh intensity chirped laser pulse both the IFEL interaction bandwidth and accelerating gradient are increased, thus yielding large gains in a compact system. In addition, the IFEL resonance condition can be maintained throughout the interaction region by using a chirped drive laser wave. In addition, diffraction can be alleviated by taking advantage of the laser optical bandwidth with negative dispersion focusing optics to produce a chromatic line focus. The combination of these features results in a compact, efficient vacuum laser accelerator which finds many applications including high energy physics, compact table-top laser accelerator for medical imaging and therapy, material science, and basic physics.

  5. The impact of timolol maleate on the ocular tolerability of fixed-combination glaucoma therapies

    Directory of Open Access Journals (Sweden)

    Radcliffe NM

    2014-12-01

    Full Text Available Nathan M Radcliffe Ophthalmology, New York University, New York, NY, USA Abstract: Glaucomatous optic atrophy is the second most common cause of blindness worldwide, and lowering intraocular pressure (IOP is the only proven method to slow or stop the progression of the disease. Approximately 40% of patients with elevated IOP will require more than one medication to obtain a modest 20% reduction in IOP, and as a result, some patients may require two medications, provided in either two separate bottles or in one bottle with the use of fixed-combination therapies. Each therapy has its own unique safety and efficacy profile. Topical beta-blockers have a particularly favorable ocular-tolerability profile, and several studies of fixed-combination medications containing the beta-blocker timolol maleate have shown a lower prevalence of some ocular adverse events for the fixed-combination therapy compared to the non-beta-blocker individual component. In this review, we examined clinical data pertaining to the ocular surface tolerability of fixed-combination medications containing timolol maleate in comparison to the individual components. In particular, preference was given to prospective, randomized, multicenter trials of 3 months in duration or longer that compared a fixed-combination therapy to monotherapy with the individual components. A review of the literature revealed that some fixed-combination therapies can provide a reduced risk of common side effects compared to their individual components, with conjunctival hyperemia and ocular allergy being less frequent in some timolol-containing fixed-combination therapies. This effect appears to be most significant for latanoprost 0.005%, bimatoprost 0.03%, and brimonidine 0.2%. Keywords: bimatoprost, brimonidine, hyperemia, latanoprost, ocular allergy

  6. Fixed-dose combination for adults accessing antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    SA HIV Clinicians Society

    2013-03-01

    Full Text Available This document serves to guide clinicians and programme managers on how to switch from 3 separate antiretroviral (ARV drugs to the new, single, fixed-dose combination (FDC tablet containing tenofovir (TDF, emtricitabine (FTC and efavirenz (EFV. Summary Transitioning from individual drugs to an FDC tablet needs to be managed carefully, particularly regarding stock management, ordering processes, supply-chain integrity and comprehensive patient counselling. Priority groups • Initially, FDC supply will be insufficient to provide for all FDC-suitable patients • Therefore, the National Department of Health (NDoH has recommended that the following patient groups be prioritized for FDC initiation/switch: • Priority group 1: All HIV-positive patients newly initiating ART – adults, adolescents and pregnant women (regardless of CD4 count (amendment to the guidelines for the prevention of mother-to-child transmission of HIV (PMTCT anticipated in April 2013 – and who do not have contra-indications to the FDC component drugs • Priority group 2: HIV-positive pregnant women and breastfeeding mothers currently stable on lamivudine (3TC, TDF and EFV • Priority group 3: Virologically suppressed patients on a stavudine (d4T-based regimen and who have normal renal function • Priority group 4: Stable patients receiving individual TDF, 3TC and EFV and who have tuberculosis (TB co-infection • Priority group 5: Stable patients receiving individual TDF, 3TC and EFV and who have other co-morbidites (e.g. hypertension, diabetes • Priority group 6: Patients receiving individual TDF, 3TC and EFV and who request to switch to the FDC treatment • Priority group 7: Patients receiving individual TDF, 3TC and EFV and who, after counselling, agree to switch to the FDC treatment. Important: Clinic staff must co-ordinate this process and only switch as many patients to the FDC tablet as stock allows. This should avoid patients being switched back and forth

  7. Combining gene therapy and fetal hemoglobin induction for treatment of β-thalassemia.

    Science.gov (United States)

    Breda, Laura; Rivella, Stefano; Zuccato, Cristina; Gambari, Roberto

    2013-06-01

    β-thalassemias are caused by nearly 300 mutations of the β-globin gene, leading to a low or absent production of adult hemoglobin (HbA). Two major therapeutic approaches have recently been proposed: gene therapy and induction of fetal hemoglobin (HbF) with the objective of achieving clinically relevant levels of Hbs. The objective of this article is to describe the development of therapeutic strategies based on a combination of gene therapy and induction of HbFs. An increase of β-globin gene expression in β-thalassemia cells can be achieved by gene therapy, although de novo production of clinically relevant levels of adult Hb may be difficult to obtain. On the other hand, an increased production of HbF is beneficial in β-thalassemia. The combination of gene therapy and HbF induction appears to be a pertinent strategy to achieve clinically relevant results.

  8. Mathematical optimization of the combination of radiation and differentiation therapies of cancer

    Directory of Open Access Journals (Sweden)

    Jeff W.N. Bachman

    2013-03-01

    Full Text Available Cancer stem cells (CSC are considered to be a major driver of cancer progression and successful therapies must control CSCs. However, CSC are often less sensitive to treatment and they might survive radiation and/or chemotherapies. In this paper we combine radiation treatment with differentiation therapy. During differentiation therapy, a differentiation promoting agent is supplied (e.g. TGF-beta such that CSCs differentiate and become more radiosensitive. Then radiation can be used to control them. We consider three types of cancer: head and neck cancer, brain cancers (primary tumors and metastatic brain cancers, and breast cancer; and we use mathematical modelling to show that combination therapy of the above type can have a large beneficial effect for the patient; increasing treatment success and reducing side effects.

  9. Clinical effect of anti-VEGF drugs combined with laser therapy for DME patients

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    Li Yin

    2017-06-01

    Full Text Available AIM:To investigate the clinical effect of anti-vascular endothelial growth factor(VEGFdrugs combined with laser photocoagulation for diabetic macular edema(DME. METHODS: Totally 94 patients(141 eyeswith DME from June to December 2015 in our hospital were selected and randomly divided into combined group of 47 cases(68 eyes, ranibizumab combined with laser therapyand the control group of 47 cases(73 eyes, laser treatment. The levels of best corrected visual acuity(BCVA, macular central retinal thickness(CRT, total macular volume(TMVand macular edema level were compared between the two groups at different time after treatment. RESULTS: The mean values of BCVA in the combined group were higher than those in the control group at 2, 6 and 12wk, and the difference was statistically significant(PPPCONCLUSION: The effect of anti-VEGF drugs combined with laser therapy for DME patients is better than that of single laser therapy alone.

  10. Combination Cell Therapy with Mesenchymal Stem Cells and Neural Stem Cells for Brain Stroke in Rats

    OpenAIRE

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-01-01

    Objectives Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stro...

  11. Intravenous iloprost in the combination therapy of vascular disorders in patients with systemic connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Aleksandr Vitalyevich Volkov

    2013-01-01

    Full Text Available Systemic connective tissue diseases, systemic scleroderma in particular, constitute a group of diseases in which vascular disorders underlying diverse clinical manifestations are one of the pathogenetic components. Raynaud 's syndrome and ulceration are the most common symptoms of these diseases, which influence quality of life in patients and require constant drug therapy. The paper discusses the authors' clinical experience with intravenous iloprost used in the combination therapy of the vascular manifestations of systemic scleroderma and systemic lupus erythematosus.

  12. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency.

    OpenAIRE

    Montiel-Equihua, C. A.; Thrasher, A. J.; Gaspar, H B

    2009-01-01

    The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID) and especially adenosine deaminase (ADA)-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. P...

  13. Polydopamine Nanoparticles as a Versatile Molecular Loading Platform to Enable Imaging-guided Cancer Combination Therapy

    OpenAIRE

    Dong, Ziliang; Gong, Hua; Gao, Min; Zhu, Wenwen; Sun, Xiaoqi; Feng, Liangzhu; Fu, Tingting; Li, Yonggang; Liu, Zhuang

    2016-01-01

    Cancer combination therapy to treat tumors with different therapeutic approaches can efficiently improve treatment efficacy and reduce side effects. Herein, we develop a theranostic nano-platform based on polydopamine (PDA) nanoparticles, which then are exploited as a versatile carrier to allow simultaneous loading of indocyanine green (ICG), doxorubicin (DOX) and manganese ions (PDA-ICG-PEG/DOX(Mn)), to enable imaging-guided chemo & photothermal cancer therapy. In this system, ICG acts as a ...

  14. The combined application of biological therapy and methotrexate in case of escape phenomenon progressing

    Directory of Open Access Journals (Sweden)

    Ponich E.S.

    2015-09-01

    Full Text Available Aim: the study of the efficacy of methotrexate in patients with the "escape effect" during the ustekinumab therapy. Materials and Methods. The results of methotrexate at a dose of 15-20mg/week in treatment of 4 patients receiving biologic and developed "escape effect". Ustekinumab is used as a hypodermic injection at a dose of 45 mg for a body weight of a patient no more than 100 kg, and 90 mg of body weight over 100 kg, at the zero week, the 4th week and then every 12 weeks. Patients control meets the standard management of patients in biological therapy. Results. The study shows that in the case of the resistance progressing when applying preparations of biological therapy, methotrexate is useful at a dose of 15-20mg/week for up to 6 months. The combined use of biologic therapy and methotrexate in the treatment of patients with psoriasis vulgaris, "escape effect" contributes to the marked regression of clinical symptoms and allows to control the process long enough, which is confirmed by the dynamics of the index PASI, BRS and DLQI. The combined method is highly safe, as evidenced by the lack of inhibition of hematopoiesis, the normal level of hepatic transaminases and serum creatinine, which greatly improves patient compliance in this type of therapy. Conclusion. The article presents the data of the combined application of biological medication therapy (ustekinumab and methotrexate for the treatment of patients with the common form of psoriasis vulgaris. In the case of the development of resistance of biological therapy recommended the appointment of methotrexate. The combined use of methotrexate and biologic therapy in the treatment of patients with psoriasis vulgaris contributes to marked regression of clinical symptoms and allows to control the process for a long time.

  15. Gene therapy for severe combined immunodeficiency due to adenosine deaminase deficiency.

    Science.gov (United States)

    Montiel-Equihua, Claudia A; Thrasher, Adrian J; Gaspar, H Bobby

    2012-02-01

    The severe combined immunodeficiency caused by the absence of adenosine deaminase (SCID-ADA) was the first monogenic disorder for which gene therapy was developed. Over 30 patients have been treated worldwide using the current protocols, and most of them have experienced clinical benefit; importantly, in the absence of any vector-related complications. In this document, we review the progress made so far in the development and establishment of gene therapy as an alternative form of treatment for ADA-SCID patients.

  16. The efficacy of mirror therapy combined with conventional stroke rehabilitation program on motor and functional recovery

    OpenAIRE

    Selen Kuzgun; Merih Özgen; Onur Armağan; Funda Taşcıoğlu; Canan Baydemir

    2012-01-01

    OBJECTIVE: A variety of methods is used in the treatment of upper extremity functional impairment after stroke.In recent years, a new therapeutic approach in the treatment of stroke rehabilitation is the mirror therapy.The purpose of this study is to investigate the efficacy of mirror therapy,which is applied through motor imagination training, combined with conventional stroke rehabilitation program on upper extremity motor and functional recovery in patients with subacute stroke...

  17. OUTCOME OF ANTIFUNGAL COMBINATION THERAPY FOR INVASIVE MOLD INFECTIONS IN HEMATOLOGICAL PATIENTS IS INDEPENDENT OF THE CHOSEN COMBINATION

    Directory of Open Access Journals (Sweden)

    Rafael Rojas

    2012-02-01

    Full Text Available Invasive mold infection (IMI remains a major cause of mortality in high-risk hematological patients. The aim of this multicenter retrospective, observational study was to evaluate antifungal combination therapy for proven and probable IMI in hematological patients. We analyzed 61 consecutive cases of proven (n=25 and probable (n=36 IMI treated with antifungal combination therapy (ACT collected from eight Spanish hospitals from January 2005 to December 2009. Causal pathogens were: Aspergillus spp (n=49, Zygomycetes (n=6, Fusarium spp (n=3, and Scedosporium spp (n=3. Patients were classified in three groups according to the antifungal combination employed: Group A, liposomal amphotericin B (L-Amb plus caspofungin (n=20; Group B, L-Amb plus a triazole (n=20, and Group C, voriconazole plus a candin (n=21. ACT was well tolerated with minimal adverse effects. Thirty-eight patients (62.3% achieved a favorable response (35 complete. End of treatment and 12-week survival rates were 62.3% and 57.4% respectively, without statistical differences among groups. Granulocyte recovery was significantly related to favorable responses and survival (p<0.001 in multivariate analysis. Our results suggest that comparable outcomes can be achieved with ACT in high risk hematological patients with proven or probable IMI, whatever the combination of antifungal agents used.

  18. Combining targeted therapy and immune checkpoint inhibitors in the treatment of metastatic melanoma

    Institute of Scientific and Technical Information of China (English)

    Teresa Kim; Rodabe N Amaria; Christine Spencer; Alexandre Reuben; Zachary A Cooper; Jennifer A Wargo

    2014-01-01

    Melanoma is the deadliest form of skin cancer and has an incidence that is rising faster than any other solid tumor. Metastatic melanoma treatment has considerably progressed in the past ifve years with the introduction of targeted therapy (BARF and MEK inhibitors) and immune checkpoint blockade (anti-CTLA4, anti-PD-1, and anti-PD-L1). However, each treatment modality has limitations. Treatment with targeted therapy has been associated with a high response rate, but with short-term responses. Conversely, treatment with immune checkpoint blockade has a lower response rate, but with long-term responses. Targeted therapy affects antitumor immunity, and synergy may exist when targeted therapy is combined with immunotherapy. hTis article presents a brief review of the rationale and evidence for the potential synergy between targeted therapy and immune checkpoint blockade. Challenges and directions for future studies are also proposed.

  19. HIV-1 CCR5 gene therapy will fail unless it is combined with a suicide gene.

    Science.gov (United States)

    Pandit, Aridaman; de Boer, Rob J

    2015-12-17

    Highly active antiretroviral therapy (ART) has successfully turned Human immunodeficiency virus type 1 (HIV-1) from a deadly pathogen into a manageable chronic infection. ART is a lifelong therapy which is both expensive and toxic, and HIV can become resistant to it. An alternative to lifelong ART is gene therapy that targets the CCR5 co-receptor and creates a population of genetically modified host cells that are less susceptible to viral infection. With generic mathematical models we show that gene therapy that only targets the CCR5 co-receptor fails to suppress HIV-1 (which is in agreement with current data). We predict that the same gene therapy can be markedly improved if it is combined with a suicide gene that is only expressed upon HIV-1 infection.

  20. The role of combination medical therapy in the treatment of acromegaly.

    Science.gov (United States)

    Lim, Dawn Shao Ting; Fleseriu, Maria

    2017-02-01

    Uncontrolled acromegaly results in approximately 2-fold excess mortality. Pituitary surgery is first-line therapy, and medical treatment is indicated for persistent disease. While cabergoline and pegvisomant are used in select patients, somatostatin receptor ligands (SRLs) remain the cornerstone of medical treatment. Management of patients poorly responsive to SRLs is therefore, challenging. The purpose of this review is to highlight the options for combination medical therapy in the treatment of acromegaly, with an emphasis on efficacy and safety. All original articles/abstracts detailing combination medical therapy in acromegaly were identified from a PubMed search. Studies reviewed included retrospective and open-label prospective studies. While the combination of SRL and cabergoline was generally well tolerated, a lower baseline insulin-like growth factor-1 (IGF-1) level was the best predictor of efficacy; this combination may be most effective in patients with mildly elevated IGF-1. SRL-pegvisomant combination normalized IGF-1 in the majority of patients; continued efficacy despite individual drug dosing reduction was also reported. The risk of significant liver enzyme elevation was, however, higher than that reported with SRL monotherapy; close monitoring is recommended. Data on pegvisomant-cabergoline combination is limited, but this may be an option in the setting of SRL intolerance. Reports on temozolomide used in combination with other medical therapies in patients with aggressive GH-secreting tumors are also summarized. While more prospective, randomized controlled trials on long-term efficacy and safety are needed, combination medical therapy remains a treatment strategy that should be considered for acromegaly patients poorly responsive to SRLs.

  1. Experience of terahertz therapy in benign prostatic hyperplasia combined with chronic abacterial prostatitis

    Directory of Open Access Journals (Sweden)

    Popkov V.M.

    2014-12-01

    Full Text Available Objective: to improve the treatment results of patients with benign prostatic hyperplasia (stage l-ll accompanied with chronic abacterial prostatitis (category III A by the use of terahertz therapy at frequencies of molecular spectrum of emission and absorption of nitric oxide 150,176-150,664 GHz. Material and methods. Atotal number of 75 patients met the inclusion criteria and were available for analysis. They were divided into three groups: 1st core group — 25 patients with BPH (stage l-ll accompanied with chronic abacterial prostatitis (category III, which received standard medical therapy in combination with THZ-therapy; second group — 25 patients with BPH (stage l-ll accompanied with CAP, which received standard medical therapy; third control group — 25 healthy men. Results. The combination of THZ — therapy with standard medical treatment allowed us to achieve marked improvements in the IPSS and QoL system, rapid anesthetic effect, more significant volume reduction of the prostate tissue in the 1st core group. Also THZ-therapy in 1st core group revealed a statistically significant increase of the maximum speed of blood vessels in the prostate tissue, improved a prostate secretion and rheological properties of blood. Conclusion. THZ-therapy as a complementary treatment has a beneficial effect on the clinical course of BPH (stage l-ll accompanied with CAP (category III.

  2. Indacaterol and tiotropium combination therapy in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Matsushima, Sayomi; Inui, Naoki; Yasui, Hideki; Kono, Masato; Nakamura, Yutaro; Toyoshima, Mikio; Shirai, Toshihiro; Suda, Takafumi

    2015-02-01

    Combination therapy with a long-acting antimuscarinic agent and a long-acting β2-agonist are recommended in chronic obstructive pulmonary disease (COPD) if control is not adequate with one long-acting bronchodilator alone. We evaluated the effects of indacaterol and tiotropium combination therapy, including the effects of adding indacaterol to tiotropium (indacaterol add-on group) and adding tiotropium to indacaterol (tiotropium add-on group). We recruited 79 patients with COPD already treated with tiotropium or indacaterol. We undertook pulmonary function tests, the COPD assessment test (CAT), and the multi-frequency forced oscillation technique (to measure respiratory resistance and reactance) before and after 8 weeks of indacaterol and tiotropium combination therapy. The median age was 72.1 years and the mean forced expiratory volume in 1 s (FEV1) as a proportion of predicted was 57.2 ± 18.3%. After 8 weeks of combination therapy, FEV1 and %predicted FEV1 had increased significantly. There was no change in CAT score. For respiratory impedance, combination therapy improved resistance at 5 Hz (R5) and resistance at 20 Hz (R20) in the whole-breath, inspiratory and expiratory phases, and resonant frequency (Fres) in the inspiratory phase. The indacaterol add-on group (43 patients) and tiotropium add-on group (36 patients) showed improvements in FEV1 and %predicted FEV1 over monotherapy, although the CAT score fell significantly in the indacaterol add-on group (p = 0.005). Indacaterol and tiotropium combination therapy improved airflow limitation and respiratory resistances. Adding indacaterol to tiotropium, or tiotropium to indacaterol, had similar effects on airflow limitation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer.

    Directory of Open Access Journals (Sweden)

    Nikita Pozdeyev

    Full Text Available NF-κB signaling plays an important role in tumor cell proliferation, cell survival, angiogenesis, invasion, metastasis and drug/radiation resistance. Combination therapy involving NF-κB pathway inhibition is an attractive strategy for the treatment of advanced forms of thyroid cancer. This study was designed to test the efficacy of NF-κB pathway inhibition in combination with cytotoxic chemotherapy, using docetaxel and ionizing radiation in in vitro models of thyroid cancer. We found that while both docetaxel and ionizing radiation activated NF-κB signaling in thyroid cancer cells, there was no synergistic effect on cell proliferation and/or programmed cell death with either genetic (transduction of a dominant negative mutant form of IκBα or pharmacologic (proteasome inhibitor bortezomib and IKKβ inhibitor GO-Y030 inhibition of the NF-κB pathway in thyroid cancer cell lines BCPAP, 8505C, THJ16T and SW1736. Docetaxel plus bortezomib synergistically decreased in vitro invasion of 8505C cells, but not in the other cell lines. Screening of a panel of clinically relevant targeted therapies for synergy with genetic NF-κB inhibition in a proliferation/cytotoxicity assay identified the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA as a potential candidate. However, the synergistic effect was confirmed only in the BCPAP cells. These results indicate that NF-κB inhibitors are unlikely to be beneficial as combination therapy with taxane cytotoxic chemotherapy, external radiation therapy or radioiodine therapy. There may be unique circumstances where NF-κB inhibitors may be considered in combination with docetaxel to reduce tumor invasion or in combination with HDAC inhibitors to reduce tumor growth, but this does not appear to be a combination therapy that could be broadly applied to patients with advanced thyroid cancer. Further research may identify which subsets of patients/tumors may respond to this therapeutic

  4. Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

    Science.gov (United States)

    Halasa, Salaheldin; Dickinson, Eva

    2014-02-01

    From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

  5. Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma.

    Science.gov (United States)

    Richter, Joshua; Neparidze, Natalia; Zhang, Lin; Nair, Shiny; Monesmith, Tamara; Sundaram, Ranjini; Miesowicz, Fred; Dhodapkar, Kavita M; Dhodapkar, Madhav V

    2013-01-17

    Natural killer T (iNKT) cells can help mediate immune surveillance against tumors in mice. Prior studies targeting human iNKT cells were limited to therapy of advanced cancer and led to only modest activation of innate immunity. Clinical myeloma is preceded by an asymptomatic precursor phase. Lenalidomide was shown to mediate antigen-specific costimulation of human iNKT cells. We treated 6 patients with asymptomatic myeloma with 3 cycles of combination of α-galactosylceramide-loaded monocyte-derived dendritic cells and low-dose lenalidomide. Therapy was well tolerated and led to reduction in tumor-associated monoclonal immunoglobulin in 3 of 4 patients with measurable disease. Combination therapy led to activation-induced decline in measurable iNKT cells and activation of NK cells with an increase in NKG2D and CD56 expression. Treatment also led to activation of monocytes with an increase in CD16 expression. Each cycle of therapy was associated with induction of eosinophilia as well as an increase in serum soluble IL2 receptor. Clinical responses correlated with pre-existing or treatment-induced antitumor T-cell immunity. These data demonstrate synergistic activation of several innate immune cells by this combination and the capacity to mediate tumor regression. Combination therapies targeting iNKT cells may be of benefit toward prevention of cancer in humans.

  6. Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Graudal, Niels; Hubeck-Graudal, Thorbjørn; Faurschou, Mikkel;

    2015-01-01

    OBJECTIVE: The costs of biologic treatment per patient with rheumatoid arthritis (RA) are approximately 100 times the costs of treatment with a combination of conventional disease-modifying antirheumatic drugs (DMARDs). Despite this, biologic agents have not been proven superior. We compared...... the effects of combination DMARD therapies with and without biologic agents as therapy for patients with RA. METHODS: Eight randomized controlled trials published in 10 articles were selected from a systematic literature search of 1,674 identified studies and integrated in a meta-analysis. These trials...

  7. Photothermal therapy combined with dinitrophenyl hapten for the treatment of late stage malignant melanoma

    Science.gov (United States)

    Li, Xiaosong; Du, Nan; Li, Haijun; Long, Shan; Chen, Dianjun; Zhou, Feifan; Xu, Yuanyuan; Wang, Fuli; Chen, Wei R.

    2017-02-01

    To evaluate the efficacy and safety of photothermal with dinitrophenyl hapten (DNP) for patients with malignant melanoma (MM), Patients with pathology confirmed stage III or IV MM were enrolled. Seventy-two patients were randomized into two groups, DNP alone group (n=36) and DNP plus photothermal therapy group (n=36). The results showed that the patients in the combination treatment group had longer median progression-free survival time (19.0m vs. 12.0m, p=0.007). No severe adverse events were observed in both groups. Thus, the combination of photothermal therapy and DNP maybe a new therapeutic strategy for patients with advanced MM.

  8. Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

    Directory of Open Access Journals (Sweden)

    Prisco L

    2011-08-01

    Full Text Available Lara Prisco1, Mario Ganau2, Federica Bigotto1, Francesca Zornada11Department of Anaesthesiology, Intensive Care and Emergency Medicine, University Hospital of Cattinara, 2Graduate School of Nanotechnology, University of Trieste, ItalyAbstract: Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.Keywords: trigeminal neuralgia, antiepileptic drugs, combination therapy

  9. The Avoiding Cardiovascular events through COMbination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial: a comparison of first-line combination therapies.

    Science.gov (United States)

    Weder, Alan B

    2005-02-01

    Although multidrug therapy is required in order to achieve good blood pressure control in many hypertensives, there are no studies directly comparing fixed-dose combinations as initial therapy. The Avoiding Cardiovascular events through COMbination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial compares regimens of benazepril plus amlodipine versus benazepril plus hydrochlorothiazide, force-titrated to 40/10 and 40/25mg, respectively. A total of 12,600 high-risk hypertensives have been randomised and will be followed for 3 - 5years, during which cardiovascular events will be monitored. The investigators hypothesise that the benazepril plus amlodipine regimen will decrease cardiovascular events by 15% compared with benazepril plus hydrochlorothiazide. Recruitment began in 2003, and the trial is expected to end in 2008. The ACCOMPLISH trial shares important limitations with many other recent trials that will make it difficult to apply the results in clinical practice. These include the focus on high-risk hypertensive patients, in whom significant reductions in relative risk will translate into meaningful reductions in absolute risk: in lower-risk hypertensives with a low absolute risk, similar relative risk reductions may not be of great impact on the population disease burden. In ACCOMPLISH, as in most industry-sponsored clinical trials, the main goal appears to be market-driven: doses of drugs tested are not those available for clinical practice. The question asked, whether the combination of benazepril with either diuretic or dihydropyridine calcium channel blocker is more efficacious, is not a clinically compelling one. Finally, the univariate subgroup analyses proposed are unlikely to lead to an understanding of whether either combination has specific advantages for patients encountered clinically, most of whom have multiple risk factors. Thus, it appears that ACCOMPLISH, as with many recent pharmacological trials, will not greatly

  10. Combination Therapy with Oleanolic Acid and Metformin as a Synergistic Treatment for Diabetes

    Directory of Open Access Journals (Sweden)

    Xue Wang

    2015-01-01

    Full Text Available Aims and Background. Type 2 diabetes is a chronic disease that cannot be treated adequately using the known monotherapies, especially when the disease progresses to an advanced stage. In this study, we explore the possibility of treating the disease with a novel combination approach of oleanolic acid (OA, a glycogen phosphorylase (GP inhibitor, and metformin. Methods. Db/db mice were randomly divided into four groups: a db/db control group, db/db mice treated with OA (250 mg/kg, db/db mice treated with metformin (100 mg/kg, and db/db mice treated with a combination of OA and metformin. All mice were treated for four weeks. The effects of the treatments on glucose homeostasis were measured using an OGTT, an assessment of insulin sensitivity and signaling in the liver, and the hepatic glucose production. Results. Combination therapy with OA and metformin significantly reduced the blood glucose and insulin levels and improved the liver pathology compared with that for the monotherapy in the db/db diabetic mouse model. We also found that the combination therapy significantly increased the mRNA expression of glycogen synthesis and decreased the GP, PGC-1α, PEPCK1, and G-6-Pase levels. In addition, the combination therapy with OA and metformin significantly increased the phosphorylation of AKT, PI3K, AMPK, and ACC and decreased the protein expression levels of G-6-Pase, PEPCK1, and TORC compared with those for either monotherapy. The combination therapy also reduced the phosphorylation of mTOR and CREB. Conclusions. Our results suggest that the combination therapy with OA and metformin has synergistic effects on the symptoms of db/db diabetic mice by improving glucose and insulin homeostasis.

  11. COMPARATIVE EFFICIENCY OF THE COMBINED THERAPY IN PATIENT’S WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    V. V. Shchekotov

    2014-07-01

    Full Text Available Objective — to assess influence of the combined therapy on a functional condition endothelium, the central haemodynamics and geometry of heart in patients with hypertensive disease.Subjects and methods. The volume of supervision has made 40 patients with arterial hypertension grade II hypertension, moderate — highrisk. Patients of the first group received the combined therapy lisinopril — 20 mg and hydrochlortiazid — 12.5 mg (iruzid — “Belupo”, Croatia, patients of the second group — therapy trandolapril and verapamil (tarka — “Ebbot”, Germany — 2 and 180 mg accordingly.Results. The combined therapy trandolapril and verapamil renders more expressed antihypertension effect, than lisinopril and hydrochlortiazid.Appointment of the combined therapy promoted normalization morphofunctional heart indicators: in group of tarka ejection fraction(EF has authentically increased by 4.34 % (р = 0,02, the thickness to a back wall of the left ventricle has decreased for 5.8 % (р = 0,03 in group of iruzid. Also in both groups optimization functional a condition endothelium vessels as on level desquamation endotheliocytes, a function indicator endothelium and on a level of a factor of Willebrand was marked. Authentically more expressed positive influence on endothelium tarka in comparison with iruzid has been noticed.Conclusion. At comparison of combinations fat-soluble ACE inhibitor with verapamil (tarka and water-soluble ACE inhibitor in a combination with hydrochlortiazid (iruzid the insignificant superiority of the first combination over the second for level of positive influence on endothelium of vessels has been revealed, more expressed antihypertensive effect and ability authentically to increase EF.

  12. COMPARATIVE EFFICIENCY OF THE COMBINED THERAPY IN PATIENT’S WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    V. V. Shchekotov

    2011-01-01

    Full Text Available Objective — to assess influence of the combined therapy on a functional condition endothelium, the central haemodynamics and geometry of heart in patients with hypertensive disease.Subjects and methods. The volume of supervision has made 40 patients with arterial hypertension grade II hypertension, moderate — highrisk. Patients of the first group received the combined therapy lisinopril — 20 mg and hydrochlortiazid — 12.5 mg (iruzid — “Belupo”, Croatia, patients of the second group — therapy trandolapril and verapamil (tarka — “Ebbot”, Germany — 2 and 180 mg accordingly.Results. The combined therapy trandolapril and verapamil renders more expressed antihypertension effect, than lisinopril and hydrochlortiazid.Appointment of the combined therapy promoted normalization morphofunctional heart indicators: in group of tarka ejection fraction(EF has authentically increased by 4.34 % (р = 0,02, the thickness to a back wall of the left ventricle has decreased for 5.8 % (р = 0,03 in group of iruzid. Also in both groups optimization functional a condition endothelium vessels as on level desquamation endotheliocytes, a function indicator endothelium and on a level of a factor of Willebrand was marked. Authentically more expressed positive influence on endothelium tarka in comparison with iruzid has been noticed.Conclusion. At comparison of combinations fat-soluble ACE inhibitor with verapamil (tarka and water-soluble ACE inhibitor in a combination with hydrochlortiazid (iruzid the insignificant superiority of the first combination over the second for level of positive influence on endothelium of vessels has been revealed, more expressed antihypertensive effect and ability authentically to increase EF.

