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Sample records for anti-amyloid combination therapy

  1. Anti-amyloid Aggregation Activity of Natural Compounds: Implications for Alzheimer's Drug Discovery.

    Science.gov (United States)

    Bu, Xian-Le; Rao, Praveen P N; Wang, Yan-Jiang

    2016-08-01

    Several plant-derived natural compounds are known to exhibit anti-amyloid aggregation activity which makes them attractive as potential therapies to treat Alzheimer's disease. The mechanisms of their anti-amyloid activity are not well known. In this regard, many natural compounds are known to exhibit direct binding to various amyloid species including oligomers and fibrils, which in turn can lead to conformational change in the beta-sheet assembly to form nontoxic aggregates. This review discusses the mechanism of anti-amyloid activity of 16 natural compounds and gives structural details on their direct binding interactions with amyloid aggregates. Our computational investigations show that the physicochemical properties of natural products do fit Lipinski's criteria and that catechol and catechol-type moieties present in natural compounds act as lysine site-specific inhibitors of amyloid aggregation. Based on these observations, we propose a structural template to design novel small molecules containing site-specific ring scaffolds, planar aromatic and nonaromatic linkers with suitably substituted hydrogen bond acceptors and donors. These studies will have significant implications in the design and development of novel amyloid aggregation inhibitors with superior metabolic stability and blood-brain barrier penetration as potential agents to treat Alzheimer's disease.

  2. 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

  3. Curcumin in combined cancer therapy.

    Science.gov (United States)

    Troselj, Koraljka Gall; Kujundzic, Renata Novak

    2014-01-01

    The mechanisms of beneficial preventive and therapeutic effects achieved by traditional and complementary medicine are currently being deciphered in molecular medicine. Curcumin, a yellow-colored polyphenol derived from the rhizome of turmeric (Curcuma longa), influences a wide variety of cellular processes through the reshaping of many molecular targets. One of them, nuclear factor kappa B (NF-κB), represents a strong mediator of inflammation and, in a majority of systems, supports the pro-proliferative features of cancer cells. The application of various anticancer drugs, cytostatics, triggers signals which lead to an increase in cellular NF-κB activity. As a consequence, cancer cells often reshape their survival signaling pathways and, over time, become resistant to applied therapy. Curcumin was shown to be a strong inhibitor of NF-κB activity and its inhibitory effect on NF-κB related pathways often leads to cellular apoptotic response. All these facts, tested and confirmed in many different biological systems, have paved the way for research aimed to elucidate the potential beneficial effects of combining curcumin and various anti-cancer drugs in order to establish more efficient and less toxic cancer treatment modalities. This review addresses certain aspects of NF-κB-related inflammatory response, its role in carcinogenesis and therapy benefits that may be gained through silencing NF-κB by selectively combining curcumin and various anticancer drugs.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. [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.

  9. 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.

  10. 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.

  11. 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.

  12. 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 malignanci......ART 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.......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...... 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...

  13. 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.

  14. 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.

  15. Combined therapy for diabetic macular edema

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    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.

  16. COMBINATION THERAPY FOR PROSTATE CANCER: CLINICAL OBSERVATIONS

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    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.

  17. 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.

  18. 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....

  19. 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.

  20. 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

  1. Novel strategies for Alzheimer's disease treatment: An overview of anti-amyloid beta monoclonal antibodies

    Directory of Open Access Journals (Sweden)

    Katarzyna Rygiel

    2016-01-01

    Full Text Available Alzheimer's disease (AD is a multifactorial, progressive neurodegenerative disorder with a poor prognosis, and thus, novel therapies for AD are certainly needed in a growing population of elderly patients or asymptomatic individuals, who are at risk for AD, worldwide. It has been established that some AD biomarkers such as amyloid-beta load in the brain, precede the onset of the disease, by approximately 20 years. Therefore, the therapy to prevent or effectively treat AD has to be initiated before the emergence of symptoms. A goal of this review is to present the results of recent clinical trials on monoclonal antibodies against amyloid beta, used for the treatment of AD and also to address some of the current challenges and emerging strategies to prevent AD. In recent trials, a monoclonal antibody, i.e. solanezumab has shown some beneficial cognitive effects among mild AD patients. Ongoing studies with gantenerumab and crenezumab will examine when exactly the AD treatment, aimed at modifying the disease course has to be started. This review was based on Medline database search for trials on passive anti-AD immunotherapy, for which the main timeframe was set from 2012 to 2015.

  2. 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.

  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. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Bacoside-A, an anti-amyloid natural substance, inhibits membrane disruption by the amyloidogenic determinant of prion protein through accelerating fibril formation.

    Science.gov (United States)

    Malishev, Ravit; Nandi, Sukhendu; Kolusheva, Sofiya; Shaham-Niv, Shira; Gazit, Ehud; Jelinek, Raz

    2016-09-01

    Bacosides, class of compounds extracted from the Bacopa monniera plant, exhibit interesting therapeutic properties, particularly enhancing cognitive functions and putative anti-amyloid activity. We show that bacoside-A exerted significant effects upon fibrillation and membrane interactions of the amyloidogenic fragment of the prion protein [PrP(106-126)]. Specifically, when co-incubated with PrP(106-126), bacoside-A accelerated fibril formation in the presence of lipid bilayers and in parallel inhibited bilayer interactions of the peptide aggregates formed in solution. These interesting phenomena were studied by spectroscopic and microscopic techniques, which suggest that bacoside A-promoted fibrillation reduced the concentration of membrane-active pre-fibrillar species of the prion fragment. This study suggests that induction of fibril formation and corresponding inhibition of membrane interactions are likely the underlying factors for ameliorating amyloid protein toxicity by bacoside-A.

  12. 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...

  13. 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 ...

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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.

  4. 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...

  5. 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...

  6. 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.

  7. 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. 

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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...... of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype...... can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma....

  16. 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...... can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma....... of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype...

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. [Piracetam in combined pathogenetic therapy of recurrent duodenal ulcer].

    Science.gov (United States)

    Tsimmerman, Ia S; Shchetkin, D I

    2002-01-01

    Duodenal ulcer cure, as a systemic gastroenterologic disease, can be achieved in some patients by the addition of the nootropic drug piracetam to current antisecretory and antihelicobacter therapy. Piracetam corrects vegetative and psychoemotional disorders in duodenal ulcer, normalizes gastric motility, has an antioxidant effect and improves cerebral circulation. An optimal effect on clinico-endoscopic manifestations of recurrent duodenal ulcer was achieved in combination of piracetam with current antisecretory (omeprazole) and antihelicobacter (de-nol, amoxicillin, metronidazole) medicines. Such combination improves both short- and long-term outcomes of duodenal ulcer treatment.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. Bapineuzumab alters aβ composition: implications for the amyloid cascade hypothesis and anti-amyloid immunotherapy.

    Directory of Open Access Journals (Sweden)

    Alex E Roher

    Full Text Available The characteristic neuropathological changes associated with Alzheimer's disease (AD and other lines of evidence support the amyloid cascade hypothesis. Viewing amyloid deposits as the prime instigator of dementia has now led to clinical trials of multiple strategies to remove or prevent their formation. We performed neuropathological and biochemical assessments of 3 subjects treated with bapineuzumab infusions. Histological analyses were conducted to quantify amyloid plaque densities, Braak stages and the extent of cerebral amyloid angiopathy (CAA. Amyloid-β (Aβ species in frontal and temporal lobe samples were quantified by ELISA. Western blots of amyloid-β precursor protein (AβPP and its C-terminal (CT fragments as well as tau species were performed. Bapineuzumab-treated (Bapi-AD subjects were compared to non-immunized age-matched subjects with AD (NI-AD and non-demented control (NDC cases. Our study revealed that Bapi-AD subjects exhibited overall amyloid plaque densities similar to those of NI-AD cases. In addition, CAA was moderate to severe in NI-AD and Bapi-AD patients. Although histologically-demonstrable leptomeningeal, cerebrovascular and neuroparenchymal-amyloid densities all appeared unaffected by treatment, Aβ peptide profiles were significantly altered in Bapi-AD subjects. There was a trend for reduction in total Aβ42 levels as well as an increase in Aβ40 which led to a corresponding significant decrease in Aβ42:Aβ40 ratio in comparison to NI-AD subjects. There were no differences in the levels of AβPP, CT99 and CT83 or tau species between Bapi-AD and NI-AD subjects. The remarkable alteration in Aβ profiles reveals a dynamic amyloid production in which removal and depositional processes were apparently perturbed by bapineuzumab therapy. Despite the alteration in biochemical composition, all 3 immunized subjects exhibited continued cognitive decline.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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...

  19. 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...

  20. 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....

  1. 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.

  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. 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

  4. 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

  5. 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.

  6. 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.

  7. 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)

  8. 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

  9. 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.

  10. Apolipoprotein E LDL receptor-binding domain-containing high-density lipoprotein: a nanovehicle to transport curcumin, an antioxidant and anti-amyloid bioflavonoid.

    Science.gov (United States)

    Khumsupan, Panupon; Ramirez, Ricardo; Khumsupan, Darin; Narayanaswami, Vasanthy

    2011-01-01

    Curcumin is an antioxidant and anti-inflammatory bioflavonoid that has been recently identified as an anti-amyloid agent as well. To make it more available in its potent form as a potential amyloid disaggregation agent, we employed high-density lipoproteins (HDL), which are lipid-protein complexes that transport plasma cholesterol, to transport curcumin. The objective of this study was to employ reconstituted HDL containing human apoE3 N-terminal (NT) domain, as a vehicle to transport curcumin. The NT domain serves as a ligand to mediate binding and uptake of lipoprotein complexes via the low-density lipoprotein receptor (LDLr) family of proteins located at the cell surface. Reconstituted HDL was prepared with phospholipids and recombinant apoE3-NT domain in the absence or presence of curcumin. Non-denaturing polyacrylamide gel electrophoresis indicated that the molecular mass and Stokes' diameter of HDL bearing curcumin were ~670kDa and ~17nm, respectively, while electron microscopy revealed the presence of discoidal particles. Fluorescence emission spectra of HDL bearing (the intrinsically fluorescent) curcumin indicated that the wavelength of maximal fluorescence emission (λ(max)) of curcumin was ~495nm, which is highly blue-shifted compared to λ(max) of curcumin in solvents of varying polarity (λ(max) ranging from 515-575nm) or in aqueous buffers. In addition, an enormous enhancement in fluorescence emission intensity was noted in curcumin-containing HDL compared to curcumin in aqueous buffers. Curcumin fluorescence emission was quenched to a significant extent by lipid-based quenchers but not by aqueous quenchers. These observations indicate that curcumin has partitioned efficiently into the hydrophobic milieu of the phospholipid bilayer of HDL. Functional assays indicated that the LDLr-binding ability of curcumin-containing HDL with apoE3-NT is similar to that of HDL without curcumin. Taken together, we report that apoE-containing HDL has a tremendous

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. [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.

  7. 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

  8. 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

    2016-05-01

    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.

  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. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. The use of combination therapy in pulmonary arterial hypertension: new developments

    Directory of Open Access Journals (Sweden)

    N. Galiè

    2009-09-01

    Full Text Available There is a strong clinical rationale for combination therapy in pulmonary arterial hypertension (PAH, as several pathological pathways have been implicated in its pathogenesis and no single agent has yet been shown to deliver completely satisfactory results. Registry data indicate that use of combination therapy is in fact common in existing clinical practice, even though support has been largely empirical or derived from small-scale observational studies. Data from large, adequately powered, randomised controlled trials of combination therapy in PAH are now emerging and suggest that combination therapy may be clinically beneficial. Studies of bosentan in combination with prostanoids and phosphodiesterase (PDE-5 inhibitors show consistent evidence of improvements in exercise capacity compared with placebo. Similar improvements have been observed with PDE-5 inhibitors in combination with prostanoids. The appropriate timing of combination therapy requires further evaluation but goal-oriented therapy using combinations of oral and inhaled drugs has been shown to provide acceptable long-term results in patients with advanced PAH. Monitoring should be performed regularly and be based on repeatable, noninvasive, measurable parameters that have prognostic value.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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...

  13. 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.

  14. 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.

  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. 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.

  18. 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

  19. 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

  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. 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

  2. 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.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    their escape from cytotoxic therapies represent prime vaccination candidates. The characterization of a high number of tumor antigens allow the concurrent or serial immunological targeting of different proteins associated with such cancer traits. Moreover, while vaccination in itself is a promising new......Harnessing of the immune system by the development of 'therapeutic' vaccines, for the battle against cancer has been the focus of tremendous research efforts over the past two decades. As an illustration of the impressive amounts of data gathered over the past years, numerous antigens expressed...... on the surface of cancer cells, have been characterized. To this end, recent years research has focussed on characterization of antigens that play an important role for the growth and survival of cancer cells. Anti-apoptotic molecules like survivin that enhance the survival of cancer cells and facilitate...

  4. 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

  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. PMID:27847783

  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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.)

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

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

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    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

  11. Fibromatoses: from postsurgical surveillance to combined surgery and radiation therapy.

    Science.gov (United States)

    Miralbell, R; Suit, H D; Mankin, H J; Zuckerberg, L R; Stracher, M A; Rosenberg, A E

    1990-03-01

    The results of management of two groups of patients with musculoaponeurotic (desmoid tumors) and plantar fibromatoses seen at Massachusetts General Hospital (MGH) during the period 1970-1985 are examined: (a) 26 patients who had had surgical resection for their primary fibromatosis but whose surgical margins were positive and who received no further treatment; and (b) 24 patients who were treated for their primary or recurrent fibromatosis by radiation alone or combined with surgery. For the 26 patients who were only observed, despite the positive surgical margins, 9 have recurred; the actuarial continuous local control rate at 5 years was 68% (a median follow-up of 70 months). Five patients had gross disease left after surgery and all of them failed. Seventeen of 21 patients who had grossly complete resection have local control; the four failures have been salvaged. This result supports the rationale for a no treatment but a thorough and close follow-up policy for patients with positive margins after grossly complete resection of a primary desmoid or fascial fibromatosis. There is no risk of metastasis in these patients and hence the effort toward a conservative policy which defers radiation merits interest and further study. Of the second group, 23 patients were treated for gross disease and one patient for microscopic disease after surgical resection. All of the 10 patients who were treated for primary desmoid tumor have local control. Among the 14 recurrent desmoid tumors there have been five local failures, after treatment by radiation alone or radiation + surgery. Three patients treated by radiation alone are currently scored as incompletely regressed tumors. Accordingly 16 of the 24 patients are scored as local controls without evidence of disease and 19 of the 24 are scored as local control (complete response or partial but stable response).

  12. 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...

  13. 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.

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  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. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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. 

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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...

  19. 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...

  20. 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...

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

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

    Directory of Open Access Journals (Sweden)

    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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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

  10. 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...

  11. 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)

  12. 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.

  13. 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

  14. 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

  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. 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

  17. 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

  18. 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.

  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. 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

  1. 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.

  2. 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...

  3. 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

  4. 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.

  5. 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.

  6. 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....

  7. 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.

  8. 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.

  9. 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.

  10. 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

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

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm; Marvig, Rasmus L.

    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 resi...

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Randomized Controlled Trial of Sertraline, Prolonged Exposure Therapy and Their Combination in OEF/OIF with PTSD

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-11-1-0073 TITLE: Randomized Controlled Trial of Sertraline , Prolonged Exposure Therapy and their Combination in OEF/OIF...NUMBER W81XWH-11-1-0073 Randomized Controlled Trial of Sertraline , Prolonged Exposure Therapy and Their Combination in OEF/OIF with PTSD 5b. GRANT...KEYWORDS PTSD, Veterans, Prolonged Exposure, Sertraline , OEF, OIF, OND, treatment, therapy, medication, fMRI, cortisol OVERALL PROJECT SUMMARY

  17. Options for empagliflozin in combination therapy in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. ECONOMIC EVALUATION OF COMBINED THERAPY OF ARTERIAL HYPERTENSION BY MARKOV’S MODELING

    Directory of Open Access Journals (Sweden)

    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

  4. 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.

  5. 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.

  6. Step-down therapy in well-controlled asthmatic patients using salmeterol xinafoate/fluticasone propionate combination therapy

    Directory of Open Access Journals (Sweden)

    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

  7. 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...

  8. 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...

  9. 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

  10. 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-

  11. 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.

  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. [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.

  14. Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing

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    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.

  15. [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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel

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    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.

  3. Sitagliptin as combination therapy in the treatment of type 2 diabetes mellitus

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    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

  4. Combination therapies: The next logical Step for the treatment of synucleinopathies?

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    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.

  5. Origins of Combination Therapy for Tuberculosis: Lessons for Future Antimicrobial Development and Application

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    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

  6. 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.

  7. Role of olmesartan in combination therapy in blood pressure control and vascular function

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    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. 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.

  9. 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.

  10. 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.

  11. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

    Science.gov (United States)

    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.

  12. 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.

  13. 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.

  14. 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.

  15. Radiation therapy with or without chemotherapy and hyperthermia for recurrent rectal cancer. Efficacy and disadvantage of combined therapy

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  16. 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.

  17. 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.

  18. pH- and NIR light responsive nanocarriers for combination treatment of chemotherapy and photodynamic therapy.

    Science.gov (United States)

    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.

  19. [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.

  20. Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Flampouri, Stella [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Zaiden, Robert [Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States); Slayton, William [Department of Pediatrics, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Sandler, Eric [Department of Pediatrics, Division of Hematology/Oncology Nemours Children' s Clinic, Jacksonville, Florida (United States); Ozdemir, Savas [Department of Radiology, Division of Functional and Molecular Imaging, University of Florida College of Medicine, Jacksonville, Florida (United States); Dang, Nam H.; Lynch, James W. [Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Li, Zuofeng; Morris, Christopher G.; Mendenhall, Nancy P. [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States)

    2014-08-01

    Purpose: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Methods and Materials: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on {sup 18}F-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. Results: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Conclusions: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes

  1. Treatment of non-Hodgkin`s lymphoma of Waldeyer`s ring: radiotherapy versus chemotherapy versus combined therapy

    Energy Technology Data Exchange (ETDEWEB)

    Aviles, A.; Delgado, S.; Ruiz, H.; Torre, A. de la; Guzman, R.; Talavera, A. [National Medical Center, Mexico City (Mexico). Oncology Hospital

    1996-01-01

    Treatment of stage IA non-Hodgkin`s lymphoma (NHL) of Waldeyer`s ring remains controversial, probably because of the small number of patients and the scarcity of controlled studies. Between 1981 and 1991, 316 patients with stage I NHL of Waldeyer`s ring were randomised for treatment with radiotherapy alone (extended fields), 101 patients; combined chemotherapy with a regimen of CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) or CHOP-like (epirubicin instead of doxorubicin), 106 patients; and combined therapy (radiotherapy followed by the same combination chemotherapy), 109 patients. Median follow-up was 6.8 years. Complete response was achieved in 93, 87 and 97%, respectively. Relapses were least frequent in patients treated with combination therapy. The 5-year rate for failure-free survival was 48% for radiation therapy, 45% for the patients who were treated with chemotherapy, which was statistically significantly less than the 83% for patients treated with combined therapy (P < 0.001). Overall survival was also better in the combined therapy arm: 90%, statistically different to 58% for the patients treated with chemotherapy alone and 56% for patients treated with radiation therapy (P < 0.001). Toxicity was mild and late side-effects were not observed in any patients. From these results combined therapy should be considered as the best therapeutic approach in patients with localised NHL of Waldeyer`s ring. (author).

  2. Combined chemotherapy and radiation therapy in limited disease small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moon Kyung; Ahn, Yong Chan; Park, Keun Chil; Lim Do Hoon; Huh, Seung Jae; Kim, Dae Yong; Shin, Kyung Hwan; Lee, Kyu Chan; Kwon, O Jung [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)

    1999-03-01

    This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The

  3. Enhanced Radiosensitization of Gold Nanospikes via Hyperthermia in Combined Cancer Radiation and Photothermal Therapy.

    Science.gov (United States)

    Ma, Ningning; Jiang, Yao-Wen; Zhang, Xiaodong; Wu, Hao; Myers, John N; Liu, Peidang; Jin, Haizhen; Gu, Ning; He, Nongyue; Wu, Fu-Gen; Chen, Zhan

    2016-10-14

    Metallic nanostructures as excellent candidates for nanosensitizers have shown enormous potentials in cancer radiotherapy and photothermal therapy. Clinically, a relatively low and safe radiation dose is highly desired to avoid damage to normal tissues. Therefore, the synergistic effect of the low-dosed X-ray radiation and other therapeutic approaches (or so-called "combined therapeutic strategy") is needed. Herein, we have synthesized hollow and spike-like gold nanostructures by a facile galvanic replacement reaction. Such gold nanospikes (GNSs) with low cytotoxicity exhibited high photothermal conversion efficiency (η = 50.3%) and had excellent photostability under cyclic near-infrared (NIR) laser irradiations. We have demonstrated that these GNSs can be successfully used for in vitro and in vivo X-ray radiation therapy and NIR photothermal therapy. For the in vitro study, colony formation assay clearly demonstrated that GNS-mediated photothermal therapy and X-ray radiotherapy reduced the cell survival fraction to 89% and 51%, respectively. In contrast, the cell survival fraction of the combined radio- and photothermal treatment decreased to 33%. The synergistic cancer treatment performance was attributable to the effect of hyperthermia, which efficiently enhanced the radiosensitizing effect of hypoxic cancer cells that were resistant to ionizing radiation. The sensitization enhancement ratio (SER) of GNSs alone was calculated to be about 1.38, which increased to 1.63 when the GNS treatment was combined with the NIR irradiation, confirming that GNSs are effective radiation sensitizers to enhance X-ray radiation effect through hyperpyrexia. In vivo tumor growth study indicated that the tumor growth inhibition (TGI) in the synergistically treated group reached 92.2%, which was much higher than that of the group treated with the GNS-enhanced X-ray radiation (TGI = 29.8%) or the group treated with the GNS-mediated photothermal therapy (TGI = 70.5%). This research

  4. 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.

  5. EFFECT OF ANTIHELMINTHIC THERAPY ON THE SKIN PROCESS IN ROSACEA PATIENTS IN COMBINATION WITH OPISTHORCHIASIS

    Directory of Open Access Journals (Sweden)

    M. L. Aripova

    2015-01-01

    Full Text Available The article presents results of examination of 144 patients, including 64 patients with rosacea in combination  with  chronic  opisthorchiasis  (group  1  and  80  patients  with  rosacea  without  opistorchiasis (group 2. Rosacea patients with concomitant chronic opisthorchosis revealed more severe clinical variants. Mean values of the index scale diagnostic assessment of rosacea is significantly higher than in patients rosacea without helminthiasis, indicating a more severe course. Dissatisfaction with the quality of life in patients with rosacea in combination with chronic opisthorchiasis was significantly higher than in patients with rosaceaonly. Patients with rosacea in combination with chronic opisthorchiasis reveled prevalence of anxiety and depression in scale of HADS. There are also were a comparative analysis of the clinical picture in patients with rosacea anthelmintic therapy and without deworming.

  6. Clinical trial success rates of anti-obesity agents: the importance of combination therapies.

    Science.gov (United States)

    Hussain, H T; Parker, J L; Sharma, A M

    2015-09-01

    The objective of this study was to construct a clinical trial profile assessing the risk of drug failure among anti-obesity agents. Research was conducted by looking at anti-obesity therapies currently on the market or in clinical trials (phases I to III) conducted from 1998 to September 2014, with the exclusion of any drugs whose phase I trial was conducted prior to January 1998. This was completed primarily through a search on http://clinicaltrials.gov where a total of 51 drugs met the search criteria. The transition probabilities were then calculated based on various classifications and compared against industry standards. The transition probability of anti-obesity agents was 8.50% whereas the transition probability of industry standards was 10.40%. Combination therapies had four times the transition probability than monotherapies, 40% and 4.75%, respectively. Therefore, it was determined that 92% of drugs fail during clinical trial testing for this indication and combination therapy appears to improve clinical trial success rates to 10-fold.

  7. Experimental Bothrops atrox envenomation: Efficacy of antivenom therapy and the combination of Bothrops antivenom with dexamethasone

    Science.gov (United States)

    dos Anjos, Isabelle Valle; Chalkidis, Hipocrates de Menezes; Mourão, Rosa Helena Veras; Moura-da-Silva, Ana Maria; Sano-Martins, Ida Sigueko; Gonçalves, Luis Roberto de Camargo

    2017-01-01

    Bothrops atrox snakes are the leading cause of snake bites in Northern Brazil. The venom of this snake is not included in the antigen pool used to obtain the Bothrops antivenom. There are discrepancies in reports on the effectiveness of this antivenom to treat victims bitten by B. atrox snakes. However, these studies were performed using a pre-incubation of the venom with the antivenom and, thus, did not simulate a true case of envenomation treatment. In addition, the local lesions induced by Bothrops venoms are not well resolved by antivenom therapy. Here, we investigated the efficacy of the Bothrops antivenom in treating the signs and symptoms caused by B. atrox venom in mice and evaluated whether the combination of dexamethasone and antivenom therapy enhanced the healing of local lesions induced by this envenomation. In animals that were administered the antivenom 10 minutes after the envenomation, we observed an important reduction of edema, dermonecrosis, and myonecrosis. When the antivenom was given 45 minutes after the envenomation, the edema and myonecrosis were reduced, and the fibrinogen levels and platelet counts were restored. The groups treated with the combination of antivenom and dexamethasone had an enhanced decrease in edema and a faster recovery of the damaged skeletal muscle. Our results show that Bothrops antivenom effectively treats the envenomation caused by Bothrops atrox and that the use of dexamethasone as an adjunct to the antivenom therapy could be useful to improve the treatment of local symptoms observed in envenomation caused by Bothrops snakes. PMID:28306718

  8. A mathematical model of combined therapies against cancer using viruses and inhibitors

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This paper deals with a procedure for combined therapies against cancer using oncolytic viruses and inhibitors. Replicating genetically modified adenoviruses infect cancer cells, reproduce inside them and eventually cause their death (lysis). As infected cells die, the viruses inside them are released and then proceed to infect other tumor cells. The successful entry of virus into cancer cells is related to the presence of the coxsackie-adenovirus receptor (CAR). Mitogen-activated protein kinase kinase (known as MEK) inhibitors can promote CAR expression, resulting in enhanced adenovirus entry into cancer cells. However, MEK inhibitors can also cause G1 cell-cycle arrest, inhibiting reproduction of the virus. To design an effective synergistic therapy, the promotion of virus infection must be optimally balanced with inhibition of virus production. We introduce a mathematical model to describe the effects of MEK inhibitors and viruses on tumor cells, and use it to explore the reduction of the tumor size that can be achieved by the combined therapies. Furthermore, we find an optimal dose of inhibitor: Poptimal = 1 - μ/δ for a certain initial density of cells (where μ is the removal rate of the dead cells and δ is the death rate of the infected cells). The optimal timing of MEK inhibitors is also numerically studied.

  9. Improved Outcomes with Intensity Modulated Radiation Therapy Combined with Temozolomide for Newly Diagnosed Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Noel J. Aherne

    2014-01-01

    Full Text Available Purpose. Glioblastoma multiforme (GBM is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months. We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

  10. A mathematical model of combined therapies against cancer using viruses and inhibitors

    Institute of Scientific and Technical Information of China (English)

    TAO YouShan; GUO Qian

    2008-01-01

    This paper deals with a procedure for combined therapies against cancer using oncolytic viruses and inhibitors. Replicating genetically modified adenoviruses infect cancer cells, reproduce inside them and eventually cause their death (lysis). As infected cells die, the viruses inside them are released and then proceed to infect other tumor cells. The successful entry of virus into cancer cells is related to the presence of the coxsackie-adenovirus receptor (CAR). Mitogen-activated protein kinase kinase (known as MEK) inhibitors can promote CAR expression, resulting in enhanced adenovirus entry into cancer cells. However, MEK inhibitors can also cause G1 cell-cycle arrest, inhibiting reproduction of the virus. To design an effective synergistic therapy, the promotion of virus infection must be optimally balanced with inhibition of virus production. We introduce a mathematical model to describe the effects of MEK inhibitors and viruses on tumor cells, and use it to explore the reduction of the tumor size that can be achieved by the combined therapies. Furthermore, we find an optimal dose of inhibitor: Poptimal = I - μ/δ for a certain initial density of cells (where μ is the removal rate of the dead cells and δ is the death rate of the infected cells). The optimal timing of MEK inhibitors is also numerically studied.

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

    Directory of Open Access Journals (Sweden)

    Salomeh Jelveh

    2011-03-01

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

  12. Gold nanostructures as a platform for combinational therapy in future cancer therapeutics.

    Science.gov (United States)

    Jelveh, Salomeh; Chithrani, Devika B

    2011-03-04

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

  13. Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency.

    Science.gov (United States)

    De Ravin, Suk See; Wu, Xiaolin; Moir, Susan; Anaya-O'Brien, Sandra; Kwatemaa, Nana; Littel, Patricia; Theobald, Narda; Choi, Uimook; Su, Ling; Marquesen, Martha; Hilligoss, Dianne; Lee, Janet; Buckner, Clarissa M; Zarember, Kol A; O'Connor, Geraldine; McVicar, Daniel; Kuhns, Douglas; Throm, Robert E; Zhou, Sheng; Notarangelo, Luigi D; Hanson, I Celine; Cowan, Mort J; Kang, Elizabeth; Hadigan, Coleen; Meagher, Michael; Gray, John T; Sorrentino, Brian P; Malech, Harry L

    2016-04-20

    X-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations inIL2RGencoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1.

