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Sample records for current therapeutic regimens

  1. Currently used dosage regimens of vancomycin fail to achieve therapeutic levels in approximately 40% of intensive care unit patients

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    Obara, Vitor Yuzo; Zacas, Carolina Petrus; Carrilho, Claudia Maria Dantas de Maio; Delfino, Vinicius Daher Alvares

    2016-01-01

    Objective This study aimed to assess whether currently used dosages of vancomycin for treatment of serious gram-positive bacterial infections in intensive care unit patients provided initial therapeutic vancomycin trough levels and to examine possible factors associated with the presence of adequate initial vancomycin trough levels in these patients. Methods A prospective descriptive study with convenience sampling was performed. Nursing note and medical record data were collected from September 2013 to July 2014 for patients who met inclusion criteria. Eighty-three patients were included. Initial vancomycin trough levels were obtained immediately before vancomycin fourth dose. Acute kidney injury was defined as an increase of at least 0.3mg/dL in serum creatinine within 48 hours. Results Considering vancomycin trough levels recommended for serious gram-positive infection treatment (15 - 20µg/mL), patients were categorized as presenting with low, adequate, and high vancomycin trough levels (35 [42.2%], 18 [21.7%], and 30 [36.1%] patients, respectively). Acute kidney injury patients had significantly greater vancomycin trough levels (p = 0.0055, with significance for a trend, p = 0.0023). Conclusion Surprisingly, more than 40% of the patients did not reach an effective initial vancomycin trough level. Studies on pharmacokinetic and dosage regimens of vancomycin in intensive care unit patients are necessary to circumvent this high proportion of failures to obtain adequate initial vancomycin trough levels. Vancomycin use without trough serum level monitoring in critically ill patients should be discouraged. PMID:28099635

  2. Establishment of TCM Standardized Therapeutic Regimen for Treating Tumor

    Institute of Scientific and Technical Information of China (English)

    林洪生

    2004-01-01

    @@ It has been of a long long history to treat tumor with traditional Chinese medicine (TCM), in the last 50years, Chinese medicine (CM) has been accepted by more and more medical professionals and patients, and used as one of the principal methods for treating tumor in China. But, tumor is a kind of disease with rapid progress and complicated causes, and applying CM in treating tumor has to meet some requirement, as improper application could induce contrary effects. To reduce the chance of blind and improper application of CM in the treatment of tumor, it is vital to work out a standardized therapeutic regimen that can be used as the guideline.

  3. Therapeutic Response In Mycetoma â€" A Study Of Different Regimens

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    Kaliswaran A V

    2003-01-01

    Full Text Available Treatment of mycetoma is always considered a challenge to the dermatologists. Hence this study was undertaken to determine the efficacy of various therapeutic regimens in actinomycotic and eumycotic mycetoma. A total of 25 patients including 18 cases of actinomycotic mycetoma and 7 cases of eumycotic mycetoma was included. Combinations of trimethoprim-sulfamethoxazole (TS with rifampicin (regimen-3, and TS monotherapy (regimen-4 were used in 9,2,1 and 6 patients with actinomycotic mycetoma respectively. Ketoconazole (regimen-A and itraconazole (regimen-B were used in patients with eumycotic mycetoma along with surgical excision (in amenable cases. Remission was observed in 10 cases of actinomycotic mycetoma (eight with Welsh regimen and one case of eumycetoma who was subjected to surgical excision followed by oral ketoconazole. Improvement was seen in 2 cases of actinomycetoma treated one each with Welsh regimen and regimen4: in 2 cases of eumycetoma treated with ketoconazole in one and itraconazole in the other. No significant adverse effect was noted in the study except ototoxicity and reaction to streptomycin in one patient. In general, therapeutic outcome was excellent in patients with actinomycotic mycetoma particularly with Welsh regimen, whereas the response to medical therapy in eumycetoma is not satisfactory. Complete surgical excision followed by antifungal therapy at an early stage for eumycotic mycetoma is perhaps the best possible therapeutic modality in the present scenario.