  13. Antibiotic combination therapy can select for broad-spectrum multidrug resistance in Pseudomonas aeruginosa.

    Science.gov (United States)

    Vestergaard, Martin; Paulander, Wilhelm; Marvig, Rasmus L; Clasen, Julie; Jochumsen, Nicholas; Molin, Søren; Jelsbak, Lars; Ingmer, Hanne; Folkesson, Anders

    2016-01-01

    Combination therapy with several antibiotics is one strategy that has been applied in order to limit the spread of antimicrobial resistance. We compared the de novo evolution of resistance during combination therapy with the β-lactam ceftazidime and the fluoroquinolone ciprofloxacin with the resistance evolved after single-drug exposure. Combination therapy selected for mutants that displayed broad-spectrum resistance, and a major resistance mechanism was mutational inactivation of the repressor gene mexR that regulates the multidrug efflux operon mexAB-oprM. Deregulation of this operon led to a broad-spectrum resistance phenotype that decreased susceptibility to the combination of drugs applied during selection as well as to unrelated antibiotic classes. Mutants isolated after single-drug exposure displayed narrow-spectrum resistance and carried mutations in the MexCD-OprJ efflux pump regulator gene nfxB conferring ciprofloxacin resistance, or in the gene encoding the non-essential penicillin-binding protein DacB conferring ceftazidime resistance. Reconstruction of resistance mutations by allelic replacement and in vitro fitness assays revealed that in contrast to single antibiotic use, combination therapy consistently selected for mutants with enhanced fitness expressing broad-spectrum resistance mechanisms.

  14. Effectiveness of combining manual therapy and acupuncture on temporomandibular joint dysfunction: a retrospective study.

    Science.gov (United States)

    Shin, Byung-Cheul; Ha, Chung-Hyo; Song, Yung-Sun; Lee, Myeong Soo

    2007-01-01

    This retrospective study investigated the effects of combining manual therapy and acupuncture on the pain and maximal mouth opening (MMO), which were associated with temporomandibular joint dysfunction (TMD). The 49 TMD patients (15 men, 34 women; mean age = 30.47 years, SD = 13.52 years) were treated with a combination of acupuncture and manual therapy two or three times a week at the hospital. The pain and maximal mouth opening were assessed before and after 1 and 4 weeks of treatment. The combination therapy produced significant changes in pain levels (p < 0.001) and mouth opening (p < 0.001). All pairwise non-parametric comparison showed a significant improvement in pain (p < 0.05 for all pairs) and MMO (p < 0.05 for all pairs). These findings suggest that combining manual therapy and acupuncture decreases the pain level and increases the MMO of TMD patients. However, future studies should further investigate the efficacy of combined treatment on TMD with more rigorous randomized clinical trials.

  15. EFFECTS OF COMBINATION THERAPY ON PLATELET COUNT IN PATIENTS OF MYOCARDIAL INFARCTION

    Directory of Open Access Journals (Sweden)

    Sadaf Ahmed

    2014-12-01

    Full Text Available Aspirin and clopidogrel are usually used individually to prevent adverse cardiovascular events and stroke. They are used in stabilizing the blood pressure in patients of myocardial infarction while combination therapy of aspirin and Clopidogrel (dual anti-platelet therapy is used for preventing adverse cardiovascular events in myocardial infarction patients. A cross-sectional observational study is conducted through a structured questionnaire from 110 patients of K.I.H.D (Karachi Institute of Heart Disease hospital, Karachi, Pakistan. Indoor/admitted patients with diagnosis of acute coronary syndrome (ACS, non-ST elevation myocardial infarction (NSTE-MI, ST elevation myocardial infarction (STE-MI, supra ventricular tachycardia (SVT were included along with those with previous or current onset of angina pectoris or heart attack. Information from the test reports of these patients was included in the data. Patients without proper test reports were excluded from the study. Combination therapy duration is considered as key tool for evaluation. Out of 100 patients (after exclusion criteria applied almost 18% patients were using the combination therapy for 10 to 25 years while 52% of patients were using the combination therapy for 1 to 10 years. Platelet count of 88% patients was found to be in between 1,50,000–3,50,000/µl. Remaining patients had less than 1,50,000 µl to more than 3,50,000 to 4,50,000 µl. Most frequently reported side effects were chest pain, respiratory issues, headache and depression. On the basis of our data analysis it is concluded that long duration dual anti-platelet therapy will not harm platelet count in human blood but it can create drug dependency in patients. Hypertension is not completely cured with this therapy but can help in stabilizing blood pressure.

  16. Vacuum fiber-fiber coupler

    Science.gov (United States)

    Heinrici, Axel; Bjelajac, Goran; Jonkers, Jeroen; Jakobs, Stefan; Olschok, Simon; Reisgen, Uwe

    2017-02-01

    Research and development carried out by the ISF Welding and Joining Institute of RWTH Aachen University has proven that combining high power laser and low vacuum atmosphere provides a welding performance and quality, which is comparable to electron beam welding. The developed welding machines are still using a beam forming which takes place outside the vacuum and the focusing laser beam has to be introduced to the vacuum via a suitable window. This inflexible design spoils much of the flexibility of modern laser welding. With the target to bring a compact, lightweight flying optics with flexible laser transport fibers into vacuum chambers, a high power fiber-fiber coupler has been adapted by II-VI HIGHYAG that includes a reliable vacuum interface. The vacuum-fiber-fiber coupler (V-FFC) is tested with up to 16 kW sustained laser power and the design is flexible in terms of a wide variety of laser fiber plug systems and vacuum flanges. All that is needed to implement the V-FFC towards an existing or planned vacuum chamber is an aperture of at least 100 mm (4 inch) diameter with any type of vacuum or pressure flange. The V-FFC has a state-of-the-art safety interface which allows for fast fiber breakage detection for both fibers (as supported by fibers) by electric wire breakage and short circuit detection. Moreover, the System also provides connectors for cooling and electric signals for the laser beam optics inside the vacuum. The V-FFC has all necessary adjustment options for coupling the laser radiation to the receiving fiber.

  17. Combination therapy for scalp angiosarcoma using bevacizumab and chemotherapy: a case report and review of literature

    Institute of Scientific and Technical Information of China (English)

    Ping Yang; Qi Zhu; Fuqiang Jiang

    2013-01-01

    Bevacizumab,an angiogenesis inhibitor,is a recombined humanized monoclonal antibody against vascular endothelial growth factor and a promising therapeutic option for angiosarcoma management.This is a case report and review of the literature using bevacizumab and combination chemotherapy for angiosarcoma.The understanding of the effectiveness of combined therapy of bevacizumab and chemotherapy agents is still limited.The benefits of bevacizumab treatment for angiosarcoma will need to be weighed against the risks of venous thromboembolism in this population.

  18. Treatment of 180 Cases of Adhesive Shoulder Periarthritis by Combined Therapy

    Institute of Scientific and Technical Information of China (English)

    WU Qiao-ling; KUAI Le

    2007-01-01

    One hundred and eighty patients of shoulder periarthritis were treated by combined traction, acupuncture, physiotherapy, Tuina and functional exercise. After 10 treatments, 133 cases were cured, 36 cases got marked effectiveness, 8 cases got effectiveness, 3 cases had no effectiveness and the total effective rate was 98.3%. Combined therapy can relieve adhesion of soft tissues induced by various causes to achieve the purpose of accelerating recovery.

  19. A Systematic Review of the Combined Use of Electroconvulsive Therapy and Psychotherapy for Depression

    Science.gov (United States)

    McClintock, Shawn M.; Brandon, Anna R.; Husain, Mustafa M.; Jarrett, Robin B.

    2011-01-01

    Objective Electroconvulsive therapy (ECT) is one of the most effective treatments for severe Major Depressive Disorder (MDD). However, after acute phase treatment and initial remission, relapse rates are significant. Strategies to prolong remission include continuation phase ECT, pharmacotherapy, psychotherapy, or their combinations. This systematic review synthesizes extant data regarding the combined use of psychotherapy with ECT for the treatment of patients with severe MDD and offers the hypothesis that augmenting ECT with depression-specific psychotherapy represents a promising strategy for future investigation. Methods The authors performed two independent searches in PsychInfo (1806 – 2009) and MEDLINE (1948 – 2009) using combinations of the following search terms: Electroconvulsive Therapy (including ECT, ECT therapy, electroshock therapy, EST, shock therapy) and Psychotherapy (including cognitive behavioral, interpersonal, group, psychodynamic, psychoanalytic, individual, eclectic, and supportive). We included in this review a total of six articles (English language) that mentioned ECT and psychotherapy in the abstract, and provided a case report, series, or clinical trial. We examined the articles for data related to ECT and psychotherapy treatment characteristics, cohort characteristics, and therapeutic outcome. Results Although research over the past seven decades documenting the combined use of ECT and psychotherapy is limited, the available evidence suggests that testing this combination has promise and may confer additional, positive functional outcomes. Conclusions Significant methodological variability in ECT and psychotherapy procedures, heterogeneous patient cohorts, and inconsistent outcome measures prevent strong conclusions; however, existing research supports the need for future investigations of combined ECT and psychotherapy in well-designed, controlled clinical studies. Depression-specific psychotherapy approaches may need special

  20. Clinical Observation on Treatment of Cervical Spondylosis with Combined Acupuncture and Cupping Therapies

    Institute of Scientific and Technical Information of China (English)

    万学文

    2007-01-01

    目的:观察针刺结合拔罐治疗颈椎病的临床疗效.方法:针罐组(30例)采用针刺结合拔罐治疗,针刺组(30例)采用单纯针刺治疗,治疗30天观察疗效.结果:两组治愈率、总有效率、半年后复发率、平均疗程经χ2检验P<0.01两组有显著性差异.结论:针刺结合拔罐治疗颈椎病疗效好,疗程短,不易复发.%Objective: To observe the clinical efficacy of treating cervical spondylosis with combined acupuncture and cupping therapies. Method: The patients in the treatment group (30 cases) were treated with combined acupuncture and cupping therapies; and the patients in the control group (30 cases) were treated with acupuncture therapy alone. Then the clinical efficacy was observed after 30 days of treatment. Result: The χ2 test showed that there was significant difference (P<0.01) between the two groups in recovery rate, total effective rate, relapse rate after six months, and average treatment course. Conclusion: Combined acupuncture and cupping therapies is a better therapy for cervical spondylosis with a shorter treatment course and low relapse rate.

  1. Potential Benefits of Combination Therapy as Primary Treatment for Sudden Sensorineural Hearing Loss.

    Science.gov (United States)

    Lee, Jong Bin; Choi, Seong Jun

    2016-02-01

    We analyzed the effectiveness of combination therapy (CT) for idiopathic sudden sensorineural hearing loss (ISSNHL) and the utility of intratympanic dexamethasone injection (ITDI) reapplication as salvage treatment for ISSNHL refractory to CT. Case series with chart review. Academic university hospital. We reviewed 229 patients with ISSNHL and divided these patients into 2 groups according to treatment: systemic steroid therapy (SST) and CT groups. The SST group received prednisolone therapy. The CT group also received ITDI daily. Patients who demonstrated no recovery (Hearing recovery rates were 77.8% (77/99) in the CT group and 60.8% (79/130) in the SST group. The difference was statistically significant (P = .011). Initial pure-tone audiometry and vertigo were affective factors on hearing recovery rates in the CT group. After salvage therapy, hearing improvement of 10 dB or greater was noted in 6 of the 22 (27.3%) patients in the CT group and 16 of the 51 (31.4%) patients in the SST group. The difference in efficacy of salvage therapy between the CT and SST groups was simply not significant (P = .612). Combination therapy was more effective for ISSNHL in achieving hearing gain than SST alone. Furthermore, ITDI reapplication for ISSNHL refractory to CT was as effective as salvage ITDI for ISSNHL refractory to SST. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  2. External beam re-irradiation, combination chemoradiotherapy, and particle therapy for the treatment of recurrent glioblastoma

    Science.gov (United States)

    Taunk, Neil K.; Moraes, Fabio Y.; Escorcia, Freddy E.; Mendez, Lucas Castro; Beal, Kathryn; Marta, Gustavo N.

    2016-01-01

    SUMMARY Glioblastoma is a common aggressive primary malignant brain tumor, and is nearly universal in progression and mortality after initial treatment. Re-irradiation presents a promising treatment option for progressive disease, both palliating symptoms and potentially extending survival. Highly conformal radiation techniques such as stereotactic radiosurgery and hypofractionated radiosurgery are effective short courses of treatment that allow delivery of high doses of therapeutic radiation with steep dose gradients to protect normal tissue. Patients with higher performance status, younger age, and longer interval between primary treatment and progression represent the best candidates for re-irradiation. Multiple studies are also underway involving combinations of radiation and systemic therapy to bend the survival curve and improve the therapeutic index. In the multimodal treatment of recurrent high-grade glioma, the use of surgery, radiation, and systemic therapy should be highly individualized. Here we comprehensively review radiation therapy and techniques, along with discussion of combination treatment and novel strategies. PMID:26781426

  3. Photodynamic therapy combined with distant gamma-ray therapy in the patient with squamous cell carcinoma of the skin

    Directory of Open Access Journals (Sweden)

    V. L. Filinov

    2015-01-01

    Full Text Available Results of clinical follow-up of the patient with squamous cell skin carcinoma of the nasal dorsum are represented. The patient underwent a course of combined photodynamic therapy (PDT with distant gamma-ray therapy. Distant gamma-ray therapy was performed daily during 12 days (single dose of 3 Gy, total dose of 36 Gy with the first session 24 h after injection of the photosensitization. For PDT the photosensitizer photosens at dose of 0,3 mg/kg was used. The method of prolonged PDT was applied, sessions of laser irradiation were performed daily during 7 days. The PDT sessions were carried out 2 h after session of gamma-ray therapy using distant (150 J/cm2, 40 mW/cm2 and contact (500 J/cm2, 100 mW/cm2 modalities. According to multiple cytological studies after treatment there were no signs of tumor, but inflammation. Four months after treatment according to cytological data continued tumor growth was detected. The patient underwent an additional course of PDT. Currently the patient is under follow-up: no recurrence during 8 months after repeated treatment. 

  4. T Cell Subsets in HIV Infected Patients after Successful Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Rönsholt, Frederikke F; Ostrowski, Sisse Rye; Katzenstein, Terese Lea;

    2012-01-01

    Immune activation is decreased by combination antiretroviral therapy (cART) in patients infected with human immunodeficiency virus (HIV), but residual activation remains and has been proposed as a cause of premature aging and death, but data are lacking. We analyzed the relationship between T...

  5. Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Sterne, Jonathan A C; Egger, Matthias

    2009-01-01

    BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started...

  6. Antiresorptives and anabolic therapy in sequence or combination for postmenopausal osteoporosis.

    Science.gov (United States)

    Palacios, S; Mejía, A

    2015-01-01

    Osteoporosis is a chronic disease which may require treatment for many years and requires not only individual management but often sequential or combination treatments. Monotherapy with antiresorptives is usually the first choice. Sometimes, it is necessary to modify this option for therapeutic failure or for the time of use and risk of side-effects. Due to their different mode of action, therapy with anabolic drugs has increased our options in the treatment of osteoporosis. Postmenopausal women and men with severe and progressive osteoporosis despite antiresorptive treatment ('therapeutic failure') should be evaluated for treatment with an anabolic option. Moreover, anabolic agents are indicated for 18-24 months in patients at high risk. Then, sequential antiresorptive therapy is recommended to maintain drug increases in bone mass and support secondary mineralization of the newly formed bone. Combination therapies of antiresorptives and anabolic agents have shown a significant increase in bone mineral density compared to monotherapies. However, none of the combinations have been studied for the prevention of fractures. Combination therapy may not be recommended because of the possible increase in cost.

  7. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

    NARCIS (Netherlands)

    Lodi, Sara; Del Amo, Julia; Moreno, Santiago; Bucher, Heiner C.; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Olson, Ashley; Van Sighem, Ard; Reiss, Peter; Sabin, Caroline; Jose, Sophie; Justice, Amy; Goulet, Joseph; Miró, José M.; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Vourli, Georgia; Antoniadou, Anastasia; Dabis, Francois; Vandenhede, Mari-Anne; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A.; Hernan, Miguel; Bansi, L.; Hill, T.; Sabin, C.; Dunn, D.; Porter, K.; Glabay, A.; Orkin, C.; Thomas, R.; Jones, K.; Fisher, M.; Perry, N.; Pullin, A.; Churchill, D.; Gazzard, B.; Nelson, M.; Asboe, D.; Bulbeck, S.; Mandalia, S.; Clarke, J.; Delpech, V.; Anderson, J.; Munshi, S.; Post, F.; Easterbrook, P.; Khan, Y.; Patel, P.; Karim, F.; Duffell, S.; Gilson, R.; Man, S.-L.; Williams, I.; Gompels, M.; Dooley, D.; Schwenk, A.; Ainsworth, J.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Ismajani Puradiredja, D.; Bansi, L.; Hill, T.; Phillips, A.; Sabin, C.; Walsh, J.; Weber, J.; Kemble, C.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Bezemer, D.O.; Gras, L.A.J.; Kesselring, A.M.; Van Sighem, A.I.; Zaheri, S.; Van Twillert, G.; Kortmann, W.; Branger, J.; Prins, J.M.; Kuijpers, T.W.; Scherpbier, H.J.; Van Der Meer, J.T.M.; Wit, F.W.M.N.; Godfried, M.H.; Reiss, P.; Van Der Poll, T.; Nellen, F.J.B.; Lange, J.M.A.; Geerlings, S.E.; Van Vugt, M.; Pajkrt, D.; Bos, J.C.; van der Valk, M.; Grijsen, M.L.; Wiersinga, W.J.; Brinkman, K.; Blok, W.L.; Frissen, P.H.J.; Schouten, W.E.M.; Van Den Berk, G.E.L.; Veenstra, J.; Lettinga, K.D.; Mulder, J.W.; Vrouenraets, S.M.E.; Lauw, F.N.; Van Eeden, A.; Verhagen, D.W.M.; Van Agtmael, M.A.; Perenboom, R.M.; Claessen, F.A.P.; Bomers, M.; Peters, E.J.G.; Richter, C.; Van Der Berg, J.P.; Gisolf, E.H.; Schippers, E.F.; Van Nieuwkoop, C.; Van Elzakker, E.P.; Leyten, E.M.S.; Gelinck, L.B.S.; Pronk, M.J.H.; Bravenboer, B.; Kootstra, G.J.; Delsing, C.E.; Sprenger, H.G.; Doedens, R.; Scholvinck, E.H.; Van Assen, S.; Bierman, W.F.W.; Soetekouw, R.; Ten Kate, R.W.; Van Vonderen, M.G.A.; Van Houte, D.P.F.; Kroon, F.P.; Van Dissel, J.T.; Arend, S.M.; De Boer, M.G.J.; Jolink, H.; Ter Vollaard, H.J.M.; Bauer, M.P.; Weijer, S.; El Moussaoui, R.; Lowe, S.; Schreij, G.; Oude Lashof, A.; Posthouwer, D.; Koopmans, P.P.; Keuter, M.; Van Der Ven, A.J.A.M.; Ter Hofstede, H.J.M.; Dofferhoff, A.S.M.; Warris, A.; Van Crevel, R.; van der Ende, Marchina E.; De Vries-Sluijs, T.E.M.S.; Schurink, C.A.M.; Nouwen, J.L.; Nispen Tot Pannerden, M.H.; Verbon, A.; Rijnders, B.J.A.; Van Gorp, E.C.M.; Hassing, R.J.; Smeulders, A.W.M.; Hartwig, N.G.; Driessen, G.J.A.; Den Hollander, J.G.; Pogany, K.; Juttmann, J.R.; Van Kasteren, M.E.E.; Hoepelman, A.I.M.; Mudrikova, T.; Schneider, M.M.E.; Jaspers, C.A.J.J.; Ellerbroek, P.M.; Oosterheert, J.J.; Arends, J.E.; Wassenberg, M.W.M.; Barth, R.E.; Geelen, S.P.M.; Wolfs, T.F.W.; Bont, L.J.; Van Den Berge, M.; Stegeman, A.; Groeneveld, P.H.P.; Alleman, M.A.; Bouwhuis, J.W.; Barin, F.; Burty, C.; Duvivier, C.; Enel, P.; Fredouille-Heripret, L.; Gasnault, J.; Khuong, M.A.; Mahamat, A.; Pilorgé, F.; Tattevin, P.; Salomon, Valérie; Jacquemet, N.; Abgrall, S.; Costagliola, D.; Grabar, S.; Guiguet, M.; Lanoy, E.; Lièvre, L.; Mary-Krause, M.; Selinger-Leneman, H.; Lacombe, J.M.; Potard, V.; Bricaire, F.; Herson, S.; Katlama, C.; Simon, A.; Desplanque, N.; Girard, P.M.; Meynard, J.L.; Meyohas, M.C.; Picard, O.; Cadranel, J.; Mayaud, C.; Pialoux, G.; Clauvel, J.P.; Decazes, J.M.; Gerard, L.; Molina, J.M.; Diemer, M.; Sellier, P.; Bentata, M.; Honoré, P.; Jeantils, V.; Tassi, S.; Mechali, D.; Taverne, B.; Bouvet, E.; Crickx, B.; Ecobichon, J.L.; Matheron, S.; Picard-Dahan, C.; Yeni, P.; Berthé, H.; Dupont, C.; Chandemerle, C.; Mortier, E.; De Truchis, P.; Tisne-Dessus, D.; Weiss, L.; Salmon, D.; Auperin, I.; Gilquin, J.; Roudière, L.; Viard, J.P.; Boué, F.; Fior, R.; Delfraissy, J.F.; Goujard, C.; Jung, C.; Lesprit, Ph.; Vittecoq, D.; Fraisse, P.; Lang, J.M.; Rey, D.; Beck-Wirth, G.; Stahl, J.P.; Lecercq, P.; Gourdon, F.; Laurichesse, H.; Fresard, A.; Lucht, F.; Bazin, C.; Verdon, R.; Chavanet, P.; Arvieux, C.; Michelet, C.; Choutet, P.; Goudeau, A.; Maître, M.F.; Hoen, B.; Eglinger, P.; Faller, J.P.; Borsa-Lebas, F.; Caron, F.; Reynes, J.; Daures, J.P.; May, T.; Rabaud, C.; Berger, J.L.; Rémy, G.; Arlet-Suau, E.; Cuzin, L.; Massip, P.; Thiercelin Legrand, M.F.; Pontonnier, G.; Viget, N.; Yasdanpanah, Y.; Dellamonica, P.; Pradier, C.; Pugliese, P.; Aleksandrowicz, K.; Quinsat, D.; Ravaux, I.; Tissot-Dupont, H.; Delmont, J.P.; Moreau, J.; Gastaut, J.A.; Poizot-Martin, I.; Retornaz, F.; Soubeyrand, J.

    2014-01-01

    Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis,

  8. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

    NARCIS (Netherlands)