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

    Energy Technology Data Exchange (ETDEWEB)

    Jelveh, Salomeh [Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, ON (Canada); Department of Radiation Physics, Princess Margaret Hospital, Toronto, ON (Canada); Chithrani, Devika B., E-mail: devika.chithrani@rmp.uhn.on.ca [Department of Radiation Physics, Princess Margaret Hospital, Toronto, ON (Canada); STTARR Innovation Centre, Toronto Medical Discovery Tower, Toronto, ON (Canada)

    2011-03-04

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

  15. Comparing the Effectiveness of the Attachment-based Therapy, Dietary Therapy, and Combined Treatment Method on Weight Loss in Obese Adolescents of Yasuj High Schools

    Directory of Open Access Journals (Sweden)

    M Chorami

    2014-10-01

    Full Text Available Background & aim: At the present time, obesity as one of the most important public health problems which has widely prevailed throughout the world. The aim of this study was to compare the effectiveness of the attachment-based therapy, dietary-therapy, and the combined treatment method on weight (body mass index loss in obese high school adolescents of Yasuj city. Methods: This clinical trial study was conducted on sixty female high school students of Yasuj, Iran, diagnosed with overweight and obesity. Subjects were randomly selected and divided into four equal groups, and their body mass indexes were assessed. Three intervention groups were exposed to the attachment-based therapy, dietary-therapy, and combined treatment method. The fourth group (control did not receive any intervention. Following the treatment period, body mass indexes of the four groups were assessed. The data were analyzed by implementing Univariate analysis of covariance and LSD post hoc tests. Results: All three intervention methods of weight loss significantly increased compared with the control group (p < 0.001. However, the combination therapy was more effective. Conclusions: According to the findings of this study, it was concluded that although interventional techniques such as attachment-based therapy and dietary therapy are effective for weight loss, the combination of these two methods were more effective for weight loss.

  16. Design, synthesis and evaluation of antimalarial potential of polyphosphazene linked combination therapy of primaquine and dihydroartemisinin.

    Science.gov (United States)

    Kumar, Sahil; Singh, Rajesh K; Sharma, Rajiv; Murthy, R S R; Bhardwaj, T R

    2015-01-23

    Various polymer drug conjugates (13-16) such as primaquine and dihydroartemisinin conjugated 2-propoxy substituted polyphosphazenes (13), primaquine and dihydroartemisinin conjugated 4-acetamidophenoxy substituted polyphosphazenes (14), primaquine and dihydroartemisinin conjugated 4-formyl substituted polyphosphazenes (15) and primaquine and dihydroartemisinin conjugated 4-aminoethylbenzoate substituted polyphosphazenes (16) were synthesized using substituted polyphosphazenes as polymer and primaquine and dihydroartemisinin as combination antimalarial pharmacophores and formulated to nanoparticles to achieve novel controlled combined drug delivery approach for radical cure of malaria. The polymeric backbone was suitably substituted to impart different physicochemical properties. The polymer-drug conjugates were characterized by IR, (1)H NMR, (31)P NMR and their molecular weights were determined by Gel Permeation Chromatography. The thermal properties of the conjugates (13-16) were studied by DSC and TGA. The conjugates (13-16) were then formulated to nanoparticles formulations to increase their uptake by hepatocytes and to achieve targeted drug delivery. The nanoparticle formulations were characterized by Zeta Sizer and their morphology were studied by TEM (Transmission Electron Microscopy) imaging. The nanoparticles formulations exhibited biphasic in vitro drug release profile, the initial burst release followed by a sustained release owing to the non-fickian diffusion during first step release and fickian diffusion during second step release. In vivo antimalarial efficacy was tested using Plasmodium berghei (NK65 resistant strain) infected swiss albino mice at different doses. The combination therapy exhibited promising antimalarial efficacy at lower doses in comparison to the standard drug combination. Further, this combination therapy provided protection over 35days without any recrudescence, thus proving to be effective against resistant malaria. The study

  17. The mechanism of local tumor irradiation combined with interleukin 2 therapy in murine renal carcinoma: histological evaluation of pulmonary metastases.

    Science.gov (United States)

    Dezso, B; Haas, G P; Hamzavi, F; Kim, S; Montecillo, E J; Benson, P D; Pontes, J E; Maughan, R L; Hillman, G G

    1996-09-01

    We have demonstrated that tumor irradiation enhanced the therapeutic effect of interleukin 2 (IL-2) on pulmonary metastases from a murine renal adenocarcinoma, Renca. To investigate the mechanism of interaction between tumor irradiation and IL-2 therapy, we have histologically evaluated the effects of each therapy alone or in combination on Renca pulmonary metastases. Following treatment of established lung metastases with irradiation and IL-2 therapy, lung sections were processed for H&E or immunohistochemical staining. We found that tumor irradiation or IL-2 therapy locally induced vascular damage, resulting in multifocal hemorrhages and mononuclear cell mobilization in the lung tissue. This effect was amplified in lungs treated with the combined therapy. Immunohistochemistry showed that irradiation produced a macrophage influx into irradiated tumor nodules, and systemic IL-2 therapy induced T-cell infiltration in tumor nodules. Lungs treated with the combined therapy exhibited massive macrophage, T-cell, and natural killer cell mobilization in disintegrating tumor nodules and in the lung tissue. This combined therapy caused a decrease in the number of proliferating tumor cells and an increase in the number of apoptotic cells, which were more marked than with either therapy alone. We suggest that the macrophages mobilized by radiation-induced tissue injury could play a role in phagocytosis of apoptotic tumor cells, processing and presenting of tumor antigens for a systemic immune response activated by IL-2. Tumor destruction may result from the concomitant action of activated T cells, natural killer cells, and macrophages infiltrating the tumor nodules.

  18. Epinephrine injection therapy versus a combination of epinephrine injection and endoscopic hemoclip in the treatment of bleeding ulcers

    Institute of Scientific and Technical Information of China (English)

    Tju-Siang Chua; Kwong-Ming Fock; Tay-Meng Ng; Eng-Kiong Teo; Jessica Yi-Lyn Tan; Tiing-Leong Ang

    2005-01-01

    AIM: To assess the efficacy of hemoclip application in combination with epinephrine injection in the treatment of bleeding peptic ulcers and to compare the clinical outcomes between patients treated with such a combination therapy and those treated with epinephrine injection alone.METHODS: A total of 293 patients (211 males, 82females) underwent endoscopic therapy for bleeding peptic ulcers. Of these, 202 patients (152 males, 50females) received epinephrine injection therapy while 91patients (59 males, 32 females) received combination therapy. The choice of endoscopic therapy was made by the endoscopist. Hemostatic rates, rebleeding rates, need for emergency surgery and 30-d mortality were the outcome measures studied.RESULTS: Patients who received combination therapy were significantly older (mean age 66±16 years, range24-90 years) and more suffered from chronic renal failure compared to those who received epinephrine injection therapy alone (mean age 61±17 years, range 21-89 years).Failure to achieve permanent hemostasis was 4% in the group who received epinephrine injection alone and 11%in the group who received combination therapy. When the differences in age and renal function between the two treatment groups were taken into account by multivariate analysis, the rates of initial hemostasis,rebleeding rates, need for surgery and 30-d mortality for both treatment options were not significantly different.CONCLUSION: Combination therapy of epinephrine injection with endoscopic hemoclip application is an effective method of achieving hemostasis in bleeding peptic ulcer diseases. However, superiority of combination therapy over epinephrine injection alone, could not be demonstrated.

  19. Combination therapy targeting the tumor microenvironment is effective in a model of human ocular melanoma

    Directory of Open Access Journals (Sweden)

    Schafer Peter H

    2007-07-01

    Full Text Available Abstract Background Ocular melanoma is the leading intraocular malignancy. There is no effective treatment for metastatic ocular melanoma. We sought a treatment targeting the tumor microenvironment as well as the tumor cells. Methods Migration of HUVEC cells, the ability of HUVEC cells to form tubes, and proliferative capacity of a human ocular melanoma cell line were tested in the presence of lenalidomide and sorafenib alone and in combination. The compounds were also tested in a rat aortic ring assay and were tested in a highly aggressive human ocular melanoma xenograft model. Results Lenalidomide and Sorafenib inhibit HUVEC ability to migrate and form tubes and when used in combination the inhibition is increased. The agents alone and in combination inhibit outgrowth in the rat aortic ring model. The combination of the agents improved the inhibition over either single agent. In a xenograft model, combination therapy inhibited tumor growth over inhibition by single agent alone in a significant fashion (p Conclusion Lenalidomide and sorafenib are effective at targeting endothelial cells, inhibiting growth of ocular melanoma cells and can inhibit growth of tumors in a xenograft model as well as inhibit development of metastases. Combining these agents works in an additive to synergistic way to inhibit the growth of tumors and development of metastases.

  20. Inhibitors of DNA Methylation, Histone Deacetylation, and Histone Demethylation: A Perfect Combination for Cancer Therapy.

    Science.gov (United States)

    Zahnow, C A; Topper, M; Stone, M; Murray-Stewart, T; Li, H; Baylin, S B; Casero, R A

    2016-01-01

    Epigenetic silencing and inappropriate activation of gene expression are frequent events during the initiation and progression of cancer. These events involve a complex interplay between the hypermethylation of CpG dinucleotides within gene promoter and enhancer regions, the recruitment of transcriptional corepressors and the deacetylation and/or methylation of histone tails. These epigenetic regulators act in concert to block transcription or interfere with the maintenance of chromatin boundary regions. However, DNA/histone methylation and histone acetylation states are reversible, enzyme-mediated processes and as such, have emerged as promising targets for cancer therapy. This review will focus on the potential benefits and synergistic/additive effects of combining DNA-demethylating agents and histone deacetylase inhibitors or lysine-specific demethylase inhibitors together in epigenetic therapy for solid tumors and will highlight what is known regarding the mechanisms of action that contribute to the antitumor response.

  1. Effects of Combination Therapy of Amiodarone and Bisoprolol in Patients With Paroxysmal Atrial Fibrillation

    Institute of Scientific and Technical Information of China (English)

    Rong-qiang YAN; Fang-sheng ZHENG; Qing-hai ZHANG

    2009-01-01

    Objectives To examine the long-term efficacy of combination therapy of amiodarone and bisoprolol in patients with paroxysmal atrial fibrillation (P-AF). Methods Eighty-eight patients with P-AF were divided into two groups: 44 pa-tients treated with bisoprolol and amiodarone were enrolled in group A; 44 patients treated with amiodarone alone were enrolled in group B. Survival rates, rates of conversing to permanent atrial fibrillation (AF), subjective symptom im-provement rates and secondary bradyarrhythmia rates of the two groups were measured and analyzed. Results At 12 and 24 months, the survival rates for patients free from atrial fibrillation recurrence were 75 % and 59. 1% in group A, and 54.5 % and 36.4 % in group B (P0.05, group A vs. Group B). Conclusions In patients with P-AF, bisoprolol appears to enhance the efficacy of amiodarone therapy in maintaining sinus rhythm and improving subjective symptoms.

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

    Directory of Open Access Journals (Sweden)

    Selen Kuzgun

    2012-12-01

    Full Text Available 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. MATERIAL and METHODS: This is a randomized,prospective,controlled single-blind trial.The study included 20 patients who were diagnosed with stroke.Patients were randomly divided into two groups:first group received conventional rehabilitation program and the second group received conventional rehabilitation program plus mirror therapy on nonparetic upper extremity consisting of wrist extension daily 4 times for 15minutes per session. Both groups received the conventional rehabilitation program for 4 weeks, 5 days a week and daily 1-2h. All patients were evaluated at baseline and at the end of the treatment(week 4.The evaluations were performed by using Brunnstrom Staging, Fugl Meyer Motor Function Scale(FM,Barthel Index(BI and goniometric measurement of wrist extension. RESULTS: The Brunnstrom stage(p<0.01, total score on FM and BI scores (p<0.01 were improved at week 4 compared to the baseline, whereas wrist subscore on FM and the goniometric measurements of the wrist and wrist extension were significantly improved only in group II.The two treatment groups were not statistically different in terms of posttreatment evaluation parameters. CONCLUSION: In our study,the mirror therapy combined with conventional rehabilitation program was not superior to conventional rehabilitation program alone in terms of upper extremity motor and functional recovery.

  3. Combination therapy with steroids and mizoribine in juvenile SLE: a randomized controlled trial.

    Science.gov (United States)

    Tanaka, Yuriko; Yoshikawa, Norishige; Hattori, Shinzaburo; Sasaki, Satoshi; Ando, Takashi; Ikeda, Masahiro; Honda, Masataka

    2010-05-01

    The initial treatment of childhood-onset systemic lupus erythematosus (SLE) is not standardized. Although corticosteroids are the first-line therapy for SLE, long-term, high-dose steroid therapy is associated with various side effects in children. The Japanese Study Group for Renal Disease in Children (JSRDC) has carried out a multi-center, randomized, controlled trial to evaluate the efficacy and safety of corticosteroid and mizoribine (MZB) therapy as an initial treatment for newly diagnosed juvenile SLE. Twenty-eight patients were treated with a combination steroid and MZB (4-5 mg/kg/day) (group S+M) drug therapeutic regimen, while 29 patients were treated with steroid only (group S); both groups were followed up for 1 year. The time to the first flare from treatment initiation was not significantly different between the two groups (Kaplan-Meier method, p = 0.09). During the period when the steroid was given daily (day 0-183), the time to the first flare from treatment initiation was significantly longer in the patients of group S+M than in those of group S (log-rank test, p = 0.02). At the end of the study period, there were no differences in the severity of proteinuria and renal function impairment between the two groups. No patients dropped out of the trial due to adverse events. In conclusion, our combined steroid and MZB drug therapeutic regimen was not shown to be significantly better than the steroid-only therapy as initial treatment for juvenile SLE. Whether MZB administered in a higher dose would be therapeutically advantageous can only be answered by further studies.

  4. Combined EGFR and VEGFR versus single EGFR signaling pathways inhibition therapy for NSCLC: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xinji Zhang

    Full Text Available BACKGROUND: Lung cancer is a heterogeneous disease with multiple signaling pathways influencing tumor cell survival and proliferation, and it is likely that blocking only one of these pathways allows others to act as salvage or escape mechanisms for cancer cells. Whether combined inhibition therapy has greater anti-tumor activity than single inhibition therapy is a matter of debate. Hence, a meta-analysis comparing therapy inhibiting both VEGFR and EGFR signaling pathways with that inhibiting EGFR signaling pathway alone was performed. METHODOLOGY AND PRINCIPAL FINDINGS: We searched PubMed, EMBASE database and the proceedings of major conferences for relevant clinical trials. Outcomes analyzed were objective tumor response rate (ORR, progression-free survival (PFS, overall survival (OS and toxicity. Besides, subgroup analyses were performed to investigate whether the combined inhibition therapy is best performed using combination of selective agents or a single agent with multiple targets. Six trials recruiting 3,302 patients were included in the analysis. Combined inhibition therapy was associated with a 3% improvement in OS as compared with single-targeted therapy, but this difference was not statistically significant (HR, 0.97; 95% CI, 0.89-1.05; P=0.472. Patients receiving combined inhibition therapy had significant longer PFS than the group with single-targeted therapy (HR, 0.80; 95% CI, 0.67-0.95; P=0.011. There was no difference in the ORR between the groups (OR, 1.44; 95% CI, 0.95-2.18; P=0.085. Subgroup analysis revealed that combined inhibition therapy using combination regimens was associated with statistically significant improvement in both ORR and PFS. Toxicity was greater in combined inhibition therapy. CONCLUSIONS: There is no evidence to support the use of combined inhibition therapy in unselected patients with advanced NSCLC. However, given the significant advantage in ORR and PFS, combined inhibition therapy using combination

  5. Multidrug Delivery Systems Based on Human Serum Albumin for Combination Therapy with Three Anticancer Agents.

    Science.gov (United States)

    Qi, Jinxu; Zhang, Yao; Gou, Yi; Lee, Philbert; Wang, Jun; Chen, Shifang; Zhou, Zuping; Wu, Xiaoyang; Yang, Feng; Liang, Hong

    2016-09-06

    When administering several anticancer drugs within a single carrier, it is important to regulate their spatial distribution so as to avoid possible mutual interference and to thus enhance the drugs' selectivity and efficiency. To achieve this, we proposed to develop human serum albumin (HSA)-based multidrug delivery systems for combination anticancer therapy. We used three anticancer agents (an organic drug [5-fluorouracil, or 5FU], a metallic agent [2-benzoylpyridine thiosemicarbazide copper II, or BpT], and a gene agent [AS1411]) to treat liver cancer and confirm our hypothesis. The structure of the HSA-palmitic acid (PA)-5FU-BpT complex revealed that 5FU and BpT, respectively, bind to the IB and IIA subdomains of HSA. Our MALDI-TOF-MS spectral data show that one AS1411 molecule is conjugated to Cys-34 of the HSA-5FU-BpT complex via a linker. Compared with unregulated three-drug combination therapy, the HSA-5FU-BpT-AS1411 complex enhances cytotoxicity in Bel-7402 cells approximately 7-fold in vitro; however, in normal cells it does not raise cytotoxicity levels. Importantly, our in vivo results demonstrate that the HSA-5FU-BpT-AS1411 complex is superior to the unregulated three-drug combination in enhancing targeting ability, inhibiting liver tumor growth, and causing fewer side effects.

  6. Fixed dose combination of arterolane and piperaquine: a newer prospect in antimalarial therapy.

    Science.gov (United States)

    Patil, Cy; Katare, Ss; Baig, Ms; Doifode, Sm

    2014-07-01

    Malaria has been very prevalent vector-borne disease in India and until date bears enormous implications on health care services of the country. Over the period of time, the development of resistance to traditional antimalarials like chloroquine has been posed as major deterrent in efforts of malaria control. As the drug resistance is today universally prevalent, especially in Plasmodium falciparum species, major burden of malarial control resides with the new artemisinin drug class. However, arterolane is one of the first fully synthetic non-artemisinin antimalarial compound with rapid schizontocidal activity, hence offering an alternative to artemisinin drugs in malaria control. Piperaquine is a synthetic bisquinoline (4-amioquinoline Antimalarial) with slow and longer schizontocidal activity. Therefore their combination has been shown to provide rapid parasitemic clearance and quick relief of most malaria-related symptoms along with prevention of recrudescences. This combination was approved by Drugs Controller General of India in 2011 for treatment of uncomplicated P. falciparum malaria. The article is aimed at to review this newer prospect in antimalarial therapy for which comprehensive database search was done in Google, Google Scholar, PubMed using the terms "Malaria," "Arterolane," "OZ277," "Piperaquine," and "Artemisinin combination therapy." A total of 323 articles were screened and 28 articles were considered for this review along with the World Health Organization and National malarial program guidelines.

  7. Photodynamic and Antibiotic Therapy in Combination to Fight Biofilms and Resistant Surface Bacterial Infections.

    Science.gov (United States)

    Barra, Federica; Roscetto, Emanuela; Soriano, Amata A; Vollaro, Adriana; Postiglione, Ilaria; Pierantoni, Giovanna Maria; Palumbo, Giuseppe; Catania, Maria Rosaria

    2015-08-28

    Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, light and O₂, has been principally considered for the treatment of specific types of cancers, other applications exist, including the treatment of infections. Unfortunately, PDT does not always guarantee full success since it exerts lethal effects only in cells that have taken up a sufficient amount of photosensitizer and have been exposed to adequate light doses, conditions that are not always achieved. Based on our previous experience on the combination PDT/chemotherapy, we have explored the possibility of fighting bacteria that commonly crowd infected surfaces by combining PDT with an antibiotic, which normally does not harm the strain at low concentrations. To this purpose, we employed 5-aminolevulinic acid (5-ALA), a pro-drug that, once absorbed by proliferating bacteria, is converted into the natural photosensitizer Protoporphyrin IX (PpIX), followed by Gentamicin. Photoactivation generates reactive oxygen species (ROS) which damage or kill the cell, while Gentamicin, even at low doses, ends the work. Our experiments, in combination, have been highly successful against biofilms produced by several Gram positive bacteria (i.e., Staphylococcus aureus, Staphylococcus epidermidis, etc.). This original approach points to potentially new and wide applications in the therapy of infections of superficial wounds and sores.

  8. Local tumor hyperthermia in combination with radiation therapy. I. Malignant cutaneous lesions

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.H. (Memorial Sloan-Kettering Cancer Center, New York); Hahn, E.W.; Tokita, N.; Nisce, L.Z.

    1977-07-01

    There is increasing evidence that the use of hyperthermia alone or in conjunction with other modalities may improve the therapeutic effectiveness of treatment of cancer. The present clinical studies were carried out to evaluate the response of normal and tumor tissues in patients with various cutaneous malignant lesions to repeated courses of hyperthermia alone or in conjunction with radiation therapy. Thirty-six patients with malignant cutaneous lesions (mycosis fungoides, Kaposi sarcoma, malignant melanoma, lymphoma cutis, and other metastatic skin lesions) have been studied. The heating methods used were: temperature regulated water bath immersion; and radiofrequency inductive heating. The normal tissue effects of the combined treatments of radiation and hyperthermia do not appear to be greater than those treated with radiation alone. The initial tumor regression rates were faster in patients treated with radiation plus hyperthermia than in radiation alone, particularly in patients with Kaposi sarcoma and lymphoma cutis. Among ten locally recurrent patients, seven showed significant prolonged benefits achieved by the combined treatments as compared with the radiation therapy alone. Fractionated hyperthermia alone caused significant tumor regression in four out of five patients. Possible mechanisms leading to the improved results from the combined treatments are discussed.

  9. Effect of alprostadil combined with conventional therapy on serum markers in patients with acute cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Li-Lan Chen; Guo-Qiang Chen; Tao Yang; Mu-Qing Long

    2016-01-01

    Objective:To study the effect of alprostadil combined with conventional therapy on serum markers in patients with acute cerebral infarction.Methods:Patients with acute cerebral infarction treated in our hospital from May 2012 to August 2014 were enrolled and randomly divided into two groups. Observation group received alprostadil combined with conventional therapy and control group received conventional treatment. Then serum markers of both groups were compared.Results:(1) contents of serum nerve function related molecules: serum NSE and S100βcontents of observation group showed a decreasing trend, and BDNF and NGF contents showed an increasing trend; (2) contents of atherosclerosis related enzymes: serum GGT, iNOS and MPO contents of observation group showed a decreasing trend, and PON1 and PON2 contents showed an increasing trend; (3) platelet activation related molecules: serum PPARγ, CD62p, YKL-40, sCD40L and Fibulin-5 contents of observation group all showed a decreasing trend.Conclusions:Alprostadil combined with conventional treatment is helpful to alleviate neuronal damage and inhibit the processes of atherosclerosis and platelet activation;it’s an ideal method for treating acute cerebral infarction.

  10. Attenuation of circadian variation by combined antianginal therapy with suppression of morning and evening increases in transient myocardial ischemia

    DEFF Research Database (Denmark)

    Egstrup, K

    1991-01-01

    three 6-hour periods (p less than 0.01); a lesser peak was noted in the evening. The effects of metoprolol and combined therapy with metoprolol and nifedipine on the circadian variation of ischemic activity were studied in two subgroups of patients in a random, double-blind study design (31 patients...... receiving metoprolol and 42 receiving combined therapy). During therapy with metoprolol the morning increase in ischemic activity was attenuated, and the highest frequency of ischemia was then noted in the evening (6 AM to 12 noon compared with 6 PM to 12 midnight; p less than 0.05). Combined therapy...... abolished the morning peak as did metoprolol monotherapy, but even the evening increase in ischemic activity was attenuated (p less than 0.05). The diurnal distribution of the mean heart rate at the onset of ischemia, when patients were off therapy, showed a morning increase similar to the increase...

  11. Combining cytotoxic and immune-mediated gene therapy to treat brain tumors.

    Science.gov (United States)

    Curtin, James F; King, Gwendalyn D; Candolfi, Marianela; Greeno, Remy B; Kroeger, Kurt M; Lowenstein, Pedro R; Castro, Maria G

    2005-01-01

    Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all be the focus of this review. Both conditional cytotoxicity and targeted toxin mediated tumor death, are aimed at eliminating an established tumor mass and preventing further growth. Tumors employ several defensive strategies that suppress and inhibit anti-tumor immune responses. A better understanding of the mechanisms involved in eliciting anti-tumor immune responses has identified promising targets for immunotherapy. Immunotherapy is designed to aid the immune system to recognize and destroy tumor cells in order to eliminate the tumor burden. Also, immune-therapeutic strategies have the added advantage that an activated immune system has the capability of recognizing tumor cells at distant sites from the primary tumor, therefore targeting metastasis distant from the primary tumor locale. Pre-clinical models and clinical trials have demonstrated that in spite of their location within the central nervous system (CNS), a tissue described as 'immune privileged', brain tumors can be effectively targeted by the activated immune system following various immunotherapeutic strategies. This review will highlight recent advances in brain tumor immunotherapy, with particular emphasis on advances made using gene therapy strategies, as well as reviewing other novel therapies that can be used in combination with immunotherapy. Another important

  12. Long-term alteration of intestinal microbiota in patients with ulcerative colitis by antibiotic combination therapy.

    Science.gov (United States)

    Koido, Shigeo; Ohkusa, Toshifumi; Kajiura, Takayuki; Shinozaki, Junko; Suzuki, Manabu; Saito, Keisuke; Takakura, Kazuki; Tsukinaga, Shintaro; Odahara, Shunichi; Yukawa, Toyokazu; Mitobe, Jimi; Kajihara, Mikio; Uchiyama, Kan; Arakawa, Hiroshi; Tajiri, Hisao

    2014-01-01

    Previous work has demonstrated that intestinal bacteria, such as Fusobacterium varium (F. varium), contribute to the clinical activity in ulcerative colitis (UC); thus, an antibiotic combination therapy (amoxicillin, tetracycline, and metronidazole (ATM)) against F. varium can induce and maintain UC remission. Therefore, we investigated whether ATM therapy induces a long-term alteration of intestinal microbiota in patients with UC. Patients with UC were enrolled in a multicenter, randomized, double-blind, placebo-controlled study. Biopsy samples at the beginning of the trial and again at 3 months after treatment completion were randomly obtained from 20 patients. The terminal restriction fragment length polymorphism (T-RFLP) in mucosa-associated bacterial components was examined to assess the alteration of the intestinal microbiota. Profile changes of T-RFLP in mucosa-associated bacterial components were found in 10 of 12 patients in the treatment group and in none of 8 in the placebo group. Dice similarity coefficients using the unweighted pair group method with arithmetic averages (Dice-UPGMA) confirmed that the similarity of mucosal microbiota from the descending colon was significantly decreased after the ATM therapy, and this change was maintained for at least 3 months. Moreover, at 3 months after treatment completion, the F. varium/β-actin ratio, examined by real-time PCR using nested PCR products from biopsy samples, was reduced less than 40% in 8 of 12 treated patients, which was higher, but not significantly, than in 4 of 8 patients in the placebo group. Together, these results suggest that ATM therapy induces long-term alterations in the intestinal microbiota of patients with UC, which may be associated, at least in part, with clinical effects of the therapy.

  13. [Drug therapy of benign prostatic hyperplasia. Is combination therapy with 5 alpha-reductase inhibitors and alpha-receptor blockers effective?].

    Science.gov (United States)

    Horninger, W; Bartsch, G

    2002-09-01

    5 alpha-reductase inhibitors and alpha 1-receptor blockers are the two main drug therapies used in the management of symptomatic benign prostatic hyperplasia. As alpha-reductase inhibitors and alpha 1-receptor blockers act through different mechanisms, a combination of the two agents might be promising. The potential benefits of combination therapy with selective alpha 1-receptor blockers and finasteride, a 5 alpha-reductase inhibitor, are currently being evaluated in several placebo-controlled prospective multicenter studies (VA Study, ALFIN Study, PREDICT Study, and MTOPS Study). The data from these studies available so far demonstrate a statistically significant benefit for the study groups receiving alpha 1-receptor blockers and combination therapy vs placebo and finasteride monotherapy in terms of symptom scores and peak urine flow rates. However, none of the studies yielded a statistically significant advantage of combination therapy over treatment with alpha 1-receptor blockers. These results should be interpreted with reference to the prostatic volume, which in the studies mentioned above was relatively low. From the results of all these studies, it can be concluded that in symptomatic patients with prostate volumes of up to 40-45 ml a combination of 5 alpha-reductase inhibitors with alpha 1-receptor blockers does not appear to provide any benefit. Yet, it can be assumed that in symptomatic patients with prostate volumes of more than 60 ml combination therapy may indeed prove more effective.

  14. Combining immunotherapy with oncogene-targeted therapy: a new road for melanoma treatment

    Directory of Open Access Journals (Sweden)

    Mariana eAris

    2015-02-01

    Full Text Available Cutaneous melanoma arises from the malignant transformation of skin melanocytes; its incidence and mortality have been increasing steadily over the last fifty-years, now representing 3% of total tumors. Once melanoma metastasizes, prognosis is somber and therapeutic options are limited. However, the discovery of prevalent BRAF mutations in at least 50% of melanoma tumors led to development of BRAF inhibitors, and other drugs targeting the MAPK pathway including MEK inhibitors, are changing this reality. These recently approved treatments for metastatic melanoma have made a significant impact on patient survival; though the results are shadowed by the appearance of drug-resistance. Combination therapies provide a rational strategy to potentiate efficacy and potentially overcome resistance. Undoubtedly, the last decade has also born an renaissance of immunotherapy, and encouraging advances in metastatic melanoma treatment are illuminating the road. Immune checkpoint blockades, such as CTLA-4 antagonist-antibodies, and multiple cancer vaccines are now invaluable arms of anti-tumor therapy. Recent work has brought to light the delicate relationship between tumor biology and the immune system. Host immunity contributes to the antitumor activity of oncogene-targeted inhibitors within a complex network of cytokines and chemokines. Therefore, combining immunotherapy with oncogene-targeted drugs may be the key to melanoma control. Here we review ongoing clinical studies of combination therapies using both oncogene inhibitors and immunotherapeutic strategies in melanoma patients. We will revisit the preclinical evidence that tested sequential and concurrent schemes in suitable animal models and formed the basis for the current trials. Finally, we will discuss potential future directions of the field.