  4. Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

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    Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    PURPOSE: The present work reports rationalized development and characterization of solidified self-nanoemulsifying drug delivery system for oral delivery of combinatorial (tamoxifen and quercetin) therapeutic regimen. METHODS: Suitable oil for the preparation of liquid SNEDDS was selected based o...

  5. Levothyroxine treatment in pregnancy: indications, efficacy, and therapeutic regimen.

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    Klubo-Gwiezdzinska, Joanna; Burman, Kenneth D; Van Nostrand, Douglas; Wartofsky, Leonard

    2011-01-01

    The prevalence of overt and subclinical hypothyroidism during pregnancy is estimated to be 0.3-0.5% and 2-3%, respectively. Thyroid autoantibodies are found in 5-18% of women in the childbearing age. The aim of this review is to underscore the clinical significance of these findings on the health of both the mother and her offspring. Methods of evaluation of thyroid function tests (TFTs) during pregnancy are described as are the threshold values for the diagnosis of overt and subclinical hypothyroidism or hypothyroxinemia. Anticipated differences in TFTs in iodine-sufficient and iodine-deficient areas are discussed and data are provided on potential complications of hypothyroidism/hypothyroxinemia and autoimmune thyroid disease during pregnancy and adverse effects for the offspring. The beneficial effects of levothyroxine therapy on pregnancy outcomes and offspring development are discussed with a proposed treatment regimen and follow up strategy.

  6. Levothyroxine Treatment in Pregnancy: Indications, Efficacy, and Therapeutic Regimen

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    Joanna Klubo-Gwiezdzinska

    2011-01-01

    Full Text Available The prevalence of overt and subclinical hypothyroidism during pregnancy is estimated to be 0.3–0.5% and 2–3%, respectively. Thyroid autoantibodies are found in 5–18% of women in the childbearing age. The aim of this review is to underscore the clinical significance of these findings on the health of both the mother and her offspring. Methods of evaluation of thyroid function tests (TFTs during pregnancy are described as are the threshold values for the diagnosis of overt and subclinical hypothyroidism or hypothyroxinemia. Anticipated differences in TFTs in iodine-sufficient and iodine-deficient areas are discussed and data are provided on potential complications of hypothyroidism/hypothyroxinemia and autoimmune thyroid disease during pregnancy and adverse effects for the offspring. The beneficial effects of levothyroxine therapy on pregnancy outcomes and offspring development are discussed with a proposed treatment regimen and follow up strategy.

  7. Renal cell carcinoma: review of novel single-agent therapeutics and combination regimens.

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    Amato, R J

    2005-01-01

    A search of the Medline database and ASCO 2003 conference proceedings was conducted to identify clinical trials currently underway using single-agent therapy for renal cell carcinoma (RCC). Combination trials were identified using the ASCO 2003 conference proceedings. Fourteen single-agent therapies employing different mechanisms of action were identified in the published literature: imatinib mesylate (Gleevec); bevacizumab (Avastin); thalidomide (Thalomid); gefitinib (ZD1839) (Iressa); cetuximab (IMC-C225) (Erbitux); bortezomib (PS-341) (Velcade); HSPPC-96 (Oncophage); BAY 59-8862; ABT-510; G250; CCI-779; SU5416; PTK/ZK; and ABX-EGF. Six distinct fields of clinical research have emerged: monoclonal antibodies, small molecules, vaccines, second-generation taxanes, nonapeptides and immunomodulators. Five combination regimens, primarily biological response modifiers (interleukin-2 or interferon-alpha), chemotherapy- or thalidomide-based, were identified. All therapies demonstrated acceptable toxicity profiles. Clinical benefit was assessed based on each study's reported criteria: antitumor response (regression or stability) ranged from 5% to 71%. In the past several years, significant advances in the underlying biological mechanisms of RCC, particularly the role of tumor angiogenesis, have permitted the design of molecularly targeted therapeutics. Based on preliminary and limited studies, combination therapies offer the greatest clinical benefit in the management of this malignancy, although additional basic research is still warranted.