    Lodi, Sara; Del Amo, Julia; Moreno, Santiago; Bucher, Heiner C.; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Olson, Ashley; Van Sighem, Ard; Reiss, Peter; Sabin, Caroline; Jose, Sophie; Justice, Amy; Goulet, Joseph; Miró, José M.; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Vourli, Georgia; Antoniadou, Anastasia; Dabis, Francois; Vandenhede, Mari-Anne; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A.; Hernan, Miguel; Bansi, L.; Hill, T.; Sabin, C.; Dunn, D.; Porter, K.; Glabay, A.; Orkin, C.; Thomas, R.; Jones, K.; Fisher, M.; Perry, N.; Pullin, A.; Churchill, D.; Gazzard, B.; Nelson, M.; Asboe, D.; Bulbeck, S.; Mandalia, S.; Clarke, J.; Delpech, V.; Anderson, J.; Munshi, S.; Post, F.; Easterbrook, P.; Khan, Y.; Patel, P.; Karim, F.; Duffell, S.; Gilson, R.; Man, S.-L.; Williams, I.; Gompels, M.; Dooley, D.; Schwenk, A.; Ainsworth, J.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Ismajani Puradiredja, D.; Bansi, L.; Hill, T.; Phillips, A.; Sabin, C.; Walsh, J.; Weber, J.; Kemble, C.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Bezemer, D.O.; Gras, L.A.J.; Kesselring, A.M.; Van Sighem, A.I.; Zaheri, S.; Van Twillert, G.; Kortmann, W.; Branger, J.; Prins, J.M.; Kuijpers, T.W.; Scherpbier, H.J.; Van Der Meer, J.T.M.; Wit, F.W.M.N.; Godfried, M.H.; Reiss, P.; Van Der Poll, T.; Nellen, F.J.B.; Lange, J.M.A.; Geerlings, S.E.; Van Vugt, M.; Pajkrt, D.; Bos, J.C.; van der Valk, M.; Grijsen, M.L.; Wiersinga, W.J.; Brinkman, K.; Blok, W.L.; Frissen, P.H.J.; Schouten, W.E.M.; Van Den Berk, G.E.L.; Veenstra, J.; Lettinga, K.D.; Mulder, J.W.; Vrouenraets, S.M.E.; Lauw, F.N.; Van Eeden, A.; Verhagen, D.W.M.; Van Agtmael, M.A.; Perenboom, R.M.; Claessen, F.A.P.; Bomers, M.; Peters, E.J.G.; Richter, C.; Van Der Berg, J.P.; Gisolf, E.H.; Schippers, E.F.; Van Nieuwkoop, C.; Van Elzakker, E.P.; Leyten, E.M.S.; Gelinck, L.B.S.; Pronk, M.J.H.; Bravenboer, B.; Kootstra, G.J.; Delsing, C.E.; Sprenger, H.G.; Doedens, R.; Scholvinck, E.H.; Van Assen, S.; Bierman, W.F.W.; Soetekouw, R.; Ten Kate, R.W.; Van Vonderen, M.G.A.; Van Houte, D.P.F.; Kroon, F.P.; Van Dissel, J.T.; Arend, S.M.; De Boer, M.G.J.; Jolink, H.; Ter Vollaard, H.J.M.; Bauer, M.P.; Weijer, S.; El Moussaoui, R.; Lowe, S.; Schreij, G.; Oude Lashof, A.; Posthouwer, D.; Koopmans, P.P.; Keuter, M.; Van Der Ven, A.J.A.M.; Ter Hofstede, H.J.M.; Dofferhoff, A.S.M.; Warris, A.; Van Crevel, R.; van der Ende, Marchina E.; De Vries-Sluijs, T.E.M.S.; Schurink, C.A.M.; Nouwen, J.L.; Nispen Tot Pannerden, M.H.; Verbon, A.; Rijnders, B.J.A.; Van Gorp, E.C.M.; Hassing, R.J.; Smeulders, A.W.M.; Hartwig, N.G.; Driessen, G.J.A.; Den Hollander, J.G.; Pogany, K.; Juttmann, J.R.; Van Kasteren, M.E.E.; Hoepelman, A.I.M.; Mudrikova, T.; Schneider, M.M.E.; Jaspers, C.A.J.J.; Ellerbroek, P.M.; Oosterheert, J.J.; Arends, J.E.; Wassenberg, M.W.M.; Barth, R.E.; Geelen, S.P.M.; Wolfs, T.F.W.; Bont, L.J.; Van Den Berge, M.; Stegeman, A.; Groeneveld, P.H.P.; Alleman, M.A.; Bouwhuis, J.W.; Barin, F.; Burty, C.; Duvivier, C.; Enel, P.; Fredouille-Heripret, L.; Gasnault, J.; Khuong, M.A.; Mahamat, A.; Pilorgé, F.; Tattevin, P.; Salomon, Valérie; Jacquemet, N.; Abgrall, S.; Costagliola, D.; Grabar, S.; Guiguet, M.; Lanoy, E.; Lièvre, L.; Mary-Krause, M.; Selinger-Leneman, H.; Lacombe, J.M.; Potard, V.; Bricaire, F.; Herson, S.; Katlama, C.; Simon, A.; Desplanque, N.; Girard, P.M.; Meynard, J.L.; Meyohas, M.C.; Picard, O.; Cadranel, J.; Mayaud, C.; Pialoux, G.; Clauvel, J.P.; Decazes, J.M.; Gerard, L.; Molina, J.M.; Diemer, M.; Sellier, P.; Bentata, M.; Honoré, P.; Jeantils, V.; Tassi, S.; Mechali, D.; Taverne, B.; Bouvet, E.; Crickx, B.; Ecobichon, J.L.; Matheron, S.; Picard-Dahan, C.; Yeni, P.; Berthé, H.; Dupont, C.; Chandemerle, C.; Mortier, E.; De Truchis, P.; Tisne-Dessus, D.; Weiss, L.; Salmon, D.; Auperin, I.; Gilquin, J.; Roudière, L.; Viard, J.P.; Boué, F.; Fior, R.; Delfraissy, J.F.; Goujard, C.; Jung, C.; Lesprit, Ph.; Vittecoq, D.; Fraisse, P.; Lang, J.M.; Rey, D.; Beck-Wirth, G.; Stahl, J.P.; Lecercq, P.; Gourdon, F.; Laurichesse, H.; Fresard, A.; Lucht, F.; Bazin, C.; Verdon, R.; Chavanet, P.; Arvieux, C.; Michelet, C.; Choutet, P.; Goudeau, A.; Maître, M.F.; Hoen, B.; Eglinger, P.; Faller, J.P.; Borsa-Lebas, F.; Caron, F.; Reynes, J.; Daures, J.P.; May, T.; Rabaud, C.; Berger, J.L.; Rémy, G.; Arlet-Suau, E.; Cuzin, L.; Massip, P.; Thiercelin Legrand, M.F.; Pontonnier, G.; Viget, N.; Yasdanpanah, Y.; Dellamonica, P.; Pradier, C.; Pugliese, P.; Aleksandrowicz, K.; Quinsat, D.; Ravaux, I.; Tissot-Dupont, H.; Delmont, J.P.; Moreau, J.; Gastaut, J.A.; Poizot-Martin, I.; Retornaz, F.; Soubeyrand, J.; Galinier, A.; Ruiz, J.M.; Allegre, T.; Blanc, P.A.; Bonnet-Montchardon, D.; Lepeu, G.; Granet-Brunello, P.; Esterni, J.P.; Pelissier, L.; Cohen-Valensi, R.; Nezri, M.; Chadapaud, S.; Laffeuillade, A.; Billaud, E.; Raffi, F.; Boibieux, A.; Peyramond, D.; Livrozet, J.M.; Touraine, J.L.; Cotte, L.; Trepo, C.; Strobel, M.; Bissuel, F.; Pradinaud, R.; Sobesky, M.; Cabié, A.; Gaud, C.; Contant, M.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Haerry, D.; Fux, C.A.; Gorgievski, M.; Günthard, H.; Hasse, B.; Hirsch, H.H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez De Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.; Casabona, J.; Gallois, A.; Esteve, A.; Podzamczer, D.; Murillas, J.; Gatell, J.M.; Manzardo, C.; Tural, C.; Clotet, B.; Ferrer, E.; Riera, M.; Segura, F.; Navarro, G.; Force, L.; Vilaró, J.; Masabeu, A.; García, I.; Guadarrama, M.; Cifuentes, C.; Dalmau, D.; Jaen, À.; Agustí, C.; Montoliu, A.; Pérez, I.; Gargoulas, Freyra; Blanco, J.L.; Garcia-Alcaide, F.; Martínez, E.; Mallolas, J.; López-Dieguez, M.; García-Goez, J.F.; Sirera, G.; Romeu, J.; Jou, A.; Negredo, E.; Miranda, C.; Capitan, M.C.; Saumoy, M.; Imaz, A.; Tiraboschi, J.M.; Murillo, O.; Bolao, F.; Peña, C.; Cabellos, C.; Masó, M.; Vila, A.; Sala, M.; Cervantes, M.; Jose Amengual, Ma.; Navarro, M.; Penelo, E.; Barrufet, P.; Bejarano, G.; Molina, J.; Guadarrama, M.; Alvaro, M.; Mercadal, J.; Fernandez, Juanse; Ospina, Jesus E.; Muñoz, M.A.; Caro-Murillo, A.M.; Sobrino, P.; Jarrín, I.; Gomez Sirvent, J.L.; Rodríguez, P.; Aleman, M.R.; Alonso, M.M.; Lopez, A.M.; Hernandez, M.I.; Soriano, V.; Labarga, P.; Barreiro, P.; Medrano, J.; Rivas, P.; Herrero, D.; Blanco, F.; Vispo, M.E.; Martín, L.; Ramírez, G.; De Diego, M.; Rubio, R.; Pulido, F.; Moreno, V.; Cepeda, C.; Hervás, Rl.; Iribarren, J.A.; Arrizabalaga, J.; Aramburu, M.J.; Camino, X.; Rodrí-guez-Arrondo, F.; Von Wichmann, M.A.; Pascual, L.; Goenaga, M.A.; Gutierrez, F.; Masia, M.; Ramos, J.M.; Padilla, S.; Sanchez-Hellín, V.; Bernal, E.; Escolano, C.; Montolio, F.; Peral, Y.; Berenguer, J.; Lopez, J.C.; Miralles, P.; Cosín, J.; Sanchez, M.; Gutierrez, I.; Ramírez, M.; Padilla, B.; Vidal, F.; Sanjuan, M.; Peraire, J.; Veloso, S.; Vilades, C.; Lopez-Dupla, M.; Olona, M.; Vargas, M.; Aldeguer, J.L.; Blanes, M.; Lacruz, J.; Salavert, M.; Montero, M.; Cuéllar, S.; De Los Santos, I.; Sanz, J.; Oteo, J.A.; Blanco, J.R.; Ibarra, V.; Metola, L.; Sanz, M.; Pérez-Martínez, L.; Sola, J.; Uriz, J.; Castiello, J.; Reparaz, J.; Arriaza, M.J.; Irigoyen, C.; Moreno, S.; Antela, A.; Casado, J.L.; Dronda, F.; Moreno, A.; Pérez, M.J.; López, D.; Gutiérrez, C.; Hernández, B.; Pumares, M.; Martí, P.; García, L.; Page, C.; García, F.; Hernández, J.; Peña, A.; Muñoz, L.; Parra, J.; Viciana, P.; Leal, M.; López-Cortés, L.F.; Trastoy, M.; Mata, R.; Justice, A.C.; Fiellin, D.A.; Rimland, D.; Jones-Taylor, C.; Oursler, K.A.; Titanji, R.; Brown, S.; Garrison, S.; Rodriguez-Barradas, M.; Masozera, N.; Goetz, M.; Leaf, D.; Simberkoff, M.; Blumenthal, D.; Leung, J.; Butt, A.; Hoffman, E.; Gibert, C.; Peck, R.; Mattocks, K.; Braithwaite, S.; Brandt, C.; Bryant, K.; Cook, R.; Conigliaro, J.; Crothers, K.; Chang, J.; Crystal, S.; Day, N.; Erdos, J.; Freiberg, M.; Kozal, M.; Gandhi, N.; Gaziano, M.; Gerschenson, M.; Good, B.; Gordon, A.; Goulet, J.L.; Hernán, M.A.; Kraemer, K.; Lim, J.; Maisto, S.; Miller, P.; Mole, L.; O'Connor, P.; Papas, R.; Robins, J.M.; Rinaldo, C.; Roberts, M.; Samet, J.; Tierney, B.; Whittle, J.; Babiker, A.; Brettle, R.; Darbyshire, J.; Gilson, R.; Goldberg, D.; Hawkins, D.; Jaffe, H.; Johnson, A.; McLean, K.; Pillay, D.; Cursley, Adam; Ewings, Fiona; Fairbrother, Keith; Louisa Gnatiuc, S.L.; Murphy, Brendan; Douglas, G.; Kennedy, N.; Pritchard, J.; Andrady, U.; Rajda, N.; Maw, R.; McKernan, S.; Drake, S.; Gilleran, G.; White, D.; Ross, J.; Toomer, S.; Hewart, R.; Wilding, H.; Woodward, R.; Dean, G.; Heald, L.; Horner, P.; Glover, S.; Bansaal, D.; Eduards, S.; Carne, C.; Browing, M.; Das, R.; Stanley, B.; Estreich, S.; Magdy, A.; O'Mahony, C.; Fraser, P.; Hayman, B.; Jebakumar, S.P.R.; Joshi, U.; Ralph, S.; Wade, A.; Mette, R.; Lalik, J.; Summerfield, H.; El-Dalil, A.; France, J.A.; White, C.; Robertson, R.; Gordon, S.; McMillan, S.; Morris, S.; Lean, C.; Vithayathil, K.; McLean, L.; Winter, A.; Gale, D.; Jacobs, S.; Tayal, S.; Short, L.; Roberts, M.; Green, S.; Williams, G.; Sivakumar, K.; Bhattacharyya, N.D.; Monteiro, E.; Minton, J.; Dhar, J.; Nye, F.; De Souza, C.B.; Isaksen, A.; McDonald, L.; McLean, K.; Franca, A.; Hawkins, D.; William, L.; Jendrulek, I.; Peters, B.; Shaunak, S.; El-Gadi, S.; Easterbrook, P.J.; Mazhude, C.; Gilson, R.; Johnstone, R.; Fakoya, A.; McHale, J.; Waters, A.; Kegg, S.; Mitchell, S.; Byrne, P.; Johnson, M.; Rice, P.; Fidler, S.; Mullaney, S.A.; McCormack, S.; David, D.; Melville, R.; Phillip, K.; Balachandran, T.; Mabey-Puttock, S.; Sukthankar, A.; Murphy, C.; Wilkins, E.; Ahmad, S.; Tayal, S.; Haynes, J.; Evans, E.; Ong, E.; Das, R.; Grey, R.; Meaden, J.; Bignell, C.; Loay, D.; Peacock, K.; Girgis, M.R.; Morgan, B.; Palfreeman, A.; Wilcox, J.; Tobin, J.; Tucker, L.; Saeed, A.M.; Chen, F.; Deheragada, A.; Williams, O.; Lacey, H.; Herman, S.; Kinghorn, D.; Devendra, V.S.; Wither, J.; Dawson, S.; Rowen, D.; Harvey, J.; Wilkins, E.; Bridgwood, A.; Singh, G.; Chauhan, M.; Kellock, D.; Young, S.; Dannino, S.; Kathir, Y.; Rooney, G.; Currie, J.; Fitzgerald, M.; Devendra, S.; Keane, F.; Booth, G.; Green, T.; Arumainayyagam, J.; Chandramani, S.; Rajamanoharan, S.; Robinson, T.; Curless, E.; Gokhale, R.; Tariq, A.; Roberts, M.; Williams, O.; Luzzi, G.; FitzGerald, M.; Fairley, I.; Wallis, F.; Smit, E.; Ward, F.; Molina, J.M.; Loze, B.; Morlat, P.; Bonarek, M.; Bonnet, F.; Nouts, C.; Louis, I.; Raffi, F.; Reliquet, V.; Sauser, F.; Biron, C.; Mounoury, O.; Hue, H.; Brosseau, D.; Delfraissy, J.F.; Goujard, C.; Ghosn, J.; Rannou, M.T.; Bergmann, J.F.; Badsi, E.; Rami, A.; Diemer, M.; Parrinello, M.; Girard, P.M.; Samanon-Bollens, D.; Campa, P.; Tourneur, M.; Desplanques, N.; Livrozet, J.M.; Jeanblanc, F.; Chiarello, P.; Makhloufi, D.; Blanc, A.P.; Allègre, T.; Reynes, J.; Baillat, V.; Lemoing, V.; Merle De Boever, C.; Tramoni, C.; Cabié, A.; Sobesky, G.; Abel, S.; Beaujolais, V.; Pialoux, G.; Slama, L.; Chakvetadze, C.; Berrebi, V.; Yeni, P.; Bouvet, E.; Fournier, I.; Gerbe, J.; Trepo, C.; Koffi, K.; Augustin-Normand, C.; Miailhes, P.; Thoirain, V.; Brochier, C.; Thomas, R.; Souala, F.; Ratajczak, M.; Beytoux, J.; Jacomet, C.; Gourdon, F.; Rouveix, E.; Morelon, S.; Dupont, C.; Olivier, C.; Lortholary, O.; Dupont, B.; Viard, J.P.; Maignan, A.; Ragnaud, J.M.; Raymond, I.; Leport, C.; Jadand, C.; Jestin, C.; Longuet, P.; Boucherit, S.; Sereni, D.; Lascoux, C.; Prevoteau, F.; Sobel, A.; Levy, Y.; Lelièvre, J.D.; Lascaux, A.S.; Dominguez, S.; Dumont, C.; Aumâitre, H.; Delmas, B.; Saada, M.; Medus, M.; Guillevin, L.; Salmon, D.; Tahi, T.; Yazdanpanah, Y.; Pavel, S.; Marien, M.C.; Drenou, B.; Beck-Wirth, G.; Beck, C.; Benomar, M.; Katlama, C.; Tubiana, R.; Ait Mohand, H.; Chermak, A.; Ben Abdallah, S.; Bentata, M.; Touam, F.; Hoen, B.; Drobacheff, C.; Folzer, A.; Massip, P.; Obadia, M.; Prudhomme, L.; Bonnet, E.; Balzarin, F.; Pichard, E.; Chennebault, J.M.; Fialaire, P.; Loison, J.; Galanaud, P.; Boué, F.; Bornarel, D.; Verdon, R.; Bazin, C.; Six, M.; Ferret, P.; Weiss, L.; Batisse, D.; Gonzales-Canali, G.; Tisne-Dessus, D.; Devidas, A.; Chevojon, P.; Turpault, I.; Lafeuillade, A.; Cheret, A.; Philip, G.; Morel, P.; Timsit, J.; Herson, S.; Amirat, N.; Simon, A.; Brancion, C.; Cabane, J.; Picard, O.; Tredup, J.; Stein, A.; Ravault, I.; Chavanet, C.; Buisson, M.; Treuvetot, S.; Choutet, P.; Nau, P.; Bastides, F.; May, T.; Boyer, L.; Wassoumbou, S.; Oksenhendeler, E.; Gérard, L.; Bernard, L.; De Truchis, P.; Berthé, H.; Domart, Y.; Merrien, D.; Greder Belan, A.; Gayraud, M.; Bodard, L.; Meudec, A.; Beuscart, C.; Daniel, C.; Pape, E.; Vinceneux, P.; Simonpoli, A.M.; Zeng, A.; Fournier, L.; Fuzibet, J.G.; Sohn, C.; Rosenthal, E.; Quaranta, M.; Dellamonica, P.; Chaillou, S.; Sabah, M.; Audhuy, B.; Schieber, A.; Moreau, P.; Niault, M.; Vaillant, O.; Huchon, G.; Compagnucci, A.; De Lacroix Szmania, I.; Richier, L.; Lamaury, I.; Saint-Dizier, F.; Garipuy, D.; Gastaut, J.A.; Drogoul, M.P.; Poizot Martin, I.; Fabre, G.; Lambert De Cursay, G.; Abraham, B.; Perino, C.; Lagarde, P.; David, F.; Roche-Sicot, J.; Saraux, J.L.; Leprêtre, A.; Fampin, B.; Uludag, A.; Morin, A.S.; Bletry, O.; Zucman, D.; Regnier, A.; Girard, J.J.; Quinsat, D.T.; Heripret, L.; Grihon, F.; Houlbert, D.; Ruel, M.; Chemlal, K.; Caron, F.; Debab, Y.; Tremollieres, F.; Perronne, V.; Lepeu, G.; Slama, B.; Perré, P.; Miodovski, C.; Guermonprez, G.; Dulioust, A.; Boudon, P.; Malbec, D.; Patey, O.; Semaille, C.; Deville, J.; Remy, G.; Béguinot, I.; Galanaud, P.; Boue, F.; Chambrin, V.; Pignon, C.; Estocq, G.A.; Levy, A.; Delfraissy, J.F.; Goujard, C.; Duracinsky, M.; Le Bras, P.; Ngussan, M.S.; Peretti, D.; Medintzeff, N.; Lambert, T.; Segeral, O.; Lezeau, P.; Laurian, Y.; Weiss, L.; Buisson, M.; Piketty, C.; Karmochkine, M.; Batisse, D.; Eliaszewitch, M.; Jayle, D.; Tisne-Dessus, D.; Kazatchkine, M.; Leport, C.; Colasante, U.; Jadand, C.; Jestin, C.; Duval, X.; Nouaouia, W.; Boucherit, S.; Vilde, J.L.; Girard, P.M.; Bollens, D.; Binet, D.; Diallo, B.; Meyohas, M.C.; Fonquernie, L.; Lagneau, J.L.; Salmon, D.; Guillevin, L.; Tahi, T.; Launay, O.; Pietrie, M.P.; Sicard, D.; Stieltjes, N.; Michot, J.; Sobel, A.; Levy, Y.; Bourdillon, F.; Lascaux, A.S.; Lelievre, J.D.; Dumont, C.; Dupont, B.; Obenga, G.; Viard, J.P.; Maignan, A.; Vittecoq, D.; Escaut, L.; Bolliot, C.; Bricaire, F.; Katlama, C.; Schneider, L.; Herson, S.; Simon, A.; Iguertsira, M.; Stein, A.; Tomei, C.; Ravaux, I.; Dhiver, C.; Tissot Dupont, H.; Vallon, A.; Gallais, J.; Gallais, H.; Gastaut, J.A.; Drogoul, M.P.; Fabre, G.; Dellamonica, P.; Durant, J.; Mondain, V.; Perbost, I.; Cassuto, J.P.; Karsenti, J.M.; Venti, H.; Fuzibet, J.G.; Rosenthal, E.; Ceppi, C.; Quaranta, M.; Krivitsky, J.A.; Bentata, M.; Bouchaud, O.; Honore, P.; Sereni, D.; Lascoux, C.; Delgado, J.; Rouzioux, C.; Burgard, M.; Boufassa, L.; Peynet, J.; Pérez-Hoyos, S.; Del Amo, J.; Alvarez, D.; Monge, S.; Muga, R.; Sanvisens, A.; Clotet, B.; Tor, J.; Bolao, F.; Rivas, I.; Vallecillo, G.; Del Romero, J.; Raposo, P.; Rodríguez, C.; Vera, M.; Hurtado, I.; Belda, J.; Fernandez, E.; Alastrue, I.; Santos, C.; Tasa, T.; Juan, A.; Trullen, J.; Garcia De Olalla, P.; Cayla, J.; Masdeu, E.; Knobel, H.; Mirò, J.M.; Sambeat, M.A.; Guerrero, R.; Rivera, E.; Guerrero, R.; Marco, A.; Quintana, M.; Gonzalez, C.; Castilla, J.; Guevara, M.; De Mendoza, C.; Zahonero, N.; Ortíz, M.; Paraskevis, D.; Touloumi, G.; Pantazis, N.; Bakoyannis, G.; Gioukari, V.; Antoniadou, A.; Papadopoulos, A.; Petrikkos, G.; Daikos, G.; Psichogiou, M.; Gargalianos-Kakolyris, P.; Xylomenos, G.; Katsarou, O.; Kouramba, A.; Ioannidou, P.; Kordossis, T.; Kontos, A.; Lazanas, M.; Chini, M.; Tsogas, N.; Panos, G.; Paparizos, V.; Leuow, K.; Kourkounti, S.; Sambatakou, H.; Mariolis, I.; Skoutelis, A.; Papastamopoulos, V.; Baraboutis, I.

    2014-01-01

    Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacteri

  9. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

    NARCIS (Netherlands)

    Lodi, Sara; Del Amo, Julia; Moreno, Santiago; Bucher, Heiner C.; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Olson, Ashley; Van Sighem, Ard; Reiss, Peter; Sabin, Caroline; Jose, Sophie; Justice, Amy; Goulet, Joseph; Miró, José M.; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Vourli, Georgia; Antoniadou, Anastasia; Dabis, Francois; Vandenhede, Mari-Anne; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A.; Hernan, Miguel; Bansi, L.; Hill, T.; Sabin, C.; Dunn, D.; Porter, K.; Glabay, A.; Orkin, C.; Thomas, R.; Jones, K.; Fisher, M.; Perry, N.; Pullin, A.; Churchill, D.; Gazzard, B.; Nelson, M.; Asboe, D.; Bulbeck, S.; Mandalia, S.; Clarke, J.; Delpech, V.; Anderson, J.; Munshi, S.; Post, F.; Easterbrook, P.; Khan, Y.; Patel, P.; Karim, F.; Duffell, S.; Gilson, R.; Man, S.-L.; Williams, I.; Gompels, M.; Dooley, D.; Schwenk, A.; Ainsworth, J.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Ismajani Puradiredja, D.; Bansi, L.; Hill, T.; Phillips, A.; Sabin, C.; Walsh, J.; Weber, J.; Kemble, C.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Bezemer, D.O.; Gras, L.A.J.; Kesselring, A.M.; Van Sighem, A.I.; Zaheri, S.; Van Twillert, G.; Kortmann, W.; Branger, J.; Prins, J.M.; Kuijpers, T.W.; Scherpbier, H.J.; Van Der Meer, J.T.M.; Wit, F.W.M.N.; Godfried, M.H.; Reiss, P.; Van Der Poll, T.; Nellen, F.J.B.; Lange, J.M.A.; Geerlings, S.E.; Van Vugt, M.; Pajkrt, D.; Bos, J.C.; van der Valk, M.; Grijsen, M.L.; Wiersinga, W.J.; Brinkman, K.; Blok, W.L.; Frissen, P.H.J.; Schouten, W.E.M.; Van Den Berk, G.E.L.; Veenstra, J.; Lettinga, K.D.; Mulder, J.W.; Vrouenraets, S.M.E.; Lauw, F.N.; Van Eeden, A.; Verhagen, D.W.M.; Van Agtmael, M.A.; Perenboom, R.M.; Claessen, F.A.P.; Bomers, M.; Peters, E.J.G.; Richter, C.; Van Der Berg, J.P.; Gisolf, E.H.; Schippers, E.F.; Van Nieuwkoop, C.; Van Elzakker, E.P.; Leyten, E.M.S.; Gelinck, L.B.S.; Pronk, M.J.H.; Bravenboer, B.; Kootstra, G.J.; Delsing, C.E.; Sprenger, H.G.; Doedens, R.; Scholvinck, E.H.; Van Assen, S.; Bierman, W.F.W.; Soetekouw, R.; Ten Kate, R.W.; Van Vonderen, M.G.A.; Van Houte, D.P.F.; Kroon, F.P.; Van Dissel, J.T.; Arend, S.M.; De Boer, M.G.J.; Jolink, H.; Ter Vollaard, H.J.M.; Bauer, M.P.; Weijer, S.; El Moussaoui, R.; Lowe, S.; Schreij, G.; Oude Lashof, A.; Posthouwer, D.; Koopmans, P.P.; Keuter, M.; Van Der Ven, A.J.A.M.; Ter Hofstede, H.J.M.; Dofferhoff, A.S.M.; Warris, A.; Van Crevel, R.; van der Ende, Marchina E.; De Vries-Sluijs, T.E.M.S.; Schurink, C.A.M.; Nouwen, J.L.; Nispen Tot Pannerden, M.H.; Verbon, A.; Rijnders, B.J.A.; Van Gorp, E.C.M.; Hassing, R.J.; Smeulders, A.W.M.; Hartwig, N.G.; Driessen, G.J.A.; Den Hollander, J.G.; Pogany, K.; Juttmann, J.R.; Van Kasteren, M.E.E.; Hoepelman, A.I.M.; Mudrikova, T.; Schneider, M.M.E.; Jaspers, C.A.J.J.; Ellerbroek, P.M.; Oosterheert, J.J.; Arends, J.E.; Wassenberg, M.W.M.; Barth, R.E.; Geelen, S.P.M.; Wolfs, T.F.W.; Bont, L.J.; Van Den Berge, M.; Stegeman, A.; Groeneveld, P.H.P.; Alleman, M.A.; Bouwhuis, J.W.; Barin, F.; Burty, C.; Duvivier, C.; Enel, P.; Fredouille-Heripret, L.; Gasnault, J.; Khuong, M.A.; Mahamat, A.; Pilorgé, F.; Tattevin, P.; Salomon, Valérie; Jacquemet, N.; Abgrall, S.; Costagliola, D.; Grabar, S.; Guiguet, M.; Lanoy, E.; Lièvre, L.; Mary-Krause, M.; Selinger-Leneman, H.; Lacombe, J.M.; Potard, V.; Bricaire, F.; Herson, S.; Katlama, C.; Simon, A.; Desplanque, N.; Girard, P.M.; Meynard, J.L.; Meyohas, M.C.; Picard, O.; Cadranel, J.; Mayaud, C.; Pialoux, G.; Clauvel, J.P.; Decazes, J.M.; Gerard, L.; Molina, J.M.; Diemer, M.; Sellier, P.; Bentata, M.; Honoré, P.; Jeantils, V.; Tassi, S.; Mechali, D.; Taverne, B.; Bouvet, E.; Crickx, B.; Ecobichon, J.L.; Matheron, S.; Picard-Dahan, C.; Yeni, P.; Berthé, H.; Dupont, C.; Chandemerle, C.; Mortier, E.; De Truchis, P.; Tisne-Dessus, D.; Weiss, L.; Salmon, D.; Auperin, I.; Gilquin, J.; Roudière, L.; Viard, J.P.; Boué, F.; Fior, R.; Delfraissy, J.F.; Goujard, C.; Jung, C.; Lesprit, Ph.; Vittecoq, D.; Fraisse, P.; Lang, J.M.; Rey, D.; Beck-Wirth, G.; Stahl, J.P.; Lecercq, P.; Gourdon, F.; Laurichesse, H.; Fresard, A.; Lucht, F.; Bazin, C.; Verdon, R.; Chavanet, P.; Arvieux, C.; Michelet, C.; Choutet, P.; Goudeau, A.; Maître, M.F.; Hoen, B.; Eglinger, P.; Faller, J.P.; Borsa-Lebas, F.; Caron, F.; Reynes, J.; Daures, J.P.; May, T.; Rabaud, C.; Berger, J.L.; Rémy, G.; Arlet-Suau, E.; Cuzin, L.; Massip, P.; Thiercelin Legrand, M.F.; Pontonnier, G.; Viget, N.; Yasdanpanah, Y.; Dellamonica, P.; Pradier, C.; Pugliese, P.; Aleksandrowicz, K.; Quinsat, D.; Ravaux, I.; Tissot-Dupont, H.; Delmont, J.P.; Moreau, J.; Gastaut, J.A.; Poizot-Martin, I.; Retornaz, F.; Soubeyrand, J.; Galinier, A.; Ruiz, J.M.; Allegre, T.; Blanc, P.A.; Bonnet-Montchardon, D.; Lepeu, G.; Granet-Brunello, P.; Esterni, J.P.; Pelissier, L.; Cohen-Valensi, R.; Nezri, M.; Chadapaud, S.; Laffeuillade, A.; Billaud, E.; Raffi, F.; Boibieux, A.; Peyramond, D.; Livrozet, J.M.; Touraine, J.L.; Cotte, L.; Trepo, C.; Strobel, M.; Bissuel, F.; Pradinaud, R.; Sobesky, M.; Cabié, A.; Gaud, C.; Contant, M.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Haerry, D.; Fux, C.A.; Gorgievski, M.; Günthard, H.; Hasse, B.; Hirsch, H.H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez De Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.; Casabona, J.; Gallois, A.; Esteve, A.; Podzamczer, D.; Murillas, J.; Gatell, J.M.; Manzardo, C.; Tural, C.; Clotet, B.; Ferrer, E.; Riera, M.; Segura, F.; Navarro, G.; Force, L.; Vilaró, J.; Masabeu, A.; García, I.; Guadarrama, M.; Cifuentes, C.; Dalmau, D.; Jaen, À.; Agustí, C.; Montoliu, A.; Pérez, I.; Gargoulas, Freyra; Blanco, J.L.; Garcia-Alcaide, F.; Martínez, E.; Mallolas, J.; López-Dieguez, M.; García-Goez, J.F.; Sirera, G.; Romeu, J.; Jou, A.; Negredo, E.; Miranda, C.; Capitan, M.C.; Saumoy, M.; Imaz, A.; Tiraboschi, J.M.; Murillo, O.; Bolao, F.; Peña, C.; Cabellos, C.; Masó, M.; Vila, A.; Sala, M.; Cervantes, M.; Jose Amengual, Ma.; Navarro, M.; Penelo, E.; Barrufet, P.; Bejarano, G.; Molina, J.; Guadarrama, M.; Alvaro, M.; Mercadal, J.; Fernandez, Juanse; Ospina, Jesus E.; Muñoz, M.A.; Caro-Murillo, A.M.; Sobrino, P.; Jarrín, I.; Gomez Sirvent, J.L.; Rodríguez, P.; Aleman, M.R.; Alonso, M.M.; Lopez, A.M.; Hernandez, M.I.; Soriano, V.; Labarga, P.; Barreiro, P.; Medrano, J.; Rivas, P.; Herrero, D.; Blanco, F.; Vispo, M.E.; Martín, L.; Ramírez, G.; De Diego, M.; Rubio, R.; Pulido, F.; Moreno, V.; Cepeda, C.; Hervás, Rl.; Iribarren, J.A.; Arrizabalaga, J.; Aramburu, M.J.; Camino, X.; Rodrí-guez-Arrondo, F.; Von Wichmann, M.A.; Pascual, L.; Goenaga, M.A.; Gutierrez, F.; Masia, M.; Ramos, J.M.; Padilla, S.; Sanchez-Hellín, V.; Bernal, E.; Escolano, C.; Montolio, F.; Peral, Y.; Berenguer, J.; Lopez, J.C.; Miralles, P.; Cosín, J.; Sanchez, M.; Gutierrez, I.; Ramírez, M.; Padilla, B.; Vidal, F.; Sanjuan, M.; Peraire, J.; Veloso, S.; Vilades, C.; Lopez-Dupla, M.; Olona, M.; Vargas, M.; Aldeguer, J.L.; Blanes, M.; Lacruz, J.; Salavert, M.; Montero, M.; Cuéllar, S.; De Los Santos, I.; Sanz, J.; Oteo, J.A.; Blanco, J.R.; Ibarra, V.; Metola, L.; Sanz, M.; Pérez-Martínez, L.; Sola, J.; Uriz, J.; Castiello, J.; Reparaz, J.; Arriaza, M.J.; Irigoyen, C.; Moreno, S.; Antela, A.; Casado, J.L.; Dronda, F.; Moreno, A.; Pérez, M.J.; López, D.; Gutiérrez, C.; Hernández, B.; Pumares, M.; Martí, P.; García, L.; Page, C.; García, F.; Hernández, J.; Peña, A.; Muñoz, L.; Parra, J.; Viciana, P.; Leal, M.; López-Cortés, L.F.; Trastoy, M.; Mata, R.; Justice, A.C.; Fiellin, D.A.; Rimland, D.; Jones-Taylor, C.; Oursler, K.A.; Titanji, R.; Brown, S.; Garrison, S.; Rodriguez-Barradas, M.; Masozera, N.; Goetz, M.; Leaf, D.; Simberkoff, M.; Blumenthal, D.; Leung, J.; Butt, A.; Hoffman, E.; Gibert, C.; Peck, R.; Mattocks, K.; Braithwaite, S.; Brandt, C.; Bryant, K.; Cook, R.; Conigliaro, J.; Crothers, K.; Chang, J.; Crystal, S.; Day, N.; Erdos, J.; Freiberg, M.; Kozal, M.; Gandhi, N.; Gaziano, M.; Gerschenson, M.; Good, B.; Gordon, A.; Goulet, J.L.; Hernán, M.A.; Kraemer, K.; Lim, J.; Maisto, S.; Miller, P.; Mole, L.; O'Connor, P.; Papas, R.; Robins, J.M.; Rinaldo, C.; Roberts, M.; Samet, J.; Tierney, B.; Whittle, J.; Babiker, A.; Brettle, R.; Darbyshire, J.; Gilson, R.; Goldberg, D.; Hawkins, D.; Jaffe, H.; Johnson, A.; McLean, K.; Pillay, D.; Cursley, Adam; Ewings, Fiona; Fairbrother, Keith; Louisa Gnatiuc, S.L.; Murphy, Brendan; Douglas, G.; Kennedy, N.; Pritchard, J.; Andrady, U.; Rajda, N.; Maw, R.; McKernan, S.; Drake, S.; Gilleran, G.; White, D.; Ross, J.; Toomer, S.; Hewart, R.; Wilding, H.; Woodward, R.; Dean, G.; Heald, L.; Horner, P.; Glover, S.; Bansaal, D.; Eduards, S.; Carne, C.; Browing, M.; Das, R.; Stanley, B.; Estreich, S.; Magdy, A.; O'Mahony, C.; Fraser, P.; Hayman, B.; Jebakumar, S.P.R.; Joshi, U.; Ralph, S.; Wade, A.; Mette, R.; Lalik, J.; Summerfield, H.; El-Dalil, A.; France, J.A.; White, C.; Robertson, R.; Gordon, S.; McMillan, S.; Morris, S.; Lean, C.; Vithayathil, K.; McLean, L.; Winter, A.; Gale, D.; Jacobs, S.; Tayal, S.; Short, L.; Roberts, M.; Green, S.; Williams, G.; Sivakumar, K.; Bhattacharyya, N.D.; Monteiro, E.; Minton, J.; Dhar, J.; Nye, F.; De Souza, C.B.; Isaksen, A.; McDonald, L.; McLean, K.; Franca, A.; Hawkins, D.; William, L.; Jendrulek, I.; Peters, B.; Shaunak, S.; El-Gadi, S.; Easterbrook, P.J.; Mazhude, C.; Gilson, R.; Johnstone, R.; Fakoya, A.; McHale, J.; Waters, A.; Kegg, S.; Mitchell, S.; Byrne, P.; Johnson, M.; Rice, P.; Fidler, S.; Mullaney, S.A.; McCormack, S.; David, D.; Melville, R.; Phillip, K.; Balachandran, T.; Mabey-Puttock, S.; Sukthankar, A.; Murphy, C.; Wilkins, E.; Ahmad, S.; Tayal, S.; Haynes, J.; Evans, E.; Ong, E.; Das, R.; Grey, R.; Meaden, J.; Bignell, C.; Loay, D.; Peacock, K.; Girgis, M.R.; Morgan, B.; Palfreeman, A.; Wilcox, J.; Tobin, J.; Tucker, L.; Saeed, A.M.; Chen, F.; Deheragada, A.; Williams, O.; Lacey, H.; Herman, S.; Kinghorn, D.; Devendra, V.S.; Wither, J.; Dawson, S.; Rowen, D.; Harvey, J.; Wilkins, E.; Bridgwood, A.; Singh, G.; Chauhan, M.; Kellock, D.; Young, S.; Dannino, S.; Kathir, Y.; Rooney, G.; Currie, J.; Fitzgerald, M.; Devendra, S.; Keane, F.; Booth, G.; Green, T.; Arumainayyagam, J.; Chandramani, S.; Rajamanoharan, S.; Robinson, T.; Curless, E.; Gokhale, R.; Tariq, A.; Roberts, M.; Williams, O.; Luzzi, G.; FitzGerald, M.; Fairley, I.; Wallis, F.; Smit, E.; Ward, F.; Molina, J.M.; Loze, B.; Morlat, P.; Bonarek, M.; Bonnet, F.; Nouts, C.; Louis, I.; Raffi, F.; Reliquet, V.; Sauser, F.; Biron, C.; Mounoury, O.; Hue, H.; Brosseau, D.; Delfraissy, J.F.; Goujard, C.; Ghosn, J.; Rannou, M.T.; Bergmann, J.F.; Badsi, E.; Rami, A.; Diemer, M.; Parrinello, M.; Girard, P.M.; Samanon-Bollens, D.; Campa, P.; Tourneur, M.; Desplanques, N.; Livrozet, J.M.; Jeanblanc, F.; Chiarello, P.; Makhloufi, D.; Blanc, A.P.; Allègre, T.; Reynes, J.; Baillat, V.; Lemoing, V.; Merle De Boever, C.; Tramoni, C.; Cabié, A.; Sobesky, G.; Abel, S.; Beaujolais, V.; Pialoux, G.; Slama, L.; Chakvetadze, C.; Berrebi, V.; Yeni, P.; Bouvet, E.; Fournier, I.; Gerbe, J.; Trepo, C.; Koffi, K.; Augustin-Normand, C.; Miailhes, P.; Thoirain, V.; Brochier, C.; Thomas, R.; Souala, F.; Ratajczak, M.; Beytoux, J.; Jacomet, C.; Gourdon, F.; Rouveix, E.; Morelon, S.; Dupont, C.; Olivier, C.; Lortholary, O.; Dupont, B.; Viard, J.P.; Maignan, A.; Ragnaud, J.M.; Raymond, I.; Leport, C.; Jadand, C.; Jestin, C.; Longuet, P.; Boucherit, S.; Sereni, D.; Lascoux, C.; Prevoteau, F.; Sobel, A.; Levy, Y.; Lelièvre, J.D.; Lascaux, A.S.; Dominguez, S.; Dumont, C.; Aumâitre, H.; Delmas, B.; Saada, M.; Medus, M.; Guillevin, L.; Salmon, D.; Tahi, T.; Yazdanpanah, Y.; Pavel, S.; Marien, M.C.; Drenou, B.; Beck-Wirth, G.; Beck, C.; Benomar, M.; Katlama, C.; Tubiana, R.; Ait Mohand, H.; Chermak, A.; Ben Abdallah, S.; Bentata, M.; Touam, F.; Hoen, B.; Drobacheff, C.; Folzer, A.; Massip, P.; Obadia, M.; Prudhomme, L.; Bonnet, E.; Balzarin, F.; Pichard, E.; Chennebault, J.M.; Fialaire, P.; Loison, J.; Galanaud, P.; Boué, F.; Bornarel, D.; Verdon, R.; Bazin, C.; Six, M.; Ferret, P.; Weiss, L.; Batisse, D.; Gonzales-Canali, G.; Tisne-Dessus, D.; Devidas, A.; Chevojon, P.; Turpault, I.; Lafeuillade, A.; Cheret, A.; Philip, G.; Morel, P.; Timsit, J.; Herson, S.; Amirat, N.; Simon, A.; Brancion, C.; Cabane, J.; Picard, O.; Tredup, J.; Stein, A.; Ravault, I.; Chavanet, C.; Buisson, M.; Treuvetot, S.; Choutet, P.; Nau, P.; Bastides, F.; May, T.; Boyer, L.; Wassoumbou, S.; Oksenhendeler, E.; Gérard, L.; Bernard, L.; De Truchis, P.; Berthé, H.; Domart, Y.; Merrien, D.; Greder Belan, A.; Gayraud, M.; Bodard, L.; Meudec, A.; Beuscart, C.; Daniel, C.; Pape, E.; Vinceneux, P.; Simonpoli, A.M.; Zeng, A.; Fournier, L.; Fuzibet, J.G.; Sohn, C.; Rosenthal, E.; Quaranta, M.; Dellamonica, P.; Chaillou, S.; Sabah, M.; Audhuy, B.; Schieber, A.; Moreau, P.; Niault, M.; Vaillant, O.; Huchon, G.; Compagnucci, A.; De Lacroix Szmania, I.; Richier, L.; Lamaury, I.; Saint-Dizier, F.; Garipuy, D.; Gastaut, J.A.; Drogoul, M.P.; Poizot Martin, I.; Fabre, G.; Lambert De Cursay, G.; Abraham, B.; Perino, C.; Lagarde, P.; David, F.; Roche-Sicot, J.; Saraux, J.L.; Leprêtre, A.; Fampin, B.; Uludag, A.; Morin, A.S.; Bletry, O.; Zucman, D.; Regnier, A.; Girard, J.J.; Quinsat, D.T.; Heripret, L.; Grihon, F.; Houlbert, D.; Ruel, M.; Chemlal, K.; Caron, F.; Debab, Y.; Tremollieres, F.; Perronne, V.; Lepeu, G.; Slama, B.; Perré, P.; Miodovski, C.; Guermonprez, G.; Dulioust, A.; Boudon, P.; Malbec, D.; Patey, O.; Semaille, C.; Deville, J.; Remy, G.; Béguinot, I.; Galanaud, P.; Boue, F.; Chambrin, V.; Pignon, C.; Estocq, G.A.; Levy, A.; Delfraissy, J.F.; Goujard, C.; Duracinsky, M.; Le Bras, P.; Ngussan, M.S.; Peretti, D.; Medintzeff, N.; Lambert, T.; Segeral, O.; Lezeau, P.; Laurian, Y.; Weiss, L.; Buisson, M.; Piketty, C.; Karmochkine, M.; Batisse, D.; Eliaszewitch, M.; Jayle, D.; Tisne-Dessus, D.; Kazatchkine, M.; Leport, C.; Colasante, U.; Jadand, C.; Jestin, C.; Duval, X.; Nouaouia, W.; Boucherit, S.; Vilde, J.L.; Girard, P.M.; Bollens, D.; Binet, D.; Diallo, B.; Meyohas, M.C.; Fonquernie, L.; Lagneau, J.L.; Salmon, D.; Guillevin, L.; Tahi, T.; Launay, O.; Pietrie, M.P.; Sicard, D.; Stieltjes, N.; Michot, J.; Sobel, A.; Levy, Y.; Bourdillon, F.; Lascaux, A.S.; Lelievre, J.D.; Dumont, C.; Dupont, B.; Obenga, G.; Viard, J.P.; Maignan, A.; Vittecoq, D.; Escaut, L.; Bolliot, C.; Bricaire, F.; Katlama, C.; Schneider, L.; Herson, S.; Simon, A.; Iguertsira, M.; Stein, A.; Tomei, C.; Ravaux, I.; Dhiver, C.; Tissot Dupont, H.; Vallon, A.; Gallais, J.; Gallais, H.; Gastaut, J.A.; Drogoul, M.P.; Fabre, G.; Dellamonica, P.; Durant, J.; Mondain, V.; Perbost, I.; Cassuto, J.P.; Karsenti, J.M.; Venti, H.; Fuzibet, J.G.; Rosenthal, E.; Ceppi, C.; Quaranta, M.; Krivitsky, J.A.; Bentata, M.; Bouchaud, O.; Honore, P.; Sereni, D.; Lascoux, C.; Delgado, J.; Rouzioux, C.; Burgard, M.; Boufassa, L.; Peynet, J.; Pérez-Hoyos, S.; Del Amo, J.; Alvarez, D.; Monge, S.; Muga, R.; Sanvisens, A.; Clotet, B.; Tor, J.; Bolao, F.; Rivas, I.; Vallecillo, G.; Del Romero, J.; Raposo, P.; Rodríguez, C.; Vera, M.; Hurtado, I.; Belda, J.; Fernandez, E.; Alastrue, I.; Santos, C.; Tasa, T.; Juan, A.; Trullen, J.; Garcia De Olalla, P.; Cayla, J.; Masdeu, E.; Knobel, H.; Mirò, J.M.; Sambeat, M.A.; Guerrero, R.; Rivera, E.; Guerrero, R.; Marco, A.; Quintana, M.; Gonzalez, C.; Castilla, J.; Guevara, M.; De Mendoza, C.; Zahonero, N.; Ortíz, M.; Paraskevis, D.; Touloumi, G.; Pantazis, N.; Bakoyannis, G.; Gioukari, V.; Antoniadou, A.; Papadopoulos, A.; Petrikkos, G.; Daikos, G.; Psichogiou, M.; Gargalianos-Kakolyris, P.; Xylomenos, G.; Katsarou, O.; Kouramba, A.; Ioannidou, P.; Kordossis, T.; Kontos, A.; Lazanas, M.; Chini, M.; Tsogas, N.; Panos, G.; Paparizos, V.; Leuow, K.; Kourkounti, S.; Sambatakou, H.; Mariolis, I.; Skoutelis, A.; Papastamopoulos, V.; Baraboutis, I.