  15. Renal denervation, adjusted drugs, or combined therapy for resistant hypertension: A meta-regression.

    Science.gov (United States)

    Qi, Xiao-Yu; Cheng, Bin; Li, Ying-Li; Wang, Yue-Feng

    2016-07-01

    The objective of this study is to systematically evaluate the efficacy of renal denervation (RD), adjusted drugs, or combined therapy for resistant hypertension (RH) through a systematic review and meta-analysis of controlled studies.Publications were comprehensively searched. Studies that investigated the effects of RD and/or adjusted drugs in lowering blood pressure (BP) were included. After quality assessment and data extraction, subgroup analyzes were first performed according to blinding method. Meta-regression and inverted funnel plots were also conducted.A total of 13 studies containing 1604 RH patients were included. Compared with control, the meta-analysis showed that RD significantly reduced office-based BP and ambulatory BP in 6 months in the unblinded studies, while no significant difference was found in the blinded studies. Meta-regression demonstrated the significant influence of blinding method on BP reduction, and further analysis revealed a significant BP reduction compared with baseline even in the control arm of blinded studies. RD had similar effects compared with adjusted drugs, and combined therapy seemed to further reduce the level of BP.The efficacy of RD was different between blinded and unblinded studies, and our data revealed a significant BP-lowering effect in the control arm of blinded studies, which was helpful to explain this finding. Furthermore, RD seemed to be equivalent to adjusted drugs, and also we suggested a potential advantage of combined therapy of RD and adjusted drugs compared with monotherapy for RH. However, more studies are warranted to better address the issue.

  16. Combination Therapy for the Cardiovascular Effects of Perinatal Lead Exposure in Young and Adult Rats

    Energy Technology Data Exchange (ETDEWEB)

    Gaspar, Andréia Fresneda [Departamento de Farmacologia, Instituto de Biociências - Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Faculdade da Alta Paulista (FAP), Tupã, SP (Brazil); Cordellini, Sandra, E-mail: cordelli@ibb.unesp.br [Departamento de Farmacologia, Instituto de Biociências - Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil)

    2014-09-15

    Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb-induced hypertension.

  17. Delayed onset, protracted delirium and aspiration pneumonitis associated with a combination of clozapine and electroconvulsive therapy

    Directory of Open Access Journals (Sweden)

    N Manjunatha

    2011-01-01

    Full Text Available Few studies reported the efficacy and safety in combination of clozapine and electroconvulsive therapy (ECT in schizophrenia; systematic studies are lacking. Side effects like seizure, and confusional state are reported. Authors report two cases of delayed onset/protracted delirium with ECT and clozapine in schizophrenia, one of whom developed aspiration pneumonitis possibly due to clozapine hyper-salivation. Delirium improved with stopping of ECT and clozapine. Clozapine monotherapy restarted to previous dosages in both cases without recurrence of delirium. Authors recommend for careful monitoring for delirium in ECT augmentation on high dose clozapine. Unilateral ECT may be preferred for augmenting clozapine.

  18. Combination therapy of temporary tracheal stenting and radiofrequency ablation for multinodular thyroid goiter with airway compression

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ji Hoon; Beak, Jung Hwan; Oh, Yeon Mok; Ha, Eun Ju; Lee, Jeong Hyun [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2013-10-15

    We report a case of multinodular thyroid goiter in an 80-year-old man who successfully underwent tracheal stent placement for respiratory distress caused by the thyroid goiter and following two radiofrequency (RF) ablation sessions performed for thyroid volume reduction. This sequential treatment allowed elective stent removals four weeks after the second RF ablation session because the thyroid volume had been progressively reduced. Combination therapy of temporary airway stenting and RF ablation for the treatment of thyroid goiter has two advantages, i.e., immediate reliefs of dyspnea with airway stenting and reductions of the thyroid volume with RF ablation, and thus, allowing symptom reliefs even after the stent removals.

  19. Regional changes over time in initial virologic response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Kirk, Ole; Gatell, Jose M;

    2006-01-01

    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS......: Virologic response (viral load Virologic.......026) and time (P virologic response after adjustment for confounders. Stratified by period, regional differences were less evident (early cART, P = 0.967; mid cART, P = 0.291; late cART, P = 0.163). Stratified by region, temporal changes were observed (south, P = 0.061; central west, P

  20. Regional changes over time in initial virological response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, W; Kirk, O; Gatell, J;

    2006-01-01

    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS......: Virologic response (viral load Virologic.......026) and time (P virologic response after adjustment for confounders. Stratified by period, regional differences were less evident (early cART, P = 0.967; mid cART, P = 0.291; late cART, P = 0.163). Stratified by region, temporal changes were observed (south, P = 0.061; central west, P

  1. [The role of immunocorrective therapy in the combined treatment of rhinosinusitis].

    Science.gov (United States)

    Antoniv, V F; Efimochkina, K V; Él'kun, G B; Grinchuk, V I; Iusupov, B Kh

    2013-01-01

    The objective of the present work was to substantiate rational pharmacotherapy allowing not only to affect the pathogen but also to restore the initial state of the compromised immune system of the patient. This paper is focused on the markers of the immunodeficiency state in the patients presenting with acute and chronic bacterial rhinosinusitis taking into consideration the nature of the pathogen. A rationale is presented for the management of this pathology with the use of the natural topical immunostimulator IRS-19 that can be recommended for the introduction into combined therapy of acute and chronic rhinosinusitis for the achievement of well-apparent and stable results.

  2. Combined exercise and cognitive behavioral therapy improves outcomes in patients with heart failure

    OpenAIRE

    2010-01-01

    ObjectiveThe purpose of this study is to compare the effectiveness of a combined 12-week home-based exercise (EX)/cognitive behavioral therapy (CBT) program (n=18) with CBT alone (n=19), EX alone (n=20), and with usual care (UC, n=17) in stable New York Heart Association Class II to III heart failure (HF) patients diagnosed with depression.MethodsDepressive symptom severity [Hamilton Rating Scale for Depression (HAM-D)], physical function [6-min walk test (6MWT)], and health-related quality o...

  3. Endoscopic Therapy of Refractory Post-Papillotomy Bleeding With Electrocautery Forceps Coagulation Method Combined With Prophylactic Pancreatic Stenting

    Directory of Open Access Journals (Sweden)

    Zsolt Dubravcsik

    2014-01-01

    Conclusion: We presented a new, effective and safe second line endoscopic hemostatic method in patients with therapy resistant post-papillotomy bleeding. Combination of prophylactic pancreatic stenting and thermal coagulation with coagulation forceps might be suggested as a rescue treatment in patients with severe post-papillotomy bleeding, resistant to standard endoscopic therapy.

  4. Combined use of radioiodine therapy and radiofrequency ablation in treating postsurgical thyroid remnant of differentiated thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Bin Long

    2015-01-01

    Conclusion: Combined use of RAI therapy and radiofrequency ablation in treating excessive postsurgical thyroid remnant of DTC can be an effective approach and avoids re-operation. Long-term efficacy monitoring would further determine its feasibility.

  5. Correction: Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy

    Science.gov (United States)

    Kim, Kyoung Sub; Kim, Jiyoung; Lee, Joo Young; Matsuda, Shofu; Hideshima, Sho; Mori, Yasurou; Osaka, Tetsuya; Na, Kun

    2016-06-01

    Correction for `Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy' by Kyoung Sub Kim, et al., Nanoscale, 2016, DOI: 10.1039/c6nr02273a.

  6. Failure of Ketoprofen and Interferon Combination Therapy to Improve Interferon-Resistant Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Frank H Anderson

    1997-01-01

    Full Text Available Preliminary reports suggest that patients with interferon (IFN-resistant chronic hepatitis C respond better to a combination of IFN-α and nonsteroidal anti-inflammatory drugs than to IFN alone. The efficacy of IFN combined with ketoprofen in the treatment of patients with IFN-resistant chronic hepatitis C was evaluated. Seventeen patients, nonresponsive after at least six months of treatment with IFN-α2b and subsequently treated with the combination of IFN-α2b plus ketoprofen for four months, were studied. Serum aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST] and serum hepatitis C virus (HCV RNA were analyzed before and throughout treatment. No patient normalized serum aminotransferases after combination therapy. There were no significant differences in mean serum ALT and AST levels before and after ketoprofen intervention. Serum HCV RNA became undetectable after treatment in only one patient, but was detectable again three months after treatment cessation. These results provide no convincing evidence that the combination of IFN-α2b with ketoprofen improves the response to IFN in patients nonresponsive to IFN alone.

  7. 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 multicenter 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. Results: (1)More Lansoprazole group patients noted RE symptoms resolution than Ranitidine group(92.3% vs 78.4%, P0.05). (2)RE significantly impaired QoL of patients(P0.05). 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.

  8. Failure of ketoprofen and interferon combination therapy to improve interferon-resistant chronic hepatitis C.

    Science.gov (United States)

    Anderson, F H; Zeng, L; Yoshida, E M; Rock, N R

    1997-01-01

    Preliminary reports suggest that patients with interferon (IFN)-resistant chronic hepatitis C respond better to a combination of IFN-alpha and nonsteroidal anti-inflammatory drugs than to IFN alone. The efficacy of IFN combined with ketoprofen in the treatment of patients with IFN-resistant chronic hepatitis C was evaluated. Seventeen patients, nonresponsive after at least six months of treatment with IFN-alpha 2b and subsequently treated with the combination of IFN-alpha 2b plus ketoprofen for four months, were studied. Serum aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and serum hepatitis C virus (HCV) RNA were analyzed before and throughout treatment. No patient normalized serum aminotransferases after combination therapy. There were no significant differences in mean serum ALT and AST levels before and after ketoprofen intervention. Serum HCV RNA became undetectable after treatment in only one patient, but was detectable again three months after treatment cessation. These results provide no convincing evidence that the combination of IFN-alpha 2b with ketoprofen improves the response to IFN in patients nonresponsive to IFN alone.

  9. Glycididazole sodium combined with radioiodine therapy for patients with differentiated thyroid carcinoma (DTC).

    Science.gov (United States)

    Wen, Qiang; Ma, Qingjie; Bai, Lin; Wang, Tongtong; Han, Yuping; Zhang, Haishan

    2015-01-01

    The aim of the present study was to evaluate efficacy and side effects of glycididazole sodium (CMNa) combined with radioiodine therapy for patients with DTC cervical metastases. 53 patients of DTC cervical lymph node metastasis were randomly divided into 2 groups, where 24 cases were treated with 4.44 GBq of (131)I alone, 29 cases were treated with 800 mg/m(2) of CMNa combined with 4.44 GBq of (131)I. Peripheral blood samples were collected before and after treatment to perform measurements of routine blood test, liver function, renal function, parathyroid hormone (PTH), lymphocyte micronucleus rates and chromosome mutation. The results showed that rates of complete response (CR) in CMNa combined with radioiodine group (65.5%) were significantly higher than that in radioiodine monotherapy group (37.5%). Furthermore, CMNa combined with adioiodine treatment significantly increased the percentage of thyroglobulin (Tg) reduction at 12 weeks after treatment (P0.05). These results indicate 4.44 GBq of (131)I treatment combined with 800 mg/m(2) of CMNa could significantly improve clinical efficacy of DTC patients without increasing side effects.

  10. Effectiveness of a home exercise program in combination with ultrasound therapy for temporomandibular joint disorders.

    Science.gov (United States)

    Ucar, Mehmet; Sarp, Ümit; Koca, İrfan; Eroğlu, Selma; Yetisgin, Alparslan; Tutoglu, Ahmet; Boyacı, Ahmet

    2014-12-01

    [Purpose] This study compared the effectiveness of home exercise alone versus home exercise combined with ultrasound for patients with temporomandibular joint disorders. [Subjects and Methods] This study enrolled 23 female and 15 male patients who were divided randomly into two groups. The home exercise group performed a home exercise program consisting of an exercise program and patient education, and the home exercise combined with ultrasound group received ultrasound therapy in addition to the home exercise program. Pain intensity was evaluated using a visual analogue scale. Pain free maximum mouth opening was evaluated at baseline and 2 weeks after the treatment. [Results] There was no difference between the two groups in baseline values. After the treatment, the visual analogue scale decreased and pain free maximum mouth opening scores improved significantly in each group. Additionally, both values were higher in the home exercise combined with ultrasound group than in the home exercise group. [Conclusion] The combination of home exercise combined with ultrasound appears to be more effective at providing pain relief and increasing mouth opening than does home exercise alone for patients with temporomandibular joint disorders.

  11. 重视胰腺癌的综合治疗%Attach importance to combined therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    孙诚谊; 陈自力

    2009-01-01

    Pancreatic cancer is a common malignancy of gastrointestinal system, with features of early metastasis, easy invasion to adjacent tissues and organs and neural metastasis. Therapies include surgery, chemotherapy, radiotherapy, physi-cal and biological therapy and so on. Surgical management, including radical resection and palliative operation, is a major approach. Radiotherapy and chemotherapy could improve the resectional rate and decrease the tumor dissemination. Physical and biological therapies are widely recommended, and there is a rapid progress in zoopery. However, the efficacy of all the thera-pies is far from satisfactory. Recently, the therapy consisting of surgical resection, radiotherapy, chemotherapy, physical and biological therapy in increasing the long-term survival rate and improving the life quality of patients, along with combined thera-py has attracted the attention of surgeons.

  12. Comparison of quality of facial scars after single low-level laser therapy and combined low-level with high-level (PDL 595 nm) laser therapy.

    Science.gov (United States)

    Vranova, Jana; Remlova, Eva; Jelinkova, Helena; Rosina, Jozef; Dostalova, Tatjana

    2015-01-01

    The main goal of our study was to compare the quality of resulting facials scar 12 weeks after single and combined laser therapy. Forty-one children from age 1.5 to 5 years with facial scars after injury participated in the study. Thirty-one underwent laser therapy, 14 were treated using single low-level laser therapy (670 nm, fluence 3-5 J/cm(-2) ), and 17 underwent combined high-level laser therapy with non-ablative pulsed dye laser (PDL; 595 nm, spot size 7 mm, delay 0.45 ms or 1.5 ms, fluence 9-11 J/cm(-2) , cryogen spray/delay 20/30 ms) and low-level laser therapy. The control group consisted of 10 untreated children. Before treatment and at week 4, 8, and, 12 the scars were evaluated using the POSAS questionnaire. A statistically significant improvement in scars (between ratings before treatment and 4 weeks after therapy, before treatment and 8 weeks after therapy and before treatment and 12 weeks after therapy) was observed in all parameters in both treatment groups (p < 0.0001). For the HLLT+LLLT group the most significant enhancement in the quality of scars was found for all items and at all evaluations, except pigmentation and pliability. There was no improvement observed in quality of facial scars in the control group.

  13. Effect of aerobic exercise and raloxifene combination therapy on senile osteoporosis.

    Science.gov (United States)

    Zhao, Chengjin; Hou, Haibing; Chen, Yutao; Lv, Kai

    2016-06-01

    [Purpose] This study assessed the effects of combined application of raloxifene and aerobic exercise on senile osteoporosis. [Subjects and Methods] A total of 70 elderly patients with osteoporosis, who treated at our hospital between April 2013 and August 2014, were divided into equal-sized observation and control groups. The control group was administered raloxifene, whereas the observation group received raloxifene treatment plus aerobic exercise. [Results] Outpatient outcomes were considered dependent variables. After treatment, the two groups differed significantly in terms of lumbar spine (L2-L4) and proximal femoral bone mineral density. The urine pyridine/creatinine ratio decreased significantly and serum calcitonin level increased significantly in the observation group. These differences were statistically significant. [Conclusion] Raloxifene combined with aerobic exercise therapy significantly improves bone density and promotes bone formation in patients with senile osteoporosis.

  14. Pioglitazone: a valuable component of combination therapy for type 2 diabetes mellitus.

    Science.gov (United States)

    Papanas, Nikolaos; Katsiki, Niki; Hatzitolios, Apostolos I; Maltezos, Efstratios

    2011-07-01

    Several classes of drugs have been developed to treat type 2 diabetes mellitus (T2DM). Pioglitazone is now the only thiazolidinedione approved for the treatment of T2DM and can be administered in combination with metformin, sulfonylureas, exenatide, dipeptidyl peptidase 4 (DPP-4) inhibitors or insulin. It improves glycemic control with an extremely low incidence of hypoglycemia. In addition to reducing insulin resistance, it may also improve pancreatic beta-cell secretory function. Moreover, it exhibits a variety of favorable pleiotropic effects. The latter include anti-inflammatory, antioxidant, vasoprotective, antihypertensive and hypolipidemic actions. Finally, this agent has been shown to improve experimental diabetic neuropathy and alleviate neuropathic pain, as well as decreasing urinary albumin excretion in patients with diabetes. Thus, pioglitazone emerges as a valuable hypoglycemic agent for combination therapy in T2DM. Importantly, however, patients should be appropriately selected, especially to avoid those with heart failure, in order to minimize adverse events attributable to water retention.

  15. Hemodynamic effects of ambrisentan-tadalafil combination therapy on progressive portopulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    Yu; Yamashita; Ichizo; Tsujino; Takahiro; Sato; Asuka; Yamada; Taku; Watanabe; Hiroshi; Ohira; Masaharu; Nishimura

    2014-01-01

    Intravenous epoprostenol is recommended for World Health Organization functional class(WHO-FC) Ⅳ patients with pulmonary arterial hypertension(PAH) in the latest guidelines. However, in portopulmonary hypertension(PoP H) patients, advanced liver dysfunction and/or thrombocytopenia often makes the use of intravenous epoprostenol challenging. Here we report the cases of two WHO-FC Ⅳ PoP H patients who were successfully treated with a combination of two oral vasodilators used to treat PAH: ambrisentan and tadalafil. Oral vasodilator therapy using a combination of ambrisentan and tadalafil may be a safe and effective therapeutic option for WHO-FC Ⅳ PoP H patients and should be considered for selected patients with severe and rapidly progressing PoP H.

  16. Efficacy of combination therapy for systolic blood pressure in patients with severe systolic hypertension: the Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study.

    Science.gov (United States)

    Neutel, Joel M; Smith, David H G; Weber, Michael A; Schofield, Lesley; Purkayastha, Das; Gatlin, Marjorie

    2005-11-01

    Systolic hypertension is predominant among patients over 50 years of age, is a more important cardiovascular risk factor than diastolic blood pressure, and is more difficult to control than diastolic blood pressure. Consequently, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends combination therapy as first-line treatment for patients with stage 2 hypertension. In the Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study, 24-hour ambulatory blood pressure monitoring was used to identify patients with systolic hypertension and to determine the impact of 8 weeks of treatment with either amlodipine besylate/benazepril HCl 5/20 mg combination therapy (n=149), amlodipine besylate 5 mg (n=146), or benazepril HCl 20 mg (n=148). Combination therapy was significantly more effective in reducing systolic blood pressure and pulse pressure than either monotherapy (pamlodipine-treated group. The combination of amlodipine besylate/benazepril HCl given to patients with stage 2 systolic hypertension resulted in significantly greater reductions in blood pressure and pulse pressure than those seen with monotherapy and was at least as well tolerated as the separate components. This data supports the recommendation of the JNC 7 for the use of combination therapy in patients with stage 2 hypertension.

  17. Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.

    Science.gov (United States)

    Horino, Satoshi; Uchiyama, Toru; So, Takanori; Nagashima, Hiroyuki; Sun, Shu-Lan; Sato, Miki; Asao, Atsuko; Haji, Yoichi; Sasahara, Yoji; Candotti, Fabio; Tsuchiya, Shigeru; Kure, Shigeo; Sugamura, Kazuo; Ishii, Naoto

    2013-01-01

    X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc) gene, and characterized by a complete defect of T and natural killer (NK) cells. Gene therapy for SCID-X1 using conventional retroviral (RV) vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV) vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO) mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.

  18. Gene Therapy for X-Linked Severe Combined Immunodeficiency: Where Do We Stand?

    Science.gov (United States)

    Cavazzana, Marina; Six, Emmanuelle; Lagresle-Peyrou, Chantal; André-Schmutz, Isabelle; Hacein-Bey-Abina, Salima

    2016-01-01

    More than 20 years ago, X-linked severe combined immunodeficiency (SCID-X1) appeared to be the best condition to test the feasibility of hematopoietic stem cell gene therapy. The seminal SCID-X1 clinical studies, based on first-generation gammaretroviral vectors, demonstrated good long-term immune reconstitution in most treated patients despite the occurrence of vector-related leukemia in a few of them. This gene therapy has successfully enabled correction of the T cell defect. Natural killer and B cell defects were only partially restored, most likely due to the absence of a conditioning regimen. The success of these pioneering trials paved the way for the extension of gene-based treatment to many other diseases of the hematopoietic system, but the unfortunate serious adverse events led to extensive investigations to define the retrovirus integration profiles. This review puts into perspective the clinical experience of gene therapy for SCID-X1, with the development and implementation of new generations of safer vectors such as self-inactivating gammaretroviral or lentiviral vectors as well as major advances in integrome knowledge. PMID:26790362

  19. Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.

    Directory of Open Access Journals (Sweden)

    Satoshi Horino

    Full Text Available X-linked severe combined immunodeficiency (SCID-X1 is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc gene, and characterized by a complete defect of T and natural killer (NK cells. Gene therapy for SCID-X1 using conventional retroviral (RV vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.

  20. Gene Therapy Model of X-linked Severe Combined Immunodeficiency Using a Modified Foamy Virus Vector

    Science.gov (United States)

    Horino, Satoshi; Uchiyama, Toru; So, Takanori; Nagashima, Hiroyuki; Sun, Shu-lan; Sato, Miki; Asao, Atsuko; Haji, Yoichi; Sasahara, Yoji; Candotti, Fabio; Tsuchiya, Shigeru; Kure, Shigeo; Sugamura, Kazuo; Ishii, Naoto

    2013-01-01

    X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc) gene, and characterized by a complete defect of T and natural killer (NK) cells. Gene therapy for SCID-X1 using conventional retroviral (RV) vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV) vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO) mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1. PMID:23990961

  1. Acupuncture Combined with Music Therapy for Treatment of 30 Cases of Cerebral Palsy

    Institute of Scientific and Technical Information of China (English)

    YU Hai-bo; LIU Yong-feng; WU Li-xiong; CHEN Zheng-qiu

    2009-01-01

    Objective: To observe clinical therapeutic effects of acupuncture combined with music therapy for treatment of cerebral palsy. Methods: Sixty children with cerebral palsy were randomly divided into an acupuncture group (Group Acup.) and an acupuncture plus music group (Group Acup.+ M). Simple acupuncture was applied in Group Acup., and acupuncture at 5 groups of points plus music were applied in Group Acup. +M. The treatment was given once every two days with 3 treatments weekly, and 36 treatments constituted a therapeutic course. Therapeutic effects including movement improvement were observed for comparison after 3 courses of treatments. Results: The comprehensive functions were elevated in both groups, and the total effective rate in Group Acup. + M was obviously better than that in Group Acup (P<0.05). Movement functions were also improved in both groups, but the differences in improvement of creeping and kneeling, standing, and walking were significant between the two groups (P<0.01), showing the effect in Group Acup. +M was better than that in Group Acup.. Conclusion: The therapy of acupuncture plus music gained better therapeutic effect on cerebral palsy than simple acupuncture, which provided new thoughts for treating the disease by comprehensive therapies.

  2. Combination therapy with metformin and coenzyme Q10 in murine experimental autoimmune arthritis.

    Science.gov (United States)

    Jhun, JooYeon; Lee, SeungHoon; Kim, Se-Young; Na, Hyun Sik; Kim, Eun-Kyung; Kim, Jae-Kyung; Jeong, Jeong-Hee; Park, Sung Hwan; Cho, Mi-La

    2016-01-01

    Metformin (Met) and coenzyme Q10 (CoQ10) are reported to have therapeutic functions in several inflammatory diseases. These drugs have shown anti-inflammatory effects and have been utilized in mouse models of rheumatoid arthritis (RA). However, there is no evidence of the additive effect of Met and CoQ10 in RA. Although Met and CoQ10 may be involved in the improvement of mitochondrial dysfunction, limited information is available regarding whether this effect can improve mitochondrial dysfunction in RA in particular. In this study, we sought to determine whether Met and CoQ10 attenuate the severity of collagen-induced arthritis (CIA) and show an additive effect in a mouse model. The combination of Met and CoQ10 improved CIA, reducing joint inflammation, Th17 differentiation and IgG production. In contrast, the combination of Met and CoQ10 induced Treg differentiation. Osteoclastogenesis was reduced by the combination of Met and CoQ10. The protein expression of interleukin-1β, interleukin-6 and tumor necrosis factor-alpha in mice splenocytes exposed to lipopolysaccharide decreased after drug combination therapy. We also found that the expression of JC-1 and COX IV were enhanced by treatment with the combination of Met and CoQ10. Moreover, the combination of Met and CoQ10 promoted mitochondrial O2 consumption. These findings suggest that the combination of Met and CoQ10 reduced CIA severity, improving mitochondrial dysfunction compared to Met or CoQ10 alone. These results present a novel, significant preventive targets in RA and may enhance our understanding of its pathogenesis.

  3. Therapy-related myelodysplastic syndrome and acute myeloid leukemia following fludarabine combination chemotherapy.

    Science.gov (United States)

    Carney, D A; Westerman, D A; Tam, C S; Milner, A; Prince, H M; Kenealy, M; Wolf, M; Januszewicz, E H; Ritchie, D; Came, N; Seymour, J F

    2010-12-01

    Fludarabine combination chemotherapy achieves high response rates in chronic lymphocytic leukemia (CLL) and indolent lymphoma. The aim of this study was to investigate the incidence and characteristics of treatment-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) after treatment with fludarabine in combination for lymphoproliferative disorders and identify risk factors for its development. In all, 176 patients treated with fludarabine combination were followed for a median of 41 months (range 6-125 months). In all, 19 cases of t-MDS/AML have been identified for an overall rate of 10.8%. Median overall survival post-t-MDS/AML diagnosis was 11 months. Patients developing t-MDS/AML included 11/54 with follicular lymphoma (FL) (crude rate 20.4%), 5/82 with CLL (6.1%) and 3/24 with Waldenstrom macroglobulinemia or marginal zone lymphoma (12.5%). Most patients had other cytotoxic treatments (median 4, range 0-7) but three with FL had fludarabine combination as their only line of treatment. Of the eleven patients (6.3%) who received mitoxantrone with their first fludarabine combination, four (36.4%) developed t-MDS/AML (P=0.007). There was a trend toward prior cytotoxic therapy increasing the risk for t-MDS/AML (P=0.067). Fludarabine combination chemotherapy is associated with a moderate risk of t-MDS/AML particularly when combined with mitoxantrone. This complication should be considered when evaluating the potential benefit of this treatment in lymphoproliferative disorders.

  4. Efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague.

    Directory of Open Access Journals (Sweden)

    Nadine Lemaître

    Full Text Available Potential benefits of combination antibiotic therapy for the treatment of plague have never been evaluated. We compared the efficacy of a ciprofloxacin (CIN and gentamicin (GEN combination therapy with that of each antibiotic administered alone (i against Yersinia pestis in vitro and (ii in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h. In vitro, the CIN+GEN combination was synergistic at 0.5x the individual drugs' MICs and indifferent at 1x- or 2x MIC. In vivo, the survival rate for mice treated with CIN+GEN was similar to that observed with CIN alone and slightly higher than that observed for GEN alone 100, 100 and 85%, respectively when treatment was started 44 h post challenge. 100% of survivors were recorded in the CIN+GEN group vs 86 and 83% in the CIN and GEN groups, respectively when treatment was delayed to 56 h post-challenge. However, these differences were not statistically significant. Five days after the end of treatment, Y. pestis were observed in lymph nodes draining the inoculation site (but not in the spleen in surviving mice in each of the three groups. The median lymph node log(10 CFU recovered from persistently infected lymph nodes was significantly higher with GEN than with CIN (5.8 vs. 3.2, p = 0.04 or CIN+GEN (5.8 vs. 2.8, p = 0.01. Taken as the whole, our data show that CIN+GEN combination is as effective as CIN alone but, regimens containing CIN are more effective to eradicate Y. pestis from the draining lymph node than the recommended GEN monotherapy. Moreover, draining lymph nodes may serve as a reservoir for the continued release of Y. pestis into the blood - even after five days of intravenous antibiotic treatment.

  5. Prevalence and predictors of anaemia in patients with HIV infection at the initiation of combined antiretroviral therapy in Xinjiang, China.

    Science.gov (United States)

    Mijiti, Peierdun; Yuexin, Zhang; Min, Liu; Wubuli, Maimaitili; Kejun, Pan; Upur, Halmurat

    2015-03-01

    We retrospectively analysed routinely collected baseline data of 2252 patients with HIV infection registered in the National Free Antiretroviral Treatment Program in Xinjiang province, China, from 2006 to 2011 to estimate the prevalence and predictors of anaemia at the initiation of combined antiretroviral therapy. Anaemia was diagnosed using the criteria set forth by the World Health Organisation, and univariate and multivariate logistic regression analyses were performed to determine its predictors. The prevalences of mild, moderate, and severe anaemia at the initiation of combined antiretroviral therapy were 19.2%, 17.1%, and 2.6%, respectively. Overall, 38.9% of the patients were anaemic at the initiation of combined antiretroviral therapy. The multivariate logistic regression analysis indicated that Uyghur ethnicity, female gender, lower CD4 count, lower body mass index value, self-reported tuberculosis infection, and oral candidiasis were associated with a higher prevalence of anaemia, whereas higher serum alanine aminotransferase level was associated with a lower prevalence of anaemia. The results suggest that the overall prevalence of anaemia at the initiation of combined antiretroviral therapy in patients with HIV infection is high in Xinjiang, China, but severe anaemia is uncommon. Patients in China should be routinely checked for anaemia prior to combined antiretroviral therapy initiation, and healthcare providers should carefully select the appropriate first-line combined antiretroviral therapy regimens for anaemic patients.

  6. Combination antibiotic therapy versus monotherapy for Pseudomonas aeruginosa bacteraemia: a meta-analysis of retrospective and prospective studies.