  8. A preliminary evaluation of comparative effectiveness of riluzole in therapeutic regimen for irritable bowel syndrome

    Institute of Scientific and Technical Information of China (English)

    Surya Prakash Mishra; Sunit Kumar Shukla; Bajrang Lal Pandey

    2014-01-01

    Objective: To develop agents that are specifically effective in controlling the key disturbance of visceral hyperalgesia besides abating of associated multiple symptoms, and evaluate comparative effectiveness for IBS symptom relief for standard regimen (antispasmodic and probiotic) and add-on amitriptyine or riluzole regimens following two weeks administration.Methods:groups were studied. First group received standard treatment (mebeverine 200 mg twice daily and probiotic 200 mg twice daily). Second group received add-on amitriptyline 25 mg before bedtime, while the third group got add-on riluzole 50 mg twice daily. Overall gastrointestinal symptom rating scale improving symptoms and hospital anxiety depression scale improving associated psychological morbidity were employed as measures at induction and at two-week follow-up period. Individual symptom scores were also examined to define the outcome profiles.Results:108 patients with visceral hypersensitivity accompanying IBS, divided into three rating scale score, not the other two regimens. Pain relief was seen with both riluzole and amitriptyline regimens significantly superior to standard treatment regimen, but riluzole effect appeared specific and independent anxiolytic effect. Amitriptyline caused relief in diarrhea and did not benefit in constipation point to non-specific remedial role in IBS. Riluzole regimen resulted in significant reduction of overall gastrointestinal symptom Conclusions: Riluzole specifically relieves visceral hypersensitivity and is proved to be superior to current treatments in IBS patients. It appears a lead remedy based on glutamate transporter mechanisms in visceral hypersensititvity.

  9. Research progress in CYP2C9 and VKORC1 gene polymorphism and individualized warfarin therapeutic regimen

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    Yue-ping LIU

    2015-04-01

    Full Text Available Warfarin is still the most clinically used oral anti-coagulant despite of its narrow therapeutic index and high risk of hemorrhage. The mean daily dose of warfarin varies widely from patient to patient, and to achieve the same therapeutic effect, the daily dose of warfarin could be varied over 20-fold. The variability in warfarin dosage depends on several factors, including gene polymorphisms, index of body mass, age and other drugs, and these factors compelled the clinicians to individualize warfarin dosage in order to optimize the therapeutic regimen. A number of genes are involved in metabolism of warfarin, such as cytochrome P450 2C9 (CYP2C9, vitamin K epoxide reductase complex subunit 1 (VKORC1, cytochrome P450 4F2 (CYP4F2, gamma-glutamylcarboxylase (GGCX, etc. Of them CYP2C9 and VKORC1 are the emphasis of current researches. The association between the polymorphism of CYP2C9 and VKORC1 and individualized warfarin therapeutic regimen are mainly discussed in this paper. DOI: 10.11855/j.issn.0577-7402.2015.02.16

  10. [Multidrug-resistant tuberculosis: current epidemiology, therapeutic regimens, new drugs].

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    Gómez-Ayerbe, C; Vivancos, M J; Moreno, S

    2016-09-01

    Multidrug and extensively resistant tuberculosis are especially severe forms of the disease for which no efficacious therapy exists in many cases. All the countries in the world have registered cases, although most of them are diagnosed in resource-limited countries from Asia, Africa and South America. For adequate treatment, first- and second-line antituberculosis drugs have to be judiciously used, but the development of new drugs with full activity, good tolerability and little toxicity is urgently needed. There are some drugs in development, some of which are already available through expanded-access programs.

  11. Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

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    Yi Hu

    2017-05-01

    Full Text Available Helicobacter pylori (H. pylori is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori.