    2014-01-01

    Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacteri

  10. Combination therapy with interferon and JAK1-2 inhibitor is feasible

    DEFF Research Database (Denmark)

    Bjørn, M E; de Stricker, K; Kjær, L

    2014-01-01

    We report a 55 year old woman with post-ET PV for 12 years, who experienced resolution of severe constitutional symptoms within 3 days, a marked reduction in splenomegaly and a rapid decline in the JAK2V617F allele burden during combination therapy with interferon-alpha2a and ruxolitinib. Within 4...

  11. Predictors and treatment strategies of HIV-related fatigue in the combined antiretroviral therapy era

    NARCIS (Netherlands)

    Jong, Eefje; Oudhoff, Lisanne A.; Epskamp, Cynthia; Wagener, Marlies N.; van Duijn, Miranda; Fischer, Steven; van Gorp, Eric C. M.

    2010-01-01

    Objective To assess predictors and reported treatment strategies of HIV-related fatigue in the combined antiretroviral (cART) era. Method Five databases were searched and reference lists of pertinent articles were checked. Studies published since 1996 on predictors or therapy of HIV-related fatigue

  12. HIV-1 subtypes and response to combination antiretroviral therapy in Europe

    DEFF Research Database (Denmark)

    Bannister, WP; Ruiz, L; Loveday, C;

    2006-01-01

    BACKGROUND: Combination antiretroviral therapy (cART) may vary in ability to suppress viral load and increase CD4+ T-cell count in people infected with different HIV-1 subtypes, possibly due to differences in resistance development. Antiretroviral drugs have predominantly been developed in Western...

  13. Systems biology analysis unravels the complementary action of combined rosuvastatin and ezetimibe therapy

    NARCIS (Netherlands)

    Verschuren, L.; Radonjic, M.; Wielinga, P.Y.; Kelder, T.; Kooistra, T.; Ommen, B. van; Kleemann, R.

    2012-01-01

    AIMS: Combination-drug therapy takes advantage of the complementary action of their individual components, thereby potentiating its therapeutic effect. Potential disadvantages include side effects that are not foreseen on basis of the data available from drug monotherapy. Here, we used a systems bio

  14. Core-Shell-structured Dendritic Mesoporous Silica Nanoparticles for Combined Photodynamic Therapy and Antibody Delivery.

    Science.gov (United States)

    Abbaraju, Prasanna Lakshmi; Yang, Yannan; Yu, Meihua; Fu, Jianye; Xu, Chun; Yu, Chengzhong

    2017-07-04

    Multifunctional core-shell-structured dendritic mesoporous silica nanoparticles with a fullerene-doped silica core, a dendritic silica shell and large pores have been prepared. The combination of photodynamic therapy and antibody therapeutics significantly inhibits the cancer cell growth by effectively reducing the level of anti-apoptotic proteins. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. A Comparison of Cognitive-Behavioral Therapy, Sertraline, and Their Combination for Adolescent Depression

    Science.gov (United States)

    Melvin, Glenn A.; Tonge, Bruce J.; King, Neville J.; Heyne, David; Gordon, Michael S.; Klimkeit, Ester

    2006-01-01

    Objective: To evaluate cognitive-behavioral therapy, antidepressant medication alone, and combined CBT and antidepressant medication in the treatment of depressive disorders in adolescents. Method: Seventy-three adolescents (ages 12-18 years) with a primary diagnosis of DSM-IV major depressive disorder, dysthymic disorder, or depressive disorder…

  16. Predictive factors for interferon and ribavirin combination therapy in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To confirm the predictive factors for interferon (IFN)-α and ribavirin combination therapy for chronic hepatitis patients with hepatitis C virus (HCV) genotype 1b.METHODS: HCV RNA from 50 patients infected with HCV genotype 1b was studied by cloning and sequencing of interferon sensitivity determining region (ISDR), PKR-eIF2α phosphorylation homology domain (PePHD).Patients were treated with IFN-α and ribavirin for 6 mo and grouped by effectiveness of the therapy. A variety of factors were analyzed.RESULTS: Our data showed that age, HCV RNA titer,and ISDR type could be used as the predictive factors for combined IFN-α and ribavirin efficacy. Characteristically,mutations in PePHD appeared only when the combination therapy was effective. Other factors, such as sex and alanine aminotransferase (ALT) level, were not related to its efficacy. Adjusting for age and HCV RNA titer indicated that the ISDR type was the most potent predictive factor.CONCLUSION: HCV RNA ISDR type is an important factor for predicting efficacy of IFN-α and ribavirin combination therapy in Korean patients.

  17. Outcomes and duration of Pneumocystis jiroveci pneumonia therapy in infants with severe combined immunodeficiency.

    Science.gov (United States)

    Lundgren, Ingrid S; Englund, Janet A; Burroughs, Lauri M; Torgerson, Troy R; Skoda-Smith, Suzanne

    2012-01-01

    This retrospective review of patients with severe combined immunodeficiency and Pneumocystis jiroveci pneumonia (PCP) evaluated the relationship between duration of therapy to treat PCP and overall survival. We found that 80% of patients receiving only 21 days of antibiotics survived to 12 months beyond hematopoietic cell transplant, whereas only 25% of patients who required longer treatment for PCP survived to stem cell engraftment.

  18. Can the combination of localized "proliferative therapy" with "minor ozonated autohemotherapy" restore the natural healing process?

    Science.gov (United States)

    Gracer, R I; Bocci, V

    2005-01-01

    Regenerative injection therapy (RIT), also known as proliferative therapy, has been used for over 30 years in the USA in patients with spinal and peripheral joint and ligamentous pathologies. It involves the injection of mildly irritating medications onto ligaments and tendons, most commonly at origins and insertions. These injections cause a mild inflammatory response which "turns on" the normal healing process and results in the regeneration of these structures. At the same time they strengthen and become less sensitive to pain through a combination of neurolysis of small nerve fibers (C-fibers) and increased stability of the underlying structures. Oxygen/ozone therapy is a well established complementary therapy practiced in many European countries. The ozone dissolves in body fluids and immediately reacts with biomolecules generating messengers responsible for biological and therapeutic activities. This results in an anti inflammatory response, which also results in a similar trophic reaction to that of RIT. It is logical to expect that combining these two modalities would result in enhanced healing and therefore improved clinical outcomes. Oxygen/ozone therapy, accomplished by autohemotherapy (AHT), is performed by either administering ozonated blood intravenously (Major AHT) or via intramuscular route (Minor AHT). These procedures result in stimulation of the immune and healing systems. Our concept is that the local injection of this activated blood injected directly to the ligamentous areas that are also being treated with RIT will act as a direct stimulation to the healing process. In addition, combining this with intravenous major AHT should stimulate the immune system to augment and support this process. RIT and oxygen/ozone therapy have been extensively studied separately. We propose a study of lumbosacral ligamentous pain to explore this therapeutic combination. We hope that this paper will stimulate general interest in this area of medicine and result

  19. Ribavirin-induced anemia in hepatitis C virus patients undergoing combination therapy.

    Directory of Open Access Journals (Sweden)

    Sheeja M Krishnan

    Full Text Available The current standard of care for hepatitis C virus (HCV infection - combination therapy with pegylated interferon and ribavirin - elicits sustained responses in only ∼50% of the patients treated. No alternatives exist for patients who do not respond to combination therapy. Addition of ribavirin substantially improves response rates to interferon and lowers relapse rates following the cessation of therapy, suggesting that increasing ribavirin exposure may further improve treatment response. A key limitation, however, is the toxic side-effect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan during therapy, and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones, such as erythropoietin, that stimulate erythrocyte production and avert the reduction of ribavirin dosage, thereby improving treatment response. Our model thus facilitates, in

  20. In vitro pressure manifolding distribution evaluation of ABThera™ Active Abdominal Therapy System, V.A.C.® Abdominal Dressing System, and Barker’s vacuum packing technique conducted under dynamic conditions

    Directory of Open Access Journals (Sweden)

    Angel Delgado

    2016-01-01

    Full Text Available Objectives: Temporary abdominal closure methods allow for management of open abdomens where immediate primary closure is not possible and/or where repeat abdominal entries are necessary. We assessed pressure mapping and fluid extraction efficiency of three open abdomen dressing systems: ABThera™ Active Abdominal Therapy System, V.A.C.® Abdominal Dressing System, and Barker’s vacuum packing technique. Methods: An in vitro test model was designed to simulate physical conditions present in an open abdomen. The model consisted of a rigid rest platform with elevated central region and a flexible outer layer with centrally located incision. Constant −125 mmHg negative pressure was applied according to the type of system, under simulated dynamic conditions, using albumin-based solution with a viscosity of 14 cP. Data were collected by pressure sensors located circumferentially into three concentric zones: Zone 1 (closest to negative pressure source, Zone 2 (immediately outside of manifolding material edge, and Zone 3 (area most distal from negative pressure source. Each value was the result of approximately 100 pressure readings/zone/experiment with a total of three experiments for each system. Results: Pressure distribution of ABThera Therapy was significantly (p < 0.05 superior to Barker’s vacuum packing technique in all three evaluated zones. Similarly, V.A.C. Abdominal Dressing System pressure distribution was significantly (p < 0.05 improved compared to Barker’s vacuum packing technique in all zones. There were no pressure distribution differences in Zone 1 between ABThera Therapy and V.A.C. Abdominal Dressing System; however, in Zones 2 and 3, ABThera Therapy was significantly (p < 0.05 superior to V.A.C. Abdominal Dressing System. Conclusions: These data suggest that all approaches to negative pressure therapy for open abdomen treatment are not equal. Additional research should be conducted to elucidate clinical

  1. Combination of psychotherapy and benzodiazepines versus either therapy alone for panic disorder: a systematic review

    Directory of Open Access Journals (Sweden)

    Furukawa Toshi A

    2007-05-01

    Full Text Available Abstract Background: The efficacy of combined psychotherapy and benzodiazepine treatment for panic disorder is still unclear despite its widespread use. The present systematic review aims to examine its efficacy compared with either monotherapy alone. Methods: All randomised trials comparing combined psychotherapy and benzodiazepine for panic disorder with either therapy alone were identified by comprehensive electronic search on the Cochrane Registers, by checking references of relevant studies and of other reviews, and by contacting experts in the field. Two reviewers independently checked eligibility of trials, assessed quality of trials and extracted data from eligible trials using a standardized data extraction form. Our primary outcome was "response" defined by global judgement. Authors of the original trials were contacted for further unpublished data. Meta-analyses were undertaken synthesizing data from all relevant trials. Results: Only two studies, which compared the combination with behaviour (exposure therapy, met our eligibility criteria. Both studies had a 16-week intervention. Unpublished data were retrieved for one study. The relative risk for response for the combination was 1.25 (95%CI: 0.78 to 2.03 during acute phase treatment, 0.78 (0.45 to 1.35 at the end of treatment, and 0.62 (0.36 to 1.07 at 6–12 months follow-up. Some secondary outcomes hinted at superiority of the combination during acute phase treatment. One study was identified comparing the combination to benzodiazepine. The relative risk for response was 1.57 (0.83 to 2.98, 3.39 (1.03 to 11.21, statistically significant and 2.31 (0.79 to 6.74 respectively. The superiority of the combination was observed on secondary outcomes at all the time points. No sub-group analyses were conducted due to the limited number of included trials. Conclusion: Unlike some narrative reviews in the literature, our systematic search established the paucity of high quality evidence for

  2. Combined analgesics in (headache pain therapy: shotgun approach or precise multi-target therapeutics?

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    Fiebich Bernd L

    2011-03-01

    Full Text Available Abstract 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

  3. Antihypertensive combination therapy in primary care offices: results of a cross-sectional survey in Switzerland

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    Roas S

    2014-12-01

    Full Text Available Susanne Roas,1 Felix Bernhart,2 Michael Schwarz,3 Walter Kaiser,4 Georg Noll5 1Department of Internal Medicine, University Hospital, Zurich, 2Private Practice, Biberist, 3Ambulatorium Wiesendamm, Basel, 4Healthworld (Schweiz AG, Steinhausen, 5HerzKlinik Hirslanden, Zurich, Switzerland Background: Most hypertensive patients need more than one substance to reach their target blood pressure (BP. Several clinical studies indicate the high efficacy of antihypertensive combinations, and recent guidelines recommend them in some situations even as initial therapies. In general practice they seem widespread, but only limited data are available on their effectiveness under the conditions of everyday life. The objectives of this survey among Swiss primary care physicians treating hypertensive patients were: to know the frequency of application of different treatment modalities (monotherapies, free individual combinations, single-pill combinations; to see whether there are relationships between prescribed treatment modalities and patient characteristics, especially age, treatment duration, and comorbidities; and to determine the response rate (percentage of patients reaching target BP of different treatment modalities under the conditions of daily practice. Methods: This cross-sectional, observational survey among 228 randomly chosen Swiss primary care physicians analyzed data for 3,888 consecutive hypertensive patients collected at one single consultation. Results: In this survey, 31.9% of patients received monotherapy, 41.2% two substances, 20.9% three substances, and 4.7% more than three substances. By combination mode, 34.9% took free individual combinations and 30.0% took fixed-dose single-pill combinations. Combinations were more frequently given to older patients with a long history of hypertension and/or comorbidities. In total, 67.8% of patients achieved their BP target according to their physician's judgment. When compared, single

  4. Terapia de vacío como adyuvante para el uso de sustitutos dérmicos monocapa Combined use of vacuum assited device and dermal monolayer substitutes

    Directory of Open Access Journals (Sweden)

    J.R. Martínez-Méndez

    2010-12-01

    conclusión, la aplicación de matrices de regeneración dérmica monocapa es segura, con una tasa de prendimiento de los injertos sobre ella del 85%. El uso del VAC® sobre las láminas monocapa de dermis sintética acorta el tiempo de integración de las mismas y el prendimiento de los injertos sobre ellas, con una tasa de complicaciones similar.Split thickness autografts are the gold standard for wound coverage. However, scars and retractions are frequent after skin grafts, and would be severe over special regions. Different authors avoid these complications using a dermal substitute interposed between the wound and the skin graft in the first surgical time. A prospective study was designed to evaluate the split thickness skin graft uptake time over a monolayer matrix, with and without a vacuum assisted therapy device (VAC®. Twenty patients with a full thickness wound over a special region were randomized between 2 groups. Epidemiological data and wound etiology (acute burn, burn sequelae or donor site after a fasciocutaneous flap raised were collected. Matriderm® (mono layer dermal substitute and a split thickness skin graft was applied over 10 cases (Group I. The dressing was changed after 7 days, and every 3-4 days until the skin graft was uptake and stable. Another 10 cases were treated with the same surgical strategy (Group II. After surgery, a vacuum assisted therapy device (VAC® was applied until the graft was uptake. The skin graft evaluation was done by a blind observer. All complications were reported until 3 months after the skin graft was stable. The homogeneity between groups was assessed. Averaged uptake time was 17, 6 ± 8 days, and the total complication rate was 20%. Statistically differences were not found between the 2 groups for the complication rate. The uptake time was 21,4 ± 9 days in the Group I and 13,9 ± 4 days in the Group II. These differences was statically significative. As a conclusion, the use of monolayer dermal substitutes is safe

  5. Terapia de vacío como adyuvante para el uso de sustitutos dérmicos monocapa Combined use of vacuum assisted device and dermal monolayer substitutes

    Directory of Open Access Journals (Sweden)

    J.R. Martínez-Méndez

    2011-12-01

    conclusión, la aplicación de matrices de regeneración dérmica monocapa es segura, con una tasa de prendimiento de los injertos sobre ella del 85%. El uso del VAC® sobre las láminas monocapa de dermis sintética acorta el tiempo de integración de las mismas y el prendimiento de los injertos sobre ellas, con una tasa de complicaciones similar.Split thickness autografts are the gold standard for wound coverage. However, scars and retractions are frequent after skin grafts, and would be severe over special regions. Different authors avoid these complications using a dermal substitute interposed between the wound and the skin graft in the first surgical time. A prospective study was designed to evaluate the split thickness skin graft uptake time over a monolayer matrix, with and without a vacuum assisted therapy device (VAC®. Twenty patients with a full thickness wound over a special region were randomized between 2 groups. Epidemiological data and wound etiology (acute burn, burn sequelae or donor site after a fasciocutaneous flap raised were collected. Matriderm® (mono layer dermal substitute and a split thickness skin graft was applied over 10 cases (Group I. The dressing was changed after 7 days, and every 3-4 days until the skin graft was uptake and stable. Another 10 cases were treated with the same surgical strategy (Group II. After surgery, a vacuum assisted therapy device (VAC® was applied until the graft was uptake. The skin graft evaluation was done by a blind observer. All complications were reported until 3 months after the skin graft was stable. The homogeneity between groups was assessed. Averaged uptake time was 17, 6 ± 8 days, and the total complication rate was 20%. Statistically differences were not found between the 2 groups for the complication rate. The uptake time was 21,4 ± 9 days in the Group I and 13,9 ± 4 days in the Group II. These differences was statically significative. As a conclusion, the use of monolayer dermal substitutes is safe

  6. Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art

    Directory of Open Access Journals (Sweden)

    Piotr Milecki

    2010-10-01

    Full Text Available Piotr Milecki1,2, Piotr Martenka1, Andrzej Antczak3, Zbigniew Kwias31Department of Radiotherapy, Greater Poland Cancer Center, Poznan, Poland; 2Department of Electroradiology, Medical University, Poznan, Poland; 3Chair of Urology, Medical University, Poznan, PolandAbstract: Androgen-deprivation therapy (ADT is used routinely in combination with definitive external beam radiation therapy (EBRT in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT–EBRT also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.Keywords: prostate cancer, radiotherapy, androgen deprivation, combined treatment

  7. Combination therapy with catechins and caffeine inhibits fat accumulation in 3T3-L1 cells

    Science.gov (United States)

    Zhu, Xiaojuan; Yang, Licong; Xu, Feng; Lin, Lezhen; Zheng, Guodong

    2017-01-01

    Catechins and caffeine, which are green tea components, have a slimming effect; however, the combinational effect of fat metabolism in 3T3-L1 cells remains unclear. In the present study, 3T3-L1 cells were treated with catechins and caffeine in combination, and it was found that combination therapy with catechins and caffeine markedly reduced intracellular fat accumulation, mRNA expression levels of peroxisome proliferator-activated receptor-γ and CCAAT/enhancer-binding protein α in the early stage of cell differentiation were significantly reduced, and mRNA expression of fatty acid synthetase(FAS) andglycerol-3-phosphate dehydrogenase protein expression levels of FAS were downregulated. Noradrenaline-induced lipolysis was enhanced by caffeine, which markedly increased the protein expression of adipose triglyceride lipase and hormone sensitive lipase. These results indicated that combination therapy with catechins and caffeine synergistically inhibited lipid accumulation by regulating the gene and protein expression levels of lipid metabolism-related enzymes. Therefore, catechins and caffeine combination therapy has potential as a functional food that may be used to prevent obesity and lifestyle-associated diseases. PMID:28352352

  8. Corneal collagen cross-linking and liposomal amphotericin B combination therapy for fungal keratitis in rabbits

    Science.gov (United States)

    Hao, Zhao-Qin; Song, Jin-Xin; Pan, Shi-Yin; Zhang, Lin; Cheng, Yan; Liu, Xian-Ning; Wu, Jie; Xiao, Xiang-Hua; Gao, Wei; Zhu, Hai-Feng

    2016-01-01

    AIM To observe the therapeutic effect of corneal collagen cross-linking (CXL) in combination with liposomal amphotericin B in fungal corneal ulcers. METHODS New Zealand rabbits were induced fungal corneal ulcers by scratching and randomly divided into 3 groups, i.e. control, treated with CXL, and combined therapy of CXL with 0.25% liposomal amphotericin B (n=5 each). The corneal lesions were documented with slit-lamp and confocal microscopy on 3, 7, 14, 21 and 28d after treatment. The corneas were examined with transmission electron microscopy (TEM) at 4wk. RESULTS A rabbit corneal ulcer model of Fusarium was successfully established. The corneal epithelium defect areas in the two treatment groups were smaller than that in the control group on 3, 7, 14 and 21d (Pulcers. The combined therapy could alleviate corneal inflammattions, accelerate corneal repair, and shorten the course of disease. PMID:27990355

  9. Dosage dependent hormonal counter regulation to combination therapy in patients with left ventricular dysfunction

    DEFF Research Database (Denmark)

    Galløe, A.M.; Skagen, K.; Christensen, N.J.

    2006-01-01

    The present study attempts to assess the efficacy combination therapy for heart failure. Genuine dose-response studies on combination therapy are not available and published studies involved adding one drug on top of 'usual treatment'. Sixteen different dosage combinations of trandolapril...... rate and plasma noradrenaline in a dose dependent manner. Doses of bumetanide of more than 0.5 mg, given twice daily significantly decreased the quality of life and increased diuresis. Weight loss was maximal on 0.5 mg bumetanide twice daily. Trandolapril significantly reduced systolic blood pressure...... of life and weight loss. Estimated by the reduction in systolic blood pressure the optimal dosage of Trandolapril appeared to be 0.5 mg once daily. CONCLUSIONS: It appears that patients should be given less than the usually recommended dosages. Patients may be treated with a low dose loop diuretic...