    Science.gov (United States)

    Hu, Yangmin; Li, Leiqing; Li, Wenlu; Xu, Huimin; He, Ping; Yan, Xiaofeng; Dai, Haibin

    2013-12-01

    The choice of antibiotic monotherapy or combination therapy to treat Pseudomonas aeruginosa bacteraemia is controversial. The aim of this review was to compare both types of therapy to determine which delivers the best outcome for P. aeruginosa bacteraemia. We systematically searched electronic bibliographic databases, including PubMed, Ovid EMBASE and The Cochrane Library, for clinical studies that compared combination therapy with monotherapy in the treatment of P. aeruginosa bacteraemia. Eligible articles were analysed using Stata(®)/SE software v.12.0. Stratification analysis was conducted by study design and treatment type. Publication bias was assessed using Begg's funnel plot and Egger's test. Ten studies (eight retrospective and two prospective) involving 1239 patients were analysed. We found no difference between combination therapy and monotherapy when the data were combined (odds ratio = 0.89, 95% confidence interval 0.57-1.40; P = 0.614) or when data were analysed in subgroups. Neither combination therapy nor monotherapy treatment appears to have a significant effect on mortality rates in patients with P. aeruginosa bacteraemia. Further studies evaluating the effects of combination therapy or monotherapy in more specialised cases, such as when encountering a multidrug-resistant organism, are necessary.

  7. Diffuse Non-toxic Goitre Therapy with Iodine Alone or with Combination of Iodine and Levothyroxine

    Directory of Open Access Journals (Sweden)

    N Galkina

    2008-12-01

    Full Text Available Aim: to assess the efficacy and tolerability of low-dose iodine therapy compared with the combination of iodine and levothyroxine in endemic goitre patients. Methods: 12-month prospective study was performed, in which 81 patients were randomized on two groups: Group 1 (n = 40 - KI (200 micrograms/day and Group 2 (n = 41 - KI (100 mcg/day + L-T4 (1.0 mcg/kg. Thyroid volume, TSH and Anti-TPO-Ab levels were evaluated at baseline, at 8 month of the treatment and at 12 month (4 month after the cessation of the therapy. Results: the significant decreasing of thyroid volumes was found in group 1 at 8 month compared with baseline (20.5 ml at baseline and 16,4 ml at 8 month р < 0.001. After the therapy cessation the further benefit of a sustained effect was demonstrated (16.4 ml at 8 month and 16.1 ml at 12 month, р = 0.31. Iodine-induced hypo- and hyperthyroidism were not observed. High Anti-TPO-Ab level was found in one of 31 patients (3%. In group 2 significant difference between thyroid volumes was found at 8 month compared with baseline (20,5 ml at baseline and 16.2 ml at 8 month р < 0.001. The sustained effect was revealed at least 4 month after the therapy cessation (16.2 ml at 8 month and 16.1 ml at 12 month, р = 0.77. One man had iodine-induced subclinical hyperthyroidism. Anti-TPO-Ab was not detected in this group. No significant difference between thyroid volume decreasing, TSH and Anti-TPO-Ab levels in two comparable groups was observed. Conclusion: KI alone (200 mcg/day or the combination of L-T4 (1.0 mcg/kg and KI (100 mcg/day are equally effective and tolerable for endemic goitre therapy.

  8. Combined partial arthroscopic synovectomy and radiation therapy for diffuse pigmented villonodular synovitis of the knee.

    Science.gov (United States)

    Blanco, C E; Leon, H O; Guthrie, T B

    2001-05-01

    We present the results of combined partial arthroscopic synovectomy and low-dose external-beam radiation therapy (RT) in the treatment of diffuse pigmented villonodular synovitis (PVNS) of the knee. Mechanical synovectomy is an effective tool in treating PVNS of the knee, but when used alone it may be insufficient to eliminate all affected tissue. Intra-articular radiation or external-beam radiation may be added to mechanical synovectomy to treat recurrence but is not routinely done at the time of initial synovectomy. Combining intra-articular synovectomy with RT at the initial treatment for PVNS of the knee may reduce the recurrence rate. We present a prospective study of the treatment of 22 patients with clinical, ultrasonic, and histologically confirmed findings of diffuse PVNS of the knee. Characteristic clinical findings included pain, swelling, and erythema. These patients were treated by the Arthroscopic Surgery Group of the Orthopaedic Service at the Hospital "Hermanos Ameijeiras" in Havana, Cuba from 1990 to 1998. The protocol included anterior (patellofemoral, medial, and lateral) arthroscopic synovectomy and postoperative RT with a total dose of 2,600 cGy. This combination therapy was effective in reducing symptoms of pain and edema, and in improving overall function of patients. Nineteen patients (86%) had good or excellent results at an average follow-up of 33 months (range, 26 to 76 months). Three patients had residual stiffness and swelling, 2 of whom also had pain. Three had clinically and ultrasonically confirmed recurrence of disease and were treated with repeat arthroscopic synovectomy without harmful effects from RT. In all of the cases requiring repeat arthroscopic synovectomy, we observed fibrous bands secondary to reorganization of synovial inflamed tissue, meniscal retraction, and microscopic findings of fibrosis and cellular paucity. Partial arthroscopic synovectomy combined with low-dose RT in anti-inflammatory doses produced good results

  9. Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda.

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    Adoke Yeka

    2005-07-01

    Full Text Available BACKGROUND: Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance, but artemisinins are expensive and relatively untested in highly endemic areas. We compared artemisinin-based and other combination therapies in four districts in Uganda with varying transmission intensity. METHODS AND FINDINGS: We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria. Patients were randomized to receive chloroquine (CQ + sulfadoxine-pyrimethamine (SP; amodiaquine (AQ + SP; or AQ + artesunate (AS. Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections. A total of 2,081 patients completed follow-up, of which 1,749 (84% were under the age of 5 y. The risk of recrudescence after treatment with CQ + SP was high, ranging from 22% to 46% at the four sites. This risk was significantly lower (p < 0.01 after AQ + SP or AQ + AS (7%-18% and 4%-12%, respectively. Compared to AQ + SP, AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection. The overall risk of repeat therapy due to any recurrent infection (recrudescence or new infection was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites (risk differences = 15% and 16%, p < 0.003. CONCLUSION: AQ + AS was the most efficacious regimen for preventing recrudescence, but this benefit was outweighed by an increased risk of new infection. Considering all recurrent infections, the efficacy of AQ + SP was at least as efficacious at all sites and superior to AQ + AS at the highest transmission sites. The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy. The registration number for this trial is ISRCTN

  10. Treatment of vitiligo vulgaris with the combination therapy of topical steroid and vitamin D3 compound

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    Yoko Konishi

    2012-06-01

    Full Text Available We reported here two cases of vitiligo vulgaris successfully treated with the combination therapy of topical steroid and vitamin D3 compound and currently maintained by vitamin D3 analog without any adverse effects: skin atrophy, striae or telangiectasia on the exposed areas. The best-known mechanism of topical vitamin D3 analog is the enhancement of keratinocytes differentiation and anti-proliferative effects. Vitamin D3 analog is also reported to suppress T-cell mediated immunity, T-cell skin recruitment, and skin infiltration via down-regulating cutaneous lymphocyte antigen expression. Furthermore, vitamin D3 compounds are known to influence melanocyte maturation and differentiation and also to up-regulate melanogenesis. Autoreactive lymphocytes against melanocytes are one of the causes. Topical vitamin D3 analog may control vitiligo itself, however stronger immunosuppressive effects of topical corticosteroid may contribute to rapid re-pigmentation suppressing auto-reactive lymphocytes. The topical combination therapy is a simple, effective and safe option for vitiligo vulgaris in sun-exposed areas.

  11. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice

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    Klein, Florian; Gruell, Henning; Scheid, Johannes F.; Bournazos, Stylianos; Mouquet, Hugo; Spatz, Linda A.; Diskin, Ron; Abadir, Alexander; Zang, Trinity; Dorner, Marcus; Billerbeck, Eva; Labitt, Rachael N.; Gaebler, Christian; Marcovecchio, Paola; Incesu, Reha-Baris; Eisenreich, Thomas R.; Bieniasz, Paul D.; Seaman, Michael S.; Bjorkman, Pamela J.; Ravetch, Jeffrey V.; Ploss, Alexander; Nussenzweig, Michel C.

    2013-01-01

    Summary Human antibodies to HIV-1 can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection1,2. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time3,4. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design5-9. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice (hu-mice). Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies (bNAbs) can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy (ART)10-12, the longer half-life of antibodies led to viremic control for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in hu-mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals. PMID:23103874

  12. Combination total lymphoid irradiation and low-dose corticosteroid therapy for progressive multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cook, S.D.; Zito, G.; Dowling, P.C. [University of Medicine and Dentistry of New Jersey, Department of Neurosciences, Newark, and Neurology Service, Department of Veterans Affairs Medical Center, NJ (United States); Devereux, C. [Univrsity of Medicine and Dentistry of New Jersey, Department of Neurosciences, Newark, and Radiation Oncology, Clara Maass Medical Center, Belleville, NU (United States); Troiano, R.; Jotkowitz, A.; Rohowsky-Kochan, C. [University of Medicine and Dentistry of New Jersey, Department of Neurosciences, Newark (United States); Sheffet, A. [University of Medicine and Dentistry of New Jersey, Department of Preventive Medicine and Community Health, Newark (United States)

    1995-01-01

    Total lymphoid irradiation (TLI) has been reported to delay deterioration in patients with progressive multiple sclerosis and other autoimmune disorders. Methods - In an open trial, the effect of TLI combined with a one year course of low dose prednisone was compared to the effect of sham TLI and TLI only in a prior double-blind study of patients with progressive multiple sclerosis. Results - Twenty-seven patients receiving TLI combined with corticosteroids had significantly greater lymphocytopenia in the year post-therapy than those receiving TLI only or sham TLI and Kaplan Meier product-limit survival analysis showed significantly less progression in the TLI plus steroid group over 4 years of follow-up. No difference in lymphocytopenia or progression was found with TLI plus corticosteroid therapy when the spleen was removed from the field of irradiation. Conclusion - These results lend further support to the hypothesis that TLI may be effective in progressive MS, and indicates that adding low-dose prednisone may enhance this effect. The study also suggests that TLI may be equally effective whether or not the spleen is irradiated. (au) (14 refs.).

  13. Double-carbapenem combination as salvage therapy for untreatable infections by KPC-2-producing Klebsiella pneumoniae.

    Science.gov (United States)

    Souli, M; Karaiskos, I; Masgala, A; Galani, L; Barmpouti, E; Giamarellou, H

    2017-02-16

    We report our experience using the double-carbapenem combination as salvage therapy for patients with untreatable infections caused by KPC-2- producing Klebsiella pneumoniae. A total of 27 patients in two institutions in Athens, Greece suffering from complicated urinary tract infections (16) with or without secondary bacteraemia (four and 12 respectively), primary (six) or catheter-related bloodstream infections (two), HAP or VAP (two) and external ventricular drainage infection (one) were treated exclusively with ertapenem and high-dose prolonged infusion meropenem because in-vitro active antimicrobials were unavailable (19) or failed (four) or were contraindicated (six). Most patients presented with severe infections with median APACHE II score of 17 and 11 of those patients (40.7%) had severe sepsis (five) or septic shock (six). The clinical and microbiological success was 77.8 and 74.1% respectively. Crude mortality was 29.6% with attributable mortality of 11.1%. Adverse events, none of them severe, were reported in four patients (14.8%). The double-carbapenem combination as an exclusive regimen represents a safe and valid salvage therapy for untreatable infections by extensively- or pandrug-resistant KPC-producing K.pneumoniae.

  14. [Efficacy of combination therapy with mirabegron for anticholinergic-resistant neurogenic bladder: videourodynamic evaluation].

    Science.gov (United States)

    Wada, Naoki; Okazaki, Satoshi; Kobayashi, Shin; Hashizume, Kazumi; Kita, Masafumi; Matsumoto, Seiji; Kakizaki, Hidehiro

    2015-01-01

    Using a videourodynamic study, we examined the efficacy of combination therapy with mirabegron for anticholinergic-resistant neurogenic bladder. We retrospectively studied 7 patients with neurogenic bladder (5 males and 2 females) who had detrusor overactivity (DO) or low compliance bladder (<10 ml/cmH2O) despite taking anticholinergic medication. Bladder deformity was categorized from G0 to G3 by Ogawa's classification. Mean age of study patients was 51 years (25-76). Underlying diseases were spinal cord injury in 3 patients, spina bifida in 2, spinal cord infarction in 1, and post-radical hysterectomy in 1. Preceding anticholinergic medication was solifenacin 5 mg in 1 patient, solifenacin 10 mg in 5, and tolterodine 4 mg in 1. Before mirabegron, bladder deformity was G1 in 4 patients, G2 in 1 and G3 in 2, and vesicoureteral reflux (VUR) was detected in 3 patients. Five and 4 patients had detrusor overactivity and low compliance bladder, respectively. Videourodynamic study was reevaluated at a mean of 7 months (2- 12 months) after mirabegron. After mirabegron, urinary incontinence was improved in all patients. G3 bladder deformity was improved to G2 and G1 in one patient each, and VUR disappeared in all 3 patients. DO disappeared in 2 of the 5 patients, and bladder compliance was improved in all 4 patients with low compliance bladder. In conclusion, combination therapy of mirabegron is effective and beneficial for anticholinergic-resistant neurogenic bladder.

  15. Hemolysis after Oral Artemisinin Combination Therapy for Uncomplicated Plasmodium falciparum Malaria

    Science.gov (United States)

    Lingscheid, Tilman; Steiner, Florian; Stegemann, Miriam S.; Bélard, Sabine; Menner, Nikolai; Pongratz, Peter; Kim, Johanna; von Bernuth, Horst; Mayer, Beate; Damm, Georg; Seehofer, Daniel; Salama, Abdulgabar; Suttorp, Norbert; Zoller, Thomas

    2016-01-01

    Episodes of delayed hemolysis 2–6 weeks after treatment of severe malaria with intravenous artesunate have been described. We performed a prospective observational study of patients with uncomplicated malaria to investigate whether posttreatment hemolysis also occurs after oral artemisinin-based combination therapy. Eight of 20 patients with uncomplicated malaria who were given oral artemisinin-based combination therapy met the definition of posttreatment hemolysis (low haptoglobin level and increased lactate dehydrogenase level on day 14). Five patients had hemolysis persisting for 1 month. Patients with posttreatment hemolysis had a median decrease in hemoglobin level of 1.3 g/dL (interquartile range 0.3–2.0 g/dL) in the posttreatment period, and patients without posttreatment hemolysis had a median increase of 0.3 g/dL (IQR −0.1 to 0.7 g/dL; p = 0.002). These findings indicate a need for increased vigilance for hemolytic events in malaria patients, particularly those with predisposing factors for anemia. PMID:27434054

  16. [Clinical benefit of HCV core antigen assay in patients receiving interferon and ribavirin combination therapy].

    Science.gov (United States)

    Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Saito, Hidetsugu

    2006-02-01

    A highly sensitive second generation HCV core antigen assay has recently been developed. We compared viral disappearance and kinetics data between commercially available core antigen assays, Lumipulse Ortho HCV Ag, and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor Test, Version 2 to estimate the predictive benefit of sustained viral response (SVR) and non-SVR in 59 patients treated with interferon and ribavirin combination therapy. We found a good correlation between HCV core Ag and HCV RNA level regardless of genotype. Although the sensitivity of the core antigen assay was lower than PCR, the dynamic range was broader than that of the PCR assay, so that we did not need to dilute the samples in 59 patients. We detected serial decline of core Ag levels in 24 hrs, 7 days and 14 days after interferon combination therapy. The decline of core antigen levels was significant in SVR patients compared to non-SVR as well as in genotype 2a, 2b patients compared to 1b. Core antigen-negative on day 1 could predict all 10 SVR patients (PPV = 100%), whereas RNA-negative could predict 22 SVR out of 25 on day 14 (PPV = 88.0%). None of the patients who had detectable serum core antigen on day 14 became SVR(NPV = 100%), although NPV was 91.2% on RNA negativity. An easy, simple, low cost new HCV core antigen detecting system seems to be useful for assessing and monitoring IFN treatment for HCV.

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

    Directory of Open Access Journals (Sweden)

    Rosario-Josefa Marrero

    Full Text Available 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 constructs in a convenience sample. Participants analysed were 48 university students (mean age 22.25, 25 assigned nonrandomized to intervention condition and 23 to no-treatment waiting-list control condition. All participants were assessed pre- and post-intervention to test the treatment program effectiveness. Repeated-measures ANCOVAs, controlling baseline differences between the two groups, indicated that the intervention group reported greater social support after the intervention period than the waiting-list control group. Within-group differences were found for happiness, selfacceptance, positive relations with others, optimism, and self-esteem in the intervention group; these differences did not appear in the waiting-list control group. These findings suggest the limited capacity of this intervention program for improving well-being through positive activities combined with cognitive-behavioral therapy. Future research should analyse what kind of activities could be more effective in promoting well-being depending on the characteristics of participants.

  18. Combination Gene Therapy for Liver Metastasis of Colon Carcinoma in vivo

    Science.gov (United States)

    Chen, Shu-Hsai; Chen, X. H. Li; Wang, Yibin; Kosai, Ken-Ichiro; Finegold, Milton J.; Rich, Susan S.

    1995-03-01

    The efficacy of combination therapy with a "suicide gene" and a cytokine gene to treat metastatic colon carcinoma in the liver was investigated. Tumor in the liver was generated by intrahepatic injection of a colon carcinoma cell line (MCA-26) in syngeneic BALB/c mice. Recombinant adenoviral vectors containing various control and therapeutic genes were injected directly into the solid tumors, followed by treatment with ganciclovir. While the tumors continued to grow in all animals treated with a control vector or a mouse interleukin 2 vector, those treated with a herpes simplex virus thymidine kinase vector, with or without the coadministration of the mouse interleukin 2 vector, exhibited dramatic necrosis and regression. However, only animals treated with both vectors developed an effective systemic antitumoral immunity against challenges of tumorigenic doses of parental tumor cells inoculated at distant sites. The antitumoral immunity was associated with the presence of MCA-26 tumor-specific cytolytic CD8^+ T lymphocytes. The results suggest that combination suicide and cytokine gene therapy in vivo can be a powerful approach for treatment of metastatic colon carcinoma in the liver.

  19. Enhanced combination therapy effect on paclitaxel-resistant carcinoma by chloroquine co-delivery via liposomes

    Directory of Open Access Journals (Sweden)

    Gao MH

    2015-10-01

    Full Text Available Menghua Gao,1 Yuzhen Xu,1 Liyan Qiu2,3 1College of Pharmaceutical Sciences, 2Ministry of Education (MOE Key Laboratory of Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 3Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: A novel composite liposomal system co-encapsulating paclitaxel (PTX with chloroquine phosphate (CQ was designed for treating PTX-resistant carcinoma. It was confirmed that liposomal CQ can sensitize PTX by means of autophagy inhibition and competitively binding with multidrug-resistance transporters. Furthermore, according to the in vitro cytotoxicity and apoptosis assay, real-time observation of cellular uptake, and in vivo tissue distribution study, co-encapsulation of PTX and CQ in liposomes was validated as superior to the mixture of PTX liposome plus CQ liposome due to the simultaneous delivery and synergetic effect of the two drugs. Consequently, this composite liposome achieved significantly stronger anticancer efficacy in vivo than the PTX liposome plus CQ liposome mixture. This study helps to guide and enlighten ongoing and future clinical trials about the optimal administration modes for drug combination therapy. Keywords: paclitaxel, chloroquine, liposome, drug resistance, combination therapy

  20. Nonoperative Korean Medicine Combination Therapy for Lumbar Spinal Stenosis: A Retrospective Case-Series Study

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    Kiok Kim

    2015-01-01

    Full Text Available This is a retrospective case series exploring the therapeutic benefits and harm of nonoperative Korean medicine combination therapy for lumbar spinal stenosis (LSS. The medical records of a total of 33 LSS patients, who were treated as inpatients at Mokhuri Neck and Back Hospital, Republic of Korea, from November 2010 to January 2012, were reviewed first and telephone survey on these patients was conducted after one year. Body acupuncture, pharmacoacupuncture, Chuna, and oral administration of herbal medicines were offered to all patients. A Visual analogue scale (VAS of pain and the walking duration without pain were used to assess the patients during the approximately 1-month treatment period. The average VAS score of pain and the walking duration improved significantly; the VAS score decreased from 9 (SD, 1.15 to 2.75 (2.22 (p<0.01, and the walking duration increased from 5.5 (6.66 to 16.75 (13.00 minutes (p<0.01. No adverse event was reported during the treatment. In addition, the decreased pain level and improved function continued for over one year. Although we did not find definitive evidence, the study results suggest that KM combination therapy may be beneficial for decreasing pain and improving function in LSS patients and may produce comparatively few adverse events.

  1. Clinical efficacy of combined therapy for perianal eczema caused by anal diseases in 160 cases

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    Zhi-Chao LIU

    2007-01-01

    Full Text Available Perianal eczema is a kind of inflammatory dermatosis on the perianal skin and mucosa. The aim of the study was to evaluate the clinical efficacy of the combined therapy of medicine and operation for the perianal eczema caused by the anal diseases such as hemorrhoids, fissures and fistulas. One hundred and sixty patients with perianal eczema were involved in this study. They were randomly divided into four groups and treated by different therapies for four weeks respectively. Group A (40 patients was only treated with medicine, Group B (40 patients only with operation, Group C (40 patients firstly with medicine and then with operation and Group D (40 patients firstly with operation and then with medicine. The efficacy was determined as reduction of lesion size relative to initial size. The cure rate was 22.50%, 32.50%, 57.50% and 45.00% in Group A, B, C and D, respectively. The effective rate was 40.00%, 52.50%, 85.00% and 75.00%, respectively. The efficacy was significantly different (H=20.8689, g = 3, P value =0.0001. The results of group comparison showed that there were significant difference between Group C and Group A, Group C and Group B, Group D and Group A (all P values, < 0.05. It was concluded that the combined therapy of medicine and operation is optimal choice for the perianal eczema caused by the anal diseases such as hemorrhoids, fissures, and fistula. It highly improves the cure rate and efficacy rate.

  2. Spatiotemporally synchronized cancer combination therapy using photo-activated nanoparticle drug delivery systems (Conference Presentation)

    Science.gov (United States)

    Hasan, Tayyaba

    2016-03-01

    This talk will introduce a new nanotechnology platform for cancer combination therapy that utilizes near infrared light activation not only for photodynamic damage but also as an extrinsic mechanism to initiate release of complimentary drugs to suppress dynamic bursts in molecular signaling networks that promote tumor cell survival and treatment escape. The goal is to achieve co-delivery with concomitant activity of photodynamic, molecular inhibitor and chemotherapeutic agents, selectively within the tumor. This approach overcomes challenges in achieving synergistic interactions using sequential drug delivery. Conventional drug delivery is compromised by the differential pharmacokinetics of individual agents and potentially antagonistic effects—such as vascular shutdown by one agent that limits delivery of the second. Here, photodynamic damage—which efficiently kills drug-resistant cells via damage of common proteins involved in drug-resistance (such as anti-apoptosis factors and drug-efflux transporters)—is synchronized spatially and temporally with the photo-initiated release of complimentary agents—to enable full interaction amongst the individual therapies. This spatiotemporal synchronization offers new prospects for exploiting time-sensitive synergistic interactions. Specific implementations of these concepts will be presented in preclinical models of cancer. Strategies to enable molecular-targeting of cancer cells via site-specific attachment of targeting moieties to the outer lipid shell of these nanovehicles will also be discussed. If successful in humans, this new paradigm for synchronized, tumor-focused combination therapy will ultimately supersede the present use of chronic drug injection by increasing efficacy per cycle whilst reducing systemic exposure to toxic drugs.

  3. Combined intraarterial cisplatin infusion and radiation therapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mizoguchi, Hiroaki; Nomura, Yoshio; Terada, Katsuhiko; Nakagawa, Masayuki; Ogata, Jiro [Oita Medical Univ., Hasama (Japan)

    1995-03-01

    Twenty-three patients with invasive bladder cancer (T2 in 17, T3 in 6) were treated initially with combined intraarterial cisplatin infusion and radiation therapy. Cisplatin (50 mg) was infused into the internal iliac artery through a subcutaneous reservoir twice a week over three weeks while concurrent radiation therapy with 30 Gy, delivered in 15 fractions, was given. In 23 patients, 6 received additional cisplatin infusion and the other 17 had transurethral resection of bladder tumor (TURBT). Two of the patients undergoing total cystectomy exhibited a complete response (CR). Thus overall response rate was 87% (CR in 13 and partial response in 7). CR was achieved in 53% for T2 patients and 67% for T3 patients. CR was slightly higher in patients with non-papillary cancer than those with papillary one. Toxic reaction included a decrease in bladder capacity in 2 patients and severe diarrhea due to methicillin-resistant Staphylococcus aureus colitis in one. The other toxicities, including nausea, vomiting, neurotoxicity and myelosuppression, were tolerable. All except for one are alive. Seven patients had a local recurrence of bladder cancer. One patient developed invasive bladder cancer reaching the prostatic urethra. One other patient had recurrence at the same site as the previous tumor. Five others had superficial bladder cancer and were managed by TURBT. Bladder function was preserved in 65% at a mean follow-up of 29 months. In conclusion, the combined intraarterial cisplatin infusion and radiation therapy is useful for the initial treatment of invasive bladder cancer. (N.K.).

  4. Comparison between single antiplatelet therapy and combination of antiplatelet and anticoagulation therapy for secondary prevention in ischemic stroke patients with antiphospholipid syndrome

    Directory of Open Access Journals (Sweden)

    Hirohisa Okuma, Yasuhisa Kitagawa, Takashi Yasuda, Kentaro Tokuoka, Shigeharu Takagi

    2010-01-01

    Full Text Available Satisfactory results have not yet been obtained in therapy for secondary prevention in ischemic stroke patients with antiphospholipid syndrome (APS. We therefore compared single antiplatelet therapy and a combination of antiplatelet and anticoagulation therapy for secondary prevention in ischemic stroke patients with APS. The subjects were 20 ischemic stroke patients with antiphospholipid antibody, 13 with primary antiphospholipid syndrome and 7 with SLE-related antiphospholipid syndrome. Diagnosis of APS was based on the 2006 Sydney criteria. Eligible patients were randomly assigned to either single antiplatelet therapy (aspirin 100 mg or a combination of antiplatelet and anticoagulation therapy (target INR: 2.0-3.0; mean 2.4±0.3 for the secondary prevention of stroke according to a double-blind protocol. There was no significant difference between the two groups in age, gender, NIH Stroke Scale on admission, mRS at discharge, or rate of hypertension, diabetes mellitus, hyperlipidemia, or cardiac disease. We obtained Kaplan-Meier survival curves for each treatment. The primary outcome was the occurrence of stroke. The mean follow-up time was 3.9±2.0 years. The cumulative incidence of stroke in patients with single antiplatelet treatment was statistically significantly higher than that in patients receiving the combination of antiplatelet and anticoagulation therapy (log-rank test, p-value=0.026. The incidence of hemorrhagic complications was similar in the two groups. The recent APASS study did not show any difference in effectiveness for secondary prevention between single antiplatelet (aspirin and single anticoagulant (warfarin therapy. Our results indicate that combination therapy may be more effective in APS-related ischemic stroke.

  5. Revisiting Dosing Regimen Using Pharmacokinetic/Pharmacodynamic Mathematical Modeling: Densification and Intensification of Combination Cancer Therapy.

    Science.gov (United States)

    Meille, Christophe; Barbolosi, Dominique; Ciccolini, Joseph; Freyer, Gilles; Iliadis, Athanassios

    2016-08-01

    Controlling effects of drugs administered in combination is particularly challenging with a densified regimen because of life-threatening hematological toxicities. We have developed a mathematical model to optimize drug dosing regimens and to redesign the dose intensification-dose escalation process, using densified cycles of combined anticancer drugs. A generic mathematical model was developed to describe the main components of the real process, including pharmacokinetics, safety and efficacy pharmacodynamics, and non-hematological toxicity risk. This model allowed for computing the distribution of the total drug amount of each drug in combination, for each escalation dose level, in order to minimize the average tumor mass for each cycle. This was achieved while complying with absolute neutrophil count clinical constraints and without exceeding a fixed risk of non-hematological dose-limiting toxicity. The innovative part of this work was the development of densifying and intensifying designs in a unified procedure. This model enabled us to determine the appropriate regimen in a pilot phase I/II study in metastatic breast patients for a 2-week-cycle treatment of docetaxel plus epirubicin doublet, and to propose a new dose-ranging process. In addition to the present application, this method can be further used to achieve optimization of any combination therapy, thus improving the efficacy versus toxicity balance of such a regimen.

  6. Artesunate – amodiaquine combination therapy for falciparum malaria in young Gabonese children

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    Lell Bertrand

    2007-03-01

    Full Text Available Abstract Background Artesunate-amodiaquine combination for the treatment of childhood malaria is one of the artemisinin combination therapies (ACTs recommended by National authorities in many African countries today. Effectiveness data on this combination in young children is scarce. Methods The effectiveness of three daily doses of artesunate plus amodiaquine combination given unsupervised (n = 32, compared with the efficacy when given under full supervision (n = 29 to children with falciparum malaria were assessed in an unrandomized study. Results 61 patients analysed revealed a PCR-corrected day-28 cure rate of 86 % (25 of 29 patients; CI 69 – 95 % in the supervised group and 63 % (20 of 32 patients; CI 45 – 77 % in the unsupervised group. The difference in outcome between both groups was statistically significant (p = 0.04. No severe adverse events were reported. Conclusion The effectiveness of this short course regimen in young children with falciparum malaria could be augmented by increased adherence and improved formulation.

  7. Analysis of Cardiotoxicity from rh-Endostatin Therapy Combined with Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Jing Qin; Penghai Zhang; Xinyu Qian; Aimin Li; Rongcheng Luo; Dingli Xu

    2008-01-01

    OBJECTIVE To evaluate the cardotoxicity from recombinant human endostatin (rh-endostatin) combined with chemotherapy.METHODS A total of 12 cancer patients treated with rh-endostatin combined with chemotherapy were selected, and their clinical data collected. Their symptoms, including cardiopalmus,chest distress, dyspnea and changes in their electrocardiogram (ECG), myocardium enzymogram and left ventricular ejection fraction (LVEF), were observed during the drug treatment. These indicators were used for early diagnosis of cardiotoxicity.RESULTS Compared with a pre-therapeutic value, there was a significant increase in the CK-MB value at one week after startingthe treatment as well as at the end of treatment (P<0.05). There was a significant change in the ECG at the end of treatment,compared to a pre-therapeutic condition (P < 0.05), but there was no significant difference when comparing the pre- and post-therapeutic LVEF values.CONCLUSION It was recognized that mild cardiac adverse reactions exist in the regimen of recombinant human endostatin combined with chemotherapy. This therapy caused definite injury to the cardiac muscle, but cardiac functions were not obviously changed. CK-MB and ECG may be used as indicators for early monitoring cardiac toxicity. Vigilance against cardiac adverse reactions should be heightened during a course of rh-endostatin combined with chemotherapy.