  12. Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

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    Hu, Yi; Zhu, Yin; Lu, Nong-Hua

    2017-01-01

    Helicobacter pylori (H. pylori) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori. PMID:28529929

  13. BRUCELLOSIS: REVIEW OF CLINICAL AND LABORATORY FEATURES AND THERAPEUTIC REGIMENS IN 44 CHILDREN

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    S Afsharpaiman

    2008-12-01

    Full Text Available "nBrucellosis is not uncommon in children in endemic areas. We described clinical and laboratory features and therapeutic regimens for brucellosis in children under 14 who admitted in the Pediatric Medical Center Hospital, Tehran, Iran from March 1988 until February 2001. The male: female ratio was 2:1. Family history of brucellosis and consumption of un-pasteurized milk and dairy products was positive in 20.4% and 65.9%, respectively. The common clinical findings were arthritis (79.5%, fever (77.4%, anorexia (61.4%, sweating (52.3%, splenomegaly (43.2%, hepatomegaly (34.1% and lymphadenopathy (13.65. Anemia, leukopenia and thrombocytopenia were recorded in 56.8%, 31.8% and 9.1%, respectively. Out of all patients, seropositivity rate for brucellosis was found in 97.7% using serum agglutination test. Culture of blood and bone marrow specimen were positive in 30% and 50% of samples obtained, respectively. Rifampin and co-trimoxazole were the most commonly used combination in 68.1%. The overall relapse rate was 13.6%. Arthritis and fever were the most common clinical findings of brucellosis. Wright test is a very sensitive method to detect brucella infection. Public education and control measures should be applied to prevent the zoonotic and human brucellosis. 

  14. [Which therapeutic regimen for eradicating Helicobacter pylori and cicatrization of a duodenal ulcer. Is there a role for short-term treatment?].

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    Chassany, Olivier; Duracinsky, Martin

    2002-08-24

    CURRENT REGIMENS: The regimen recommended for the eradication of Helicobacter pylori and cicatrization of a duodenal ulcer is the association, for 7 days, of a double-dose of gastric anti-secretory drug and 2 antibiotics, followed by a usual dose of an anti-secretory for a further 3 weeks. During randomized studies, this therapeutic regimen led to an eradication rate of 80 to 90%. However, in current practice in France, the eradication rate is of only 60 to 75%. THE QUESTIONS RAISED: Phenomena of resistance to antibiotics are not the only cause. Lack of compliance is frequent, partly generated by poor tolerance to the antibiotherapy. Many recently published studies have provided elements of response to several questions concerning the eradication of Helicobacter pylori: can one reduce the duration of treatment by associating a triple antibiotherapy or, to the contrary, should one prolong treatment to be sure that patients fully comply to the 7 days of treatment? Should the dose of anti-secretory drug be doubled? And, with regard to cicatrizing the duodenal ulcer: can one reduce the duration of the anti-secretory agent? WITH THE RESULTS OF RECENTLY PUBLISHED CLINICAL TRIALS: It is legitimate today to prescribe double antibiotherapy for 10 to 14 days, associated with a double dose of an anti-secretory, without having to prolong the anti-secretory after this initial period, in order to cicatrize the duodenal ulcer. Further studies will specify the optimal duration between 10 and 14 days. However, till now, this therapeutic regimen for eradicating Helicobacter pylori and cicatrizing a duodenal ulcer has not obtained marketing authorization and is not appropriate for treating gastric ulcers and for complicated (notably hemorrhagic) gastroduodenal lesions.