  10. Rational Design and Adaptive Management of Combination Therapies for Hepatitis C Virus Infection.

    Directory of Open Access Journals (Sweden)

    Ruian Ke

    2015-06-01

    Full Text Available Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensate when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design.

  11. Rational Design and Adaptive Management of Combination Therapies for Hepatitis C Virus Infection

    Science.gov (United States)

    Ke, Ruian; Loverdo, Claude; Qi, Hangfei; Sun, Ren; Lloyd-Smith, James O.

    2015-01-01

    Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensate when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design. PMID:26125950

  12. Anemia in patients on combined androgen block therapy for prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Li-XinQian; Li-XinHua; Hong-FeiWu; Yuan-GengSui; Shuang-GuanCheng; WeiZhang,JieLi; Xin-RuWang

    2004-01-01

    Aim: To study the effect of combined androgen block therapy on hemoglobin and hematocrit values in patients with prostate cancer. Methods: One hundred and thirty-six patients with adenocarcinoma of prostate were treated with combined androgen block (orchiectomy and flutamide 250 mg, tid). Complete blood counts were determined before and after 1,2,3,6,9 and 12 months of therapy. Results: The hemoglobin and hematocrit levels declined significantly in all patients and at all the time points after treatment (P<0.05). Conclusion: Prostate cancer patients treated with combined androgen block would develop obvious anemia. Recombinant human erythropoietin can be used to treat patients with severe anemia. (Asian J Androl 2004 Dec;6: 383-384)

  13. Combination of positioning therapy and venovenous extracorporeal membrane oxygenation in ARDS patients.

    Science.gov (United States)

    Kredel, M; Bischof, L; Wurmb, T E; Roewer, N; Muellenbach, R M

    2014-03-01

    Positioning therapy may improve lung recruitment and oxygenation and is part of the standard care in severe acute respiratory distress syndrome (ARDS). Venovenous extracorporeal membrane oxygenation (vvECMO) is a rescue strategy that may ensure sufficient gas exchange in ARDS patients failing conventional therapy. The aim of this case series was to describe the feasibility and pitfalls of combining positioning therapy and vvECMO in patients with severe ARDS. A retrospective cohort of nine patients is described. The patients received 20 (15-86) hours (median, 25(th) and 75(th) percentile) of positioning therapy while being treated with vvECMO. The initial PaO2/FiO2 index was 64 (51-67) mmHg and the arterial carbon dioxide tension was 60 (50-71) mmHg. Positioning therapy included 135 degrees prone, prone positioning and continuous lateral rotational therapy. During the first three days, the oxygenation index improved from 47 (41-47) to 12 (11-14) cmH2O/mmHg. The lung compliance improved from 20 (17-28) to 42 (27-43) ml/cmH2O. Complications related to positioning therapy were facial oedema (n=9); complications related to vvECMO were entrance of air (n=1) and pump failure (n=1). However, investigation of root causes revealed no association with the positioning therapy and had no documented effect on the outcome. The reported cases suggest that positioning therapy can be performed safely in ARDS patients treated with vvECMO, providing appropriate precautions are in place and a very experienced team is present.

  14. Combination Therapy with Olmesartan and Amlodipine in the Treatment of Hypertension

    Directory of Open Access Journals (Sweden)

    Menco G. Niemeijer

    2009-12-01

    Full Text Available Background: Combination therapy with antihypertensive agents utilises different mechanisms of action and may be responsible for a more effective decrease in blood pressure. Objective: To review the recently published trials on efficacy and safety of the combination therapy with olmesartan and amlodipine. Results: The double-blind American COACH (Combination of Olmesartan Medoxomil and Amlopdine Besylate in Controlling High Blood Pressure study (2008 showed in 1,940 patients that after eight weeks of treatment the BP goals were most frequently achieved in the ‘combination therapy group’, with 56.3% (54.1–58.5% and 54.0% (51.8–56.2% of patients reaching adequate blood pressure of <140/90 mmHg with olmesartan/amlodipine 20/10 and 40/10 respectively. Combination therapy was generally well tolerated. The most common side effect was oedema [olmesartan 20 mg 9.9% (8.6–11.3%, amlodipine 10 mg 36.8% (34.7–39.0%, placebo 12.3% (10.9–13.8%]. The frequency of oedema was lower in the groups combining amlodipine 10 mg with olmesartan 10 mg (26.5%, 24.5–28.5%, 20 mg (25.6%, 23.7–27.6% or 40 mg (23.5%, 21.6–25.4%. In 2009 three double-blind controlled European studies including 500–1,000 patients each and performed independently of one another have confirmed the above study, and have demonstrated similar efficacy-safety effects from the combination of olmesartan medoxomil with amlodipine, particularly for patients not achieving adequate blood pressure control with olmesartan monotherapy. Conclusions: Combinations of olmesartan and amlodipine were significantly more effective at reducing blood pressure and realising guideline blood pressure goals in patients with mild to severe hypertension than monotherapy (with a placebo component. Combination therapy is well tolerated and is associated with a lower incidence of side effects, such as oedema, compared to monotherapy with high amlodipine dosages (10 mg.

  15. [A case of combination therapy with MMF and steroids for idiopathic membranoproliferative glomerulonephritis].

    Science.gov (United States)

    Mori, Yutaro; Ihara, Katsuhito; Yamaguchi, Wakaba; Fujii, Tetsuro; Toda, Takayuki; Nagata, Michio; Matsui, Noriaki

    2013-01-01

    A 26-year-old man diagnosed with nephrotic syndrome was administered steroid monotherapy. Urinary protein excretion was 2-3 g/day despite the therapy. Percutaneous renal biopsy revealed Type I idiopathic membranoproliferative glomerulonephritis (IMPGN). Although intravenous steroid therapy at the dose of 1,000 mg/day for 3 days was administered, proteinuria persisted at the level of 1 g/day. Renal dysfunction (cystatin C, 1.33 mg/L) was evident. Strong inflammation was suggested by occult blood (3+) and urinary (red blood cells: 30-50/high power field) sediment. We considered steroid monotherapy to be ineffective, and initiated combina-tion therapy with mycophenolate mofetil (MMF) and steroids. Consequently, urinary protein excretion moderately decreased to 0.34 g/day without adverse events or worsening of the renal function. The steroid quantity could be reduced without relapse. Subsequently, we were able to reduce the dose of MMF gradually, then terminated the medication. IMPGN is a rare disease with a poor renal prognosis. Recently, MMF therapies for IMPGN have been attempted, but there are few cases in Japan. Our case suggests that combination therapy with MMF and steroids is effective and safe for treating IMPGN.

  16. Response of spinal myoclonus to a combination therapy of autogenic training and biofeedback

    Directory of Open Access Journals (Sweden)

    Kempuraj Duraisamy

    2007-10-01

    Full Text Available Abstract Introduction Clinical evidence indicates that certain types of movement disorders are due to psychosomatic factors. Patients with myoclonic movements are usually treated by a variety of therapeutic agents. Autogenic training (AT, a recognized form of psychosomatic therapies, is suitable for certain types of neurological diseases. We describe a patient with myoclonus who failed to respond to conventional medical therapy. His symptoms were exaggerated by psychogenic factors, especially anger. Case presentation A 42-year-old man was admitted to our hospital, Preventive Welfare Clinic, for severe paroxysmal axial myoclonus of the left shoulder and abdominal muscles. The initial diagnosis was "combination of spinal segmental myoclonus and propriospinal myoclonus". The myoclonic movements did not occur during sleep but were aggravated by bathing, alcohol drinking, and anger. Psychological examination indicated hostile attribution. Although considered not to be a case of psychogenic myoclonus, a "psychogenic factor" was definitely involved in the induction of the organic myoclonus. The final diagnosis was "combination of spinal segmental myoclonus and propriospinal myoclonus accompanied by features of psychosomatic disorders". The patient underwent psychosomatic therapy including AT and surface electromyography (EMG-biofeedback therapy and treatment with clonazepam and carbamazepine. Results AT and EMG-biofeedback resulted in shortening the duration and reducing the amplitude and frequency of the myoclonic discharges. Conclusion Psychosomatic therapy with AT and surface EMG-biofeedback produced excellent improvement of myoclonic movements and allowed the reduction of the dosage of conventional medications.

  17. Combining Dopaminergic Facilitation with Robot-Assisted Upper Limb Therapy in Stroke Survivors: A Focused Review.

    Science.gov (United States)

    Tran, Duc A; Pajaro-Blazquez, Marta; Daneault, Jean-Francois; Gallegos, Jaime G; Pons, Jose; Fregni, Felipe; Bonato, Paolo; Zafonte, Ross

    2016-06-01

    Despite aggressive conventional therapy, lasting hemiplegia persists in a large percentage of stroke survivors. The aim of this article is to critically review the rationale behind targeting multiple sites along the motor learning network by combining robotic therapy with pharmacotherapy and virtual reality-based reward learning to alleviate upper extremity impairment in stroke survivors. Methods for personalizing pharmacologic facilitation to each individual's unique biology are also reviewed. At the molecular level, treatment with levodopa was shown to induce long-term potentiation-like and practice-dependent plasticity. Clinically, trials combining conventional therapy with levodopa in stroke survivors yielded statistically significant but clinically unconvincing outcomes because of limited personalization, standardization, and reproducibility. Robotic therapy can induce neuroplasticity by delivering intensive, reproducible, and functionally meaningful interventions that are objective enough for the rigors of research. Robotic therapy also provides an apt platform for virtual reality, which boosts learning by engaging reward circuits. The future of stroke rehabilitation should target distinct molecular, synaptic, and cortical sites through personalized multimodal treatments to maximize motor recovery.

  18. Chlorin e6 conjugated copper sulfide nanoparticles for photodynamic combined photothermal therapy.

    Science.gov (United States)

    Bharathiraja, Subramaniyan; Manivasagan, Panchanathan; Moorthy, Madhappan Santha; Bui, Nhat Quang; Lee, Kang Dae; Oh, Junghwan

    2017-09-01

    The photo-based therapeutic approaches have attracted tremendous attention in recent years especially in treatment and management of tumors. Photodynamic and photothermal are two major therapeutic modalities which are being applied in clinical therapy. The development of nanomaterials for photodynamic combined with photothermal therapy has gained significant attention for its treatment efficacy. In the present study, we designed chlorin e6 (Ce6) conjugated copper sulfide (CuS) nanoparticles (CuS-Ce6 NPs) through amine functionalization and the synthesized nanoparticles act as a dual-model agent for photodynamic therapy and photothermal therapy. CuS-Ce6 NPs showed enhanced photodynamic effect through generation of singlet oxygen upon 670nm laser illumination. The same nanoparticles exerted thermal response under an 808nm laser at 2W/cm(2). The fabricated nanoparticles did not show any cytotoxic effect toward breast cancer cells in the absence of light. In vitro cell viability assay showed a potent cytotoxicity in photothermal and photodynamic treatment. Rather than singular treatment, the photodynamic combined photothermal treatment showed an enhanced cytotoxic effect on treated cells. In addition, the CuS-Ce6 NPs exert a photoacoustic signal for non-invasive imaging of treated cells in tissue-mimicking phantom. In conclusion the CuS-Ce6 NPs act as multimodal agent for photo based imaging and therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy

    Science.gov (United States)

    Eroglu, Zeynep; Ribas, Antoni

    2016-01-01

    Treatment with BRAF inhibitors such as vemurafenib or dabrafenib in patients with advanced BRAFV600 mutated melanoma has shown objective tumor responses in approximately half of the patients. However, the duration of responses is limited in a majority of these patients, with progression-free survival rates around 6 months due to tumor progression from development of acquired resistance. Preclinical studies have suggested that concurrent inhibition of the BRAF kinases and MEK of the mitogen-activated protein kinase (MAPK) pathway could decrease MAPK-driven acquired resistance, resulting in longer duration of responses, higher rate of tumor responses, and a decrease in the cutaneous toxicities observed from paradoxical MAPK pathway activation with BRAF inhibitor monotherapy. This review provides an overview of the currently available clinical trial data on BRAF and MEK inhibitors together and in combinations with other therapeutic agents. PMID:26753005

  20. Combination photodynamic therapy of human breast cancer using salicylic acid and methylene blue

    Science.gov (United States)

    Hosseinzadeh, Reza; Khorsandi, Khatereh; Jahanshiri, Maryam

    2017-09-01

    The objective of this study was to evaluate the effects of combination therapy with methylene blue (MB) assisted photodynamic therapy (PDT) and salicylic acid (SA) as chemo-therapy anticancer agent. The binding of salicylic acid to methylene blue was studied using spectrophotometric method. The results show the 1:2 complex formation between SA and MB. The binding constants and related Gibbs free energies o are obtained (Kb1 = 183.74, Kb2 = 38.13 and ∆ Gb1° = 12.92 kJ·mol- 1, ∆ Gb2° =9.02 kJ·mol- 1). The spectrophotometric results show the improvement in solubilization and reduction prevention for SA and MB in the complex form. These results are in agreements with cellular experiments. The dark toxicity measurements represent the improve efficacy of chemotherapy using combination of SA and MB. The photodynamic therapy results (using red LED as light source (630 nm; power density: 30 mW cm- 2)) show that the cancer cell killing efficiency of MB increases in the combination with SA due to reduction prevention and stabilization of monomeric form of MB.

  1. Combination therapy for chronic invasive rhinocerebral aspergillosis in a clinically immunocompetent patient

    Science.gov (United States)

    Lujber, László; Gerlinger, Imre; Kuncz, Ádám; Pytel, József

    2003-01-01

    Background: Adequate therapy for chronic invasive rhinocerebral aspergillosis in immunocompetent patients is controversial. The incidence of the disease is high in the Sudan and the Middle East. Misinterpretation of diagnostic criteria, failure to verify tissue invasion of fungi, and a lack of understanding of the pathophysiology of various forms of fungal rhinosinusitis lead to controversies in nomenclature, diagnosis, and therapy. Objective: The aim of this report was to detail the clinical presentation and the endoscopic and imaging study findings of a patient with invasive Aspergillus rhinosinusitis with endocranial and orbital extension. This patient was treated with surgical débridement and a combination of antifungal drugs and immunomodulatory therapy. Methods: Endoscopic débridement and high-dose liposomal amphotericin B, in combination with flucytosine and immunomodulators, were used to treat this patient. Results: After treatment, the patient experienced 3 years of disease-free follow-up. Conclusion: Surgical débridement and high-dose systemic combined antifungal therapy with immunomodulatory drugs produced an excellent long-term result for this apparently immunocompetent patient with extensive invasive fungal rhinosinusitis with cerebral and orbital involvement. PMID:24944397

  2. The role of fluticasone propionate/salmeterol combination therapy in preventing exacerbations of COPD

    Directory of Open Access Journals (Sweden)

    Barbara P Yawn

    2010-06-01

    Full Text Available Barbara P Yawn1, Ibrahim Raphiou2, Judith S Hurley3, Anand A Dalal21Olmsted Medical Center, University of Minnesota, Rochester, Minnesota, USA; 2GlaxoSmithKline, Research Triangle Park, North Carolina, USA; 3Hurley Consulting, Placitas, New Mexico, USAAbstract: Exacerbations contribute significantly to the morbidity of COPD, leading to an accelerated decline in lung function, reduced functional status, reduced health status and quality of life, poorer prognosis and increased mortality. Prevention of exacerbations is thus an important goal of COPD management. In patients with COPD, treatment with a combination of the inhaled corticosteroid fluticasone propionate (250 μg and the long-acting β2-agonist salmeterol (50 μg in a single inhaler (250/50 μg is an effective therapy option that has been shown to reduce the frequency of exacerbations, to improve lung function, dyspnea and health status, and to be relatively cost-effective as a COPD maintenance therapy. Importantly, results of various studies suggest that fluticasone propionate and salmeterol have synergistic effects when administered together that improve their efficacy in controlling symptoms and reducing exacerbations. The present non-systematic review summarizes the role of fluticasone propionate/salmeterol combination therapy in the prevention of exacerbations of COPD and its related effects on lung function, survival, health status, and healthcare costs.Keywords: Advair, COPD, disease exacerbation, fluticasone propionate, salmeterol, combination drug therapy

  3. Polydopamine Nanoparticles as a Versatile Molecular Loading Platform to Enable Imaging-guided Cancer Combination Therapy.

    Science.gov (United States)

    Dong, Ziliang; Gong, Hua; Gao, Min; Zhu, Wenwen; Sun, Xiaoqi; Feng, Liangzhu; Fu, Tingting; Li, Yonggang; Liu, Zhuang

    2016-01-01

    Cancer combination therapy to treat tumors with different therapeutic approaches can efficiently improve treatment efficacy and reduce side effects. Herein, we develop a theranostic nano-platform based on polydopamine (PDA) nanoparticles, which then are exploited as a versatile carrier to allow simultaneous loading of indocyanine green (ICG), doxorubicin (DOX) and manganese ions (PDA-ICG-PEG/DOX(Mn)), to enable imaging-guided chemo & photothermal cancer therapy. In this system, ICG acts as a photothermal agent, which shows red-shifted near-infrared (NIR) absorbance and enhanced photostability compared with free ICG. DOX, a model chemotherapy drug, is then loaded onto the surface of PDA-ICG-PEG with high efficiency. With Mn(2+) ions intrinsically chelated, PDA-ICG-PEG/DOX(Mn) is able to offer contrast under T1-weighted magnetic resonance (MR) imaging. In a mouse tumor model, the MR imaging-guided combined chemo- & photothermal therapy achieves a remarkable synergistic therapeutic effect compared with the respective single treatment modality. This work demonstrates that PDA nanoparticles could serve as a versatile molecular loading platform for MR imaging guided combined chemo- & photothermal therapy with minimal side effects, showing great potential for cancer theranostics.

  4. Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin.

    Directory of Open Access Journals (Sweden)

    José Manuel Cuevas

    Full Text Available We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective pressures.

  5. Hyperbaric oxygen therapy in tinnitus with normal hearing in association with combined treatment.

    Science.gov (United States)

    Holy, Richard; Prazenica, Pavol; Stolarikova, Eva; Dosel, Petr; Fundova, Petra; Kovar, Daniel; Astl, Jaromir

    2016-01-01

    Tinnitus is a phantom perception of sound in the absence of overt acoustic stimulation. The focus of our attention is a combined therapy of tinnitus. In this prospective study (2013-2014) we evaluated the data of normal-hearing patients with tinnitus treated with various treatment modalities. In Group 1 we evaluated the data of 84 patients/124 ears after six weeks of treatment with betahistine dihydrochloride (72 mg). In Group 2, we evaluated the data of 36 patients/ 55 ears unimproved from Group 1 who were then treated for six weeks with hyperbaric oxygen (HBO₂) therapy combined with gingko biloba extract (120 mg). In Group 1, tinnitus disappeared in 9.7%, alleviated in 18.5% and improved overall in 28.2%. Average intensity of tinnitus before/after treatment was 37 decibels (dB)/33 dB. Tinnitus intensities after treatment are statistically significantly lower (p = 0.001) than the values before treatment. In Group 2 tinnitus disappeared in 5.4%, 36.4% achieved alleviation, and 41.8% showed overall improvement. The average intensity of tinnitus before/after treatment was 41dB/ 38dB. The values of tinnitus intensity after combined therapy are statistically significantly lower (p = 0.046). We have shown that both methods treatment of tinnitus are statistically significant. HBO₂therapy was recommended for the general public.

  6. Vacuum phenomenon.

    Science.gov (United States)

    Yanagawa, Youichi; Ohsaka, Hiromichi; Jitsuiki, Kei; Yoshizawa, Toshihiko; Takeuchi, Ikuto; Omori, Kazuhiko; Oode, Yasumasa; Ishikawa, Kouhei

    2016-08-01

    This article describes the theory of the formation of the vacuum phenomenon (VP), the detection of the VP, the different medical causes, the different locations of the presentation of the VP, and the differential diagnoses. In the human body, the cavitation effect is recognized on radiological studies; it is called the VP. The mechanism responsible for the formation of the VP is as follows: if an enclosed tissue space is allowed to expand as a rebound phenomenon after an external impact, the volume within the enclosed space will increase. In the setting of expanding volume, the pressure within the space will decrease. The solubility of the gas in the enclosed space will decrease as the pressure of the space decreases. Decreased solubility allows a gas to leave a solution. Clinically, the pathologies associated with the VP have been reported to mainly include the normal joint motion, degeneration of the intervertebral discs or joints, and trauma. The frequent use of CT for trauma patients and the high spatial resolution of CT images might produce the greatest number of chances to detect the VP in trauma patients. The VP is observed at locations that experience a traumatic impact; thus, an analysis of the VP may be useful for elucidating the mechanism of an injury. When the VP is located in the abdomen, it is important to include perforation of the digestive tract in the differential diagnosis. The presence of the VP in trauma patients does not itself influence the final outcome.

  7. Studies on effect of psychological intervention combination with music therapy on nursing for abdominal MRI scans

    Directory of Open Access Journals (Sweden)

    Yun-xia SUN

    2014-06-01

    Full Text Available Objective: To investigate the effectiveness and significance of the Psychological intervention combined with music therapy in abdominal MRI examination. Methods: 230 cases who underwent abdominal MRI examination between 2010 January and 2012 December were collected. They were divided into three groups randomly: routine nursing group, Psychological intervention group and music therapy group. Differences in age, gender, educational level, blood pressure and heart rate were compared between the three groups; To analyze the changes of vital signs after MRI examination, MRI examination results , psychological reaction before and after MRI examination of the three groups. Results: (1There was no significant difference in the general information (P>0.05; (2The heart rate, respiration and blood pressure after MRI examination of patients with routine nursing increased significantly than the other two groups. And psychological nursing group was higher than the music therapy group to some extent;The MRI detection time of routine nursing group was significantly longer than the other two groups (P <0.05; (3The one-time completion rate of the last two groups was significantly higher than the routine nursing  group (P <0.05, and music therapy group was significantly higher than that of the psychological intervention group.The adverse psychological reaction in Psychological intervention group was significantly decreased compared with routine nursing group; and music therapy group decreased significantly compared with the psychological  intervention  group (P <0.05; (4Although the anxiety / depression score of psychological  intervention  group increased slightly ,but it significantly lower than the usual care group (P <0.05; The anxiety / depression scores of music therapy group were significantly decreased, significantly lower than the other two groups (P <0.05. Conclusion: Psychological nursing combined with music therapy is a good way to eliminate the

  8. Vacuum and magnetic field constraints in a H -/light ion synchrotron

    Science.gov (United States)

    Arduini, G.; Martin, R. L.; Rossi, S.; Silari, M.

    1994-08-01

    Acceleration of H - ions in a synchrotron imposes severe restrictions on the level of residual pressure in the vacuum chamber and the maximum magnetic field in the magnets of the ring. Significant vacuum requirements are also imposed by the acceleration of ions. This paper discusses these two aspects of the design of a combined H -/light ion synchrotron for radiation therapy. The fractional loss of the accelerated beam induced by the two processes is evaluated on the basis of a general treatment of the physics of these phenomena. The values of the vacuum and magnetic field necessary for normal operation of the machine are specified and a discussion is given of the behaviour of the above quantities as a function of several parameters such as beam energy, composition and pressure of the residual gas in the vacuum chamber and beam extraction time.

  9. Fate of hormones and pharmaceuticals during combined anaerobic treatment and nitrogen romoval by partial nitritation-anammox in vacuum collected black water

    NARCIS (Netherlands)

    Graaff, de M.S.; Vieno, N.M.; Kujawa, K.; Zeeman, G.; Temmink, B.G.; Buisman, C.J.N.

    2011-01-01

    Vacuum collected black (toilet) water contains hormones and pharmaceuticals in relatively high concentrations (mu g/L to mg/L range) and separate specific treatment has the potential of minimizing their discharge to surface waters. In this study, the fate of estrogens (natural and synthetical

  10. Fate of hormones and pharmaceuticals during combined anaerobic treatment and nitrogen romoval by partial nitritation-anammox in vacuum collected black water

    NARCIS (Netherlands)

    Graaff, de M.S.; Vieno, N.M.; Kujawa, K.; Zeeman, G.; Temmink, B.G.; Buisman, C.J.N.

    2011-01-01

    Vacuum collected black (toilet) water contains hormones and pharmaceuticals in relatively high concentrations (mu g/L to mg/L range) and separate specific treatment has the potential of minimizing their discharge to surface waters. In this study, the fate of estrogens (natural and synthetical hormon

  11. Smart micelle@polydopamine core-shell nanoparticles for highly effective chemo-photothermal combination therapy

    Science.gov (United States)

    Zhang, Ruirui; Su, Shishuai; Hu, Kelei; Shao, Leihou; Deng, Xiongwei; Sheng, Wang; Wu, Yan

    2015-11-01

    In this investigation, we have designed and synthesized a novel core-shell polymer nanoparticle system for highly effective chemo-photothermal combination therapy. A nanoscale DSPE-PEG micelle encapsulating doxorubicin (Dox-M) was designed as a core, and then modified by a polydopamine (PDA) shell for photothermal therapy and bortezomib (Btz) administration (Dox-M@PDA-Btz). The facile conjugation of Btz to the catechol-containing PDA shell can form a reversible pH-sensitive boronic acid-catechol conjugate to create a stimuli-responsive drug carrier system. As expected, the micelle@PDA core-shell nanoparticles exhibited satisfactory photothermal efficiency, which has potential for thermal ablation of malignant tissues. In addition, on account of the PDA modification, both Dox and Btz release processes were pH-dependent and NIR-dependent. Both in vitro and in vivo studies illustrated that the Dox-M@PDA-Btz nanoparticles coupled with laser irradiation could enhance the cytotoxicity, and thus combinational therapy efficacy was achieved when integrating Dox, Btz, and PDA into a single nanoplatform. Altogether, our current study indicated that the micelle@polydopamine core-shell nanoparticles could be applied for NIR/pH-responsive sustained-release and synergized chemo-photothermal therapy for breast cancer.In this investigation, we have designed and synthesized a novel core-shell polymer nanoparticle system for highly effective chemo-photothermal combination therapy. A nanoscale DSPE-PEG micelle encapsulating doxorubicin (Dox-M) was designed as a core, and then modified by a polydopamine (PDA) shell for photothermal therapy and bortezomib (Btz) administration (Dox-M@PDA-Btz). The facile conjugation of Btz to the catechol-containing PDA shell can form a reversible pH-sensitive boronic acid-catechol conjugate to create a stimuli-responsive drug carrier system. As expected, the micelle@PDA core-shell nanoparticles exhibited satisfactory photothermal efficiency, which has

  12. Vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective Systemic chemotherapy for metastatic pancreatic cancer is still a difficult problem in clinical practice.The standard chemotherapy of pancreatic cancer has been gemcitabine,but the response rate is low.Therefore,it is in urgent need to explore an effective clinical therapy for this cancer.This paper,a case report,is aimed at discussing the effectiveness of vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer.Methods A 52-year-old female pati...

  13. Combined oral and local therapy for the dissolution of urinary calculi.

    Science.gov (United States)

    Götz, F; Frang, D; Hübler, J; Nagy, Z

    1982-01-01

    The factors underlying the formation of Ca-phosphate and struvite calculi, as well as the present possibilities for oral and local therapy, their advantages and drawbacks are discussed in the light of published evidence. In this context a clinical case of multiple injuries is reported in which practically complete chemolitholysis has been achieved by combined oral and local therapy. The rapid growth of the calculi and their alarming tendency to recurrence in case of inadequate treatment is emphasized. The therapeutic method used in this case is regarded as suitable for practical purposes.

  14. Use of tacrolimus ointment in vitiligo alone or in combination therapy.

    Science.gov (United States)

    Berti, S; Buggiani, G; Lotti, T

    2009-05-01

    Current treatments for vitiligo are largely unsatisfactory. Topical corticosteroids and phototherapy (narrow-band UVB and psoralen+UVA) are the most prescribed, however, these therapies are often not effective and have important side-effect, especially when used for a long time. Many studies have reported the efficacy and safety of tacrolimus ointment in adults and children with vitiligo, particularly when located on the head and neck. Successful treatment is possible when it is combined with other therapies, such as narrow-band UVB, microphototherapy, helium-neon laser, or narrow-band excimer laser.

  15. Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Mogensen, U. M.; Andersson, C.; Fosbøl, E. L.

    2014-01-01

    with metformin were safe compared with conventional combinations of glucose-lowering therapy. Use of incretin-based therapy may be target for strategies to lower CV risk in type 2 diabetes, although it should be recognized that the multivariable analysis may not have fully accounted for important baseline......AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long-term safety compared with conventional combination therapies are limited. METHODS: Danish individuals...... differences....

  16. Effects of pentoxifylline and pentosan polysulphate combination therapy on diabetic neuropathy in type 2 diabetes mellitus.

    Science.gov (United States)

    Laczy, Boglárka; Cseh, Judit; Mohás, Márton; Markó, Lajos; Tamaskó, Mónika; Koszegi, Tamás; Molnár, Gergo A; Wagner, Zoltán; Wagner, László; Wittmann, István

    2009-06-01

    Vascular dysfunction, including impaired perfusion has a pivotal role in the pathogenesis of microvascular complications in diabetes mellitus. Both pentoxifylline (PF) and pentosan polysulphate (PPS) are known to improve microcirculation. Antioxidant and antiproteinuric effects of PF are also known. In a placebo-controlled study, we determined the possible efficacy of PF-PPS combination therapy on diabetic neuropathy and nephropathy in type 2 diabetic patients. Patients in Verum group (n = 77) received PF-PPS infusions (100-100 mg/day) for 5 days. Control diabetics (Placebo group; n = 12) were given only saline infusions. Specialized cardiovascular autonomic reflex tests, vibration threshold values and urinary albumin excretion were assessed before and after therapy. In Verum group, autonomic score, indicating the severity of cardiac autonomic dysfunction, decreased after therapy (p < or = 0.001). Of the reflexes, deep breath and handgrip tests also improved after therapy (p < or = 0.001). Vibration threshold values, an indicator of the loss of sensory nerve function, were increased after therapy (p < or = 0.001). Results of cardiac autonomic tests and vibration threshold values remained unaltered in Placebo group. Majority of patients had normalbuminuria, which was not affected by PF-PPS. In conclusion, short-term PF-PPS therapy was effective on cardiovascular autonomic function and vibration perception, whereas it failed to reduce albuminuria within normal range in type 2 diabetic patients.

  17. EFFICACY OF FIXED COMBINATION OF VALSARTAN, AMLODIPINE AND HYDROCHLOROTHIAZIDE IN COMPLEX THERAPY OF THE PATIENT OF VERY HIGH CARDIOVASCULAR RISK

    Directory of Open Access Journals (Sweden)

    I. M. Sokolov

    2012-01-01

    Full Text Available The high prevalence of arterial hypertension in association with high and very high cardiovascular risk requires widespread use of combined therapy. Current approaches to selection of combination components of antihypertensive drugs are based the efficacy of these drugs proven in multicenter randomized clinical trials. The triple combination of calcium antagonist, angiotensin II receptor blocker and thiazide diuretic is regarded as the best option for combined therapy in patients with arterial hypertension and ischemic heart disease to reduce cardiovascular risk.