  8. A brief introduction to combined stem cell/gene therapy%干细胞/基因联合治疗

    Institute of Scientific and Technical Information of China (English)

    章静波

    2012-01-01

    细胞治疗与基因治疗的相互交融形成了更行之有效的干细胞/基因联合治疗,本文简要介绍干细胞/基因联合治疗中常用的细胞类型、各种载体以及它们的优缺点;例举了迄今已报道有成效的某些人类疾病的治疗或动物实验治疗的结果.此外,指出干细胞/基因联合治疗中可能遇到的致瘤性问题及其对策.%The merge of cell therapy with gene therapy forms a more effective combined stem cell therapy/ gene therapy. An introduction to combined stem cell therapy/gene therapy is made in this minireview briefly, including the often used cell types, vectors and their advantages and disadvantages. Examples of some diseases in human being or in animals which have been treated with combined stem cell therapy/gene therapy successfully are given also. It is pointed out that carcinogenesis might occur during the treatment and how to overcome such problems.

  9. Physical therapy combined with corticosteroid intervention for systemic lupus erythematosus with central nervous system involvement: a case report.

    Science.gov (United States)

    Lee, In-Hee; Ryu, Young Uk

    2014-11-01

    [Purpose] Systemic lupus erythematosus (SLE) is a chronic, immune-mediated disease, affecting 0.1% of the general population. To date, few studies have investigated the efficacy of physical therapy for SLE patients with CNS involvement. The aim of this study was to report whether the combined use of corticosteroids and physical therapy, consisting of reflex inhibition and functional training, was beneficial to functional recovery. [Subjects and Methods] A 22-year-old male SLE patient with CNS involvement requested physical therapy due to strong spasticity of the trunk and limbs in a bedridden state. Corticosteroid intervention and physical therapy were undertaken for 16 days. [Result] After 16 days of the interventions, the patient demonstrated stabilized and alleviated neurological symptoms and an improved functional level. [Conclusion] The present case indicates that physical therapy combined with corticosteroids might be a possible treatment and rehabilitation method to effectively recover motor function for SLE patients who have strong spasticity due to CNS involvement.

  10. Pilot Cases of Combined Cognitive Processing Therapy and Smoking Cessation for Smokers With Posttraumatic Stress Disorder.

    Science.gov (United States)

    Dedert, Eric A; Resick, Patricia A; McFall, Miles E; Dennis, Paul A; Olsen, Maren; Beckham, Jean C

    2016-01-01

    Posttraumatic stress disorder (PTSD) and smoking are often comorbid, and both problems are in need of improved access to evidence-based treatment. The combined approach could address two high-priority problems and increase patient access to both treatments, but research is needed to determine whether this is feasible and has promise for addressing both PTSD and smoking. We collected data from 15 test cases that received a treatment combining two evidence-based treatments: cognitive processing therapy-cognitive version (CPT-C) for PTSD and integrated care for smoking cessation (ICSC). We explored two combined treatment protocols including a brief (six-session) CPT-C with five follow-up in-person sessions focused on smoking cessation (n=9) and a full 12-session CPT-C protocol with ICSC (n=6). The combined interventions were feasible and acceptable to patients with PTSD making a quit attempt. Initial positive benefits of the combined treatments were observed. The six-session dose of CPT-C and smoking cessation resulted in 6-month bioverified smoking abstinence in two of nine participants, with clinically meaningful PTSD symptom reduction in three of nine participants. In the second cohort (full CPT-C and smoking treatment), both smoking and PTSD symptoms were improved, with three of six participants abstinent from smoking and four of six participants reporting clinically meaningful reduction in PTSD symptoms. Results suggested that individuals with PTSD who smoke are willing to engage in concurrent treatment of these problems and that combined treatment is feasible.

  11. Combination phenylbutyrate/gemcitabine therapy effectively inhibits in vitro and in vivo growth of NSCLC by intrinsic apoptotic pathways

    Directory of Open Access Journals (Sweden)

    Schniewind Bodo

    2006-11-01

    Full Text Available Abstract Background Standard chemotherapy protocols in NSCLC are of limited clinical benefit. Histone deacetylase (HDAC inhibitors represent a new strategy in human cancer therapy. In this study the combination of the HDAC inhibitor phenylbutyrate (PB and the nucleoside analogue gemcitabine (GEM was evaluated and the mechanisms underlying increased cell death were analyzed. Methods Dose escalation studies evaluating the cytotoxicity of PB (0.01–100 mM, GEM (0.01–100 μg/ml and a combination of the two were performed on two NSCLC cell lines (BEN and KNS62. Apoptotic cell death was quantified. The involvement of caspase-dependent cell death and MAP-kinase activation was analyzed. Additionally, mitochondrial damage was determined. In an orthotopic animal model the combined effect of PB and GEM on therapy was analyzed. Results Applied as a single drug both GEM and PB revealed limited potential to induce apoptosis in KNS62 and Ben cells. Combination therapy was 50–80% (p = 0.012 more effective than either agent alone. On the caspase level, combination therapy significantly increased cleavage of the pro-forms compared to single chemotherapy. The broad spectrum caspase-inhibitor zVAD was able to inhibit caspase cleavage completely, but reduced the frequency of apoptotic cells only by 30%. Combination therapy significantly increased changes in MTP and the release of cyto-c, AIF and Smac/Diabolo into the cytoplasm. Furthermore, the inhibitors of apoptosis c-IAP1 and c-IAP2 were downregulated and it was shown that in combination therapy JNK activation contributed significantly to induction of apoptosis. The size of the primary tumors growing orthotopically in SCID mice treated for 4 weeks with GEM and PB was significantly reduced (2.2–2.7 fold compared to GEM therapy alone. The Ki-67 (KNS62: p = 0.015; Ben: p = 0.093 and topoisomerase IIα (KNS62: p = 0.008; Ben: p = 0.064 proliferation indices were clearly reduced in tumors treated by combination

  12. Combined transcranial direct current stimulation and home-based occupational therapy for upper limb motor impairment following intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Mortensen, Jesper; Figlewski, Krystian; Andersen, Henning

    2016-01-01

    PURPOSE: To investigate the combined effect of transcranial direct current stimulation (tDCS) and home-based occupational therapy on activities of daily living (ADL) and grip strength, in patients with upper limb motor impairment following intracerebral hemorrhage (ICH). METHODS: A double......-blind randomized controlled trial with one-week follow-up. Patients received five consecutive days of occupational therapy at home, combined with either anodal (n = 8) or sham (n = 7) tDCS. The primary outcome was ADL performance, which was assessed with the Jebsen-Taylor test (JTT). RESULTS: Both groups improved...... with the sham group, from baseline to post-assessment (p = 0.158). CONCLUSIONS: Five consecutive days of tDCS combined with occupational therapy provided greater improvements in grip strength compared with occupational therapy alone. tDCS is a promising add-on intervention regarding training of upper limb motor...

  13. Influences of BRAF Inhibitors on the Immune Microenvironment and the Rationale for Combined Molecular and Immune Targeted Therapy

    Science.gov (United States)

    Reddy, Sangeetha M.; Reuben, Alexandre; Wargo, Jennifer A.

    2017-01-01

    The identification of key driver mutations in melanoma has led to the development of targeted therapies aimed at BRAF and MEK, but responses are often limited in duration. There is growing evidence that MAPK pathway activation impairs antitumor immunity and that targeting this pathway may enhance responses to immunotherapies. There is also evidence that immune mechanisms of resistance to targeted therapy exist, providing the rationale for combining targeted therapy with immunotherapy. Preclinical studies have demonstrated synergy in combining these strategies, and combination clinical trials are ongoing. It is, however, becoming clear that additional translational studies are needed to better understand toxicity, proper timing, and sequence of therapy, as well as the utility of multidrug regimens and effects of other targeted agents on antitumor immunity. Insights gained through translational research in preclinical models and clinical studies will provide mechanistic insight into therapeutic response and resistance and help devise rational strategies to enhance therapeutic responses. PMID:27215436

  14. Combination therapy or monotherapy for the depressed type of schizoaffective disorder

    Directory of Open Access Journals (Sweden)

    Lubomira Izáková

    2009-02-01

    Full Text Available Lubomira Izáková1, Ivan Andre1, Angelos Halaris21Psychiatric Clinic, Faculty of Medicine Comenius University and Faculty Hospital, Bratislava, Slovakia; 2Department of Psychiatry and Behavioral Neurosciences, Loyola University Medical Center, Maywood, IL, USAAbstract: Several studies have demonstrated the effectiveness of adjunctive antidepressant drug therapy to improve the depressive or negative symptoms of schizoaffective disorder, however, monotherapy with atypical antipsychotics may be advantageous. We compared the efficacy and safety of risperidone monotherapy versus combination therapy of haloperidol with sertaline for the acute treatment of schizoaffective disorder, depressed type. This is an open label study of 52 female inpatients randomly assigned to risperidone alone (N = 26 or haloperidol in combination with sertraline (N = 26 for 12 weeks. The mean daily doses of medications were: risperidone: 3.75–3.29 mg/day, haloperidol: 5.35–4.15 mg/day, sertraline: 65.39–133.82 mg/day. Efficacy was measured using clinical rating scales of treatment, safety, and tolerability. Risperidone patients showed statistically significant greater improvement than haloperidol-sertraline patients on efficacy measures including Positive and Negative Syndrome Scale and Clinical Global Impressions rating. A higher number of risperidone patients dropped out of the study early. Fewer adverse events and lesser need for concomitant medications occurred in patients on risperidone. The risperidone group showed better psychological, social and occupational functioning (Global Assessment of Functioning and higher quality of life (Heinrich’s Quality of Life Scale. Risperidone has higher antipsychotic efficacy and tolerability compared with haloperidol-sertraline combination for the acute treatment of schizoaffective disorder, depressed type. Both treatments were comparable in terms of antidepressant efficacy.Keywords: schizoaffective disorder, depressed type

  15. Pemetrexed and cyclophosphamide combination therapy for the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Li, Dong; He, Song

    2015-01-01

    Lung cancer is the leading cause of cancer-related mortality. This study was undertaken to investigate the efficacy and safety of adding regulatory T cell inhibitor cyclophosphamide to pemetrexed therapy for the second-line treatment of NSCLC with wild-type epidermal growth factor receptor (EGFR). A total of 70 patients were screened between March 2011 and December 2013, out of which 62 patients were enrolled in the study. Patients were randomized to receive 500 mg/m(2) pemetrexed in combination with 20 mg/kg cyclophosphamide in a 21 day cycle (n=30) or 500 mg/m(2) pemetrexed (n=32), and followed up for 30 months. Disease progression was observed in 23 patients in the pemetrexed plus cyclophosphamide arm and 27 patients in the pemetrexed monotherapy arm. Median progression-free survival was 3.6 months (95% confidence interval [CI], 1.3 to 5.9 months) in the pemetrexed plus cyclophosphamide arm and 2.2 months (95% CI, 1.3 to 3.1 months) in the pemetrexed monotherapy arm. The 6-month PFS rates were 22% (95% CI, 10 to 34) and 14.5% (95% CI, 6 to 23) in the pemetrexed plus cyclophosphamide arm and pemetrexed monotherapy arm, respectively. Median overall survival was 9.8 months for the pemetrexed combination therapy arm and 8.8 months for the pemetrexed arm, and the 1-year survival rates were 46% and 33%, respectively. The present study showed that pemetrexed in combination with low-dose cyclophosphamide may be a better treatment approach than pemetrexed monotherapy when considering second-line treatment for wild-type EGFR NSCLC.

  16. Antioxidative potential of a combined therapy of anti TNFα and Zn acetate in experimental colitis

    Institute of Scientific and Technical Information of China (English)

    Michela Barollo; Giacomo Carlo Sturniolo; Valentina Medici; Renata D'Incà; Antara Banerjee; Giuseppe Ingravallo; Marco Scarpa; Surajit Patak; Cesare Ruffolo; Romilda Cardin

    2011-01-01

    AIM: To evaluate whether combination therapy with anti-tumour necrosis factor α (TNFα). Zantibody and Zn acetate is beneficial in dextran sodium sulphate(DSS) colitis. METHODS: Colitis was induced in CD1-Swiss mice with 5% DS for 7 d. The exp erimental mice were th en randomised into the following subgroups: standard diet + DSS treated (induced colitis group); standard diet + DSS + subcutaneous 25. Μg anti-TNFα treated group; Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα; standard diet + DS + subcut aneou s 6.25 μg anti-TNFα treated group and Zn acetate treated group + DS + subcut aneou s 6.25 μg anti-TNFα. Each group of mice was matched with a similar group of sham contro l animals. Macro scop ic and histo logical featur es were scor ed blindly. Homo genates of th e colonic mu cosa were assessed for myeloperoxidase activity as a biochemical marker of inflamm ation and DNA addu cts (8OHdG) as a measur e of ox idative damage. RESULTS: DSS produced submucosal erosions, ulcers, inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or com bined with zinc. The effect was more pronounced in the latter group. .(vs Zn diet, P < 0.02).Myeloperoxidase activity (vs controls, P < 0.02) and DNA addu cts, greatly elevated in th e DSS fed colitis group (vs controls,. P < 0.05), were significantly redu ced in th e tr eated group s, with a mor e remarkable effect in the group receiving combined therapy (vs standard diet,. P < 0.04). CONCLUSION: DSS induces colonic inflammation which is modulated by the administration of anti-TNFα. Combining anti-TNFα Zwith Zn acetate offers marginal benefit in colitis severity.

  17. Potential benefits of combining cytosine deaminase/5-fluorocytosine gene therapy and irradiation for prostate cancer. Experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Hiroaki; Koshida, Kiyoshi; Yokoyama, Kunihiko; Mizokami, Atsushi; Namiki, Mikio [Kanazawa Univ. (Japan). School of Medicine

    2002-10-01

    The purpose of this study was to investigate the potential of combining cytosine deaminase/5-fluorocytosine (CD/5-FC) gene therapy and radiation therapy (either external beam radiation or radioimmunotherapy [RIT]), for the treatment of prostate cancer. Tumor xenografts of CD-transduced LNCaP cells grown in the testes of severe combined immunodeficiency (SCID) mice were used to evaluate antitumor effect. The mice were injected intraperitoneally with 500 mg/kg of 5-FC, or with 5, 15 or 30 mg/kg of 5-fluorouracil (5-FU), for 9 days. The tumors were treated with fractionated radiation at a dose of 1 or 3 Gy/day for 3 days, or I-131 labelled anti-prostate specific antigen (anti-PSA) monoclonal antibody (mAb) administration at a subtherapeutic dose of 20 or 80 {mu}Ci. Intratumoral and serum concentrations of 5-FU were measured using high performance liquid chromatography. Mice treated with CD/5-FC gene therapy presented a significant tumor growth inhibition comparable to that obtained with 15 mg/kg, 5-FU systemic administration without marked weight loss. Treatment with CD/5-FC gene therapy resulted in higher tumor but lower serum concentrations of 5-FU than treatment with systemic 5-FU chemotherapy. An additive antitumor effect was obtained when CD/5-FC therapy was combined with 1 Gy irradiation, which by itself did not produce a significant antitumor effect. However, the efficacy of CD/5-FC therapy was not enhanced when combined with RIT, probably due to poor accumulation of the mAb as the tumor/blood ratio never exceeded 1. These findings indicate that CD/5-FC gene therapy for prostate cancer may function with enhanced antitumor effect when combined with external beam radiation. However, combining CD/5-FC gene therapy and RIT using an anti-PSA mAb may not be effective because of insufficient accumulation of the mAb at the target tumors. (author)

  18. Combination therapy of murine liver cancer with IL-12 gene and HSV-TK gene

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the synergistic anti-tumor effects of murine IL-12 gene and HSV-TK gene therapy in mice bearing liver cancer. Methods: Mouse liver cancer MM45T. Li (H-2d) cells were transfected with retroviral vector containing IL-12 gene or HSV-TK gene insert. Gene-modified liver cancer cells, MM45T. Li/IL-12 and MM45T. Li/TK, with stable expression of IL-12 and TK were obtained. Balb/c mice were inoculated subcutaneously with 2′ 105 MM45T. Li cells. When the tumor reached a size of 0.5-1.0 cm, a mixture of MM45T.Li/TK cells and 60Co-irradiated MM45T. Li/IL-12 cell were injected intratumoraly. Ganciclovir (GCV) was injected ip (40 mg.kg-1.d-1) for 10 days. Intratumoral injection of 60Co-irradiated MM45T. Li/IL-12 cells was repeated twice in one week apart. Mice with distant tumors were treated according to the same protocol. CTL activity of spleen cells was measured by 51Cr-release assay and phenotype of tumor infiltrating lymphocytes by immunohistochemical staining. Results: In mice treated with MM45T. Li/IL-12 or MM45T. Li/TK+GCV individually led to moderate reduction in tumor growth, but neither could eradicate the tumor completely, while in 60% of mice treated with a mixture of MM45T. Li/IL-12 and MM45T. Li/TK cells plus GCV, complete tumor regression was observed, with no tumor recurrence for two months. The growth of distant tumor was also inhibited significantly in mice similarly treated. Most of the mice received combined gene therapy plus GCV had abundant CD4+, CD8+T lymphocyte infiltration. Their CTL activity was significantly higher than in mice received single gene therapy. Conclusion Combination therapy with IL-12 gene and HSV-TK gene plus GCV is effective for mouse liver cancer.

  19. Increased skin and mucosal toxicity in the combination of vemurafenib with radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Merten, Ricarda; Hecht, Markus; Haderlein, Marlen; Distel, Luitpold; Fietkau, Rainer; Semrau, Sabine [Department of Radiation Oncology University Hospital Erlangen, Erlangen (Germany); Heinzerling, Lucie [University Hospital Erlangen, Department of Dermatology, Erlangen (Germany)

    2014-12-15

    Palliative radiotherapy is often required for patients with metastatic malignant melanoma in the case of bone or brain metastases. Since BRAF inhibitor therapy is highly efficient in V600-mutated melanomas, there is hesitation to stop it during radiotherapy. Consequently, radiotherapy under simultaneous vemurafenib treatment is frequently needed. We report the case of a patient receiving palliative radiotherapy of spinal bone metastases before and during vemurafenib therapy. The skin reactions were quantitatively scored using computer-assisted digital image evaluation. Radiotherapy without vemurafenib was tolerated very well, whereas radiotherapy under simultaneous vemurafenib treatment resulted in accentuated skin reactions. Furthermore, the patient developed dysphagia and had to be hospitalized for parenteral nutrition. In the quantitative analysis, there was a twofold increase in pigmentation and erythema of the irradiated skin area of the thoracic spine when vemurafenib was combined with radiotherapy compared with radiotherapy treatment alone. This is the first reported case of a patient showing no complications during radiotherapy without vemurafenib but remarkable skin and mucosal toxicity under concurrent vemurafenib therapy. Thus, a genetically conditioned individually elevated radiosensitivity can definitely be excluded. Compared with other reported cases, radiosensitization was not limited to the skin, but also affected the esophageal mucosa. Vemurafenib is a strong radiosensitizer. Patients receiving radiotherapy under simultaneous vemurafenib treatment should be monitored very closely. (orig.) [German] Bei Patienten mit metastasiertem Melanom ist die palliative Bestrahlung von Knochen- oder Hirnmetastasen haeufig erforderlich. Da eine Therapie mit BRAF-Inhibitoren bei Patienten mit V600-mutierten Melanomen hoch effektiv ist, sollte man sie waehrend einer Strahlentherapie nicht unterbrechen. Daher ist eine Strahlentherapie unter laufender Behandlung mit

  20. Combination of Aprepitant, Azasetron, and Dexamethasone as Antiemetic Prophylaxis in Women with Gynecologic Cancers Receiving Paclitaxel/Carboplatin Therapy

    Science.gov (United States)

    Koshiyama, Masafumi; Matsumura, Noriomi; Imai, Saeko; Yamanoi, Koji; Abiko, Kaoru; Yoshioka, Yumiko; Yamaguchi, Ken; Hamanishi, Junzo; Baba, Tsukasa; Konishi, Ikuo

    2017-01-01

    Background The aim of this study was to evaluate the antiemetic effect of aprepitant and to determine how to provide triple combination therapy (aprepitant/azasetron/dexamethasone) to women receiving paclitaxel/carboplatin moderately emetogenic chemotherapy (MEC). Material/Methods The current study was a prospective study of 163 women with gynecologic cancers. We compared the digestive symptoms scores (nausea, vomiting, appetite loss, and dietary intake) of 37 women with ovarian cancers before and after aprepitant administration. We also compared these symptoms in women who underwent 193 cycles of triple combination therapy with symptoms of women who underwent 226 cycles of double combination therapy. For triple combination therapy, azasetron, dexamethasone (reduced dose: 40% of 20 mg), and aprepitant (125 mg) were administered on Day 1, followed by only aprepitant (80 mg) administration on Days 2 and Day 3. Results In 37 women with ovarian cancer, three symptoms, nausea, appetite loss, and dietary intake, were significantly improved by primarily adding aprepitant to double combination therapy in the delayed phase of MEC. Upon comparing their digestive symptoms in all cycles, however, these three symptoms were not significantly different in the delayed phase. Furthermore, all four symptoms in all cycles were worse following triple combination therapy than following double combination therapy in the acute phase (p<0.02). The control of digestive symptoms was generally insufficient without the administration of dexamethasone. Conclusions Primary aprepitant as an addition to MEC demonstrated efficacy in improving digestive symptoms in the delayed phase. However, its effect may decrease with repeated use. To improve the antiemetic effect, the dose reduction of dexamethasone should be restricted on Day 1 and dexamethasone should be used throughout the delayed phase as well. PMID:28198358

  1. BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy

    Directory of Open Access Journals (Sweden)

    Chowdhary M

    2016-12-01

    Full Text Available Mudit Chowdhary,1,2 Kirtesh R Patel,1 Hasan H Danish,1 David H Lawson,3 Mohammad K Khan1 1Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 2Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, 3Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA Abstract: Melanoma is an aggressive malignancy that frequently spreads to the brain, resulting in rapid deterioration in both quality and quantity of life. Historically, treatment options for melanoma brain metastases (MBM have predominantly consisted of surgery and radiotherapy. While these options can help provide local control, the majority of patients still develop intracranial progression. Indeed, novel therapeutic options, including molecularly targeted agents and immunotherapy, have improved outcomes and are now changing the role of radiotherapy. Up to 50% of melanomas contain an activating BRAF mutation, resulting in hyperactive cellular proliferation and survival. Drugs that target BRAF have been introduced for the treatment of metastatic melanoma and offer hope in improving disease outcomes; however, many of these trials either excluded or had a limited amount of patients with MBM. Recent studies have revealed that melanoma cell lines become more radiosensitive following BRAF inhibition, thus providing a potential synergistic mechanism when combining BRAF inhibitor (BRAFi and radiotherapy. However, neurotoxicity concerns also exist with this combination. This article reviews the efficacy and limitations of BRAFi therapy for MBM, describes current evidence for combining BRAFis with radiation, discusses the rationale and evidence for combination modalities, and highlights emerging clinical trials specifically investigating this combination in MBM. Keywords: brain metastases, melanoma, radiation, BRAF inhibitors, vemurafenib, dabrafenib

  2. Evaluation of the local dose enhancement in the combination of proton therapy and nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Rovira, I., E-mail: immamartinez@gmail.com; Prezado, Y. [Laboratoire d’Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC), Centre National de la Recherche Scientifique (CNRS), Université Paris 7 and 11, Campus Universitaire, Bât. 440, 1er étage, 15 rue Georges Clemenceau, Orsay Cedex 91406 (France)

    2015-11-15

    Purpose: The outcome of radiotherapy can be further improved by combining irradiation with dose enhancers such as high-Z nanoparticles. Since 2004, spectacular results have been obtained when low-energy x-ray irradiations have been combined with nanoparticles. Recently, the same combination has been explored in hadron therapy. In vitro studies have shown a significant amplification of the biological damage in tumor cells charged with nanoparticles and irradiated with fast ions. This has been attributed to the increase in the ionizations and electron emissions induced by the incident ions or the electrons in the secondary tracks on the high-Z atoms, resulting in a local energy deposition enhancement. However, this subject is still a matter of controversy. Within this context, the main goal of the authors’ work was to provide new insights into the dose enhancement effects of nanoparticles in proton therapy. Methods: For this purpose, Monte Carlo calculations (GATE/GEANT4 code) were performed. In particular, the GEANT4-DNA toolkit, which allows the modeling of early biological damages induced by ionizing radiation at the DNA scale, was used. The nanometric radial energy distributions around the nanoparticle were studied, and the processes (such as Auger deexcitation or dissociative electron attachment) participating in the dose deposition of proton therapy treatments in the presence of nanoparticles were evaluated. It has been reported that the architecture of Monte Carlo calculations plays a crucial role in the assessment of nanoparticle dose enhancement and that it may introduce a bias in the results or amplify the possible final dose enhancement. Thus, a dosimetric study of different cases was performed, considering Au and Gd nanoparticles, several nanoparticle sizes (from 4 to 50 nm), and several beam configurations (source-nanoparticle distances and source sizes). Results: This Monte Carlo study shows the influence of the simulations’ parameters on the local

  3. Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yoo EJ

    2013-06-01

    Full Text Available Eun Jin Yoo,1,* Hye Sun Shin,1,* Seung Up Kim,1,2,7 Dong Jin Joo,3,4 Jun Yong Park,1,2,7 Gi Hong Choi,3 Do Young Kim,1,2,7 Sang Hoon Ahn,1,2,7 Jinsil Seong,5 Myung Joo Koh,6 Kwang-Hyub Han,1,2,7 Chae Yoon Chon1,2,7 1Department of Internal Medicine, 2Institute of Gastroenterology, 3Department of Surgery, 4Research Institute for Transplantation, 5Department of Radiation Oncology, 6Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea; 7Liver Cirrhosis Clinical Research Center, Seoul, South Korea *These authors contributed equally to this work Abstract: We herein report a patient with advanced hepatitis B virus-related hepatocellular carcinoma (HCC beyond the Milan criteria. He underwent orthotopic liver transplantation after successful HCC downstaging that satisfied the University of California, San Francisco criteria, using concurrent chemoradiation therapy with a combination of repeated hepatic arterial infusion chemotherapy (HAIC and sorafenib. A 52-year-old male was diagnosed with advanced hepatitis B virus-related HCC beyond the Milan criteria. He underwent concurrent chemoradiation therapy (50 Gy with 20 fractions over 5 weeks with HAIC using 5-fluorouracil at a dose of 500 mg/day, which was administered during the first and fifth weeks of radiation therapy as an initial treatment modality. This was followed by the combined use of HAIC using 5-fluorouracil (500 mg/m2 for 5 hours on days 1–3 and cisplatin (60 mg/m2 for 2 hours on day 2 every 4 weeks (twelve cycles and sorafenib (from the third to the twelfth cycle of HAIC to treat the remaining HCC. Because a remarkable decrease in the tumor burden that satisfied the University of California, San Francisco criteria was observed after these combination treatments, the patient underwent orthotopic liver transplantation with curative aim and survived for 11 months without evidence of HCC recurrence. Keywords: hepatocellular carcinoma, liver transplantation

  4. Metabolic effect of combined telmisartan and nifedipine CR therapy in patients with essential hypertension

    Directory of Open Access Journals (Sweden)

    Shimizu Y

    2012-09-01

    Full Text Available Yuji Shimizu,1,4 Fumiyasu Yamasaki,4 Takashi Furuno,1,4 Toru Kubo,1 Takayuki Sato,3,4 Yoshinori Doi,1 Tetsuro Sugiura21Medicine and Geriatrics, 2Clinical Laboratory, 3Cardiovascular Control, Kochi Medical, School, Nankoku, Japan; 4Section of Cardiology, Inoue Hospital, Takaoka, JapanBackground: In addition to exerting a blood pressure (BP-lowering effect, telmisartan produces favorable metabolic effects via peroxisome proliferator-activated receptor γ activation. While a combination of telmisartan and a calcium channel blocker is often used to achieve a target BP level, the metabolic effects of this drug combination remain unclear. Therefore, this study evaluated the metabolic effects of telmisartan plus nifedipine controlled release (CR therapy, in hypertensive patients without metabolic disease.Methods: Sixteen patients with essential hypertension, who had not undergone antihypertensive therapy in the previous 6 months, were studied. Patients were initiated on telmisartan (40 mg/day. If their office BP was not reduced to 140/90 mmHg after 6 weeks, nifedipine CR (20–40 mg per day was added for 18 weeks. The other patients whose BP had achieved the target of 140/90 mmHg, continued only telmisartan.Results: Telmisartan reduced BP (174 ± 13/92 ± 10 to 143 ± 22/78 ± 11 mmHg; P < 0.01 at 6 weeks in 16 patients, but eight patients did not achieve target BP levels and required addition of nifedipine. Telmisartan also resulted in a reduction in the homeostatic model assessment of insulin resistance (HOMA-IR (1.30 ± 0.65 to 1.10 ± 0.42; P < 0.05 at 6 weeks, but did not affect adiponectin or leptin levels. Addition of nifedipine (n = 8 resulted in a reduction in BP (158 ± 18/80 ± 13 to 131 ± 8/73 ± 13 mmHg; P < 0.01 at 18 weeks, but did not affect the HOMA-IR (1.10 ± 0.40 to 1.02 ± 0.56; ns. In patients who did not require addition of nifedipine (n = 8, BP levels remained nearly identical at 18 weeks (127 ± 13/73 ± 9 to 128 ± 13/68 ± 8

  5. EFFICACY OF COMBINED ANTIHYPERTENSIVE THERAPY IN ACHIEVEMENT OF TARGET BLOOD PRESSURE IN DIABETIC PATIENTS

    Directory of Open Access Journals (Sweden)

    O. A. Koshel'skaya

    2012-01-01

    Full Text Available Aim. To evaluate the efficacy of long-term combined antihypertensive therapy (AHT based on renin-angiotensin-aldosterone system (RAAS blockers, indapamide and calcium channel blocker (CCB in hypertensive patients with diabetes mellitus (DM in accordance with target blood pressure (BP <130/80 mm Hg achievement rate, dynamics of 24-hour BP profile, metabolic indices, and local stiffness of the main arteries. Besides, to study the effects of the CCB addition to dual therapy on these parameters. Material and methods. Patients (16 men, 31 women, 57.2±6.6 years old with arterial hypertension degrees 1–3 and mild to moderate DM type 2 were included into the study. The patients were treated with perindopril (5–10 mg/day or valsartan (80–160 mg/day in combination with indapamide SR (1.5 mg/day and amlodipine (5–10 mg/day. Examination included office BP measurement and ambulatory BP monitoring (ABPM, common carotid arteries sonarography , evaluation of serum levels of potassium, creatinine, uric acid, glucose metabolism and lipid profile parameters, calculation of insulin resistance index (HOMA at baseline and after 30–32 weeks of treatment. Results. Target BP was achieved in 86.7% of patients. Evenly reduction of day and night BP without reflex tachycardia and hypotension episodes was observed. Office BP decreased from 149.5±12.0/90.0±8.3 to 125.0±7.6/76.8±4.9 mm Hg (p<0.05 and average daily BP (ABPM decreased to 120.1±10.0/71.7±6.9 mmHg. Three drugs were needed to achieve target BP in baseline systolic BP >150 mm Hg (office or >134 mmHg (ABPM. Marked beneficial effect on the morphological and functional characteristics of the vascular wall and its elastic properties, improvement of glycemic control, tissue insulin sensitivity and lipids profile were found. These effects were associated mainly with amlodipine inclusion into the therapy. Conclusion. The combined AHT based on RAAS blockers, indapamide SR and CCB provides achievement of

  6. Early orthopedic correction of skeletal Class III malocclusion using combined reverse twin block and face mask therapy

    Directory of Open Access Journals (Sweden)

    Vinay Kumar Chugh

    2015-01-01

    Full Text Available A 6-year 8-month-old girl presented with a moderate Class III malocclusion characterized by mid-face deficiency and an anterior cross bite. In the first phase, the patient was treated with combination of reverse twin block and facemask therapy. In phase two, fixed appliances were placed in the permanent dentition. The post treatment results were good and a favorable growth tendency could be observed. The correction of the Class III malocclusion occurred by a combination of skeletal and dental improvements. This report shows successful correction of skeletal Class III malocclusion in the early transitional dentition using combination therapy.