  15. Current therapeutic concepts in peripartum cardiomyopathy.

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    Krejci, Jan; Poloczkova, Hana; Nemec, Petr

    2015-01-01

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

  16. Antisense therapeutics in oncology: current status

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    Farooqi AA

    2014-11-01

    Full Text Available Ammad Ahmad Farooqi,1 Zia ur Rehman,2 Jordi Muntane3,4 1Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan; 2Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST, Kohat, Pakistan; 3Department of General Surgery, Institute of Biomedicine of Seville (IBiS, Hospital Universitary "Virgen del Rocío"/CSIC/University of Seville, Sevilla, Spain; 4Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD o Ciberehd, Instituto de Salud Carlos III, Spain Abstract: There is increasing progress in translational oncology and tremendous breakthroughs have been made as evidenced by preclinical and clinical trials. Data obtained from high-throughput technologies are deepening our understanding about the molecular and gene network in cancer cells and rapidly emerging in vitro and in vivo evidence is highlighting the role of antisense agents as specific inhibitors of the expression of target genes, thus modulating the response of cancer cells to different therapeutic strategies. Much information is continuously being added into various facets of molecular oncology and it is now understood that overexpression of antiapoptotic proteins, oncogenes, oncogenic microRNAs (miRNA, and fusion proteins make cancer cells difficult to target. Delivery of antisense oligonucleotides has remained a challenge and technological developments have helped in overcoming hurdles by improving the ability to penetrate cells, effective and targeted binding to gene sequences, and downregulation of target gene function. Different delivery systems, including stable nucleic acid lipid particles, have shown potential in enhancing the delivery of cargo to the target site. In this review, we attempt to summarize the current progress in the development of antisense therapeutics and their potential in medical research. We partition this multicomponent

  17. Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

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    2014-01-01

    Background To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits. PMID:24920963

  18. Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens

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    Vittorino Gaddi, A; Capello, F; Di Pietro, C; Cinconze, E; Rossi, E; De Sando, V; Cevenini, M; D'Alò, G

    2014-01-01

    Objectives: To define the main features of patients treated with oral antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT) and fixed-dose combination therapy (FDCT); to describe medication adherence to the different therapies; and to evaluate the differences in compliance with the prescribed therapy regimen among prevalent and incident patient cohorts. Study design: This study was a retrospective cohort analysis based on the ARNO database, a national record that tracks reimbursable prescription claims submitted from selected pharmacies to the Italian national health system. In total, 169,375 subjects, from an overall population of 4,040,624 were included in this study. The patients represented 12 different local health units. Each patient had at least one oral antidiabetic prescription claim (A10B ATC code). Methods: Patients were divided into four groups according to their treatment regimen during the recruitment period (1 January 2008-31 December 2008): MT, FDCT, LDCT and swi...

  19. Current therapeutic procedures in Dravet syndrome.

    Science.gov (United States)

    Chiron, Catherine

    2011-04-01

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

  20. Drug susceptibility testing and pharmacokinetics question current treatment regimens in Mycobacterium simiae complex disease.

    NARCIS (Netherlands)

    Ingen, J. van; Totten, S.E.; Heifets, L.B.; Boeree, M.J.; Daley, C.L.

    2012-01-01

    The Mycobacterium simiae complex bacteria can cause opportunistic infections in humans. In the case of definite disease, there are no evidence-based treatment regimens and outcomes are very disappointing. To increase the evidence base underpinning treatment regimens for M. simiae complex disease, dr

  1. Evaluation of Tensile Strength of the Superficial Digital Flexor Tendon in Horses Subjected to Transcutaneous Electrical Neural Stimulation Therapeutic Regimen