  18. Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges.

    Science.gov (United States)

    Hu-Lieskovan, Siwen; Robert, Lidia; Homet Moreno, Blanca; Ribas, Antoni

    2014-07-20

    Recent breakthroughs in the treatment of advanced melanoma are based on scientific advances in understanding oncogenic signaling and the immunobiology of this cancer. Targeted therapy can successfully block oncogenic signaling in BRAF(V600)-mutant melanoma with high initial clinical responses, but relapse rates are also high. Activation of an immune response by releasing inhibitory check points can induce durable responses in a subset of patients with melanoma. These advances have driven interest in combining both modes of therapy with the goal of achieving high response rates with prolonged duration. Combining BRAF inhibitors and immunotherapy can specifically target the BRAF(V600) driver mutation in the tumor cells and potentially sensitize the immune system to target tumors. However, it is becoming evident that the effects of paradoxical mitogen-activated protein kinase pathway activation by BRAF inhibitors in non-BRAF-mutant cells needs to be taken into account, which may be implicated in the problems encountered in the first clinical trial testing a combination of the BRAF inhibitor vemurafenib with ipilimumab (anti-CTLA4), with significant liver toxicities. Here, we present the concept and potential mechanisms of combinatorial activity of targeted therapy and immunotherapy, review the literature for evidence to support the combination, and discuss the potential challenges and future directions for rational conduct of clinical trials.

  19. Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art.

    Science.gov (United States)

    Milecki, Piotr; Martenka, Piotr; Antczak, Andrzej; Kwias, Zbigniew

    2010-10-11

    Androgen-deprivation therapy (ADT) is used routinely in combination with definitive external beam radiation therapy (EBRT) in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT-EBRT) also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.

  20. Cost-effectiveness analysis of combination therapies for visceral leishmaniasis in the Indian subcontinent.

    Directory of Open Access Journals (Sweden)

    Filip Meheus

    Full Text Available BACKGROUND: Visceral leishmaniasis is a systemic parasitic disease that is fatal unless treated. We assessed the cost and cost-effectiveness of alternative strategies for the treatment of visceral leishmaniasis in the Indian subcontinent. In particular we examined whether combination therapies are a cost-effective alternative compared to monotherapies. METHODS AND FINDINGS: We assessed the cost-effectiveness of all possible mono- and combination therapies for the treatment of visceral leishmaniasis in the Indian subcontinent (India, Nepal and Bangladesh from a societal perspective using a decision analytical model based on a decision tree. Primary data collected in each country was combined with data from the literature and an expert poll (Delphi method. The cost per patient treated and average and incremental cost-effectiveness ratios expressed as cost per death averted were calculated. Extensive sensitivity analysis was done to evaluate the robustness of our estimations and conclusions. With a cost of US$92 per death averted, the combination miltefosine-paromomycin was the most cost-effective treatment strategy. The next best alternative was a combination of liposomal amphotericin B with paromomycin with an incremental cost-effectiveness of $652 per death averted. All other strategies were dominated with the exception of a single dose of 10mg per kg of liposomal amphotericin B. While strategies based on liposomal amphotericin B (AmBisome were found to be the most effective, its current drug cost of US$20 per vial resulted in a higher average cost-effectiveness. Sensitivity analysis showed the conclusion to be robust to variations in the input parameters over their plausible range. CONCLUSIONS: Combination treatments are a cost-effective alternative to current monotherapy for VL. Given their expected impact on the emergence of drug resistance, a switch to combination therapy should be considered once final results from clinical trials are

  1. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro.

    Science.gov (United States)

    Khdair, Ayman; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

    2009-02-01

    Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.

  2. Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis.

    Science.gov (United States)

    Drusano, George L; Neely, Michael; Van Guilder, Michael; Schumitzky, Alan; Brown, David; Fikes, Steven; Peloquin, Charles; Louie, Arnold

    2014-01-01

    Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy. Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism) for susceptible organisms and subpopulations resistant to each drug in the combination. We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics. All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant). For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end. These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.

  3. Targeted Therapy of Cancer Using Photodynamic Therapy in Combination with Multi-faceted Anti-Tumor Modalities

    Directory of Open Access Journals (Sweden)

    Malini Olivo

    2010-05-01

    Full Text Available Photodynamic therapy (PDT has emerged as one of the important therapeutic options in the management of cancer and other diseases. PDT involves a tumor-localized photosensitizer (PS, which when appropriately illuminated by visible light converts oxygen into cytotoxic reactive oxygen species (ROS, that attack key structural entities within the targeted cells, ultimately resulting in necrosis or apoptosis. Though PDT is a selective modality, it can be further enhanced by combining other targeted therapeutic strategies that include the use of synthetic peptides and nanoparticles for selective delivery of photosensitizers. Another potentially promising strategy is the application of targeted therapeutics that exploit a myriad of critical pathways involved in tumorigenesis and metastasis. Vascular disrupting agents that eradicate tumor vasculature during PDT and anti-angiogenic agents that targets specific molecular pathways and prevent the formation of new blood vessels are novel therapeutic approaches that have been shown to improve treatment outcome. In addition to the well-documented mechanisms of direct cell killing and damage to the tumor vasculature, PDT can also activate the body’s immune response against tumors. Numerous pre-clinical studies and clinical observations have demonstrated the immuno-stimulatory capability of PDT. Herein, we aim to integrate the most important findings with regard to the combination of PDT and other novel targeted therapy approaches, detailing its potential in cancer photomedicine.

  4. Options for empagliflozin in combination therapy in type 2 diabetes mellitus

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    Hershon KS

    2016-05-01

    Full Text Available Kenneth S Hershon1,2 1North Shore Diabetes and Endocrine Associates, New Hyde Park, 2Department of Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA Objective: To update clinicians with an overview of empagliflozin for the treatment of type 2 diabetes mellitus (T2DM, with focus on use in combination regimens. Methods: Keyword searches were conducted in the Medline database to identify literature reporting clinical trials of at least 12 weeks' duration using empagliflozin treatment in patients with T2DM. Results: When given as monotherapy or in combination therapy (as add-on or single-pill therapy with metformin, pioglitazone, sulfonylurea, linagliptin, and insulin, empagliflozin produced clinically meaningful reductions in glycated hemoglobin levels, plasma glucose concentrations, bodyweight, and blood pressure. These changes were sustained during long-term treatment. In a dedicated cardiovascular event trial, empagliflozin on top of standard of care demonstrated a significant reduction in the risk of cardiovascular mortality and all-cause mortality. Across the clinical trials, empagliflozin combination therapies were well tolerated, and empagliflozin used alone was not associated with increased risk of hypoglycemia versus placebo. Indeed, the combination of empagliflozin and metformin had a significantly reduced rate of hypoglycemia compared with the combination of metformin and a sulfonylurea. On the other hand, empagliflozin treatment did have increased risk of genital infections compared with placebo. In clinical trials to date, diabetic ketoacidosis was not seen more frequently with empagliflozin than with placebo, but physicians should be alert to the possibility of this rare event. Conclusion: Empagliflozin has the potential to make an important contribution to the treatment of patients with T2DM. In some patients, empagliflozin may be used as monotherapy, but it is most likely to be used in combination with other

  5. Combination therapy with biologic agents in rheumatic diseases: current and future prospects

    Science.gov (United States)

    Inui, Kentaro; Koike, Tatsuya

    2016-01-01

    Strategies in rheumatoid arthritis (RA) based on ‘treat to target’ aim to control disease activity, minimize structural damage, and promote longer life. Several disease-modifying antirheumatic drugs (DMARDs) have been shown to be effective including biological DMARDs (bDMARDs). Treatment guidelines and recommendations for RA have also been published. According to those guidelines, conventional synthetic DMARDs (csDMARDs), as monotherapy or combination therapy, should be used in DMARD-naïve patients, irrespective of the addition of glucocorticoids (GCs). Combination therapies with bDMARDs are also essential for conducting treatment strategies for RA, because in every recommendation or guideline for the management of RA, combination therapies of csDMARDs with bDMARDs are recommended for RA patients with moderate or high disease activity after failure of csDMARD treatment. bDMARDs are more efficacious if used concomitantly with methotrexate (MTX) than with MTX monotherapy or bDMARD monotherapy. Thus, retention has been reported to be longer when combined with MTX. The superior efficacy of combination therapy compared with MTX monotherapy or bDMARD monotherapy could be because: (1) it could help to minimize MTX toxicity by reducing the dose of MTX, thus retention rate of the same therapeutic regimen would become high; (2) anti-bDMARD antibodies are observed at lower concentrations when using MTX concomitantly, so less clearance of bDMARDs via less formation of bDMARD and an anti-bDMARD immune complex; (3) of the additive effects of MTX to bDMARD, especially the combination of tumor necrosis factor inhibitors (TNFis) with MTX. Hence, evidence suggests that combination therapy with bDMARDs is more efficacious than monotherapy using a csDMARD or bDMARD, and that MTX is the best drug for this purpose (if MTX is not contraindicated). Finding the most effective drug regimen at the lowest cost will be the aim of RA treatment in the future. PMID:27721905

  6. Combination Therapy of Ursodeoxycholic Acid and Corticosteroids for Primary Biliary Cirrhosis with Features of Autoimmune Hepatitis: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2013-01-01

    Full Text Available A meta-analysis was performed of RCTs comparing therapies that combine UDCA and corticosteroids with UDCA monotherapy. In this paper, we found that the combination therapy of UDCA and corticosteroids was more effective for PBC-AIH.

  7. Sofosbuvir and simeprevir combination therapy in the setting of liver transplantation and hemodialysis.

    Science.gov (United States)

    Perumpail, R B; Wong, R J; Ha, L D; Pham, E A; Wang, U; Luong, H; Kumari, R; Daugherty, T J; Higgins, J P; Younossi, Z M; Kim, W R; Glenn, J S; Ahmed, A

    2015-04-01

    We report safety, tolerability, and 12-week sustained virologic response with half-standard dose sofosbuvir and standard-dose simeprevir combination therapy in a hepatitis C virus genotype 1a-infected liver transplant recipient on hemodialysis - uncharted territory for sofosbuvir-based therapy. The patient was a non-responder to prior treatment with pegylated interferon plus ribavirin. Sofosbuvir efficacy was maintained despite pill-splitting and administration of half-standard dose, 200 mg per day. No drug-drug interactions were noted with tacrolimus-based immunosuppression. Laboratory tests remained stable or improved during therapy. Our observation, if reproduced in a larger study, may lead to significant improvement in clinical outcomes and cost savings in this patient population.

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

    Science.gov (United States)

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

    2012-01-01

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

  9. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency

    Science.gov (United States)

    Montiel-Equihua, Claudia A; Thrasher, Adrian J; Gaspar, H Bobby

    2010-01-01

    The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID) and especially adenosine deaminase (ADA)-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. Patients in trials in three different countries have shown long-term immunological and metabolic correction. Nevertheless, improvements to the safety profile of viral vectors are underway and will undoubtedly reinforce the position of stem cell gene therapy as a treatment option for ADA-SCID. PMID:24198507

  10. Combined treatment of exudative age related macular degeneration with photodynamic therapy and intravitreal triamcinolone

    Directory of Open Access Journals (Sweden)

    José Mª Ruiz-Moreno

    2008-03-01

    Full Text Available José Mª Ruiz-Moreno1,2, Javier A Montero21Department of Ophthalmology, Miguel Hernández University School of Medicine, Alicante, Spain; 2Vitreo-Retinal Unit, Alicante Institute of Ophthalmology, Alicante, SpainAbstract: Choroidal neovascularization (CNV secondary to age related macular degeneration is among the leading causes of legal blindness in developed countries. Photodynamic therapy (PDT with verteporfin induces CNV closure causing little damage to healthy tissue, but the need to re-treat may lead to low final visual acuity at an unacceptable cost. The association of intravitreous triamcinolone or antiangiogenic drugs with PDT has been used in order to reduce these limitations of the therapy. The combination of PDT and intravitreous triamcinolone, its complications and outcome at one and two-year follow-up are discussed.Keywords: age related macular degeneration, choroidal neovascularization, photodynamic therapy, steroid, triamcinolone

  11. Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents.

    Science.gov (United States)

    Cox, Georgina R; Callahan, Patch; Churchill, Rachel; Hunot, Vivien; Merry, Sally N; Parker, Alexandra G; Hetrick, Sarah E

    2014-11-30

    Depressive disorders are common in children and adolescents and, if left untreated, are likely to recur in adulthood. Depression is highly debilitating, affecting psychosocial, family and academic functioning. To evaluate the effectiveness of psychological therapies and antidepressant medication, alone and in combination, for the treatment of depressive disorder in children and adolescents. We have examined clinical outcomes including remission, clinician and self reported depression measures, and suicide-related outcomes. We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 11 June 2014. The register contains reports of relevant randomised controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). RCTs were eligible for inclusion if they compared i) any psychological therapy with any antidepressant medication, or ii) a combination of psychological therapy and antidepressant medication with a psychological therapy alone, or an antidepressant medication alone, or iii) a combination of psychological therapy and antidepressant medication with a placebo or'treatment as usual', or (iv) a combination of psychological therapy and antidepressant medication with a psychological therapy or antidepressant medication plus a placebo.We included studies if they involved participants aged between 6 and 18 years, diagnosed by a clinician as having Major Depressive Disorder (MDD) based on Diagnostic and Statistical Manual (DSM) or International Classification of Diseases (ICD) criteria. Two review authors independently selected studies, extracted data and assessed the quality of the studies. We applied a random-effects meta-analysis, using the odds ratio (OR) to describe dichotomous outcomes, mean difference (MD) to describe continuous outcomes when the same measures were used, and standard mean difference (SMD) when

  12. Feasibility assessment of vacuum cooling followed by immersion vacuum cooling on water-cooked pork.

    Science.gov (United States)

    Dong, Xiaoguang; Chen, Hui; Liu, Yi; Dai, Ruitong; Li, Xingmin

    2012-01-01

    Vacuum cooling followed by immersion vacuum cooling was designed to cool water-cooked pork (1.5±0.05 kg) compared with air blast cooling (4±0.5°C, 2 m/s), vacuum cooling (10 mbar) and immersion vacuum cooling. This combined cooling method was: vacuum cooling to an intermediate temperature of 25°C and then immersion vacuum cooling with water of 10°C to the final temperature of 10°C. It was found that the cooling loss of this combined cooling method was significantly lower (Pvacuum cooling. This combined cooling was faster (Pvacuum cooling in terms of cooling rate. Moreover, the pork cooled by combined cooling method had significant differences (P<0.05) in water content, color and shear force. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Combined Intratympanic and Systemic Steroid Therapy for Poor-Prognosis Sudden Sensorineural Hearing Loss

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    Shima Arastou

    2012-12-01

    Full Text Available Introduction: The aim of this study was to evaluate the efficacy of combined intratympanic and systemic steroid therapy compared with systemic steroid therapy alone in idiopathic sudden sensorineural hearing loss (ISSNHL patients with poor prognostic factors.     Materials and Methods: Seventy-seven patients with sudden sensorineural hearing loss (SSNHL who had at least one poor prognostic factor (age greater than 40 years, hearing loss more than 70 db, or greater than a 2-week delay between the onset of hearing loss and initiation of therapy were included in this study. Patients were randomized to the intervention group (combined intratympanic and systemic steroid therapy or the control group (systemic steroid therapy alone. All patients received oral treatment with systemic prednisolone (1 mg/kg/day for 10 days, acyclovir (2 g/day for 10 days, divided into four doses, triamterene H (daily, and omeprazole (daily, during steroid treatment, and were advised to follow a low salt diet. The intervention group also received intratympanic dexamethasone injections (0.4 ml of 4 mg/ml dexamethasone two times a week for two consecutive weeks (four injections in total. A significant hearing improvement was defined as at least a 15-db decrease in pure tone average (PTA.  Results: Among all participants, 44 patients (57.14% showed significant improvement in hearing evaluation. More patients showed hearing improvement in the intervention group than in the control group (27 patients (75% versus 17 patients (41.4%, respectively; P = 0.001.  Conclusion:  The combination of intratympanic dexamethasone and systemic prednisolone is more effective than systemic prednisolone alone in the treatment of poor-prognosis SSNHL.

  14. Combined Intratympanic and Systemic Steroid Therapy for Poor-Prognosis Sudden Sensorineural Hearing Loss

    Directory of Open Access Journals (Sweden)

    Shima Arastou

    2012-12-01

    Full Text Available Introduction: The aim of this study was to evaluate the efficacy of combined intratympanic and systemic steroid therapy compared with systemic steroid therapy alone in idiopathic sudden sensorineural hearing loss (ISSNHL patients with poor prognostic factors.     Materials and Methods: Seventy-seven patients with sudden sensorineural hearing loss (SSNHL who had at least one poor prognostic factor (age greater than 40 years, hearing loss more than 70 db, or greater than a 2-week delay between the onset of hearing loss and initiation of therapy were included in this study. Patients were randomized to the intervention group (combined intratympanic and systemic steroid therapy or the control group (systemic steroid therapy alone. All patients received oral treatment with systemic prednisolone (1 mg/kg/day for 10 days, acyclovir (2 g/day for 10 days, divided into four doses, triamterene H (daily, and omeprazole (daily, during steroid treatment, and were advised to follow a low salt diet. The intervention group also received intratympanic dexamethasone injections (0.4 ml of 4 mg/ml dexamethasone two times a week for two consecutive weeks (four injections in total. A significant hearing improvement was defined as at least a 15-db decrease in pure tone average (PTA.  Results: Among all participants, 44 patients (57.14% showed significant improvement in hearing evaluation. More patients showed hearing improvement in the intervention group than in the control group (27 patients (75% versus 17 patients (41.4%, respectively; P = 0.001.  Conclusion:  The combination of intratympanic dexamethasone and systemic prednisolone is more effective than systemic prednisolone alone in the treatment of poor-prognosis SSNHL.

  15. A combined intervention of art therapy and clown visits to reduce preoperative anxiety in children.

    Science.gov (United States)

    Dionigi, Alberto; Gremigni, Paola

    2017-03-01

    To test whether a combined intervention of art therapy and clown visits could enhance the efficacy of oral medication in reducing children's anxiety at parental separation prior to induction of anaesthesia. Approximately 50% of children undergoing surgery report high anxiety at anaesthesia induction. Complementary therapies have been used to decrease children's anxiety, but no study has evaluated the efficacy of a combination of such therapies. This is an observational study, which involved allocating different interventions to two groups and measuring their anxiety at two time points. This study assigned 78 children (aged 3-11 years) undergoing general anaesthesia for surgery to two conditions. The control group underwent general anaesthesia following standard practice, and the intervention group received an intervention of integrated art therapy and clown visits upon their arrival at the hospital and throughout their time in the preoperating room. Each child in both groups received 0·5 mg/kg oral midazolam 30 minutes before surgery and had a parent present throughout their time in the preoperating room. Each child's anxiety was evaluated twice using the Modified Yale Preoperative Anxiety Scale: at baseline and at separation from parents. Repeated measures anova was used to test for differences between the time points and the two groups. Children in the intervention group showed a significant (p art therapy and clown visits enhanced the effect of midazolam in reducing children's anxiety at preoperative separation from parents. Paediatric staffs may consider using such a combination of strategies in preparing children for anaesthesia induction. © 2016 John Wiley & Sons Ltd.

  16. Is combined lipid-regulating therapy safe and feasible for the very old patients with mixed dyslipidemia?

    OpenAIRE

    Zou, Xiao; Si, Quan-Jin

    2013-01-01

    Objectives To detect the efficacy and safety of combined lipid-regulating therapies in the very old patients with mixed dyslipidemia and determine an appropriate therapy for them. Methods Four hundred and fifty patients aged over 75 with mixed dyslipidemia were divided into five groups according to different combination therapies. Lipid levels and drug related adverse events were tested during the study. Results Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels wer...

  17. [Efficacy of combined 5-nitroimidazole and probiotic therapy of bacterial vaginosis: randomized open trial].

    Science.gov (United States)

    Kovachev, S; Vatcheva-Dobrevski, R

    2013-01-01

    The aim of the current research is to identify the clinical and microbiological effect of 5-nitroimidazol therapy for the treatment of bacterial vaginosis and in combination with probiotics and the influence of such therapy upon vaginal flora. Women (n = 539) with bacterial vaginosis who meet the criteria were included in the study. They were randomized into two groups with the following therapeutic regimes: in the first group (n = 242 women) the treatment included applications of 2g BID tinidazole for two days and vaginal suppositories of 1000 mg metronidazol at day 1 and 3 (T+M). In the second group (n = 297) the women were cured with the same treatment as those in the first group. In addition to it from the fifth day of the treatment was added a topical administration of vaginal probiotic which contains species of alive lactobacilli: Lactobacillus acidophilus, Lactobacillus rhamnosus (T+M+P). The efficacy from the therapy was evaluated using the clinical compliances of the women, the data from the clinical examination and the microbiological tests results. The results showed expected increase of clinical therapy efficacy (Amsel - criteria) from 42.8% (T+M; n = 211/242) to 84.06% (T+M+P; n = 274/297) in groups and of microbiological efficacy (Nugent) from 44.7% (T+M; n = 211/242) to 83.3% (T+M+P; n = 274/297), in follow up 35-40 days from the beginning of treatment. The percentage of women with normal vaginal flora on 35-40 day after the therapy increase with 57% in the (T+M) first group while in the second group (T+M+P) with 94%. Combining the therapies of 5-nitroimidazoles and vaginal probiotic reduce bacterial vaginosis recurrence and restores permanently normal vaginal flora.

  18. ECONOMIC EVALUATION OF COMBINED THERAPY OF ARTERIAL HYPERTENSION BY MARKOV’S MODELING

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    N. S. Maksimchuk-Kolobova

    2015-09-01

    Full Text Available Aim. To evaluate the economic effectiveness of the combined two-drug antihypertensive therapy in patients with arterial hypertension (HT and high cardiovascular risk by Markov’s modeling.Material and methods. Patients (n= 65; 19 males and 46 females with essential HT accompanied by metabolic disorders, history of previous ineffective antihypertensive therapy were included into the study. Patients were randomized into 2 groups. Group V/A was treated with valsartan and amlodipine in fixed-dose combinations of 160/5 and 160/10 mg depending on blood pressure (BP level. Patients of group L/A were treated with losartan 100 mg and amlodipine 5 or 10 mg daily. Treatment duration was 24 weeks. Changes in BP level, and left ventricular hypertrophy (LVH regression were assessed. Economic evaluation was performed on the basis of modeling with specialized software Decision Tree 4.xla.Results. Effect of the two variants of combination therapy on LVH was used to estimate treatment effectiveness and to build the model. Patients were distributed according to the left ventricular mass (LVM at baseline and after 24 weeks of therapy. Significant decrease in LVM was observed in V/A group: from 225.1±71.7 to 186.3±44.5 g (p<0.05. There was no LVM dynamics in L/A group. The model took into account economic and frequency factors for 10 years forecast. V/A therapy is able to prevent 94 deaths, 22 strokes, and 64 myocardial infarction per 1000 patients. Absence of need in treatment of these prevented events can save about 5.5 million RUR for every 1000 patients. It would reduce the total costs per patient during 10 years. V/A therapy is able to save maximal number of quality adjusted life years (QALY due to LVM regression (5.016 years. L/A combination is the most economical variant of pharmacotherapy due to low cost of treatment (16.491.25 RUR per 1 QALY. It would take 286.698.7 RUR additionally for one additional QALY in the treatment with V/A, and it is

  19. The application and efficacy of combined neurofeedback therapy and imagery training in adolescents with Tourette syndrome.

    Science.gov (United States)

    Zhuo, Chuanjun; Li, Li

    2014-07-01

    We aimed to examine the effectiveness of combined neurofeedback therapy and imagery training in adolescent patients with refractory Tourette syndrome. Two patients, aged respectively 14 and 16 years, had been treated with haloperidol and tiapride; however, this medication was ineffective and accompanied by intolerable side effects. In this study, the patients completed 80 sessions of neurofeedback treatment followed by imagery training. The patients were assessed with behavior rating scales both before and after the treatment as well as during follow-up examinations to evaluate the effect of the combined therapy. Patients showed significant improvement in motor tic and vocal tic symptoms, exemplified by a reduction in the frequency and intensity of tics, indicating that neurofeedback, together with imagery training, has a positive therapeutic effect on adolescent patients with medication-refractory Tourette syndrome.

  20. Development and characterization of nanocarriers for topical treatment of psoriasis by using combination therapy.

    Science.gov (United States)

    Parnami, Nupur; Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2014-12-01

    Psoriasis is an autoimmune, chronic, inflammatory skin disease characterized by epidermal hyperplasia, proliferation of blood vessels, and infiltration of leukocytes in dermis and epidermis. Several immunosuppressants such as methotrexate (MXT) and cyclosporine are used but they are associated with adverse effects due to down regulation of immune system. Numerous approaches have been explored to overcome the problems of conventional topical system such as high frequency of application, impermeability to skin barrier, and limited efficacy. Photodynamic therapy is another non-invasive technique currently used for skin diseases. The combination of two drugs is also commonly observed to achieve more effective therapy. In the present study, antipsoriatic activity of niosomal formulations for the treatment of psoriasis in combination with narrow and broad band UV radiation had been explored in experimental animal model.

  1. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency

    Directory of Open Access Journals (Sweden)

    Claudia A Montiel-Equihua

    2009-12-01

    Full Text Available Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID and especially adenosine deaminase (ADA-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. Patients in trials in three different countries have shown long-term immunological and metabolic correction. Nevertheless, improvements to the safety profile of viral vectors are underway and will undoubtedly reinforce the position of stem cell gene therapy as a treatment option for ADA-SCID.Keywords: adenosine deaminase, severe combined immunodeficiency, gene therapy, hematopoietic stem cell, retrovirus, clinical trial

  2. Combination of photodynamic and ultrasonic therapy for treatment of infected wounds in animal model

    Science.gov (United States)

    Menyaev, Yulian A.; Zharov, Vladimir P.

    2006-02-01

    One of the important problems of modern medicine is treatment of infected wounds. There are many diversified expedients of treatment, but none of them obey the modern physician completely. The aim of this study is to develop and test a new combined method of photodynamic ultrasonic therapy (PDUST) for treatment of infected wounds with focus on experimental trials. PDUST is based on a combination of two methods: photodynamic (PD) therapy (PDT) with photosensitizer and low frequency ultrasonic (US) therapy with antibiotic as tools for treatment of wounds and effectively killing bacteria. The main parameters are: US frequency - 26.5 kHz; US tip elongation - 40+/-20 μm wavelength of light emitting diodes (LED) array - 660+/-10 nm; light intensity on biotissue surface - 1-2 mW/cm2; photosensitizer - an aluminum disulfonated phtalocyanine dissolved in a physiological solution in concentration 10 mg/l. The experiments were carried out with 70 male chinchilla rabbits divided into 7 groups, thus the dynamics of wounds healing were studied in different modes of PDUST. The PD and US methods supplement each other and in conjunction provide additive and especially synergetic effects. The experimental data demonstrated advantages of new technology in comparison with conventional methods in cases of treatment of extended suppurative inflammatory and profound wounds. The more detailed study of PDUST method's mechanism, which is based on low intensity of LED light, PD therapy and US influence is required.

  3. [The Effectiveness of Cognitive Behavioral Therapy, Medication, or Combined Treatment For Child Hood Anxiety Disorders].

    Science.gov (United States)

    Sevi Tok, Emine Sevinç; Arkar, Haluk; Bildik, Tezan

    2016-01-01

    The aims of this study were to evaluate the effectiveness of the Fear Hunter cognitive behavioral therapy program, which was developed for the treatment of childhood anxiety disorders, and to compare its effectiveness with standard medication treatment. A total of 46 participants (aged 8 to 12) that applied to the Ege University, Faculty of Medicine, Child and Adolescent Psychiatry clinic and had a diagnosis of anxiety disorder were recruited for the study. The participants were randomly assigned to cognitive behavioral therapy (CBT), standard drug treatment (ST), or combined treatment (CBT+ ST) groups according to the order of application. Subjects were evaluated using pretest, posttest and 3 months follow-up measurements. The participants were assessed by the researcher using The Screen for Child Anxiety Related Emotional Disorders (SCARED), The Children's Negative Cognitive Errors Questionnaire (CNCEQ), Health Related Quality of Life in Children (Kid-KINDL), and Children's Depression Inventory (CDI). The results of repeated measures ANOVA showed that, although general anxiety scores of all treatment conditions significantly decreased at posttest and follow up, a combination of two therapies (CBT+ST) had a significantly superior response rate. Moreover, all treatment conditions including CBT (CBT+ST and CBT) were superior to ST in terms of negative cognitive errors, quality of life, and depression. It is thought that The Fear Hunter Therapy Program is an effective treatment technique because; it provides significant improvement in the primary and secondary symptoms (e.g. quality of life, depression, negative automatic thoughts) of childhood anxiety disorders.

  4. Clinical significance of anaemia in chronic hepatitis c on the combined antiviral therapy with pegylated

    Directory of Open Access Journals (Sweden)

    K. V. Zhdanov

    2011-01-01

    Full Text Available In order to study the effect of combination antiviral therapy for hemoglobin and red blood cells in patients with chronic hepatitis C were estimated absolute numbers of red blood parameters. To determine the relation between the content of red blood cells and hemoglobin at different stages of antiviral therapy with the initial clinical and laboratory  parameters (gender, age, body mass index, genotype, level of viremia, ALT, fibrosis, as well as the results of combined antiviral therapy. Established that the decrease in hemoglobin levels were observed more frequently than the decline in the number of erythrocytes (63,6% and 21,1% respectively. In addition, anemia that occurred during treatment of HCV patients with pegylated interferon-α, directly correlated with the rate of sustained virological response. The study established prognostic criteria, indicating the possible development of anemia in the background of anti-viral therapy: the female sex, BMI <20 kg/m2, 1 genotype of HCV.

  5. Childhood vitiligo : Response to methylprednisolone oral minipulse therapy and topical fluticasone combination

    Directory of Open Access Journals (Sweden)

    Majid Imran

    2009-01-01

    Full Text Available Background: Childhood vitiligo is always a challenge to treat, especially when the disease is progressing rapidly in such a patient. Oral minipulse with betamethasone has been tried in childhood vitiligo and also in some other immune mediated skin disorders with good results. Aims: The aim of the present study was to see the overall efficacy of methylprednisolone oral minipulse therapy in combination with topical fluticasone in progressive childhood vitiligo. The combination was tried to achieve a significant amount of repigmentation of vitiligo lesions already present at the initial visit. Materials and Methods: Four hundred children with progressive vitiligo were enrolled for this study and were prescribed oral methylprednisolone on two consecutive days every week in a minipulse form for a period of six months. In addition, the patients were instructed to apply fluticasone ointment topically once a day on their vitiligo lesions. The patients were assessed for the remission achieved as well as the extent of repigmentation of their already existent lesions. Results: More than 90% of patients went into complete remission after the start of the therapy. Moreover, about 65% (two-thirds of patients achieved good to excellent repigmentation of lesions at the end of six months of therapy. The therapy was also well tolerated and the side effects seen were almost negligible. Conclusions: Oral minipulse treatment with methylprednisolone is an effective treatment option for controlling the disease spread in childhood vitiligo and with the addition of topical fluticasone the extent of repigmentation achieved is also quite significant.