  7. Early orthopedic correction of skeletal Class III malocclusion using combined reverse twin block and face mask therapy.

    Science.gov (United States)

    Chugh, Vinay Kumar; Tandon, Pradeep; Prasad, Veerendra; Chugh, Ankita

    2015-01-01

    A 6-year 8-month-old girl presented with a moderate Class III malocclusion characterized by mid-face deficiency and an anterior cross bite. In the first phase, the patient was treated with combination of reverse twin block and facemask therapy. In phase two, fixed appliances were placed in the permanent dentition. The post treatment results were good and a favorable growth tendency could be observed. The correction of the Class III malocclusion occurred by a combination of skeletal and dental improvements. This report shows successful correction of skeletal Class III malocclusion in the early transitional dentition using combination therapy.

  8. Pleiotropic Role of Dietary Phytochemicals in Cancer: Emerging Perspectives for Combinational Therapy.

    Science.gov (United States)

    Banudevi, Sivanantham; Swaminathan, Sethuraman; Maheswari, Krishnan Uma

    2015-01-01

    Cancer is considered a complicated health issue worldwide. The mean cancer survival through standard therapeutic strategies has not been significantly improved over the past few decades. Hence, alternate remedies are needed to treat or prevent this dreadful disease being explored. Currently, it has been recognized that repeated treatment with chemotherapeutic agents has been largely ineffective due to multidrug resistance and further conventional treatment possesses limited drug accessibility to cancerous tissues, which in turn necessitates a higher dose resulting in increased cytotoxicity. Drug combinations have been practiced to address the problems associated with conventional single drug treatment. Recently, natural dietary agents have attracted much attention in cancer therapy because of their synergistic effects with anticancer drugs against different types of cancer. Natural phytochemicals may execute their anticancer activity through targeting diverse cancer cell signaling pathways, promoting cell cycle arrest and apoptosis, regulating antioxidant status and detoxification. This review focuses mainly on the anticancer efficacy of dietary phytochemicals in combination with standard therapeutic drugs reported from various in vitro and in vivo experimental studies apart from clinical trials. This review adds knowledge to the field of intervention studies using combinational modalities that opens a new window for cancer treatment/chemoprevention.

  9. Graphene oxide mediated delivery of methylene blue for combined photodynamic and photothermal therapy.

    Science.gov (United States)

    Sahu, Abhishek; Choi, Won Il; Lee, Jong Hyun; Tae, Giyoong

    2013-08-01

    Nano graphene oxide sheet (nanoGO) was non-covalently functionalized with Pluronic block copolymer and complexed with methylene blue, a hydrophilic and positively charged photosensitizer, via electrostatic interaction for combined photodynamic-photothermal therapy of cancer. Pluronic coating of nanoGO ensured its stability in biological fluids. NanoGO plays dual role of a photothermal material as well as a delivery agent for photosensitizer. The release of the photosensitizer from nanoGO surface was pH-dependent and an acidic condition increased the release rate considerably. This nanocomplex showed enhanced uptake by cancer cells than normal cells and in the absence of light it showed no major toxicity towards the cells. In contrast, when irradiated with selective NIR laser lights, it induced significant cell death. Intravenous injection of the complex into tumor bearing mice showed high tumor accumulation, and when the tumors were exposed to NIR lights, it caused total ablation of tumor tissue through the combined action of photodynamic and photothermal effects. This work shows the potential of nanoGO for synergistic combination phototherapy of tumor in vivo.

  10. Hyperbaric oxygen combined with drug therapy in the treatment of acute cerebral infarction clinical analysis

    Institute of Scientific and Technical Information of China (English)

    Wen-Cui Lin; Kang Lin; Jing Wang; Shuai Li

    2015-01-01

    Objective:To explore the effects of hyperbaric oxygen combined with edaravone, salviae miltiorrhizae and ligustrazine and sodium ozagrel in the treatment of acute cerebral infarction clinical analysis.Methods: A total of 200 cases of acute cerebral infraction patients were randomly divided into observation group and control group. The control group was treated with edaravone, salvia miltiorrhizae and ligustrazine and sodium ozagrel; on the basis of treatment in control group, the observation group was combined with hyperbaric oxygen therapy. The neurological deficit scores were observed before and after treatment in patients of two groups, meanwhile the activities of daily living (ADL) and clinical effects were compared.Results: The total effective rate in observation group (92%) was significantly higher than control group (79%), the differences were statistically significant; the score of ADL in observation group after treatment was obviously higher than control group [(79.91±5.16)vs (61.62±5.60)], and the differences were statistically significant. The neurological deficit scores after treatment were obviously lower than the control group [(9.55±4.13)vs (15.46±4.92)], the differences were statistically significant.Conclusion: Hyperbaric oxygen combined with edaravone, salvia miltiorrhizae and ligustrazine and sodium ozagrel in the treatment of acute cerebral infarction can improve the symptoms of microcirculation and neurologic impairment, and improve the patient s quality of life.

  11. Hemodiafiltration combined with resin-mediated absorption as a therapy for hyperlipidemic acute pancreatitis.

    Science.gov (United States)

    Li, Mao-qin; Shi, Zai-xiang; Xu, Ji-yuan; Lu, Bo; Li, Jia-qiong; Xu, Yan-jun; Wang, Xiao-Meng; Li, Song-mei; Mo, Xun

    2014-07-01

    The aim of this study is to investigate whether hemodiafiltration combined with resin-mediated absorption is a better therapy for hyperlipidemic acute pancreatitis. Patients (n = 67) with acute pancreatitis treated in ICU from January 2009 to December 2012 were included in this study. Seven of these 67 cases were diagnosed hyperlipidemic acute pancreatitis (HLAP). All the 7 HLAP patients went through fast, gastrointestinal decompression, anti-shock treatment, inhibition of pancreatic secretion, antiseptic treatments, and hemoperfusion (HP) combined with continuous veno venous hemodiafiltration (CVVHDF). After one round of treatment by resin adsorption, there was a significant decrease in serum triglycerides (TG) (29.78 %) and total cholesterol (TC) (24.02 %) levels (p < 0.01). TG and TC levels dropped by 49.02 and 37.66 %, respectively, after 1-day treatment of HP + CVVHDF; by 62.81 and 47.37 % on day 2 post-treatment; and by 69.57 and 49.47 % on day 3 post-treatment. All the 7 patients survived. The average time spent in the ICU was 7 ± 3.8 days, and the average duration of hospitalization was 19 ± 15.1 days. Our results show that hemoperfusion combined with hemodiafiltration is an efficient treatment as this approach can reduce plasma lipid levels effectively and reduce the risk of acute pancreatitis due to hyperlipidemia.

  12. Efficacy of monotherapies and artesunate-based combination therapies in children with uncomplicated malaria in Somalia.

    Science.gov (United States)

    Warsame, Marian; Atta, Hoda; Klena, John D; Waqar, Butt Ahmed; Elmi, Hussein Haji; Jibril, Ali Mohamed; Hassan, Hassan Mohamed; Hassan, Abdullahi Mohamed

    2009-02-01

    In order to guide the antimalarial treatment policy of Somalia, we conducted therapeutic efficacy studies of routinely used antimalarial monotherapies as well as artemisinin-based combination therapies (ACTs) for uncomplicated malaria in three sentinel sites during 2003-2006. Therapeutic efficacy of chloroquine (CQ), amodiaquine (AQ) and sulfadoxine/pyrimetahmine (SP) monotherapies, and artesunate plus SP (AS+SP) or AQ (AS+AQ) were evaluated in children 6 months to 10 years old with uncomplicated malaria. For the assessment of the monotherapies, 2003 WHO protocol with 14-day follow-up was used while the 2005 WHO protocol with 28-day follow-up was used for testing the ACTs. Of the monotherapies, CQ performed very poorly with treatment failures varying from 76.5% to 88% between the sites. AQ treatment failure was low except for Janale site with treatment failure of 23.4% compared to 2.8% and 8% in Jamame and Jowhar, respectively. For SP, treatment failures from 7.8% to 12.2% were observed. A 28-day test of artemisinin-based combinations, AS+SP and AS+AQ, proved to be highly efficacious with cure rates of 98-100% supporting the choice of AS+SP combination as first line treatment for uncomplicated malaria for Somalia.

  13. Scoliosis treatment using a combination of manipulative and rehabilitative therapy: a retrospective case series

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    Lawrence Gary

    2004-09-01

    Full Text Available Abstract Background The combination of spinal manipulation and various physiotherapeutic procedures used to correct the curvatures associated with scoliosis have been largely unsuccessful. Typically, the goals of these procedures are often to relax, strengthen, or stretch musculotendinous and/or ligamentous structures. In this study, we investigate the possible benefits of combining spinal manipulation, positional traction, and neuromuscular reeducation in the treatment of idiopathic scoliosis. Methods A total of 22 patient files were selected to participate in the protocol. Of these, 19 met the study criterion required for analysis of treatment benefits. Anteroposterior radiographs were taken of each subject prior to treatment intervention and 4–6 weeks following the intervention. A Cobb angle was drawn and analyzed on each radiograph, so pre and post comparisons could be made. Results After 4–6 weeks of treatment, the treatment group averaged a 17° reduction in their Cobb angle measurements. None of the patients' Cobb angles increased. A total of 3 subjects were dismissed from the study for noncompliance relating to home care instructions, leaving 19 subjects to be evaluated post-intervention. Conclusions The combined use of spinal manipulation and postural therapy appeared to significantly reduce the severity of the Cobb angle in all 19 subjects. These results warrant further testing of this protocol.

  14. Surgery combined with topical photodynamic therapy for the treatment of squamous cell carcinoma of the lip.

    Science.gov (United States)

    Wang, Yuanyuan; Yang, Yadong; Yang, Yunchuan; Lu, Yuangang

    2016-06-01

    Due to the unique location of the squamous cell carcinoma (SCC) of the lip, using a single method such as extended resection or radiotherapy probably causes morphological and functional defects. So we used surgery combined with topical photodynamic therapy (PDT) to treat SCC of the lip. Under local anesthesia with 5% lidocaine, the hyperplastic and ulcerative SCC of the lip were curetted and assisted by topical PDTs after surgery. The 20% 5-aminolevulinic acid cream was used as a photosensitizer and applied evenly to the surface of the tumor lesion for 4h. Then the lesion site was irradiated with a 635-nm laser at 120J/cm(2). A total of five PDTs were performed postoperatively at an interval of 2 weeks. Photos were taken before and after every PDT to compare the skin lesions, treatment effects, and side effects. A long-term follow-up was undertaken to observe tumor recurrence. After surgery combined with five topical PDTs, the SCC of the lip disappeared without the compromised morphology of the lip, significant side effects, or tumor recurrence in one-year follow-up. Surgery combined with topical PDT can reduce the excision size of tumors and play a positive role in the treatment of tumors of special locations.

  15. Combined MMF and insulin therapy prevents renal injury in experimental diabetic rats.

    Science.gov (United States)

    Wu, Xiaoyan; Zha, Dongqing; Xiang, Guangsheng; Zhang, Bo; Xiao, Shu-Yuan; Jia, Ruhan

    2006-12-01

    Conventional therapies for diabetic mellitus are not effective in preventing the progression from early diabetic nephropathy (DN) to end-stage renal disease. The role of inflammation in the pathogenesis of DN has been implicated both clinically and experimentally, which provides an alternative therapeutic target for DN. Anti-inflammatory impact of mycophenolate mofetil (MMF) alone and in combination with insulin had been observed in a rat model of experimental DN. In this study, the diabetic rats were subjected to different treatments. Compared to control, the expression levels of CD68, NGF, and NF-kappaB p65, as determined immunohistochemically, were elevated in diabetic rats. Treatment with combined MMF/insulin is associated with a significant reduction in renal tissue of NGF and NF-kappaB p65 expression, macrophage infiltration. It also partially improved the renal function and attenuated renal hypertrophy at early stage of DN. CD68 was found to positively correlate with urinary albumin excretion and NGF. The combined use of MMF/insulin seemed to offer more protections in rats with experimental diabetic renal injury, and the protective effects of MMF might be due to its anti-inflammatory actions through inhibition of NF-kappaB activation and reduction of T cells and macrophage infiltration and/or other kidney chemokine productions.

  16. Sequential Combination Therapy Leading to Sustained Remission in a Patient with SAPHO Syndrome.

    Science.gov (United States)

    Huber, C E; Judex, A G; Freyschmidt, J; Feuerbach, S; Schölmerich, J; Müller-Ladner, U

    2009-03-27

    The SAPHO syndrome represents a variety of clinically similar disorders with the key features of hyperostotic bone lesions in combination with chronic pustular skin disease. The respective pathophysiology of bone and joint manifestations in SAPHO syndrome is still a matter of discussion. For example it does not appear to represent reactive arthritis and HLA B27 antigen, with the latter being typically present in patients with spondyloarthopathies. Treatment of SAPHO syndrome is also not well established and consists of various antiinflammatory and antirheumatic drugs. Here, we report a female patient with active SAPHO syndrome suffering from sternal swelling of unknown origin that had been known for 10 years and a 4-year-history of severe lower back pain. Remarkable were also a typical pustulous palmar erythema associated with swelling and decreased motility of both MCP-I joints. Inflammation parameters were high with an ESR 68 mm/1st hour and a CRP of 19.6 mg/l. She was initially treated with rofecoxib and doxycycline, followed by sulfasalazine with only partial clinical response. Thereafter, both articular symptoms as well as cutaneous lesions responded well to a combination therapy with methotrexate and sulfasalazine. Thus, the case illustrates nicely that methotrexate in combination with another DMARD can be successfully applied to patients with long-term active SAPHO syndrome.

  17. Acceptable Safety of Bevacizumab Therapy in Combination with Chemotherapy in Patients with Advanced Lung Cancer

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    Wei WU

    2009-03-01

    Full Text Available Background and objective Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that selectively binds to and neutralizes the biologic activity of human vascular endothelial growth factor (VEGF. Bevacizumab was approved by the U.S. Food and Drug Administration (FDA in October 2006 for use in combination withcarboplatin and paclitaxel for the initial treatment of patients with unresectable, locally advanced, recurrent, or metastatic,nonsquamous, non-small cell lung cancer (NSCLC. The aim of this study is to observe the safety of bevacizumab therapy in combination with chemotherapy in Chinese patients with NSCLC. Methods Patients with advanced non-squamous NSCLC were treated with Bevacizumab 15 mg/kg, d1, repeated every 21 days until PD; Plus paclitaxel 175 mg/m2, on dl and carboplatin AUC=6 on dl. The cycle was repeated every 21 days. Results One grade 3 epistaxis was observed in onepatient. One grade 4 thrombosis was observed in one patient. 3/4-grade epistaxis and thrombosis was the most significant adverse events. Other adverse effects, such as hemoptysis, hypertension and proteinuria, were not severe and could be well tolerated. Conclusion Most chemotherapy-naive patients with advanced non-squamous NSCLC treated with bevacizumab in combination with paclitaxel and carboplatin have little adverse effects that can be well tolerated.

  18. Effects of bowel rehabilitation and combined trophic therapy on intestinal adaptation in short bowel patients

    Institute of Scientific and Technical Information of China (English)

    Guo-Hao Wu; Zhao-Han Wu; Zhao-Guang Wu

    2003-01-01

    AIM: To evaluate the effects of bowel rehabilitation and combined trophic therapy on intestinal adaptation in short bowel patients.METHODS: Thirty-eight patients with severe short-bowel syndrome (SBS) were employed in the present study, whose average length of jejunum-ileum was 35.8±21.2 cm. The TPN treatment was initiated early to attain positive nitrogen balance and prevent severe weight loss. The TPN composition was designated to be individualized and altered when necessary. Enteral feeding was given as soon as possible after resection and increased gradually. Meals were distributed throughout the day. Eight patients received treatment of growth hormone (0.14 mg/kg.day) and glutamine (0.3 g/kg.day) for 3 weeks. D-xylose test, 15N-Gly trace test and 13C-palmitic acid breath test were done to determine the patients' absorption capability.RESULTS: Thirty-three patients maintained well body weight and serum albumin concentration. The average time of follow-up for 33 survival patients was 5.9±4.3 years.Twenty-two patients weaned from TPN with an average TPN time of 9.5±6.6 months. Two patients, whose whole small bowel, ascending and transverse colon were resected received home TPN. An other 9 patients received parenteral or enteral nutritional support partly as well as oral diet. Three week rhGH+GLN therapy increased nutrients absorption but the effects were transient.CONCLUSION: By rehabilitation therapy, most short bowel patients could wean from parenteral nutrition. Dietary manipulation is an integral part of the treatment of SBS.Treatment with growth hormone and glutamine may increase nutrients absorption but the effects are not sustained beyond the treatment period.

  19. The Efficacy and Safety of Entecavir and Interferon Combination Therapy for Chronic Hepatitis B Virus Infection: A Meta-Analysis.

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    Qiao-Ling Xie

    Full Text Available The objective of this study was to evaluate the effectiveness and safety of entecavir (ETV and interferon (IFN combination therapy in the treatment of chronic hepatitis B (CHB mono-infection via a meta-analysis of randomized controlled trials (RCTs. All eligible RCTs evaluating combination therapy for treating CHB were identified from nine electronic databases. A meta-analysis was performed in accordance with the Cochrane Systemic Review handbook. Eleven trials encompassing 1010 participants were included in this meta-analysis. It showed that at 12 and ≥ 96 weeks of therapy, the combination of ETV and IFN was not better than ETV in improving the undetectable HBV DNA (12 weeks: RR=1.12, 95% CI=0.88-1.42; ≥ 96 weeks: RR = 0.64, 95% CI=0.21-1.98, respectively and HBeAg seroconversion rates (12 weeks: RR=1.35, 95% CI=0.60-3.04; ≥ 96 weeks: RR=1.36, 95% CI=0.75-2.64, respectively. But at 48 weeks of therapy and approximately 2 years of follow up, combination therapy was superior to ETV in improving the undetectable HBV DNA (48 weeks: RR=1.46, 95% CI=1.13-1.90; follow up: RR=2.20, 95% CI=1.26-3.81, respectively and HBeAg seroconversion rates (48 weeks: RR=1.82, 95% CI=1.44-2.30; follow up: RR=1.92, 95% CI=1.19-3.11, respectively. When compared to IFN group, at 24 and 48 weeks of therapy, combination group showed a greater undetectable HBV DNA (24 weeks: RR=2.14, 95% CI=1.59-2.89; 48 weeks: RR=2.28, 95% CI=1.54-3.37, respectively and ALT normalization rate (24 weeks: RR=1.56, 95% CI= 1.24-1.96; 48 weeks: RR=1.55, 95% CI = 1.16-2.07, respectively. At 48 weeks of therapy, combination group achieved a greater HBeAg seroconversion rate than IFN (48 weeks: RR=1.58, 95% CI=1.24-2.00. No significant differences were observed in the side effects of the three therapies. So we can conclude that ETV and IFN combination therapy is more effective than ETV or IFN mono-therapy in CHB treatment. ETV, IFN, and the combination of the two are safe in CHB treatment.

  20. The efficiency analysis of thrombolytic rt-PA combined with intravascular interventional therapy in patients with acute basilar artery occlusion

    Science.gov (United States)

    Xianxian, Zhao; Chengsong, Yue; Qiang, Mei; Fei, Wei; Lin, Shen; Huiyan, Ding; Zili, Gong

    2017-01-01

    In order to further optimize the treatment strategy for the patients with acute basilar artery occlusion, we were dedicated to study the therapeutic effects and influential factors in the process of treated basilar artery occlusion with thrombolytic combined vascular interventional therapy. 75 patients with acute basilar artery occlusion treated with arterial thrombolytic therapy were analyzed retrospectively. In accordance with the discharge records of patients, their short-term curative effect with 24-hour treatment and 14-days treatment were evaluated. Our data showed that the survival condition of the patients with acute acute basilar artery occlusion were visibly improved by combination thrombolytic and interventional therapy. Moreover, their BI scores were remarkably improved, while NIHSS and mRS scores were evidently reduced. These data proved that our treatment strategy was able to improve the survival condition of patients with acute basilar artery occlusion. Furthermore, our data showed that coagulation related factors remarkably improved in the patients, when they treated by combination thrombolytic therapy with interventional therapy. In addition, our results suggested that the patients' bilateral Babinski(+), revascularization and coma symptom were closely related to their prognosis after treated the patients with combination thrombolytic and vascular interventional therapy, and the difference was statistically significant (pBabinski(+), and revascularization in the patients with acute basilar artery occlusion have an appreciable impact on the patients' prognosis. PMID:28123346

  1. Effects of photobiomodulation therapy, pharmacological therapy, and physical exercise as single and/or combined treatment on the inflammatory response induced by experimental osteoarthritis.

    Science.gov (United States)

    Tomazoni, Shaiane Silva; Leal-Junior, Ernesto Cesar Pinto; Pallotta, Rodney Capp; Teixeira, Simone; de Almeida, Patricia; Lopes-Martins, Rodrigo Álvaro Brandão

    2017-01-01

    Osteoarthritis (OA) triggers increased levels of inflammatory markers, including prostaglandin (PG) E2 and proinflammatory cytokines. The elevation of cytokine levels is closely associated with increased articular tissue degeneration. Thus, the use of combination therapies may presumably be able to enhance the effects on the modulation of inflammatory markers. The present study aimed to evaluate and compare the effects of photobiomodulation therapy (PBMT), physical exercise, and topical nonsteroidal anti-inflammatory drug (NSAID) use on the inflammatory process after they were applied either alone or in different combinations. OA was induced by intra-articular papain injection in the knee of rats. After 21 days, the animals began treatment with a topical NSAID and/or with physical exercise and/or PBMT. Treatments were performed three times a week for eight consecutive weeks, totaling 24 therapy sessions. Analysis of real-time polymerase chain reaction (RT-PCR) gene expression; interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) protein expression; and PGE2 levels by enzyme-linked immunosorbent assay (ELISA) was conducted. Our results showed that PBMT alone and Exerc + PBMT significantly reduced IL-1β gene expression (p therapies significantly reduced IL-6 and TNF-α protein expression (p therapies, except Exerc, reduced the levels of PGE2 (p therapies tested.

  2. Gene Therapy Studies in a Canine Model of X-Linked Severe Combined Immunodeficiency

    Science.gov (United States)

    De Ravin, Suk See; Malech, Harry L.; Sorrentino, Brian P.; Burtner, Christopher; Kiem, Hans-Peter

    2015-01-01

    Abstract Since the occurrence of T cell leukemias in the original human γ-retroviral gene therapy trials for X-linked severe combined immunodeficiency (XSCID), considerable effort has been devoted to developing safer vectors. This review summarizes gene therapy studies performed in a canine model of XSCID to evaluate the efficacy of γ-retroviral, lentiviral, and foamy viral vectors for treating XSCID and a novel method of vector delivery. These studies demonstrate that durable T cell reconstitution and thymopoiesis with no evidence of any serious adverse events and, in contrast to the human XSCID patients, sustained marking in myeloid cells and B cells with reconstitution of normal humoral immune function can be achieved for up to 5 years without any pretreatment conditioning. The presence of sustained levels of gene-marked T cells, B cells, and more importantly myeloid cells for almost 5 years is highly suggestive of transduction of either multipotent hematopoietic stem cells or very primitive committed progenitors. PMID:25603151

  3. Use of hyaluronic acid preparations in the combination therapy of osteoarthritis

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    Yu. A. Olyunin

    2016-01-01

    Full Text Available The current recommendations for the pharmacotherapy of osteoarthritis (OA primarily focus on analgesics and main concern is with the use of paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs. Intraarticular injections of first of all hyaluronic acid (HA preparations that have proven to be effective in clinical practice are a promising treatment for OA. By taking into account the favorable safety profile of HA preparations, it may be suggested that these injections may be an acceptable alternative to NSAIDs or successfully used in combination with the latter. There have been recently the recommendations for the administration of HA preparations in OA treatment, which characterize the current practice of HA use for OA and had been prepared by a group of experts from 5 European countries. The experts consider that there is today rather solid evidence to demonstrate the efficacy of HA in mild and moderately severe knee OA; moreover, its effect is clinically significant in such patients. In the authors’ view, topical HA therapy should be a compulsory component of treatment for knee OA, since the alternative possibilities of therapy for this disease are limited. Although the optimal effect of HA is observed when it is applied in the early stage of OA, this treatment may be also useful in its late stage. HA should be regarded as an adjunct method that must be applied if surgery cannot be performed in these patients.

  4. Effectiveness of combined laser photocoagulation therapy with intravitreal anti -VEGF in Retinal arterial macroaneurysms: case report

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    Fernanda Pacella

    2014-12-01

    Full Text Available Background: Retinal arterial macroaneurysms (RAM is a pathological dilatation of retinal arterial vessel. Argon laser photocoagulation has been for a long time the gold standard of many vascular diseases of the retina such as macroaneurysm. From this work emerges how the introduction of intravitreal anti-VEGF therapies have enhanced the 'effectiveness of the combination of argon laser photocoagulation in cases of persistent retinal edema, we present the case of a retinal macroaneurysm with macular hemorrhage focus and oedema in a patient with a history of systemic arterial hypertension. Methods: A 77 year-old woman patient reported sudden decline in visual acuity in the left eye; the best corrected visual acuity (BCVAwas 1/10 in left eye. Fluorescein angiography (FAG resulted in diagnosis of Macroaneurysm at the posterior pole with macular hemorrhage focus and oedema. The patient was treated with laser treatment in the left eye; after 30 days, the visual acuity was 1/50 and at optical coherence tomography (OCT the retinal profile was significantly altered. After 30 days, a single intravitreal ranibizumab injection was performed and, after 7 days, visual acuity was 1/10. After 24 months from ranibizumab-based therapy the final visual acuity was 10/10 and OCT examination revealed a normal retinal profile. Conclusion: In this case report the association of argon laser photocoagulation with intravitreal anti-VEGF injection has been proven to be effective and safe in case of persistent retinal oedema.