  6. Successful treatment of a large oral verrucous hyperplasia with photodynamic therapy combined with cryotherapy

    Directory of Open Access Journals (Sweden)

    Yu-Chao Chang

    2013-03-01

    Full Text Available Studies have shown that topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT can be used successfully for the treatment of oral verrucous hyperplasia (OVH. Studies have also demonstrated that cryotherapy could be used as a treatment modality for OVH lesions. In this case report, we tested the efficacy of topical ALA-PDT, combined with cryogun cryotherapy, for an extensive OVH lesion on the right buccal mucosa of a 65-year-old male areca quid chewer. The tumor was cleared after six treatments of combined topical ALA-PDT and cryogun cryotherapy. No recurrence of the lesion was found after a follow-up period of 18 months. We suggest that our combined treatment protocol may be effective in treating OVH lesions. The treatment course may be slightly shortened with this combined protocol and was well tolerated by the patient.

  7. THE EFFECTIVENESS OF COMBINED THERAPY OF POSTMENOPAUSAL OSTEOPOROSIS WITH DUAL ACTION DRUGS

    Directory of Open Access Journals (Sweden)

    T. B. Minasov

    2011-01-01

    Full Text Available Osteoporosis is one of the most dangerous diseases occurred in elderly persons. Results of application of strontium ranelate in combination with calcium for treatment a women with a postmenopausal osteoporosis are resulted. The influence of this complex therapy on dynamics of mineral density indexes of a bone tissue and the level of bone metabolism were studied. Strontium ranelate both at monotherapy, and in combination with calcium promotes the augmentation of mineral density of bone tissue in an axial skeleton. The taking Strontium ranelate doesn’t cause serious side effect.

  8. Combined concurrent nanoshell loaded macrophage-mediated photothermal and photodynamic therapies

    Science.gov (United States)

    Hirschberg, Henry; Trinidad, Anthony; Christie, Catherine E.; Peng, Qian; Kwon, Young J.; Madsen, Steen

    2015-02-01

    Macrophages loaded with gold nanoshells (AuNS), that convert near infrared light to heat, can be used as transport vectors for photothermal hyperthermia of tumors. The purpose of this study was to investigate the effects of combined macrophage mediated photothermal therapy (PTT) and PDT on head and neck squamous cell carcinoma (HNSCC). The results provide proof of concept for the use of macrophages as a delivery vector of AuNS for photothermal enhancement of the effects of PDT on squamous cell carcinoma. A significant synergy was demonstrated with combined PDT and PTT compared to each modality applied separately.

  9. Circulating beliefs, resilient metaphors and faith in biomedicine: hepatitis C patients and interferon combination therapy.

    Science.gov (United States)

    Jenner, Anton; Scott, Anne

    2008-03-01

    In this paper, we argue that circulating metaphors and beliefs can create an environment in which particular biomedical treatments make cultural sense, even if they seem to be ineffective or are associated with unpleasant side effects. We develop this argument in relation to interferon combined therapy. An innovative methodology combining the collection and deconstructive analysis of visual and narrative texts produced by people with hepatitis C is used to demonstrate links between a predisposition towards Western biomedical practice, discomfort with uncertainty, a desire to reassert control, and adoption of conflict metaphors associated with the tropes of invasion and eradication.

  10. Combination therapy with sivelestat and recombinant human soluble thrombomodulin for ARDS and DIC patients

    Directory of Open Access Journals (Sweden)

    Miyoshi S

    2014-09-01

    Full Text Available Seigo Miyoshi,1 Ryoji Ito,1 Hitoshi Katayama,1 Kentaro Dote,2 Mayuki Aibiki,3 Hironobu Hamada,1,4 Takafumi Okura,1 Jitsuo Higaki1 1Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, 2Intensive Care Division, Ehime University Hospital, 3Department of Emergency and Critical Care Medicine, School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 4Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi, Minami-ku, Hiroshima, Japan Background: Neutrophil elastase, alveolar thrombin generation, and fibrin deposition play crucial roles in the development of acute respiratory distress syndrome (ARDS and disseminated intravascular coagulation (DIC. However, the usefulness of combination therapy with a selective neutrophil elastase inhibitor, sivelestat, and recombinant human soluble thrombomodulin (rhTM for patients with ARDS and DIC remains unknown. Methods: We conducted a retrospective data analysis of 142 ARDS patients with DIC to assess the effects of sivelestat combined with rhTM. Patients were divided into four groups: control (no sivelestat or rhTM treatment, sivelestat treatment alone, rhTM treatment alone, and combined treatment with sivelestat and rhTM. A Cox proportional hazard model was used to assess subject mortality rates. The efficacy of these drugs was evaluated based on survival rate, number of ventilator-free days, and change in PaO2/FIO2 (P/F ratios and DIC scores before and at 7 days after a diagnosis of ARDS with DIC. Results: Multivariate analysis showed that patient age, combination therapy, gas exchange, organ failure, cause, associated disease score, and serum C-reactive protein levels were predictors of mortality for patients with ARDS and DIC. As compared with untreated controls, combination therapy significantly improved the 60-day survival rate of patients with ARDS and DIC

  11. Vacuum mechatronics. Proceedings.

    Science.gov (United States)

    Belinski, S. E.; Shirazi, M.; Hackwood, S.; Beni, G.

    The discipline of vacuum mechatronics is the design and development of vacuum-compatible, computer-controlled mechanisms for manipulating, sensing and testing in a vacuum environment. Vacuum mechantronics is relevant to research engineers in integrated circuit manufacturing, surface physics, food processing, biotechnology, materials handling, space sciences and manufacturing.

  12. Disseminated mucormycosis in a paediatric patient: Lictheimia corymbifera successfully treated with combination antifungal therapy

    Directory of Open Access Journals (Sweden)

    Anita Campbell

    2014-10-01

    Full Text Available Mucormycosis is a severe fungal infection that largely affects immunocompromised individuals. It carries a high morbidity and mortality rate and is characterised by extensive angioinvasion and necrosis of host tissue. This case report details success in treating disseminated mucormycosis in a paediatric patient with an underlying haematological malignancy. Treatment included institution of combination antifungal therapy with liposomal amphotericin B and caspofungin, aggressive surgical debridement of infected tissue and reversal of underlying immunosuppression.

  13. Combination of internal radiation therapy and hyperthermia to treat liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Grady, E.D.; McLaren, J.; Auda, S.P.; McGinley, P.H.

    1983-09-01

    Sixteen patients were treated for liver cancer (primary and metastatic) by a combination of internal radiation therapy with intra-arterial yttrium 90 microspheres and regional hyperthermia with electromagnetic radiation. Four patients have their liver disease apparently controlled; two had a partial regression of more than 50%; and two had a partial regression of less than 50%. The complications consisted of one case of radiation hepatitis and one of peptic ulcer.

  14. Combined use of transmyocardial stents with gene therapy in the treatment of acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    王永武

    2006-01-01

    Objective To determine the efficacy of combined use of transmyocardial stent with gene therapy to treat acute myocardial infarction in porcine model. Methods 24 Chinese mini swines have been devided into 4 groups randomly: group myocardial infarction (group MI n1 = 6), group transmyocardial stent (group ST n2 = 6) , group vascular endothelial growth factor (group VEGF n3 = 6) , group transmyocardial stent and VEGF (group ST + VEGF n4 = 6). In group MI,acute myocardial infarc-

  15. Combined endodontic therapy and surgery in the treatment of dens invaginatus Type 3: case report.

    Science.gov (United States)

    da Silva Neto, Ulisses Xavier; Hirai, Vinício Hidemitsu Goto; Papalexiou, Vula; Gonçalves, Silvana Beltrami; Westphalen, Vânia Portela Ditzel; Bramante, Clovis Monteiro; Martins, Wilson Denis

    2005-12-01

    An accurate understanding of the morphology of the root canal system is a prerequisite for successful root canal treatment. Invaginated teeth have a complex root canal configuration that cannot be instrumented effectively and should be treated by both endodontic therapy and surgery. A case of dens invaginatus Type 3 in a maxillary lateral incisor with a periapical lesion and its successful treatment by these combined methods is reported.

  16. Rationale supporting basal insulin-incretin combined therapies in type 2 diabetes

    OpenAIRE

    Scheen, André; Paquot, Nicolas

    2013-01-01

    Type 2 diabetes is characterized by an insulin secretory defect that cannot compensate for insulin resistance. Such relative defect is present in the fasting state (insufficient basal insulin levels) and contributes to overnight hyperglycaemia; it is even more pronounced in the postprandial state when it is then the main responsible factor for hyperglycaemia following meals. An original approach to correct these two disturbances is to propose a therapy combining the injection of a basal insul...

  17. Combining Mindfulness Meditation with Cognitive-Behavior Therapy for Insomnia: A Treatment-Development Study

    OpenAIRE

    Ong, Jason C.; Shapiro, Shauna L.; Manber, Rachel

    2007-01-01

    This treatment-development study is a Stage I evaluation of an intervention that combines mindfulness meditation with cognitive-behavior therapy for insomnia (CBT-I). Thirty adults who met research diagnostic criteria for Psychophysiological Insomnia (Edinger et al., 2004) participated in a 6-week, multi-component group intervention using mindfulness meditation, sleep restriction, stimulus control, sleep education, and sleep hygiene. Sleep diaries and self-reported pre-sleep arousal were asse...

  18. Outcomes and Duration of Pneumocystis jirovecii Pneumonia Therapy in Infants with Severe Combined Immunodeficiency

    Science.gov (United States)

    Lundgren, Ingrid S.; Englund, Janet A.; Burroughs, Lauri M.; Torgerson, Troy R.; Skoda-Smith, Suzanne

    2011-01-01

    This retrospective review of patients with severe combined immunodeficiency and Pneumocystis jirovecii pneumonia (PCP) evaluated the relationship between duration of therapy to treat PCP and overall survival. We found that 80% of patients receiving only 21 days of antibiotics survived to 12 months beyond hematopoetic cell transplant, whereas only 25% of patients who required longer treatment for PCP survived to stem cell engraftment. PMID:21817949

  19. Seizure-freedom with combination therapy in localization-related epilepsy.

    Science.gov (United States)

    Peltola, Jukka; Peltola, Maria; Raitanen, Jani; Keränen, Tapani; Kharazmi, Elham; Auvinen, Anssi

    2008-04-01

    We analyzed the effect of combination therapy on seizure frequency in all adult patients (N=193) with focal epilepsy followed at a single institution in a cross-sectional study. One hundred and thirty-five patients were on two AEDs, of them, 37 (27%) were seizure-free, 50 patients were on three AEDs including 5 (10%) seizure-free patients (pseizure-freedom with two AEDs versus three AEDs). Thirty-five different combinations were used in patients on two AEDs and 40 combinations on patients on three drugs emphasizing the difficulties involved in evaluation of the efficacy and tolerability of specific combinations. The significant proportion of seizure-free cases (27%) on duotherapy is suggesting the usefulness of combination therapy in achieving seizure-freedom in epilepsies refractory to single drug treatment. The material in the study was not from a randomized trial and therefore the comparability of patients on different AEDs is uncertain, but on the other hand the clinical practice followed provides a natural experiment suitable for comparative, non-randomized assessment of treatment outcomes.

  20. Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel

    Directory of Open Access Journals (Sweden)

    Li-Xia Feng

    2014-03-01

    Full Text Available Ceramide (CE-based combination therapy (CE combination as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX (CE + DTX and to explore the synergy mechanisms of CE + DTX. The 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and combination index (CI assay showed that simultaneous administration of CE and DTX with a molar ratio of 0.5:1 could generate the optimal synergistic effect on murine malignant melanoma cell (B16, CI = 0.31 and human breast carcinoma cell (MCF-7, CI = 0.48. The apoptosis, cell cycle, and cytoskeleton destruction study demonstrated that CE could target and destruct the microfilament actin, subsequently activate Caspase-3 and induce apoptosis. Meanwhile, DTX could target and disrupt the microtubules cytoskeleton, leading to a high proportion of cancer cells in G2/M-phase arrest. Moreover, CE plus DTX could cause a synergistic destruction of cytoskeleton, which resulted in a significantly higher apoptosis and a significantly higher arrest in G2/M arrest comparing with either agent alone (p < 0.01. The in vivo antitumor study evaluated in B16 tumor-bearing mice also validated the synergistic effects. All these results suggested that CE could enhance the antitumor activity of DTX in a synergistic manner, which suggest promising application prospects of CE + DTX combination treatment.

  1. The rationale of combination antifungal therapy in severely immunocompromised patients: empiricism versus evidence-based medicine.

    Science.gov (United States)

    Chamilos, Georgios; Kontoyiannis, Dimitrios P

    2006-08-01

    Despite expansion of the antifungal armamentarium over the past decade, the mortality rate for invasive fungal infections remains high in severely immunocompromised patients. Furthermore, in recent years, difficult-to-treat invasive infections caused by rare molds and yeasts have emerged in high-risk patients receiving antifungal prophylaxis or empirical treatment. Antifungal combinations are increasingly used in clinical practice to improve outcomes for refractory mycoses because of the suboptimal efficacy of current antifungal agents. Herein we review recent advances in the area of antifungal combinations in high-risk patients to separate empiricism from evidence-based medicine. Thus far, the benefits of combination antifungal therapy have been difficult to prove for invasive fungal infections other than cryptococcal meningitis. The recent introduction of a new class of antifungal agents (the echinocandins) and extended-spectrum triazoles has rejuvenated interest in studying those combinations for difficult-to-treat aspergillosis, as recent observational studies show promise. In view of the evolving epidemiology of invasive fungal infections, combination antifungal therapy could be most valuable in preemptive management of carefully selected high-risk patients; however, this should be studied in appropriate trials.

  2. Sitagliptin as combination therapy in the treatment of type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Shannon A Miller

    2009-05-01

    Full Text Available Shannon A Miller1, Erin L St Onge2, J Roger Accardi31Pharmacotherapy Faculty, Florida Hospital East Family Practice Residency, Orlando, Florida, USA; 2University of Florida College of Pharmacy, Orlando Campus, Florida, USA; 3Accardi Clinical Pharmacy, Orange City, Florida, USAAbstract: The American Diabetes Association and The European Association for the Study of Diabetes recommend metformin as the initial agent of choice in the treatment of type 2 diabetes mellitus. Unfortunately, most patients require multiple medications to obtain glycemic control. One of the newest additions to the antidiabetic armamentarium is the class of drugs known as dipeptidyl-peptidase IV (DPP-IV inhibitors. This novel approach focuses on harnessing the beneficial effects of GLP-1, an incretin hormone released from the gut postprandially. The first DPP-IV inhibitor approved in the United States was sitagliptin. It has been studied in both monotherapy and combination therapy. Combination studies with metformin realize a hemoglobin A1c reduction of 0.65%–1.1%. The combination of the two has a modest positive effect on body weight with the convenience of an oral route of administration. It has also been shown to be highly tolerable, efficacious and with little risk of hypoglycemia. This review will focus on combination therapy with sitagliptin with emphasis on combination with metformin. Keywords: DPP-IV inhibitor, sitagliptin, metformin, type 2 diabetes, incretins

  3. Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yong Zheng; Ri-Bao Wei; Li Tang; Ping Li; Xiao-Dong Zheng

    2012-01-01

    AIM:To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBVGN) patients.METHODS:A computerized literature search was carried out in the PubMed database,Embase,the Cochrane Library,Chinese BioMedical Literature on disc,Chinese Medical Current Contents,Chinese National Knowledge Infrastructure,Wanfang and VIP (Chinese Technological Journal of Database) to collect articles between June 1980 and December 2010 on therapy with immunosuppressants,e.g.,glucorticosteroids,mycophenolate mofetil and leflunomide,combined with antivirals,e.g.,interferon,lamivudine,entecavir and adefovir dipivoxil,in adult HBV-GN patients.The primary outcomes were remission of proteinuria,clearance of HBV e-antigen,and elevation of serum albumin.The secondary outcomes were blood levels of alanine aminotransferase,serum creatinine,and HBV-DNA titer.Meta-analysis was performed using Review Manager 5.1.Fixed or random effect models were employed to combine the results after a heterogeneity test.The effects of the combined therapy were analyzed for different doses of glucorticosteroid and different types of HBV-GN.RESULTS:Twelve clinical trials with 317 patients were included.A significantly higher incidence of HBV-GN was found in male patients (relative risk =2.40,95%CI:1.98-2.93).Combined therapy reduced the proteinuria significantly with a mean difference of 4.19(95% CI:3.86-4.53) and increased the serum albumin concentration significantly with a mean difference of -11.95 (95% CI:-12.97-10.93) without significant alterations of liver function (mean difference:4.62,95%CI:-2.55-11.79) and renal function (mean difference:10.29,95% CI:0.14-20.45).No significant activation of HBV-DNA replication occurred (mean difference:0.12,95% CI:-0.37-0.62).There was no significant difference between the high dose glucorticosteroid group and the low dose glucorticosteroid group in terms of proteinuria

  4. Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing

    Directory of Open Access Journals (Sweden)

    Paulo Cesar Fagundes Neves

    2013-09-01

    Full Text Available OBJECTIVES: The purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures. METHODS: A total of 128 male New Zealand albino rabbits, between 6-8 months old, were subjected to a total osteotomy of the proximal portion of the right fibula. After surgery, the animals were divided into four groups (n = 32 each: control group, in which animals were subjected to osteotomy; autologous platelet concentrate group, in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site; hyperbaric oxygen group, in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions; and autologous platelet concentrate and hyperbaric oxygen group, in which animals were subjected to osteotomy, autologous platelet concentrate applied at the fracture site, and 9 consecutive daily hyperbaric oxygen therapy sessions. Each group was divided into 4 subgroups according to a pre-determined euthanasia time points: 2, 4, 6, and 8 weeks postoperative. After euthanasia at a specific time point, the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red. RESULTS: Autologous platelet concentrates and hyperbaric oxygen therapy, applied together or separately, increased the rate of bone healing compared with the control group. CONCLUSION: Hyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model.

  5. [The combined DAK therapy of obesity for children and adolescents. Evaluation after 1 year].

    Science.gov (United States)

    Adam, S; Westenhöfer, J; Rudolphi, B; Kraaibeek, H K

    2008-04-10

    In 2003, the program "The combined DAK therapy of obesity for children and adolescents", funded and conducted by the Deutsche Angestellten Krankenkasse (DAK) (A German Health Insurance Company), has started. The whole treatment lasts for 1 year including an initial inpatient therapy for 6 weeks followed by an outpatient treatment at home that adresses the overweight patients and their families. The therapy contents are developed according to the recommendations of the "Arbeitsgemeinschaft Adipositas im Kindes- und Jugendalter (AGA)". In a prospective cohort study a sample of 604 subjects was studied in order to examine the achievement of the treatment goals weight reduction, behaviour modification and improvement of quality of life. The development of weight was evaluated using BMI-SDS. 44,1% of children and adolescents had a successful weight reduction, they reduced their weight at least by 0,3 BMI-SDS. Furthermore, significant changes of health behaviour, physical fitness and quality of life were observed. However, during the outpatient treatment an impairment of some behaviour changes were observed. Nevertheless, the study has identified significant, positive effects in weight loss, behaviour modifications, changes in physical fitness and in the development of quality of life as a result of the therapy. It is demonstrated that a relapse in "old behaviour" followed by an increase of weight after the inpatient treatment can be avoided bythe subsequent outpatient therapy.

  6. [Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer].

    Science.gov (United States)

    Yamamoto, Mari; Ikeda, Masahiko; Kubo, Shinichiro; Tsukioki, Takahiro; Nakamoto, Shougo

    2016-07-01

    We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

  7. Role of olmesartan in combination therapy in blood pressure control and vascular function

    Directory of Open Access Journals (Sweden)

    Carlos M Ferrario

    2010-08-01

    Full Text Available Carlos M Ferrario, Ronald D SmithWake Forest University School of Medicine, Winston-Salem, North Carolina, USAAbstract: Angiotensin receptor blockers have emerged as a first-line therapy in the management of hypertension and hypertension-related comorbidities. Since national and international guidelines have stressed the need to control blood pressure to <140/90 mmHg in uncomplicated hypertension and <130/80 mmHg in those with associated comorbidities such as diabetes or chronic kidney disease, these goal blood pressures can only be achieved through combination therapy. Of several drugs that can be effectively combined to attain the recommended blood pressure goals, fixed-dose combinations of angiotensin receptor blockers and the calcium channel blocker amlodipine provide additive antihypertensive effects associated with a safe profile and increased adherence to therapy. In this article, we review the evidence regarding the beneficial effects of renin–angiotensin system blockade with olmesartan medoxomil and amlodipine in terms of blood pressure control and improvement of vascular function and target organ damage.Keywords: amlodipine, angiotensin receptor blockers, angiotensin-converting enzyme 2, hypertension, renin–angiotensin system

  8. Smart Porous Silicon Nanoparticles with Polymeric Coatings for Sequential Combination Therapy.

    Science.gov (United States)

    Xu, Wujun; Thapa, Rinez; Liu, Dongfei; Nissinen, Tuomo; Granroth, Sari; Närvänen, Ale; Suvanto, Mika; Santos, Hélder A; Lehto, Vesa-Pekka

    2015-11-01

    In spite of the advances in drug delivery, the preparation of smart nanocomposites capable of precisely controlled release of multiple drugs for sequential combination therapy is still challenging. Here, a novel drug delivery nanocomposite was prepared by coating porous silicon (PSi) nanoparticles with poly(beta-amino ester) (PAE) and Pluronic F-127, respectively. Two anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately loaded into the core of PSi and the shell of F127. The nanocomposite displayed enhanced colloidal stability and good cytocompatibility. Moreover, a spatiotemporal drug release was achieved for sequential combination therapy by precisely controlling the release kinetics of the two tested drugs. The release of PTX and DOX occurred in a time-staggered manner; PTX was released much faster and earlier than DOX at pH 7.0. The grafted PAE on the external surface of PSi acted as a pH-responsive nanovalve for the site-specific release of DOX. In vitro cytotoxicity tests demonstrated that the DOX and PTX coloaded nanoparticles exhibited a better synergistic effect than the free drugs in inducing cellular apoptosis. Therefore, the present study demonstrates a promising strategy to enhance the efficiency of combination cancer therapies by precisely controlling the release kinetics of different drugs.

  9. Origins of Combination Therapy for Tuberculosis: Lessons for Future Antimicrobial Development and Application

    Directory of Open Access Journals (Sweden)

    Christopher A. Kerantzas

    2017-03-01

    Full Text Available Tuberculosis is a global health problem that causes the death of approximately 1.5 million people worldwide each year (WHO, p. 1–126, Global Tuberculosis Report, 2015. Treatment of drug-susceptible tuberculosis requires combination antimicrobial therapy with a minimum of four antimicrobial agents applied over the course of 6 months. The first instance of combination antimicrobial therapy applied to tuberculosis was the joint use of streptomycin and para-aminosalicylic acid as documented by the Medical Research Council of the United Kingdom in 1950. These antimicrobial drugs were the product of many decades of investigation into both organism-derived antibiotics and synthetic chemotherapy and were the first agents in those respective categories to show substantial clinical efficacy and widespread use for tuberculosis. The events leading to the discovery and application of these two agents demonstrate that investments in all aspects of research, from basic science to clinical application, are necessary for the continued success of science in finding treatments for human disease. This observation is especially worth considering given the expanded role that combination therapy may play in combating the current rise in resistance to antimicrobial drugs.

  10. Origins of Combination Therapy for Tuberculosis: Lessons for Future Antimicrobial Development and Application

    Science.gov (United States)

    Kerantzas, Christopher A.

    2017-01-01

    ABSTRACT Tuberculosis is a global health problem that causes the death of approximately 1.5 million people worldwide each year (WHO, p. 1–126, Global Tuberculosis Report, 2015). Treatment of drug-susceptible tuberculosis requires combination antimicrobial therapy with a minimum of four antimicrobial agents applied over the course of 6 months. The first instance of combination antimicrobial therapy applied to tuberculosis was the joint use of streptomycin and para-aminosalicylic acid as documented by the Medical Research Council of the United Kingdom in 1950. These antimicrobial drugs were the product of many decades of investigation into both organism-derived antibiotics and synthetic chemotherapy and were the first agents in those respective categories to show substantial clinical efficacy and widespread use for tuberculosis. The events leading to the discovery and application of these two agents demonstrate that investments in all aspects of research, from basic science to clinical application, are necessary for the continued success of science in finding treatments for human disease. This observation is especially worth considering given the expanded role that combination therapy may play in combating the current rise in resistance to antimicrobial drugs. PMID:28292983

  11. Origins of Combination Therapy for Tuberculosis: Lessons for Future Antimicrobial Development and Application.

    Science.gov (United States)

    Kerantzas, Christopher A; Jacobs, William R

    2017-03-14

    Tuberculosis is a global health problem that causes the death of approximately 1.5 million people worldwide each year (WHO, p. 1-126, Global Tuberculosis Report, 2015). Treatment of drug-susceptible tuberculosis requires combination antimicrobial therapy with a minimum of four antimicrobial agents applied over the course of 6 months. The first instance of combination antimicrobial therapy applied to tuberculosis was the joint use of streptomycin and para-aminosalicylic acid as documented by the Medical Research Council of the United Kingdom in 1950. These antimicrobial drugs were the product of many decades of investigation into both organism-derived antibiotics and synthetic chemotherapy and were the first agents in those respective categories to show substantial clinical efficacy and widespread use for tuberculosis. The events leading to the discovery and application of these two agents demonstrate that investments in all aspects of research, from basic science to clinical application, are necessary for the continued success of science in finding treatments for human disease. This observation is especially worth considering given the expanded role that combination therapy may play in combating the current rise in resistance to antimicrobial drugs. Copyright © 2017 Kerantzas and Jacobs.

  12. Combination therapies: The next logical Step for the treatment of synucleinopathies?

    Science.gov (United States)

    Valera, Elvira; Masliah, Eliezer

    2016-02-01

    Currently there are no disease-modifying alternatives for the treatment of most neurodegenerative disorders. The available therapies for diseases such as Parkinson's disease (PD), PD dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), in which the protein alpha-synuclein (α-Syn) accumulates within neurons and glial cells with toxic consequences, are focused on managing the disease symptoms. However, using strategic drug combinations and/or multi-target drugs might increase the treatment efficiency when compared with monotherapies. Synucleinopathies are complex disorders that progress through several stages, and toxic α-Syn aggregates exhibit prion-like behavior spreading from cell to cell. Therefore, it follows that these neurodegenerative disorders might require equally complex therapeutic approaches to obtain significant and long-lasting results. Hypothetically, therapies aimed at reducing α-Syn accumulation and cell-to-cell transfer, such as immunotherapy against α-Syn, could be combined with agents that reduce neuroinflammation with potential synergistic outcomes. Here we review the current evidence supporting this type of approach, suggesting that such rational therapy combinations, together with the use of multi-target drugs, may hold promise as the next logical step for the treatment of synucleinopathies.

  13. Retinal vein thrombosis associated with pegylated-interferon and ribavirin combination therapy for chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Iman Zandieh; Mohamed Adenwalla; Cindy Cheong-Lee; Patrick E Ma; Eric M Yoshida

    2006-01-01

    An estimated 300 million people worldwide suffer fromchronic hepatitis C with a prevalence of 0.8%-1.0% of the general population in Canada. An increasing pool of evidence exists supporting the use of pegylatedinterferon (pegIFN) and ribavirin combination therapy for hepatitis C. We report a 49-year old male of North American aboriginal descent with chronic hepatitis C (genotype 2b). Biopsy confirmed that he had cirrhosis with a 2-wk history of left eye pain and decreased visual acuity. He developed retinal vein thrombosis after 16 of 24 wk of pegIFN-α 2a and ribavirin combination therapy. He was urgently referred to a retinal specialist and diagnosed with non-ischemic central retinal vein occlusion of the left eye. PegIFN and ribavirin combination therapy was discontinued and HCV RNA was undetectable after 16 wk of treatment. Hematologic investigations revealed that the patient was a factor V Leiden heterozygote with mildly decreased protein C activity. Our patient had a number of hypercoagulable risk factors, including factor V Leiden heterozygosity, cirrhosis, and hepatitis C that alone would have most likely remained clinically silent. We speculate that in the setting of pegIFN treatment, these risk factors may coalesce and cause the retinal vein thrombosis.