  5. Combination Therapy of Interferon-alpha (PDferon B® and Ribavirin for Chronic Hepatitis C

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    Seyed-Moayed Alavian

    2004-04-01

    Full Text Available Introduction: The addition of ribavirin (RIBA to the standard treatment with interferon(IFN alpha led to an improvement in sustained virologic response (SVR from less than20% with IFN monotherapy to 40-45% in combination therapy. The aim of this study isto assess the therapeutic efficacy and safety of IFN alpha (PDferon B® in combinationwith RIBA on Iranian patients with chronic hepatitis C (CHC.Methods: 48 naive patients aged 18 years or more with CHC were enrolled and treatedwith 3 mega units (MU IFN alpha-2b three times a week plus 800-1000 mg RIBA perday for 48 weeks. Follow-up after therapy was 6 months. The efficacy was evident at theend of treatment and at the end of follow-up in terms of sustained normalization of alanineaminotransferase and sustained serum HCV-RNA loss.Results: The rate of sustained biochemical and virologic response were 68.3% and78%, respectively. Virologic response was 80.9% and 86.4% at weeks 12 and 48 as well.Any patient didn’t have serious complication.Conclusion: Although we had no control group who used standard IFN, our preliminaryfinding showed acceptable and promising response rate of PDferon. On the other hand,it seems that adverse events with PDferon are as like as other standard IFNs.Fax: +98-21-8975730

  6. Management of the open abdomen using combination therapy with ABRA and ABThera systems

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    Mukhi, Alfin N.; Minor, Samuel

    2014-01-01

    Background The open abdomen is an increasingly used technique that is applied in a wide variety of clinical situations. The ABThera Open Abdomen Negative Pressure Therapy System is one of the most common and successful temporary closure systems, but it has limited ability to close the fascia in approximately 30% of patients. The abdominal reapproximation anchor system (ABRA) is a dynamic closure system that seems ideal to manage patients who may not achieve primary fascial closure with ABThera alone. We report on the use of the ABRA in conjunction with the ABThera in patients with an open abdomen. Methods We retrospectively analyzed patients with an open abdomen managed with the ABThera and ABRA between January 2007 and December 2012 at the Halifax Infirmary, QEII Health Science Centre, Halifax, Nova Scotia. Results Sixteen patients had combination therapy using the ABRA and ABThera systems for treatment of the open abdomen. After removing patients who died prior to closure, primary fascial closure was achieved in 12 of 13 patients (92%). Conclusion We observed a high rate of primary fascial closure in patients with an open abdomen managed with the ABThera system in conjuction with the ABRA. Applying mechanical traction in addition to the ABThera should be considered in patients predicted to be at high risk for failure to achieve primary fascial closure. PMID:25265104

  7. Combined Néel and Brown rotational Langevin dynamics in magnetic particle imaging, sensing, and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, Daniel B., E-mail: dbr@Dartmouth.edu [Department of Physics and Astronomy, Dartmouth College, Hanover, New Hampshire 03755 (United States); Weaver, John B. [Department of Physics and Astronomy, Dartmouth College, Hanover, New Hampshire 03755 (United States); Department of Radiology, Geisel School of Medicine, Hanover, New Hampshire 03755 (United States)

    2015-11-30

    Magnetic nanoparticles have been studied intensely because of their possible uses in biomedical applications. Biosensing using the rotational freedom of particles has been used to detect biomarkers for cancer, hyperthermia therapy has been used to treat tumors, and magnetic particle imaging is a promising new imaging modality that can spatially resolve the concentration of nanoparticles. There are two mechanisms by which the magnetization of a nanoparticle can rotate, a fact that poses a challenge for applications that rely on precisely one mechanism. The challenge is exacerbated by the high sensitivity of the dominant mechanism to applied fields. Here, we demonstrate stochastic Langevin equation simulations for the combined rotation in magnetic nanoparticles exposed to oscillating applied fields typical to these applications to both highlight the existing relevant theory and quantify which mechanism should occur in various parameter ranges.

  8. [Efficacy of emoxypine in combined therapy for elderly patients with postinfarct cardiosclerosis and heart failure].

    Science.gov (United States)

    Zaslavskaia, R M; Lilitsa, G V; Kalinina, E V

    2004-01-01

    Forty-four patients with coronary heart disease, angina pectoris, prior myocardial infarction, and NYHA Functional Class II-IV heart failure were examined. Group 1 patients received emoxypine during combined therapy (CT). Group 2 patients took CT alone (a control group). The results of the study suggest that emoxypine significantly improves the clinical symptomatology and shows marked antianginal and antiischemic effects. As compared with the control group, Group 1 shows a more significant hemodynamic improvement. Moreover, the inclusion of emoxypine into CT for elderly patients with prior myocardial infarction produces a normalizing effect on oxidative stress. By taking into account the foregoing, it should be stated that it is expedient to include emoxypine into CT for this category of patients.

  9. Trials of combined radiation and hyperthermia with various heating modalities in cancer therapy.

    Science.gov (United States)

    Egawa, S; Ishioka, K; Kawada, Y

    1984-01-01

    A microwave heating apparatus with a frequency of 2,450 MHz and an inductive radio-frequency heating apparatus were developed for hyperthermia for cancer therapy, and clinical trials of combined radiation and hyperthermia were conducted. During the same period, a capacitive type radiofrequency unit was used. The tumors included superficial tumors, cancer of the uterine cervix, recurrent tumors at the stump of the cervix, and some deep-seated tumors. Cases showing complete response were as follows: 5 out of 13 cases treated with 2,450 MHz heating for superficial tumors, 8 out of 17 cases treated with 2,450 MHz intracavitary heating, and 2 out of 15 cases treated with radiofrequency heating. A feasibility study of various heating modalities was performed.

  10. Combined mirror visual and auditory feedback therapy for upper limb phantom pain: a case report

    Directory of Open Access Journals (Sweden)

    Yan Kun

    2011-01-01

    Full Text Available Abstract Introduction Phantom limb sensation and phantom limb pain is a very common issue after amputations. In recent years there has been accumulating data implicating 'mirror visual feedback' or 'mirror therapy' as helpful in the treatment of phantom limb sensation and phantom limb pain. Case presentation We present the case of a 24-year-old Caucasian man, a left upper limb amputee, treated with mirror visual feedback combined with auditory feedback with improved pain relief. Conclusion This case may suggest that auditory feedback might enhance the effectiveness of mirror visual feedback and serve as a valuable addition to the complex multi-sensory processing of body perception in patients who are amputees.

  11. Enhanced combination therapy effect on paclitaxel-resistant carcinoma by chloroquine co-delivery via liposomes.

    Science.gov (United States)

    Gao, Menghua; Xu, Yuzhen; Qiu, Liyan

    2015-01-01

    A novel composite liposomal system co-encapsulating paclitaxel (PTX) with chloroquine phosphate (CQ) was designed for treating PTX-resistant carcinoma. It was confirmed that liposomal CQ can sensitize PTX by means of autophagy inhibition and competitively binding with multidrug-resistance transporters. Furthermore, according to the in vitro cytotoxicity and apoptosis assay, real-time observation of cellular uptake, and in vivo tissue distribution study, co-encapsulation of PTX and CQ in liposomes was validated as superior to the mixture of PTX liposome plus CQ liposome due to the simultaneous delivery and synergetic effect of the two drugs. Consequently, this composite liposome achieved significantly stronger anticancer efficacy in vivo than the PTX liposome plus CQ liposome mixture. This study helps to guide and enlighten ongoing and future clinical trials about the optimal administration modes for drug combination therapy.

  12. Impact of folate therapy on combined immunodeficiency secondary to hereditary folate malabsorption.

    Science.gov (United States)

    Kishimoto, Kenji; Kobayashi, Ryoji; Sano, Hirozumi; Suzuki, Daisuke; Maruoka, Hayato; Yasuda, Kazue; Chida, Natsuko; Yamada, Masafumi; Kobayashi, Kunihiko

    2014-07-01

    Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder. Severe folate deficiency in HFM can result in immunodeficiency. We describe a female infant with HFM who acquired severe Pneumocystis pneumonia. The objective of the present study was to elucidate her immunological phenotype and to examine the time course of immune recovery following parenteral folate therapy. The patient demonstrated a combined immunodeficiency with an impaired T cell proliferation response, pan-hypogammaglobulinemia, and an imbalanced pro-inflammatory cytokine profile. She had normal white blood cell count, normal lymphocyte subsets, and normal complement levels. Two novel mutations were identified within the SLC46A1 gene to produce a compound heterozygote. We confirmed full recovery of her immunological and neurophysiological status with parenteral folate replacement. The time course of recovery of her immunological profile varied widely, however. HFM should be recognized as a unique form of immunodeficiency.

  13. Combination of thrombolytic therapy and angioplastic stent insertion in a patient with Budd-Chiari syndrome

    Institute of Scientific and Technical Information of China (English)

    Fatemi Reza; Daryani E Naser; Ganaati Hossein; Zahmatkesh Mehrdad

    2007-01-01

    A 31-year-old female who had well-established polycythemia vera one year before, presented with the sudden onset. She had severe ascites and hepatic encephalopathy 12 d prior to admission. Real-time ultrasonography revealed a supra hepatic thrombosis extending toward the inferior vena cava (IVC).Thrombolytic therapy with systemic streptokinase (250000 IU loading + 100000 IU/h infusion) was started. At the end of 72 h infusion, the patient's general condition improved. A color Doppler ultrasonography then showed complete and partial resolution of the thrombosis in the supra hepatic vein and IVC,respectively. Despite this good response, 12 d later, the symptoms recurred. Venography detected complete obstruction of the IVC. Percutanous balloon angioplasty with stent insertion was performed successfully and the patient was discharged without any evidence of liver disease. A combination of systemic streptokinase and radiological intervention was effective in our patient.

  14. 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......, observational cohort with 11,928 HIV-1-infected patients. METHODS: Response to cART was analysed in patients with subtypes determined pre-cART, via multivariable logistic regression on the first measurements 6–12 months after starting cART. A virological response was defined as a viral load ...-B-infected patients (P=0.334). After adjustment, there was no significant difference in odds of an immunological response (OR: 1.17, 95% CI: 0.73–1.87, P=0.524). CONCLUSIONS: There was no evidence of significant differences in virological or immunological response to cART between patients infected with HIV-1 B...

  15. Initial high-dose prednisolone combination therapy using COBRA and COBRA-light in early rheumatoid arthritis.

    Science.gov (United States)

    Rasch, Linda A; van Tuyl, Lilian H D; Lems, Willem F; Boers, Maarten

    2015-01-01

    Treatment with initial high-dose prednisolone and a combination of methotrexate (MTX) and sulfasalazine (SSZ) according to the COBRA regimen (Dutch acronym for combinatietherapie bij reumatoide artritis, 'combination therapy for rheumatoid arthritis'), has repeatedly been demonstrated to be very effective in early rheumatoid arthritis (RA). COBRA combination therapy is superior to initial monotherapy of SSZ and MTX, is also associated with a good long-term outcome, is as safe as other treatment regimes, and performs as well as the combination of high-dose MTX and the tumor necrosis factor antagonist infliximab. A pilot study with an intensified version of the COBRA combination therapy showed that strict monitoring and aggressive treatment intensification based on the Disease Activity Score can result in a remission rate of 90% in patients with active early RA. Also, the first results indicate that an attenuated variation on COBRA combination therapy, called 'COBRA-light', is effective in decreasing disease activity and is generally well tolerated. Based on these results, we conclude that initial high-dose prednisolone in combination with MTX and SSZ could or should be the first choice in early active RA since it is effective and safe, and the cost price of the drugs is low.

  16. Risk factors for retinopathy associated with interferon α-2b and ribavirin combination therapy in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Chiaki Okuse; Hiroshi Yotsuyanagi; Yoshihiko Nagase; Yuhtaro Kobayashi; Kiyomi Yasuda; Kazuhiko Koike; Shiro Iino; Michihiro Suzuki; Fumio Itoh

    2006-01-01

    AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy.METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy.RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%)despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension,or pretreatment arteriosclerotic changes in the optic fundj. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P=0.004,OR=245.918, 95% CI=5.6-10786.2).CONCLUSION: Retinopathy associated with combination therapy of interferon α-2b and ribavirin tends to develop in patients with hypertension.

  17. Up-front combination therapy in pulmonary arterial hypertension: from clinical trials to 'real world' observational studies.

    Science.gov (United States)

    Grignola, Juan C

    2014-05-15

    Combination therapy in pulmonary arterial hypertension is widely used in daily clinical practice. There is a wide variation among reference centers, with respect to not only when and how combination therapy should be initiated, but also what constitutes the most effective multidrug regimen. Presently, no combination therapy has proven to be more effective than the other. However, add-on therapy, in case of unsatisfactory improvements after initiation of specific monotherapy, seems to have more evidence of effectiveness than up-front therapy at the diagnosis. Data from national pulmonary arterial hypertension registries provide valuable information on practice patterns on diagnosis and treatment in 'real world'. In the study of Bergot et al. the current use of epoprostenol in newly diagnosed patients with severe idiopathic, heritable or anorexigen-use associated pulmonary arterial hypertension enrolled in the French pulmonary hypertension registry was investigated. Up-front combination of epoprostenol and oral pulmonary arterial hypertension tended to be more beneficial compared with epoprostenol alone. New drug trials with well-defined morbidity and mortality end-points are likely to help not only identify novel agents that may help in the treatment of pulmonary arterial hypertension but also determine the most useful combination strategies to maximize efficacy of existing drugs.

  18. Effectiveness of combined salmon calcitonin and aspirin therapy for osteoporosis in ovariectomized rats.

    Science.gov (United States)

    Wei, Jinsong; Wang, Jian; Gong, Yan; Zeng, Rong

    2015-08-01

    The objective of the present study was to assess the effectiveness of combined salmon calcitonin (sCT) and aspirin [acetylsalicylic acid (ASA)] treatment in an ovariectomized (OVX) rat model of postmenopausal osteoporosis. Following 12 weeks of treatment, therapeutic efficacy was assessed by evaluating changes in the biochemical and biophysical properties of bone (n=8 rats per group). Serological markers of bone metabolism were measured by ELISA; bone mineral densities (BMD) by dual energy X-ray absorptiometry; bone biomechanics of the femur and lumbar vertebrae by three-point stress test; trabecular bone morphology of lumbar vertebrae by hematoxylin and eosin staining; messenger RNA expression levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in bone marrow cells by reverse transcription-quantitative polymerase chain reaction and OPG and RANKL protein expression levels in the proximal tibia were analyzed by immunohistochemistry. Compared with treatment by sCT or ASA alone, combined treatment (sCT+ASA) increased BMD, improved femur bone strength, normalized trabecular network architecture and morphology, and increased mRNA and protein expression of OPG, while reducing the expression of RANKL. Collectively, these results demonstrated that combined treatment (sCT+ASA) of osteoporotic symptoms in OVX rats was more effective than treatment with sCT or ASA alone. Furthermore, these two drugs appeared to alter the expression of two distinct factors in the OPG/RANKL/RANK system, suggesting that their effects may be synergistic. Since sCT and ASA are currently approved for use in humans, the results of the present study suggest that the safety and efficacy of sCT+ASA combined therapy for post-menopausal osteoporosis should be assessed in clinical trials.

  19. Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shang-Wen, E-mail: sjfchiou@gmail.com [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, China Medical University, Taichung, Taiwan (China); Lin, Li-Ching [Department of Radiation Oncology, Chi-Mei Hospital, Tainan, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Kuo, Yu-Cheng [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan (China); Liang, Ji-An [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); School of Medicine, China Medical University, Taichung, Taiwan (China); Kuo, Chia-Chun [Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan (China); Chiou, Jeng-Fong [Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2014-04-01

    Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

  20. Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Rajiv, E-mail: r.kumar@neu.edu [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Belz, Jodi [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Markovic, Stacey [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Jadhav, Tej; Fowle, William [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Niedre, Mark [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Cormack, Robert; Makrigiorgos, Mike G. [Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Sridhar, Srinivas [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States)

    2015-02-01

    administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy.

  1. Comparison of the effects of auditory subliminal stimulation and rational-emotive therapy, separately and combined, on self-concept.

    Science.gov (United States)

    Möller, A T; Kotzé, H F; Sieberhagen, K J

    1993-02-01

    The present study investigated the effects on self-concept of Rational-Emotive Therapy and auditory subliminal stimulation (separately and in combination) on 141 undergraduate students with self-concept problems. They were randomly assigned to one of four groups receiving either Rational-Emotive Therapy, subliminal stimulation, both, or a placebo treatment. Rational-Emotive Therapy significantly improved scores on all the dependent measures (cognition, self-concept, self-esteem, anxiety), except for behavior. Results for the subliminal stimulation group were similar to those of the placebo treatment except for a significant self-concept improvement and a decline in self-concept related irrational cognitions. The combined treatment yielded results similar to those of Rational-Emotive Therapy, with tentative indications of continued improvement in irrational cognitions and self-concept from posttest to follow-up.

  2. Effect of growth hormone, hyperbaric oxygen and combined therapy on the gastric serosa

    Science.gov (United States)

    Adas, Gokhan; Adas, Mine; Arikan, Soykan; Sarvan, Ahu Kemik; Toklu, Akin Savas; Mert, Selva; Barut, Gul; Kamali, Sedat; Koc, Bora; Tutal, Firat

    2013-01-01

    AIM: To investigate the role of growth hormone (GH), hyperbaric oxygen therapy (HBOT) and combined therapy on the intestinal neomucosa formation of the gastric serosa. METHODS: Forty-eight male Wistar-albino rats, weighing 250-280 g, were used in this study. The rats were divided into four groups (n = 12): Group 1, control, gastric serosal patch; Group 2, gastric serosal patch + GH; Group 3, gastric serosal patch + HBOT; and Group 4, gastric serosal patch + GH + HBOT. Abdominal access was achieved through a midline incision, and after the 1-cm-long defect was created in the jejunum, a 1 cm × 1 cm patch of the gastric corpus was anastomosed to the jejunal defect. Venous blood samples were taken to determine the insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) basal levels. HBOT was performed in Groups 3 and 4. In Groups 2 and 4, human GH was given subcutaneously at a dose of 2 mg per kg/d for 28 d, beginning on the operation day. All animals were sacrificed 60 d after surgery. The jejunal segment and the gastric anastomotic area were excised for histological examination. The inflammatory process, granulation, collagen deposition and fibroblast activity at the neomucosa formation were studied and scored. Additionally, the villus density, villus height, and crypt depth were counted and recorded. The measurements of villus height and crypt depth were calculated with an ocular micrometer. New vessel growth was determined by calculatingeach new vessel in a 1 mm2 area. RESULTS: In the histological comparison of groups, no significant differences were observed between the control group and Groups 2 and 3 with respect to epithelialization, granulation, fibroblastic activity and the inflammatory process, but significant differences were present between the control group and all others groups (Groups 2-4) with respect to angiogenesis (P < 0.01) and collagen deposition (P < 0.05, P < 0.01). Significant differences between the

  3. Cholelithiasis and Nephrolithiasis in HIV-Positive Patients in the Era of Combination Antiretroviral Therapy.

    Directory of Open Access Journals (Sweden)

    Kuan-Yin Lin

    Full Text Available This study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy.We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT 1A1*28 and multidrug resistance gene 1 (MDR1 G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed.During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9% with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%, unboosted atazanavir (34.4%, ritonavir-boosted lopinavir (20.4%, and ritonavir-boosted atazanavir (5.5%. The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12-35.16 and older age (AOR, 1.04; 95% CI, 1.00-1.09. The positive association between duration of exposure to ritonavir-boosted atazanavir and incident

  4. Physical Therapy Combined with Corticosteroid Intervention for Systemic Lupus Erythematosus with Central Nervous System Involvement: A Case Report

    OpenAIRE

    Lee, In-Hee; Ryu, Young Uk

    2014-01-01

    [Purpose] Systemic lupus erythematosus (SLE) is a chronic, immune-mediated disease, affecting 0.1% of the general population. To date, few studies have investigated the efficacy of physical therapy for SLE patients with CNS involvement. The aim of this study was to report whether the combined use of corticosteroids and physical therapy, consisting of reflex inhibition and functional training, was beneficial to functional recovery. [Subjects and Methods] A 22-year-old male SLE patient with CNS...

  5. The clinical impact of immunodeficiency and viraemia in the era of combined antiretroviral therapy for HIV-1 infection

    OpenAIRE

    Zhang, S.

    2015-01-01

    Despite treatment with combined antiretroviral therapy (cART), patients may experience viraemia at different levels and for varying periods of time, and CD4 count recovery, even in patients with sustained virus suppression, frequently remains suboptimal. We studied the characteristics of episodes of low- and high-level viraemia, including during cART interruption, and evaluated their immunologic, virologic and clinical impact in patients enrolled in the AIDS Therapy Evaluation in the Netherla...

  6. Urate crystal degradation for treatment of gout: a nanoparticulate combination therapy approach.

    Science.gov (United States)

    Tiwari, Sanjay; Dwivedi, Harinath; Kymonil, Koshy M; Saraf, Shubhini A

    2015-06-01

    The objective of the present work was to develop polymeric nanoparticles of uricase and aceclofenac (NSAID) and to incorporate them into gel, for delivering drugs to synovial joints, for effective treatment of Gout. Nanoparticles containing uricase and aceclofenac were prepared by double emulsion solvent evaporation method and emulsion solvent evaporation, using PLGA (50:50) as carrier, respectively. Process parameters were optimized using Taguchi L4 orthogonal array and L9 array, respectively. The formulations were characterized for particle size, entrapment efficiency, surface charge, in vitro drug release, ex vivo drug permeation, and urate crystal degradation activity. The particle size and entrapment efficiency for optimized batch was found to be 228.8 nm and 81.26% for uricase nanoparticles and 288.5 nm and 85.36% for aceclofenac nanoparticles, respectively. The developed nanoparticles formulations displayed zero order and Higuchi release kinetics with non-Fickian diffusion, respectively. The in vivo studies were performed in rabbit model. Topical application of gel containing polymeric uricase nanoparticles alone and a combination of both, uricase nanoparticles and aceclofenac nanoparticles in rabbit model test groups, provided complete removal of urate crystals and inflammation within 40 and 25 days of treatment, respectively. The combination treatment therapy resulted in effective treatment of gout due to degradation of crystals and anti-inflammatory response.

  7. Combining mindfulness meditation with cognitive-behavior therapy for insomnia: a treatment-development study.

    Science.gov (United States)

    Ong, Jason C; Shapiro, Shauna L; Manber, Rachel

    2008-06-01

    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 assessed weekly while secondary measures of insomnia severity, arousal, mindfulness skills, and daytime functioning were assessed at pre-treatment and post-treatment. Data collected on recruitment, retention, compliance, and satisfaction indicate that the treatment protocol is feasible to deliver and is acceptable for individuals seeking treatment for insomnia. The overall patterns of change with treatment demonstrated statistically and clinically significant improvements in several nighttime symptoms of insomnia as well as statistically significant reductions in pre-sleep arousal, sleep effort, and dysfunctional sleep-related cognitions. In addition, a significant correlation was found between the number of meditation sessions and changes on a trait measure of arousal. Together, the findings indicate that mindfulness meditation can be combined with CBT-I and this integrated intervention is associated with reductions in both sleep and sleep-related arousal. Further testing of this intervention using randomized controlled trials is warranted to evaluate the efficacy of the intervention for this population and the specific effects of each component on sleep and both psychological and physiological arousal.

  8. Bevacizumab (Avastin and Thermal Laser Combination Therapy for Peripapillary Choroidal Neovascular Membranes

    Directory of Open Access Journals (Sweden)

    Sean D. Adrean

    2017-01-01

    Full Text Available Objective. This is a retrospective interventional case series describing the results of 5 eyes from 5 patients with symptomatic peripapillary choroidal neovascularization (CNVM receiving initial bevacizumab treatment followed by thermal laser and bevacizumab combination therapy. Methods. Patients received intravitreal bevacizumab injections until the lesions were well-defined. Thermal laser ablation was then administered and followed by an additional bevacizumab injection after one week. Visual outcomes, OCT changes, and rates of recurrence were recorded and analyzed. Results. Median visual outcomes improved from 20/50 to 20/30 (p=0.0232. Median central macular thickness decreased from 347 μm to 152 μm (p=0.0253. The mean visual improvement was 3 lines. An average of 3.8 bevacizumab injections per patient were given overall. Patients were followed for an average of 24 months, during which all eyes were absent for recurrence. Conclusion. Symptomatic peripapillary CNVM may be successfully managed with bevacizumab followed by a combination of thermal laser and bevacizumab without the need for frequent retreatment. The area requiring treatment may be better defined using bevacizumab, limiting the ablation of the healthy retina and improving treatment margins. With this treatment regimen, the patients experience improved visual outcomes and have a low rate of recurrence.

  9. [Efficacy of complex therapy with metformin and ramipril combination for patients with metabolic syndrome].

    Science.gov (United States)

    Kaĭdashev, I P; Savchenko, L H; Kaĭdasheva, E I; Kutsenko, N L; Kutsenko, L O; Solokhina, I L; Mamontova, T V

    2010-01-01

    We have studied efficiency of a complex therapy with metformin and ramipril combination (1000 mg and 5 mg per day) respectively in patients with metabolic syndrome (MS). The group of patients with MS which answered the basic criteria IDF (2005) was determined. Carbohydrate and Lipidic metabolism were studied. Patients were characterized with raised weight index (WI), arterial hypertension, increased concentration of triglycerides in blood serum, of glucose, of HbAlc level and S-peptide, and also high level of endotelin (1-38) and CD32+CD40+circulating particles of endothelium. Three months treatment lead to decrease in WI, arterial pressure, triglycerides concentration, HbAlc, glucose, except CD32+CD40+. Six months treatment lead to more expressed positive dynamics. Thus, metformin and ramipril combination in patients with MS leads to decrease in insulin resistancy, carbohydrate and lipid metabolism normalization, to restoration of endothelium functions that is possible to consider as prophylaxis of the development of type 2 diabetes melitus and its cardiovascular complications.

  10. Combination Trimodality Therapy Using Vismodegib for Basal Cell Carcinoma of the Face.

    Science.gov (United States)

    Block, Alec M; Alite, Fiori; Diaz, Aidnag Z; Borrowdale, Richard W; Clark, Joseph I; Choi, Mehee

    2015-01-01

    Background. For large basal cell carcinomas (BCCs) of the head and neck, definitive surgery often requires extensive resection and reconstruction that may result in prolonged recovery and limited cosmesis. Vismodegib, a small-molecule inhibitor of the hedgehog pathway, is approved for advanced and metastatic BCCs. We present a case of advanced BCC treated with combination of vismodegib, radiotherapy, and local excision resulting in excellent response and cosmesis. Case Presentation. A 64-year-old gentleman presented with a 5-year history of a 7 cm enlarging right cheek mass, with extensive vascularization, central ulceration, and skin, soft tissue, and buccal mucosa involvement. Biopsy revealed BCC, nodular type. Up-front surgical option involved a large resection and reconstruction. After multidisciplinary discussion, we recommended and he opted for combined modality of vismodegib, radiotherapy, and local excision. The patient tolerated vismodegib well and his right cheek lesion decreased significantly in size. He was then treated with radiotherapy followed by local excision that revealed only focal residual BCC. Currently, he is without evidence of disease and has excellent cosmesis. Conclusions. We report a case of locally advanced BCC treated with trimodality therapy with vismodegib, radiotherapy, and local excision, resulting in excellent outcome and facial cosmesis, without requiring extensive resection or reconstructive surgery.

  11. Combination Trimodality Therapy Using Vismodegib for Basal Cell Carcinoma of the Face

    Directory of Open Access Journals (Sweden)

    Alec M. Block

    2015-01-01

    Full Text Available Background. For large basal cell carcinomas (BCCs of the head and neck, definitive surgery often requires extensive resection and reconstruction that may result in prolonged recovery and limited cosmesis. Vismodegib, a small-molecule inhibitor of the hedgehog pathway, is approved for advanced and metastatic BCCs. We present a case of advanced BCC treated with combination of vismodegib, radiotherapy, and local excision resulting in excellent response and cosmesis. Case Presentation. A 64-year-old gentleman presented with a 5-year history of a 7 cm enlarging right cheek mass, with extensive vascularization, central ulceration, and skin, soft tissue, and buccal mucosa involvement. Biopsy revealed BCC, nodular type. Up-front surgical option involved a large resection and reconstruction. After multidisciplinary discussion, we recommended and he opted for combined modality of vismodegib, radiotherapy, and local excision. The patient tolerated vismodegib well and his right cheek lesion decreased significantly in size. He was then treated with radiotherapy followed by local excision that revealed only focal residual BCC. Currently, he is without evidence of disease and has excellent cosmesis. Conclusions. We report a case of locally advanced BCC treated with trimodality therapy with vismodegib, radiotherapy, and local excision, resulting in excellent outcome and facial cosmesis, without requiring extensive resection or reconstructive surgery.

  12. Combination therapy targeting both cancer stem-like cells and bulk tumor cells for improved efficacy of breast cancer treatment.

    Science.gov (United States)

    Wang, Tao; Narayanaswamy, Radhika; Ren, Huilan; Torchilin, Vladimir P

    2016-06-01

    Many types of tumors are organized in a hierarchy of heterogeneous cell populations. The cancer stem-like cells (CSCs) hypothesis suggests that tumor development and metastasis are driven by a minority population of cells, which are responsible for tumor initiation, growth and recurrences. The inability to efficiently eliminate CSCs during chemotherapy, together with CSCs being highly tumorigenic and invasive, may result in treatment failure due to cancer relapse and metastases. CSCs are emerging as a promising target for the development of translational cancer therapies. Ideal panacea for cancer would kill all malignant cells, including CSCs and bulk tumor cells. Since both chemotherapy and CSCs-specific therapy are insufficient to cure cancer, we propose combination therapy with CSCs-targeted agents and chemotherapeutics for improved breast cancer treatment. We generated in vitro mammosphere of 2 breast cancer cell lines, and demonstrated ability of mammospheres to grow and enrich cancer cells with stem-like properties, including self-renewal, multilineage differentiation and enrichment of cells expressing breast cancer stem-like cell biomarkers CD44(+)/CD24(-/low). The formation of mammospheres was significantly inhibited by salinomycin, validating its pharmacological role against the cancer stem-like cells. In contrast, paclitaxel showed a minimal effect on the proliferation and growth of breast cancer stem-like cells. While combination therapies of salinomycin with conventional chemotherapy (paclitaxel or lipodox) showed a potential to improve tumor cell killing, different subtypes of breast cancer cells showed different patterns in response to the combination therapies. While optimization of combination therapy is warranted, the design of combination therapy should consider phenotypic attributes of breast cancer types.

  13. P17.63COMBINATION THERAPY WITH TEMOZOLOMIDE, INTERFERON-BETA, AND RIBAVIRIN IN GLIOMA CELL LINES

    Science.gov (United States)

    Ochiai, Y.; Sano, E.; Yamamuro, S.; Ogino, A.; Fukushima, T.; Tsumoto, K.; Ueda, T.; Yutaka, O.; Yoshino, A.; Yoichi, K.