  14. Efficacy of Gene Therapy for X-Linked Severe Combined Immunodeficiency

    Science.gov (United States)

    Hacein-Bey-Abina, Salima; Hauer, Julia; Lim, Annick; Picard, Capucine; Wang, Gary P.; Berry, Charles C.; Martinache, Chantal; Rieux-Laucat, Frédéric; Latour, Sylvain; Belohradsky, Bernd H.; Leiva, Lily; Sorensen, Ricardo; Debré, Marianne; Casanova, Jean Laurent; Blanche, Stephane; Durandy, Anne; Bushman, Frederic D.; Fischer, Alain; Cavazzana-Calvo, Marina

    2010-01-01

    BACKGROUND The outcomes of gene therapy to correct congenital immunodeficiencies are unknown. We reviewed long-term outcomes after gene therapy in nine patients with X-linked severe combined immunodeficiency (SCID-X1), which is characterized by the absence of the cytokine receptor common γ chain. METHODS The nine patients, who lacked an HLA-identical donor, underwent ex vivo retrovirus-mediated transfer of γ chain to autologous CD34+ bone marrow cells between 1999 and 2002. We assessed clinical events and immune function on long-term follow-up. RESULTS Eight patients were alive after a median follow-up period of 9 years (range, 8 to 11). Gene therapy was initially successful at correcting immune dysfunction in eight of the nine patients. However, acute leukemia developed in four patients, and one died. Transduced T cells were detected for up to 10.7 years after gene therapy. Seven patients, including the three survivors of leukemia, had sustained immune reconstitution; three patients required immunoglobulin-replacement therapy. Sustained thymopoiesis was established by the persistent presence of naive T cells, even after chemotherapy in three patients. The T-cell–receptor repertoire was diverse in all patients. Transduced B cells were not detected. Correction of the immunodeficiency improved the patients’ health. CONCLUSIONS After nearly 10 years of follow-up, gene therapy was shown to have corrected the immunodeficiency associated with SCID-X1. Gene therapy may be an option for patients who do not have an HLA-identical donor for hematopoietic stem-cell transplantation and for whom the risks are deemed acceptable. This treatment is associated with a risk of acute leukemia. (Funded by INSERM and others.) PMID:20660403

  15. Step-down therapy in well-controlled asthmatic patients using salmeterol xinafoate/fluticasone propionate combination therapy

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    Horiuchi K

    2016-03-01

    Full Text Available Kazuya Horiuchi, Keita Kasahara, Yusuke Kuroda, Haruna Morohoshi, Yosuke Hagiwara, Gen Ishii Respiratory Disease Center, Showa University Northern Yokohama Hospital, Yokohama-shi, Kanagawa-ken, Japan Purpose: A combination therapy with inhaled corticosteroid (ICS and a long-acting β agonist (LABA is the standard treatment for asthmatic patients, and step-down treatment is recommended once control has been achieved. However, little data exist that evaluate the long-term outcomes after step-down treatment. Objective: To compare the long-term outcomes of step-down therapy with ICS/LABA or ICS alone for asthmatic patients who have achieved well-controlled asthma by the ICS (250 µg fluticasone/LABA (50 µg salmeterol combination (SFC, two puffs per day. Patients and methods: We randomized 40 well-controlled patients with asthma receiving SFC (250 µg to two groups; one group of patients received step-down therapy with low-dose SFC (100 µg, two puffs daily and another group of patients received step-down therapy with high-dose fluticasone propionate (FP alone (500 µg, daily. The two groups were monitored over 12 months for changes in asthma control test scores, respiratory function (percent forced expiratory volume in 1 second, maximal expiratory flow rate at 50% of the vital capacity [%FEF50], and maximal expiratory flow rate at 25% of the vital capacity [%FEF25], and the concentration of fractional exhaled nitric oxide. Results: There was no significant difference in the dropout rate between the SFC and FP groups. Low-dose SFC maintained the stability of all parameters over 12 months, whereas the FP group exhibited a rapid 5% decrease in forced expiratory volume in 1 second within 2 months after discontinuation of salmeterol; furthermore, after 10 months, there was a gradual decrease in %FEF50 and %FEF25. Conclusion: This study suggests that a balanced step-down protocol, including both ICS and LABA, is essential in providing long-term stability

  16. Combination therapy of sorafenib and TACE for unresectable HCC: a systematic review and meta-analysis.

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    Lei Liu

    Full Text Available BACKGROUND AND AIM: A large number of studies have tried to combine sorafenib with TACE for patients with unresectable hepatocellular carcinoma (HCC and the results were controversial. We conducted this systematic review and meta-analysis to evaluate the safety and efficacy of combination therapy of sorafenib and TACE in the management of unresectable HCC. METHODS: MEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Library were searched from January 1990 to October 2013 and these databases were searched for appropriate studies combining TACE and sorafenib in treatment of HCC. Two authors independently reviewed the databases and extracted the data and disagreements were resolved by discussion. Effective value and safety were analyzed. Effective value included disease control rate (DCR, time to progression (TTP and overall survival (OS. RESULTS: 17 studies were included in the study. In the 10 noncomparative studies, DCR ranged from 18.4 to 91.2%. Median TTP ranged from 7.1 to 9.0 months, and median OS ranged from 12 to 27 months. In the 7 comparative studies, the hazard ratio (HR for TTP was found to be 0.76 (95% CI 0.66-0.89; P<0.001 with low heterogeneity among studies (P = 0.243; I(2 = 25.5%. However, the HR for OS was found to be 0.81 (95% CI 0.65-1.01; P = 0.061 with low heterogeneity among studies (P = 0.259; I(2 = 25.4%. The common toxicities included fatigue, diarrhea, nausea, hand foot skin reaction (HFSR, hematological events, hepatotoxicity, alopecia, hepatotoxicity, hypertension and rash/desquamation. AEs are generally manageable with dose reductions. CONCLUSIONS: Combination therapy may bring benefits for unresectable HCC patients in terms of TTP but not OS. Further well-designed randomized controlled studies are needed to confirm the efficacy of combination therapy.

  17. Combination therapy with telmisartan and parecoxib induces regression of endometriotic lesions.

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    Nenicu, Anca; Gu, Yuan; Körbel, Christina; Menger, Michael D; Laschke, Matthias W

    2017-08-01

    Telmisartan suppresses the development of endometriotic lesions. However, the drug also up-regulates the expression of COX-2, which has been suggested to promote the progression of endometriosis. Accordingly, in the present study we analysed whether a combination therapy with telmisartan and a COX-2 inhibitor may be more effective in the treatment of endometriotic lesions than the application of telmisartan alone. Endometriotic lesions were induced in the peritoneal cavity of C57BL/6 mice, which were treated daily with an i.p. injection of telmisartan (10 mg·kg(-1) ), parecoxib (5 mg·kg(-1) ), a combination of telmisartan and parecoxib or vehicle. Therapeutic effects on lesion survival, growth, vascularization, innervation and protein expression were studied over 4 weeks by high-resolution ultrasound imaging as well as immunohistochemical and Western blot analyses. Telmisartan-treated lesions exhibited a significantly reduced lesion volume when compared with vehicle-treated controls and parecoxib-treated lesions. This inhibitory effect of telmisartan was even more pronounced when it was used in combination with parecoxib. The combination therapy resulted in a reduced microvessel density as well as lower numbers of proliferating Ki67-positive cells and higher numbers of apoptotic cleaved caspase-3-positive stromal cells within the lesions. This was associated with a lower expression of COX-2, MMP-9 and p-Akt/Akt when compared with controls. The application of the two drugs further inhibited the ingrowth of nerve fibres into the lesions. Combination therapy with telmisartan and a COX-2 inhibitor represents a novel, effective pharmacological strategy for the treatment of endometriosis. © 2017 The British Pharmacological Society.

  18. What's next after metformin? focus on sulphonylurea: add-on or combination therapy

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    Lim PC

    2015-09-01

    Full Text Available Introduction: The pathophysiology of type 2 diabetes (T2DM mainly focused on insulin resistance and insulin deficiency over the past decades. Currently, the pathophysiologies expanded to ominous octet and guidelines were updated with newer generation of antidiabetic drug classes. However, many patients had yet to achieve their target glycaemic control. Although all the guidelines suggested metformin as first line, there was no definite consensus on the second line drug agents as variety of drug classes were recommended. Objectives: The aim of this review was to evaluate the drug class after metformin especially sulphonylurea and issues around add-on or fixed dose combination therapy. Methods: Extensive literature search for English language articles, clinical practice guidelines and references was performed using electronic databases. Results: Adding sulphonylurea to metformin targeted both insulin resistance and insulin deficiency. Sulphonylurea was efficacious and cheaper than thiazolidinedione, dipeptidyl peptidase-4 inhibitor, glucagon-like peptide 1 analogue and insulin. The main side effect of sulphonylurea was hypoglycaemia but there was no effect on the body weight when combining with metformin. Fixed dose sulphonylurea/metformin was more efficacious at lower dose and reported to have fewer side effects with better adherence. Furthermore, fixed dose combination was cheaper than add-on therapy. In conclusion, sulphonylurea was feasible as the second line agent after metformin as the combination targeted on two pathways, efficacious, cost-effective and had long safety history. Fixed dose combination tablet could improve patient’s adherence and offered an inexpensive and more efficacious option regardless of original or generic product as compared to add-on therapy.

  19. Combined therapy with desferrioxamine and deferiprone in beta thalassemia major patients with transfusional iron overload.

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    Daar, S; Pathare, A V

    2006-05-01

    Iron overload is the main cause of morbidity and mortality especially from heart failure in patients with beta thalassemia major (TM). Successful iron chelation is therefore essential for the optimal management of TM. Although desferrioxamine (DFX) has been the major iron-chelating treatment of transfusional iron overload, compliance is a major hindrance in achieving optimal therapeutic results. The availability of oral iron chelation with deferiprone (L(1)) since 1987 is useful but showed poor efficacy when used alone as compared to DFX. We therefore decided to compare DFX alone with a prospective combined therapy with DFX and L(1) in beta thalassemia major patients with iron overload. We studied 91 patients with beta thalassemia major (mean age+/-SD, 15.02+/-5.8; range 2-30 years) attending the day care unit for regular transfusional support. They received packed red cells every 3-4 weeks to maintain pretransfusion hemoglobin concentration above 9 g/dl. They had been receiving DFX at a daily dose of 40 mg kg(-1) day(-1) by subcutaneous infusion for 8-10 h on 4-5 nights each week for the past several years. However, due to various reasons, they had developed considerable transfusional iron overload. These patients were allocated to prospectively receive additional therapy with oral iron chelator L(1) at 75 mg kg(-1) day(-1) body weight in three divided doses with food after informed consent and continued to receive treatment with DFX as per the above dosage. Of the 91 patients, six developed severe gastrointestinal (GI) upset, two agranulocytosis, two arthropathy, one persistently raised liver enzymes, two died owing to sepsis, and two received allogeneic bone marrow transplantation. Amongst the remaining 76 patients, 21 were found noncompliant (not taking DFX regularly, but taking L(1) regularly). Thus, in the 55 evaluable patients {6-48 months on combination therapy; mean [(+/-SD)22+/-12 months]}, the mean serum ferritin (+/-SD) fell dramatically from 3

  20. Patients’ views about treatment with combination therapy for Rheumatoid Arthritis: a comparative qualitative study

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    Lempp Heidi

    2012-10-01

    Full Text Available Abstract Background Combinations of disease-modifying anti-rheumatic drugs (DMARDs are increasingly used to control active rheumatoid arthritis (RA; however there is little information about patients’ perspectives, their expectations, concerns and experiences of this intensive treatment. Method We interviewed a quota sample of 18 patients from a single tertiary outpatient clinic, stratified by gender, ethnicity and age, based on the outpatient clinic population. Patients with early RA (2 years received combined conventional DMARDs or DMARDs with biologics. Results Four main themes emerged from the analytical framework: (i patients’ expectations about the combined treatment focuses mainly on physical symptoms; (ii the impact of the treatment on quality of life varied with the new medication in both groups (iii concerns about new interventions concentrated mainly on potential side effects; and (iv combination therapy can be self-managed in close collaboration with clinic staff, but this requires individualised management approaches. These themes resonate with von Korff’s collaborative management of chronic illness model. Conclusion To our knowledge this is the first qualitative study that examined systematically in patients with early and established RA their expectations, impact on quality of life, concerns about side effects and the management of the treatment when taking combined medication with DMARDs or DMARDs and biologics. Patients have generally positive views of combination DMARDs. Within routine practice settings, achieving medication concordance with complex combined DMARD regimens is challenging, and the concerns vary between patients; careful individual assessments are essential to successfully deliver such intensive treatment.

  1. Immunotherapy and radiation therapy: considerations for successfully combining radiation into the paradigm of immuno-oncology drug development.

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    Sharon, Elad; Polley, Mei-Yin; Bernstein, Michael B; Ahmed, Mansoor

    2014-08-01

    As the immunotherapy of cancer comes of age, adding immunotherapeutic agents to radiation therapy has the potential to improve the outcomes for patients with a wide variety of malignancies. Despite the enormous potential of such combination therapy, laboratory data has been lacking and there is little guidance for pursuing novel treatment strategies. Animal models have significant limitation in combining radiation therapy with immunotherapy and some of the limitations of preclinical models are discussed in this article. In addition to the preclinical challenges, radiation therapy and immunotherapy combinations may have overlapping toxicities, and for both types of therapy, early and late manifestations of toxicity are possible. Given these risks, special attention should be given to the design of the specific Phase I clinical trial that is chosen. In this article, we describe several Phase I design possibilities that may be employed, including the 3 + 3 design (also known as the cohort of 3 design), the continual reassessment method (CRM), and the time-to-event continual reassessment method (TITE-CRM). Efficacy end points for further development of combination therapy must be based on multiple factors, including disease type, stage of disease, the setting of therapy and the goal of therapy. While the designs for future clinical trials will vary, it is clear that these two successful modalities of therapy can and should be combined for the benefit of cancer patients.

  2. Combination quetiapine therapy in the long-term treatment of patients with bipolar I disorder

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    Calabrese JR

    2005-07-01

    Full Text Available Abstract Objective Determine the long-term effectiveness of quetiapine in combination with standard treatments in preventing relapses for patients with bipolar I disorders Method Twenty-one outpatients with type I bipolar disorder who had inadequate responses to ongoing standard therapies were treated with add-on quetiapine in an open-label study. The quetiapine dose was increased until clinical response occurred. Illness response was assessed using the Clinical Global Impression (CGI scale. Relapse rates before and during quetiapine treatment were compared by calculating incidence risk ratios. Results Quetiapine was added to ongoing standard therapy for 26 to 78 weeks. Thirteen patients received combination therapy for at least 52 weeks. The mean quetiapine dose received was 518 ± 244 mg/day. There were highly significant improvements in overall relapse rate, manic/mixed relapse rate, and depression relapse rate in the period during quetiapine treatment compared with the period before quetiapine was initiated. The calculated relative risk of relapse in the absence of quetiapine treatment was 2.9 overall (95% confidence interval, 1.5~5.6, 3.3 for manic/mixed relapse (95% confidence interval, 1.5~7.1, and 2.4 for depressive relapse (95% confidence interval, 1.3~4.4. The mean Clinical Global Impression scores improved significantly from baseline during 26 weeks of quetiapine treatment in 21 patients (p = 0.002 and remained significantly better during a 52-week treatment period in 13 patients (p = 0.036. Conclusion Long-term treatment with quetiapine combination therapy reduced the probability of manic/mixed and depressive relapses and improved symptoms in patients with bipolar I disorder who had inadequate responses to ongoing standard treatment.

  3. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

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    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag

    2016-01-01

    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs.

  4. Neuroprotective effect of butylphthalide combined with aspirin and clopidogrel antiplatelet therapy on progressive cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Xing-Bing He

    2016-01-01

    Objective:To analyze the neuroprotective effect of butylphthalide combined with aspirin and clopidogrel antiplatelet therapy on progressive cerebral infarction.Methods:A total of 86 patients with progressive cerebral infarction were randomly divided into observation group and control group (n=43), control group received aspirin and clopidogrel antiplatelet therapy, observation group received butylphthalide combined with aspirin and clopidogrel antiplatelet therapy, and then the differences in platelet function, blood coagulation function, middle cerebral artery blood flow state and nerve function index levels were compared between two groups after treatment.Results: After 1 course of treatment, the relative content of P-selectin and GPIIb/IIIa on platelet surface as well as TXB2, vWF and D-D content in plasma of observation group were significantly lower than those of control group, while 6-Keto-PGF1 content in plasma was significantly higher than that of control group); thrombelastogram indexes R and K value were higher than those of control group while MA, Angle and CI value were lower than those of control group; middle cerebral artery PSV, EDV, Vm and PI were higher than those of control group while RI value was lower than that of control group; nerve function indexes BDNF and H2S content in plasma were higher than those of control group while NSE, MBP, S100B and MMP-9 content were lower than those of control group (P<0.05). Conclusions:Butylphthalide combined with aspirin and clopidogrel antiplatelet therapy can effectively optimize the platelet and blood coagulation function in patients with progressive cerebral infarction, promote the middle cerebral artery blood flow recovery and exert positive neuroprotective effect.

  5. Targeted Chemo-Photodynamic Combination Platform Based on the DOX Prodrug Nanoparticles for Enhanced Cancer Therapy.

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    Zhang, Yumin; Huang, Fan; Ren, Chunhua; Yang, Lijun; Liu, Jianfeng; Cheng, Zhen; Chu, Liping; Liu, Jinjian

    2017-04-19

    Chemo-photodynamic combination therapy has been received widespread attention in cancer treatment due to its excellent characteristics, such as reducing the adverse side effects of chemo-drugs and improving the therapeutic effects for various cancers. In this study, RGD and DOX was conjugated to PEG by thiol-ene addition and Schiff's base reaction, respectively, to prepare the targeted and pH-sensitive antitumor prodrug nanoparticles (RGD-PEG-DOX NPs, RGD-NPs). Subsequently, the photosensitizer chlorin e6 (Ce6) was encapsulated into RGD-NPs, thus obtaining a simple and efficient chemo-photodynamic combination platform (RGD-PEG-DOX/Ce6 NPs, RGD-NPs/Ce6). This nanoparticle possessed high drug loading property of both the chemo-drug and photosensitizer and could simultaneously release them under the mild acidic microenvironment of cancer cells, which was expected to realize the synchronization therapy of chemotherapy and photodynamic therapy (PDT). Compared with free DOX and Ce6, RGD-NPs/Ce6 could significantly improve the cellular uptake capacities of DOX and Ce6, resulting in the increased contents of ROS in cancer cells and effective cytotoxicity for tumor cells (MDA-MB-231 cells and MCF-7 cells) upon a laser radiation. The in vivo experiment showed that RGD-NPs/Ce6 displayed superior tumor targeting, accumulation, and retention ability than the other groups (free DOX, free Ce6 and NPs/Ce6), and thus significantly enhancing the antitumor effect in vivo with a laser radiation. In addition, the cardiotoxicity induced by DOX was thoroughly wiped out after being loaded and delivered by the nanoparticles according to the pathological analysis. Therefore, the targeted chemo-photodynamic combination therapeutic platform may be a promising candidate for enhanced cancer therapy.

  6. Aspirin and low-molecular weight heparin combination therapy effectively prevents recurrent miscarriage in hyperhomocysteinemic women.

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    Pratip Chakraborty

    Full Text Available The management of recurrent pregnancy loss (RPL still remains a great challenge, and women with polycystic ovarian syndrome (PCOS are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy, insulin resistance (IR and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 women with history of 2 or more consecutive first trimester abortions were screened and 336 were selected for the study. The selected patients were initially divided on the basis of presence or absence of PCOS, while subsequent stratification was based on HHcy, IR and/or obesity. The subjects had treatment with aspirin during one conception cycle and aspirin-LMWH combined anticoagulant therapy for the immediate next conception cycle, if the first treated cycle was unsuccessful. Pregnancy salvage was the sole outcome measure. The overall rate of pregnancy salvage following aspirin therapy was 43.15%, which was mostly represented by normohomocysteinemic women, while the salvage rate was lower in the HHcy populations irrespective of the presence or absence of PCOS, IR, or obesity. By contrast, aspirin-LMWH combined therapy could rescue 66.84% pregnancies in the aspirin-failed cases. Logistic regression analyses showed that HHcy remained a significant factor in predicting salvage rates in the PCOS, IR, and obese subpopulations controlled for other confounding factors. With regard to pregnancy salvage, combined anticoagulant therapy with aspirin and LMWH conferred added benefit to those with HHcy phenotype.

  7. pH- and NIR light responsive nanocarriers for combination treatment of chemotherapy and photodynamic therapy.

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    Wang, Sheng; Yang, Weitao; Cui, Jing; Li, Xue; Dou, Yan; Su, Lin; Chang, Jin; Wang, Hanjie; Li, Xiaodong; Zhang, Bingbo

    2016-02-01

    The side effects of antitumor drugs and low treatment efficacy are two major challenges of current chemotherapy. To address these issues, we developed a new kind of smart nanocarriers that combine pH-responsive chemotherapy and near-infrared (NIR) light triggered photodynamic therapy. These nanocarriers were based on upconversion nanoparticle (UCN)-loaded folate-conjugated polymeric lipid vesicles (UFPLVs). Merocyanine 540 (MC540), as a photosensitizer, was loaded in the UFPLVs; doxorubicin hydrochloride (DOX), as an antitumor drug, was conjugated to the surfaces of UFPLVs by pH-sensitive hydrazone bonds. The newly developed MC540&DOX-UFPLVs had a nanosized structure with targeting ligand modification, so they had the potential to accumulate into tumor sites via a combination of passive and active targeting effects. An in vitro singlet oxygen test showed that the nanocarriers can generate cytotoxic singlet oxygen successfully under the irradiation of NIR light. In vitro DOX release profiles demonstrated that the nanocarriers can achieve a pH-triggered drug release. It has been demonstrated by a cellular uptake study that the nanocarriers can efficiently deliver drugs and photosensitizers into tumor cells. In vitro and in vivo combination treatments evidenced the high antitumor effects of MC540&DOX-UFPLVs under NIR light irradiation. These results suggest that the MC540&DOX-UFPLVs may be promising nanocarriers for tumor combination therapy applications.

  8. Combination therapy including serratiopeptidase improves outcomes of mechanical-antibiotic treatment of periimplantitis.

    Science.gov (United States)

    Sannino, G; Gigola, P; Puttini, M; Pera, F; Passariello, C

    2013-01-01

    This study was designed as a retrospective analysis of clinical outcomes of cases of periimplantitis treated by mechanical debridement and the administration of antibiotics combined or not with the administration of either the proteolytic enzyme serratiopeptidase (SPEP) or non-steroidal anti-inflammatory drugs (NSAIDs). Clinical charts of 544 partially edentulous patients treated for periimplantitis between June 1996 and December 2010 were analyzed to obtain clinical data of the affected implants just before the beginning of treatment and 12 months later to evaluate the outcomes of combined mechanical antibiotic treatment alone or in combination with the co-administration of the anti-inflammatory SPEP or NSAIDs. The comparative analysis revealed that therapeutic outcomes were significantly different in the three groups. Failure rate in the group that received SPEP (6 percent) was significantly lower compared to the group that received NSAIDS (16.9 percent; P less than 0.01) and to the group that received no anti-inflammatory therapy (18.9 percent; P less than 0.01). Treatment including SPEP was associated with significantly better healing also when successful treatments alone were considered. The data reported in this paper strongly support the hypothesis that SPEP is a valid addition to protocols for the combined therapy of peri-implantitis. In fact, it allows to enhance success rates significantly and also favors better tissue repair around successfully treated implants as compared to other regimens.

  9. Comparison possibilities of ultrasound and its combination with laser in surgery and therapy

    Science.gov (United States)

    Zharov, Vladimir P.; Menyaev, Yulian A.; Kabisov, Ruslan K.; Alkov, Sergey V.; Nesterov, A. V.; Loshchilov, Vladimir I.; Suen, James Y.

    2000-05-01

    This article presents the further developments of combined laser-ultrasound medical technologies with paying attention the possibility ultrasound in surgery and therapy. The analyses of main effects at the low frequency ultrasonic treatment of biotissues including cavitation, acoustic streams, acoustic pressure, mechanical influence etc are analyzed. The main promising areas of application of low frequency ultrasound are considered including bactericidal treatment of infections wounds, spray treatment of wounds in head and neck surgery, tumor treatment etc. In particular the clinical result of using ultrasonic devices based on imposing ultrasonic oscillations in a range of 22-66 kHz on a cutting instrument with a special form, radiation intensity up to 10 W/cm2 and oscillation amplitude up to 40-60 micrometers with respect to oncology for halt bleeding from a tumor, liquidating pain, acoustic denervation are presented. Some limitation of medical application of ultrasound are discussed and perspective combination with laser for increasing efficiency of new combined technologies are found. Among them: combination photodynamic therapy and ultrasonic treatment of tumors, laser-ultrasonic treatment of infections wounds including using spray, laser-ultrasonic drug delivery. The preliminary result of experimental study of some of above-mentioned technologies are presented.

  10. [Sildenafil and alprostadil in the combined drug therapy of erectile dysfunction].

    Science.gov (United States)

    Mazo, E B; Dmitriev, D G; Gamidov, S I; Ovchinnikov, R I

    2002-01-01

    Forty-four patients with erectile dysfunction (ED) aged 21-72 years aged 21-72 years (mean age 61 years) were examined and treated with sildenafil and alprostadil monotherapy or combined therapy. ED was psychogenic in 9(20.5%), arterial in 12(27.2%), vein occlusive in 9(20.5%) and neurogenic in 14(31.8%) patients. Monotherapy was most effective in psychogenic ED (alprostadil--100%, sildenafil--88.9%), least effective in vein occlusive ED (alprostadil--33.3%, sildenafil--22.2%). Alprostadil was more effective in arterial and neurogenic ED (83.3 vs 66.7 and 78.6 vs 57.1%, respectively). Combination of the two drugs produced much high response: 100, 85.7 and 55.5% in arterial, neurogenic and vein occlusive ED, respectively. Thus, combined treatment with sildenafil and alprostadil is a method of choice in the treatment of ED in failure of monotherapy with these drugs or in vein occlusive ED. In the combined treatment dose of the drugs, number of side effects and cost of therapy are lower.

  11. Radiation therapy with or without chemotherapy and hyperthermia for recurrent rectal cancer. Efficacy and disadvantage of combined therapy

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    Murata, Takashi; Fujii, Ikuzo; Yoshino, Masanari; Nagata, Kenji; Imamura, Masahiro; Uda, Mitsunobu; Yamamoto, Keizo; Tanaka, Yoshimasa [Kansai Medical Univ., Moriguchi, Osaka (Japan)

    1997-03-01

    Forty-seven patients with intrapelvic recurrent rectal cancer were prescribed radiation alone (17 cases), radiation and chemotherapy (18 cases) or radiation with hyperthermia (12 cases) from 1989 to 1995. To discuss efficacies and disadvantages of these combined therapies, tumor response rate, pain control rate, duration of tumor control and pain control, and influence on patients` survival were evaluated. Radiation was delivered to the whole pelvis. Mean total dose was 45.5 Gy (1.5-2 Gy/fraction). Chemotherapy consisted 5-FU or CDDP and ADM. Hyperthermia were added 3-6 times concomitantly to the radiation. In all patients receiving more than 30 Gy radiation, tumor response rate was 56.8%. Tumor response rates were 35.3%, 43.7% and 41.7% in the radiation alone group, radiation and chemotherapy group and radiation with hyperthermia group respectively. Radiation combined chemotherapy was more effective for the tumor less than 5 cm diameter than radiation alone. In cases receiving over 50 Gy radiation, combined treatments were more effective than radiation alone. Pain relief was obtained in 75.9% of patients and there were no difference between three treatment groups. Tumor control was significantly prolonged in combined groups. Median survival periods were 6, 10 and 7 months for radiation alone, radiation and chemotherapy, and radiation with hyperthermia respectively. In PR cases and for tumors under 5 cm in diameter, there were no difference between three groups. In cases receiving over 50 Gy radiation, survival period was prolonged in radiation with hyperthermia. Fourteen patients developed acute toxicity (Leucopenia) and late complication due to bowel obstruction. The incidence of bowel complication was 27.8% for radiation and chemotherapy and 33.3% for radio-hyperthermia, while 17.6%, significantly low percentage, for radiation alone. Bowel obstruction may occur positively correlated with postsurgical adhesions and infections at initial surgery. (K.H.)

  12. Successful achievement of sustained virological response to triple combination therapy containing simeprevir in two patients with chronic hepatitis C who had failed asunaprevir:Daclatasvir combination therapy.

    Science.gov (United States)

    Ozeki, Itaru; Nakajima, Tomoaki; Yamaguchi, Masakatsu; Kimura, Mutsuumi; Arakawa, Tomohiro; Kuwata, Yasuaki; Ohmura, Takumi; Sato, Takahiro; Hige, Shuhei; Karino, Yoshiyasu; Toyota, Joji

    2016-10-01

    Patients 1 and 2 were treatment-naive women who had genotype 1b chronic hepatitis C. Both had IL-28B genotype TT, and amino acid substitutions of core 70 and 91 were both wild type. Search for the presence of resistance-associated variants (RAV) in non-structural (NS)3 and NS5A regions confirmed wild-type D168 and L31, along with Y93H, in both patients. These patients participated in a Japanese phase III clinical study of asunaprevir and daclatasvir at the age of 52 and 67 years, respectively, and were treated with the combination regimen for 24 weeks. However, both experienced post-treatment relapse, and then treated with triple combination therapy with simeprevir, pegylated interferon (IFN) and ribavirin at the age of 53 and 68 years, respectively, and achieved sustained virological response. A search for RAV prior to simeprevir treatment identified multiple resistance including D168E, Y93H and L31V in both patients. It has been demonstrated that, in many cases, a treatment failure with a combination of asunaprevir and daclatasvir results in acquisition of RAV in NS3 and NS5A regions and that drug-resistant mutants, particularly those in the NS5A region, survive for a long time. In these cases, direct-acting antivirals targeted towards the NS5A region may have a limited efficacy. The present case report is based on an idea that a regimen containing IFN with simeprevir could be a therapeutic option particularly for those who are likely to be highly sensitive and tolerable to IFN.

  13. Attractor Explosions and Catalyzed Vacuum Decay

    Energy Technology Data Exchange (ETDEWEB)

    Green, Daniel; Silverstein, Eva; Starr, David

    2006-05-05

    We present a mechanism for catalyzed vacuum bubble production obtained by combining moduli stabilization with a generalized attractor phenomenon in which moduli are sourced by compact objects. This leads straightforwardly to a class of examples in which the Hawking decay process for black holes unveils a bubble of a different vacuum from the ambient one, generalizing the new endpoint for Hawking evaporation discovered recently by Horowitz. Catalyzed vacuum bubble production can occur for both charged and uncharged bodies, including Schwarzschild black holes for which massive particles produced in the Hawking process can trigger vacuum decay. We briefly discuss applications of this process to the population and stability of metastable vacua.

  14. APS Storage Ring vacuum chamber fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Goeppner, G.A.

    1990-01-01

    The 1104-m circumference Advanced Photon Source Storage Ring Vacuum System is composed of 240 individual sections, which are fabricated from a combination of aluminum extrusions and machined components. The vacuum chambers will have 3800 weld joints, each subject to strict vacuum requirements, as well as a variety of related design criteria. The vacuum criteria and chamber design are reviewed, including a discussion of the weld joint geometries. The critical fabrication process parameters for meeting the design requirements are discussed. The experiences of the prototype chamber fabrication program are presented. Finally, the required facilities preparation for construction activity is briefly described. 6 refs., 6 figs., 1 tab.

  15. Nondrug therapy in the combination rehabilitation of patients with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    V. L. Golubev

    2014-01-01

    Full Text Available Non-drug rehabilitation in Parkinson’s disease (PD has recently attracted the increasing attention of neurologists worldwide. Symptomatic medical treatment only prolongs the period of relative wellbeing and little affects the course of the disease, without preventing its progression. Today this raises the question of whether other or additional therapeutic approaches to rehabilitating patients with this disease should be sought. The elaboration and practical implementation of a program for multidisciplinary patient rehabilitation are most effective to date. This program includes combination therapy based on the use of current drugs and different variants of nondrug therapy. Within the current concept of medical treatment for PD, there are two strategic approaches: 1 to search for agents that are able to slow, delay, or stop its progression (the so-called neuroprotection and 2 to develop more effective symptomatic therapies. The latter approach is presently considered to be basic. At large, more than 40-year experience in using dopaminergic and other antiparkinsonian agents indicates that this therapy cannot drastically solve the problem of PD treatment. So nondrug care methods whose improvement has become a relevant task of current therapeutic strategy in this disease are the focus of attention today. A nonpharmacological approach to treating PD is appropriate at all its stages. Here are just some of these methods: medicinal vacation, phototherapy, sleep deprivation, electroconvulsive therapy, and transcranial magnetic stimulation. Patients’ compliance to dietary advice is of significance. The experience shows that the most accessible and efficient and safe nondrug treatment is of course a package of measures to stimulateand restore a patient’s physical activity, which encompasses special functional training programs, kinesitherapy, multisensory training,physical exercises, etc. There is a need to further accumulate experience

  16. Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Staunstrup, Line Maersk; Michaelsen, Signe Regner

    2017-01-01

    Background: Bevacizumab combined with chemotherapy pro