    2014-01-01

    INTRODUCTION: Although Temozolomide (TMZ) with radiotherapy significantly improves the survival of newly diagnosed glioblastoma although most patients develop tumor progression within 1-2 years. The Japan Clinical Oncology Group (JCOG) are ongoing a phase II randomized study to evaluate the clinical effectiveness of TMZ and Interferon-β (IFN-β) combination therapy in glioblastoma patients. Meanwhile, Ribavirin (RBV) is a standard agent of treating of chronic hepatitis C together with interferon-α. Recently, an anti-tumor effect of RBV was reported in breast cancer and chronic myelocytic leukemia. We evaluated the effect of TMZ, IFN-β, and RBV combination therapy in glioma cell lines. METHODS: Glioma cell lines used were A-172, AM-38, T98G, U-87MG, U-138MG, U-251MG, and YH-13. Glioma cell lines were cultured in an incubator for 48 hours and administered with either 1. TMZ (10 µM) + IFN-β (10 IU/ml) or 2. TMZ (10 µM) + IFN-β (10 IU/ml) + RBV (10 µM). At 72 to 96 hours post-treatment, the number of remaining glioma cells were counted to evaluate the growth-inhibitory effects of each therapy. In addition, cell cycle changes by flow cytemetry and p53 activity with western blot analysis were examined from U-87 MG cell line. RESULTS AND CONCLUSIONS: In all cell lines, the triple combination therapy enhanced the growth-inhibitory effect compared to dual combination therapy. Triple therapy led to distribution of G2/M phase of the cell cycle and accumulated p53 activety. Rivabirin enhanced antitumor effect of TMZ and IFN combination therapy in glioma cell lines.

  14. Effectiveness of cognitive behavioral therapy integrated with systematic desensitization, cognitive behavioral therapy combined with eye movement desensitization and reprocess­ing therapy, and cognitive behavioral therapy combined with virtual reality exposure therapy methods in the treatment of flight anxiety: a randomized trial

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    Triscari MT

    2015-10-01

    Full Text Available Maria Teresa Triscari,1 Palmira Faraci,2 Dario Catalisano,3 Valerio D’Angelo,1 Viviana Urso1 1Laboratory for Psychosomatic Disorders, Local Health Trust, Palermo, Italy; 2Faculty of Human and Social Sciences, University of Enna “Kore”, Enna, Italy; 3Italian Flight Safety Committee, Aeroporto di Fiumicino, Fiumicino (RM, Italy Abstract: The purpose of the research was to compare the effectiveness of the following treatment methods for fear of flying: cognitive behavioral therapy (CBT integrated with systematic desensitization, CBT combined with eye movement desensitization and reprocessing therapy, and CBT combined with virtual reality exposure therapy. Overall, our findings have proven the efficacy of all interventions in reducing fear of flying in a pre- to post-treatment comparison. All groups showed a decrease in flight anxiety, suggesting the efficiency of all three treatments in reducing self-report measures of fear of flying. In particular, our results indicated significant improvements for the treated patients using all the treatment programs, as shown not only by test scores but also by participation in the post-treatment flight. Nevertheless, outcome measures maintained a significant effect at a 1-year follow-up. In conclusion, combining CBT with both the application of eye movement desensitization and reprocessing treatment and the virtual stimuli used to expose patients with aerophobia seemed as efficient as traditional cognitive behavioral treatments integrated with systematic desensitization. Keywords: flight anxiety, fear of flying, aerophobia, cognitive behavioral therapy, EMDR, VRET 

  15. Treatment of severe active systemic lupus erythematosus by PMC therapy combined Langchuang Fuzheng Jiedu capsule: a clinical observation

    Institute of Scientific and Technical Information of China (English)

    宋欣伟

    2013-01-01

    Objective To evaluate the efficacy and safety of PMC therapy (Prednisone,Methotrexate,Chloroquine) combined Langchuang Fuzheng Jiedu Capsule (LFJC) ,thus choosing a better therapy of integrative medicine for SLE in the period of glucocorticoid use.Methods Sixty active SLE patients were randomly assigned to two groups,the control group and the treatment group.Those in the control group received PMC therapy (As for Prednisone,it was given at the daily dose of 1 mg/kg till 2weeks after the condition being stable or after 8 weeks of

  16. Test of critical steps towards a combined cell and gene therapy approach for the treatment of Duchenne muscular dystrophy

    DEFF Research Database (Denmark)

    Kajhøj, Tine Qvistgaard; Duch, Mogens R.; Pedersen, Finn Skou

    2015-01-01

    Background: Therapies for muscular dystrophies remain a major challenge in spite of advanced strategies using either cell or gene therapy. We here propose a combined approach of cell and gene therapy. As gene delivery vehicles with specific homing potential we have chosen mesoangioblasts which...... into mesoangioblasts did not interfere with the myogenic properties of mesoangioblasts in culture or in vivo. Mesoangioblasts are able to function as retroviral packaging cells in vitro. While a possible therapeutic application of this new gene delivery system will require further detailed analysis of the long...

  17. [A Case of Portal Vein Thrombosis Occurring during CapeOX and Bevacizumab Combination Therapy for Liver Metastasis].

    Science.gov (United States)

    Uno, Yasuo; Tsuboi, Kenji; Shimizu, Mitsuya; Tomosugi, Toshihide; Shoka, Michita; Hibino, Soki; Matsushita, Hidenobu; Takahashi, Takuji; Okochi, Osamu; Kawase, Yoshihisa

    2016-07-01

    A73 -year-old man underwent a sigmoidectomy for sigmoid colon cancer with liver metastasis. After the operation, he received CapeOX combined with bevacizumab therapy. After 6 courses, the liver metastasis was undetectable on computed tomography scans. After 15 courses, computed tomography revealed ascites, and chemotherapy was discontinued. Two months later, computed tomography revealed portal vein thrombosis. Owing to the chronic nature of the thrombosis, thrombolytic therapy was not initiated. However, preservation therapy using antiplatelet drugs for 1 month resolved the ascites and the thrombosis. The risk of serious thrombosis must be considered when using bevacizumab.

  18. Efficacy of combination therapy with amlodipine besylate/benazepril hydrochloride for lowering systolic blood pressure in stage 2 hypertension.

    Science.gov (United States)

    Neutel, Joel M; Smith, David H G; Weber, Michael A; Schofield, Lesley; Purkayastha, Das; Gatlin, Marjorie

    2006-01-01

    The Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study compared daily treatment with combination amlodipine besylate/benazepril hydrochloride 5/20 mg, amlodipine besylate 5 mg, and benazepril hydrochloride 20 mg in 505 patients aged 55 years of age or older with stage 2 hypertension (systolic blood pressure [BP] > or =160 and or =60 and < or =100 mm Hg). BP and pulse pressure were assessed by conventional office BP measurements and 24-hour ambulatory BP monitoring. In this analysis, combination therapy was associated with significantly greater reductions in mean 24-hour BP, pulse pressure, and mean ambulatory BP during various time intervals compared with either monotherapy in the intent-to-treat population, in those with isolated and predominantly systolic hypertension, and in dippers and nondippers. Adverse event rates were low and similar in all treatment groups. This study demonstrated that combination therapy is superior to monotherapy in older patients with stage 2 systolic hypertension and is well tolerated.

  19. [Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose Cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer].

    Science.gov (United States)

    Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi

    2002-02-01

    We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m2/day) was continuously infused over 24 hours, and CDDP (3-7 mg/m2/day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer.

  20. Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi [Kochi Municipal Central Hospital, Nankoku (Japan). Cancer Research Center

    2002-02-01

    We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m{sup 2}/day) was continuously infused over 24 hours, and CDDP (3-7 mg/m{sup 2}/day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer. (author)

  1. Is Yangxue Qingnao Granule Combined with Antihypertensive Drugs, a New Integrative Medicine Therapy, More Effective Than Antihypertensive Therapy Alone in Treating Essential Hypertension?

    Directory of Open Access Journals (Sweden)

    Jie Wang

    2013-01-01

    Full Text Available Background. Yangxue Qingnao granule (YQG combined with antihypertensive drugs, a new integrative medicine therapy, has been widely used for essential hypertension (EH in China. This study aims to assess the current clinical evidence of YQG combined with antihypertensive drugs for EH. Methods. Randomized controlled trials(RCTs published between 1996 and 2012 on YQG combined with antihypertensive drugs versus antihypertensive drugs in treating EH were retrieved from six major electronic databases, including The Cochrane Library, PubMed, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, and Wanfang Data. Meta-analysis was performed on the overall effects on blood pressure. Results. Twelve randomized trials were included. Methodological quality of the trials was evaluated as generally low. Meta-analysis showed that YQG combined with antihypertensive drugs demonstrated potential effect for lowing either SBP (MD: −7.31 [−11.75, −2.87]; P=0.001 or DBP (MD: −5.21 [−8.19, −2.24]; P=0.0006 compared to antihypertensive drugs alone. Conclusions. It indicated that YQG combined with antihypertensive drugs is more effective than antihypertensive drugs alone in treating EH. However, more RCTs of larger scale, multicentre/country, longer follow-up periods, and higher quality are required to verify the efficacy of integrative medicine therapy over all antihypertensive therapies.

  2. Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer.

    Science.gov (United States)

    Dhillon, Sohita

    2013-08-01

    Bevacizumab (Avastin®) is a recombinant, humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody that neutralizes the biological activity of VEGF and inhibits tumor angiogenesis. In the EU, in adult patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, bevacizumab (in combination with carboplatin and paclitaxel) is approved for the first-line treatment of advanced disease and (in combination with carboplatin and gemcitabine) is approved for the treatment of patients with first recurrence of platinum-sensitive disease who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. This article summarizes the pharmacology of bevacizumab and reviews the efficacy and tolerability of bevacizumab combination therapy in well-designed clinical studies in these indications. The addition of bevacizumab to first-line carboplatin plus paclitaxel, followed by bevacizumab maintenance therapy significantly prolonged progression-free survival in women with newly-diagnosed advanced disease (GOG-0218 and ICON7 studies). Progression-free survival was also significantly prolonged after second-line treatment with bevacizumab in combination with carboplatin and gemcitabine, followed by maintenance treatment with bevacizumab alone in women with recurrence (≥ 6 months after front-line platinum-based therapy) of platinum-sensitive disease (OCEANS study). Bevacizumab combination therapy had a generally acceptable tolerability profile in these studies, with the nature of adverse events generally similar to that observed in previous clinical trials in patients with other solid tumors. Although several unanswered questions remain, such as the optimal dosage and duration of treatment, current evidence suggests that bevacizumab combination therapy extends the treatment options available for patients with ovarian cancer.

  3. Combination therapy for rheumatoid arthritis with rituximab and leflunomide(preliminary results of the Russian ARBITR Registry

    Directory of Open Access Journals (Sweden)

    Evgeniy L'vovich Nasonov

    2011-01-01

    Full Text Available The paper analyzes the efficiency and tolerability of a combination of rituximab (RTM and leflunomide (LEF for the treatment of rheumatoid arthritis (RA versus the conventional combination of RTM and methotrexate (MT. The results of 24-week therapy were assessed in the RA patients included into the Russian Biological Therapy Register. A good effect of therapy was achieved in 31.8% of the patients who had received RTM+LEF (p = 0.1. The development of clinical remissions in RA was observed at a practically equal frequency of 13.6 and 11.7%, respectively. The doses of glucocorticoids and nonsteroidal anti-inflammatory drugs used in concurrent anti-inflammatory therapy could be substantially reduced in both groups. In both groups, the rate of side effects was very equal: 21.7% for the RTM+LEF group and 25.7% for the RTM+MT group. Thus, the combination therapy of RTM and LEF in real clinical practice is not considerably different from the most commonly used combination of RMT and MT in efficiency and tolerability and may be successfully used if there are any contraindications to the use of MT.

  4. Combination therapy of established cancer using a histone deacetylase inhibitor and a TRAIL receptor agonist.

    Science.gov (United States)

    Frew, Ailsa J; Lindemann, Ralph K; Martin, Ben P; Clarke, Christopher J P; Sharkey, Janelle; Anthony, Desiree A; Banks, Kellie-Marie; Haynes, Nicole M; Gangatirkar, Pradnya; Stanley, Kym; Bolden, Jessica E; Takeda, Kazuyoshi; Yagita, Hideo; Secrist, J Paul; Smyth, Mark J; Johnstone, Ricky W

    2008-08-12

    Histone deacetylase inhibitors (HDACi) and agents such as recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic anti-TRAIL receptor (TRAIL-R) antibodies are anticancer agents that have shown promise in preclinical settings and in early phase clinical trials as monotherapies. Although HDACi and activators of the TRAIL pathway have different molecular targets and mechanisms of action, they share the ability to induce tumor cell-selective apoptosis. The ability of HDACi to induce expression of TRAIL-R death receptors 4 and 5 (DR4/DR5), and induce tumor cell death via the intrinsic apoptotic pathway provides a molecular rationale to combine these agents with activators of the TRAIL pathway that activate the alternative (death receptor) apoptotic pathway. Herein, we demonstrate that the HDACi vorinostat synergizes with the mouse DR5-specific monoclonal antibody MD5-1 to induce rapid and robust tumor cell apoptosis in vitro and in vivo. Importantly, using a preclinical mouse breast cancer model, we show that the combination of vorinostat and MD5-1 is safe and induces regression of established tumors, whereas single agent treatment had little or no effect. Functional analyses revealed that rather than mediating enhanced tumor cell apoptosis via the simultaneous activation of the intrinsic and extrinsic apoptotic pathways, vorinostat augmented MD5-1-induced apoptosis concomitant with down-regulation of the intracellular apoptosis inhibitor cellular-FLIP (c-FLIP). These data demonstrate that combination therapies involving HDACi and activators of the TRAIL pathway can be efficacious for the treatment of cancer in experimental mouse models.

  5. Effectiveness of Combined Therapy with Pirfenidone and Erythromycin for Unclassifiable Interstitial Pneumonia Induced by HTLV-1-associated Bronchioloalveolar Disorder (HABA)

    Science.gov (United States)

    Yokohori, Naoko; Sato, Akitoshi; Hasegawa, Mizue; Katsura, Hideki; Hiroshima, Kenzo; Takemura, Tamiko

    2017-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus involved in the pathogenesis of adult T-cell leukemia (ATL) and HTVL-1-associated bronchioloalveolar disorder (HABA). The clinical and pathological findings of HABA have been characterized as either a diffuse panbronchiolitis (DPB) pattern or idiopathic interstitial pneumonia (IIP) pattern. Treatments for HABA include corticosteroids for the IIP pattern and erythromycin for the DPB pattern. We herein report a case of HABA-associated unclassifiable interstitial pneumonia that improved with combined therapy with pirfenidone and erythromycin. This is the first report on the effectiveness of combined therapy with pirfenidone and erythromycin for HABA. PMID:28050003

  6. In vitro and in vivo antimicrobial activity of combined therapy of silver nanoparticles and visible blue light against Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Nour El Din S

    2016-04-01

    Full Text Available Suzanne Nour El Din,1 Tarek A El-Tayeb,2 Khaled Abou-Aisha,1 Mohamed El-Azizi1 1Department of Microbiology, Immunology and Biotechnology, Faculty of Pharmacy and Biotechnology, German University in Cairo, 2National Institute for Laser Enhanced Sciences, Cairo University, Cairo, Egypt Abstract: Silver nanoparticles (AgNPs have been used as potential antimicrobial agents against resistant pathogens. We investigated the possible therapeutic use of AgNPs in combination with visible blue light against a multidrug resistant clinical isolate of Pseudomonas aeruginosa in vitro and in vivo. The antibacterial activity of AgNPs against P. aeruginosa (1×105 colony forming unit/mL was investigated at its minimal inhibitory concentration (MIC and sub-MIC, alone and in combination with blue light at 460 nm and 250 mW for 2 hours. The effect of this combined therapy on the treated bacteria was then visualized using transmission electron microscope. The therapy was also assessed in the prevention of biofilm formation by P. aeruginosa on AgNP-impregnated gelatin biopolymer discs. Further, in vivo investigations were performed to evaluate the efficacy of the combined therapy to prevent burn-wound colonization and sepsis in mice and, finally, to treat a real infected horse with antibiotic-unresponsive chronic wound. The antimicrobial activity of AgNPs and visible blue light was significantly enhanced (P<0.001 when both agents were combined compared to each agent alone when AgNPs were tested at MIC, 1/2, or 1/4 MIC. Transmission electron microscope showed significant damage to the cells that were treated with the combined therapy compared to other cells that received either the AgNPs or blue light. In addition, the combined treatment significantly (P<0.001 inhibited biofilm formation by P. aeruginosa on gelatin discs compared to each agent individually. Finally, the combined therapy effectively treated a horse suffering from a chronic wound caused by mixed

  7. Protective effect of creatine phosphate sodium, vitamin C combined with antiviral therapy on myocardial damage in children with viral myocarditis

    Institute of Scientific and Technical Information of China (English)

    Cai-Hong Li

    2016-01-01

    Objective:To analyze the protective effect of creatine phosphate sodium, vitamin C combined with antiviral therapy on myocardial damage in children with viral myocarditis.Methods: A total of 141 cases of children with viral myocarditis were divided into conventional treatment group (conventional antiviral therapy) and combined treatment group (creatine phosphate sodium, vitamin C combined with antiviral therapy) according to different treatment methods, and then the differences in myocardial damage markers, echocardiography parameters, inflammatory factors and oxidation/anti-oxidation indexes were compared between two groups of children after 1 course of treatment.Results: Serum myocardial damage markers IMA, CK-MB, LDH, HBDH, cTNⅠ and MYO levels as well as echocardiography parameters LAD, LVDD, RVDD, IVSD and RVOT values of combined treatment group after treatment were lower than those of conventional treatment group; serum inflammatory factors IL-10, IL-17, IL-23 and IFN-γ levels were lower than those of conventional treatment group; serum oxidation indexes NO, •OH, LPO and MDA levels were lower than those of conventional treatment group while anti-oxidation indexes SOD and SeGSH-Px levels were higher than those of conventional treatment group.Conclusion:Creatine phosphate sodium, vitamin C combined with antiviral therapy can actively protect the cardiac function of children with viral myocarditis, which is specifically related to its effect such as anti-inflammation and anti-oxidative stress.

  8. Artemisinin-based combination therapies (ACTs): best hope for malaria treatment but inaccessible to the needy!

    Science.gov (United States)

    Mutabingwa, T K

    2005-09-01

    Artemisinin-based combination therapies (ACTs) are the best anti-malarial drugs available now. Artemisinin enhances efficacy and has the potential of lowering the rate at which resistance emerges and spreads. Under low transmission intensity, ACTs have an additional public health benefit of reducing the overall malaria transmission and studies are urgently needed to investigate modalities of attaining similar benefits under high transmission. Despite being recommended by WHO since 2001, overall deployment of ACT has been slow. Limiting factors are high cost, limited knowledge and public awareness on the concept of combination therapy (CT) and ACT in particular, limited knowledge on safety of ACTs in pregnancy, operational issue such as inappropriate drug use, lack of suitable drug formulations, lack of post-marketing surveillance (PMS) systems, and the imbalance between demand and supply. Through concerted efforts of multilateral organizations, the local scientific community with involvement of policy-makers progress has been on several fonts leading to improved ACT uptake rates in the last 2 years. Of 43 countries that had adopted ACT by February 2005, 18 (42%) adopted the policy in 2004. Preference to co-formulated Coartem has led to a surge in its demand with consequent shortage. Alternative ways for increased production of ACTs are urgently needed otherwise most policies will remain adopted on paper. Despite limitations, opportunities are opening up for effective malaria control. Insecticides, insecticide-treated nets (ITNs) and ACTs are proven efficacious controls available that should be accessed by many. Substantial funding is now available for biomedical malaria research and for policy implementation. While the Global Fund is the financial engine behind the scaling up of ACT uptake, delays in cash flow after grant approval has led to many countries adopting ACT in 2004 but only few (nine) implementing it. Clear policies on granted funds and minimal politics

  9. Curcumin-arteether combination therapy of Plasmodium berghei-infected mice prevents recrudescence through immunomodulation.

    Directory of Open Access Journals (Sweden)

    Palakkod G Vathsala

    Full Text Available Earlier studies in this laboratory have shown the potential of artemisinin-curcumin combination therapy in experimental malaria. In a parasite recrudescence model in mice infected with Plasmodium berghei (ANKA, a single dose of alpha,beta-arteether (ART with three oral doses of curcumin prevented recrudescence, providing almost 95% protection. The parasites were completely cleared in blood with ART-alone (AE or ART+curcumin (AC treatments in the short-term, although the clearance was faster in the latter case involving increased ROS generation. But, parasites in liver and spleen were not cleared in AE or AC treatments, perhaps, serving as a reservoir for recrudescence. Parasitemia in blood reached up to 60% in AE-treated mice during the recrudescence phase, leading to death of animals. A transient increase of up to 2-3% parasitemia was observed in AC-treatment, leading to protection and reversal of splenomegaly. A striking increase in spleen mRNA levels for TLR2, IL-10 and IgG-subclass antibodies but a decrease in those for INFγ and IL-12 was observed in AC-treatment. There was a striking increase in IL-10 and IgG subclass antibody levels but a decrease in INFγ levels in sera leading to protection against recrudescence. AC-treatment failed to protect against recrudescence in TLR2(-/- and IL-10(-/- animals. IL-10 injection to AE-treated wild type mice and AC-treated TLR2(-/- mice was able to prolong survival. Blood from the recrudescence phase in AE-treatment, but not from AC-treatment, was able to reinfect and kill naïve animals. Sera from the recrudescence phase of AC-treated animals reacted with several parasite proteins compared to that from AE-treated animals. It is proposed that activation of TLR2-mediated innate immune response leading to enhanced IL-10 production and generation of anti-parasite antibodies contribute to protective immunity in AC-treated mice. These results indicate a potential for curcumin-based combination therapy to

  10. Ranibizumab in monotherapy and combined with photodynamic therapy for retinal angiomatous proliferation

    Directory of Open Access Journals (Sweden)

    Arias L

    2016-05-01

    Full Text Available Luis Arias,1–3 Francisco Gómez-Ulla,2–4 José M Ruiz-Moreno2,3,51Ophthalmology Department, Bellvitge University Hospital, C/Feixa Llarga, L’Hospitalet de Llobregat, Barcelona, 2Spanish Vitreoretinal Society (SERV, C/Xosé Chao Rego, Santiago de Compostela, 3RETICS OFTARED, Institute of Health Carlos III, C/Sinesio Delgado, Madrid, 4Gómez-Ulla Eye Institute, Santiago de Compostela, 5Department of Ophthalmology, Albacete University Hospital, Avenida de Almansa s/n, Albacete, Spain Purpose: To compare the effects of intravitreal ranibizumab in monotherapy (group A and combined with photodynamic therapy (PDT with verteporfin (group B in retinal angiomatous proliferation (RAP treatment.Methods: This was a multicentric, prospective, randomized clinical study conducted with parallel groups. The study eye in both groups received ranibizumab on days 1, 30, and 60 (loading dose; group B received PDT additionally on day 1. Early Treatment Diabetic Retinopathy Study (ETDRS visual acuity (VA testing and optical coherence tomography were performed monthly, and fluorescein angiography and indocyanine green angiography were performed quarterly. Retreatment criteria were leakage in fluorescein angiography or indocyanine green angiography, mean foveal thickness increase ≥100 µm, or VA decrease ≥5 letters.Results: Twenty patients were recruited (ten patients in each group. Six eyes had previous treatment (three eyes in group A and three eyes in group B, so only 14 eyes were naïve. At 12-month follow-up, mean VA improved +1.5 letters in group A and +5.6 letters in group B (analysis of variance test; P>0.05. Two patients (20% in both groups gained ≥15 letters (chi-square test; P>0.05. Mean changes in greatest linear dimension and in foveal thickness were not statistically significant between groups of treatment (analysis of variance test; P>0.05. Mean retreatments per patient were 1.8 (group A and 0.9 (group B (Mann–Whitney U-test; P>0.05. One

  11. Propofol-Remifentanil Combination for Management of Electroconvulsive Therapy in a Patient with Neuroleptic Malignant Syndrome

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    Modabber Arasteh

    2012-01-01

    Full Text Available Electroconvulsive therapy can be effective in severe or treatment resistant neuroleptic malignant syndrome patients. Anesthesia and use of muscle relaxant agents for electroconvulsive therapy in such patients may encounter anesthesiologists with specific challenges. This case report describes successful management of anesthesia in 28-year-old male patient undergoing eight electroconvulsive therapy sessions for treatment of neuroleptic malignant syndrome.

  12. A retrospective claims analysis of combination therapy in the treatment of adult attention-deficit/hyperactivity disorder (ADHD

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    Pohl Gerhardt M

    2009-06-01

    Full Text Available Abstract Background Combination therapy in managing psychiatric disorders is not uncommon. While combination therapy has been documented for depression and schizophrenia, little is known about combination therapy practices in managing attention-deficit/hyperactivity disorder (ADHD. This study seeks to quantify the combination use of ADHD medications and to understand predictors of combination therapy. Methods Prescription dispensing events were drawn from a U.S. national claims database including over 80 managed-care plans. Patients studied were age 18 or over with at least 1 medical claim with a diagnosis of ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 314.0, a pharmacy claim for ADHD medication during the study period July2003 to June2004, and continuous enrollment 6 months prior to and throughout the study period. Dispensing events were grouped into 6 categories: atomoxetine (ATX, long-acting stimulants (LAS, intermediate-acting stimulants (IAS, short-acting stimulants (SAS, bupropion (BUP, and Alpha-2 Adrenergic Agonists (A2A. Events were assigned to calendar months, and months with combined use from multiple categories within patient were identified. Predictors of combination therapy for LAS and for ATX were modeled for patients covered by commercial plans using logistic regression in a generalized estimating equations framework to adjust for within-patient correlation between months of observation. Factors included age, gender, presence of the hyperactive component of ADHD, prior diagnoses for psychiatric disorders, claims history of recent psychiatric visit, insurance plan type, and geographic region. Results There were 18,609 patients identified representing a total of 11,886 months of therapy with ATX; 40,949 months with LAS; 13,622 months with IAS; 38,141 months with SAS; 22,087 months with BUP; and 1,916 months with A2A. Combination therapy was present in 19.7% of continuing

  13. Multiple Channel Exposure Therapy: Combining Cognitive-Behavioral Therapies for the Treatment of Posttraumatic Stress Disorder with Panic Attacks

    Science.gov (United States)

    Falsetti, Sherry A.; Resnick, Heidi S.; Davis, Joanne

    2005-01-01

    A large proportion of patients who present for treatment of posttraumatic stress disorder (PTSD) experience comorbid panic attacks, yet it is unclear to what extent currently available PTSD treatment programs address this problem. Here we describe a newly developed treatment, multiple-channel exposure therapy (M-CET), for comorbid PTSD and panic…

  14. THE ROLE OF S-AMLODIPINE IN ARTERIAL HYPERTENSION THERAPY WITH COMBINATION OF CALCIUM CHANNEL BLOCKERS AND BETA-BLOCKERS

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    M. A. Maksimova

    2013-01-01

    Full Text Available Aim. To study efficacy and safety of calcium channel blocker, S-amlodipine, in combination with β-blocker, atenolol, in patients with arterial hypertension (HT 1-2 degree com- pared to fixed combination of racemic amlodipine and atenolol.Material and methods. Patients (n=31, 7 men and 24 women with HT 1–2 degree were included into the study. The patients were randomized into two groups by the com- binations sequence. Treatment with each combination lasted 4 weeks. Office blood pressure (BP was assessed at baseline and at the end of the treatment periods, possible side effects were registered.Results. All patients completed the study. Both combination of S-amlodipine+atenolol and fixed combination of racemic amlodipine+atenolol reduced systolic (in average, -15.9 and -12.7 mm Hg, respectively and diastolic (in average, -7.3 and -5.3 mmHg, respectively BP significantly. Heart rate also decreased during therapy (in average, -3 and -4 bt/min, respectively. The differences between combinations BP and heart rate effects were not significant. 8 and 16 adverse events were registered during S-amlodipine+atenolol and racemic amlodipine+atenolol therapies, respectively Conclusion. Combination of S-amlodipine+atenolol, as well as combination of racemic amlodipine+atenolol are effective in the treatment of patients with HT 1-2 degree, however combination with S-amlodipine has less number of adverse events.

  15. Potentiated anti-inflammatory effect of combined 780 nm and 660 nm low level laser therapy on the experimental laryngitis.

    Science.gov (United States)

    Marinho, Renata R; Matos, Renata M; Santos, Jandson S; Ribeiro, Maria A G; Smaniotto, Salete; Barreto, Emiliano O; Ribeiro, Ronaldo A; Lima, Roberto C P; Albuquerque, Ricardo L C; Thomazzi, Sara M

    2013-04-01

    Reflux laryngitis is a common clinic complication of nasogastric intubation (NSGI). Since there is no report concerning the effects of low level laser therapy (LLLT) on reflux laryngitis, this study aimed to analyze the protective effect of single and combined therapies with low level laser at the doses of 2.1J and 2.1+1.2 J with a total irradiation time of 30s and 30+30 s, respectively, on a model of neurogenic reflux laryngitis. NSGI was performed in Wistar rats, assigned into groups: NGI (no treatment), NLT17.5 (single therapy), and NLT17.5/10.0 (combined therapy, applied sequentially). Additional non-intubated and non-irradiated rats were use as controls (CTR). Myeloperoxidase (MPO) activity was assessed by colorimetric method after the intubation period (on days 1, 3, 5, and 7), whereas paraffin-embedded laryngeal specimens were used to carry out histopathological analysis of the inflammatory response, granulation tissue, and collagen deposition 7 days after NSGI. Significant reduction in MPO activity (p0.05). NLT17.5/10.0 group also showed better collagenization pattern, in comparison to NGI and NLT17.5 groups. This study suggests that the combined therapy successfully modulated the inflammatory response and collagenization in experimental model of NSGI-induced neurogenic laryngitis.

  16. INFLUENCE OF COMBINED ANTIHYPERTENSIVE AND ANTIDEPRESSANT THERAPY ON LEFT VENTRICULAR REMODELING IN PATIENTS WITH ARTERIAL HYPERTENSION, ANXIETY AND DEPRESSION

    Directory of Open Access Journals (Sweden)

    Y. A. Vasyuk

    2008-01-01

    Full Text Available Aim. To assess influence of combined antihypertensive (