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    Davood Sharifi

    2009-01-01

    Full Text Available We would like to sincerely express our gratitude to the university of Tehran and faculty of veterinary medicine research council for approval and financial support for this extensive evaluation of tensile strength of the superficial digital flexor tendon in horses subjected to Transcutaneous Electrical Neural Stimulation (TENS therapeutic regimen Problems statement: The purpose of this study was to determine the effect of TENS on the tensile strength of experimentally traumatized SDFT in horses. Approach: Eight adult castrated horses between 4-9 years -old and 310- 395 Kg body - weight were considered. The left fore -limb superficial digital flexor tendon of each horse was splitted longitudinally in the middle portion in full thickness of 10 cm in length using B.P. blade (15 Times strike, then the connective tissue and skin were approximated using No 2 Nylon. Horses were divided into two groups of control and treated with 4 horses each. No treatment was given to control one, whereas treated group was subjected to the transcutaneous electrical neural stimulation (Newtens 900c therapeutic regimens10 min daily with intensity of 80 µs, 100 Hz frequency for 14 days. After 60 days, the full length of SDFT (20 cm was removed from the right normal countralaleral and left traumatized tendon of control and treated limbs of all horses to be subjected to test of tensile strength using Zwick/Roell MDTL Machine with speed of 0.07 mM sec-1 having Proportional Integral Deferential (PID controller. In assessing the variation obtained data was analyzed using paired-t-test. Results: Data of the tensile strength was revealed an average 0.6625 KN for normal SDFT, 0.6375 KN for treated tendon and 0.6175 KN for control tendon .There was significant improvement in regaining tensile strength in treated tendons comparison to control ones in Conclusion: TENS significantly accelerated healing and remodeling of traumatized tendon to regain its tensile strength.

  2. Therapeutic profile of T11TS vs. T11TS+MiADMSA: a hunt for a more effective therapeutic regimen for arsenic exposure.

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    Chaudhuri, Suhnrita; Acharya, Sagar; Chatterjee, Sirshendu; Kumar, Pankaj; Singh, Manoj Kumar; Bhattacharya, Debanjan; Basu, Anjan Kumar; Dasgupta, Shyamal; Flora, S J S; Chaudhuri, Swapna

    2012-01-01

    Arsenic exposure is a serious health hazard worldwide. We have previously established that it may result in immune suppression by upregulating Th2 cytokines while downregulating Th1 cytokines and causing lymphocytic death. Treatment modalities for arsenic poisoning have mainly been restricted to the use of chelating agents in the past. Only recently have combination therapies using a chelating agent in conjunction with other compounds such as anti-oxidants, micronutrients and various plant products, been introduced. In the present study, we used T11TS, a novel immune potentiating glycopeptide alone and in combination with the sulfhydryl-containing chelator, mono-iso-amyl-dimarcaptosuccinic acid (MiADMSA) as a therapeutic regimen to combat arsenic toxicity in a mouse model. Results indicated that Th1 cytokines such as TNF-α, IFNγ, IL12 and the Th2 cytokines such as IL4, IL6, IL10 which were respectively downregulated and upregulated following arsenic induction were more efficiently restored to their near normal levels by T11TS alone in comparison with the combined regimen. Similar results were obtained with the apoptotic proteins studied, FasL, BAX, BCL2 and the caspases 3, 8 and 9, where again T11TS proved more potent than in combination with MiADMSA in preventing lymphocyte death. The results thus indicate that T11TS alone is more efficient in immune re-establishment after arsenic exposureas compared to combination therapy with T11TS+MiADMSA.

  3. STUDY OF THERAPEUTIC RESPONSE TO SECOND LINE ART REGIMEN IN TERTIARY CARE TEACHING HOSPITAL OF SOUTH INDIA

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    Padmalatha

    2016-04-01

    Full Text Available BACKGROUND The widespread use of HAART therapy resulted in marked decline in the incidence of most AIDS defining conditions and mortality, both in the developed and developing world. As the scope of ART in developing countries continues, the number of patients failing in first line therapy and switching to second line therapy will inevitably increase. The aim of the study is to assess the therapeutic response by CD4 count and plasma viral load in HIV patients who received 2nd line regimen consisting of tenofovir, lamivudine, Ritonavir and atazanavir. METHODS This was a retrospective observational study. The data was collected retrospectively from the case sheets of the 50 patients of ART Centre of King George Hospital, Visakhapatnam, a tertiary care teaching hospital in South India. Patients in the age group of 18-70 years who were started on 2nd line ART therapy after failure of 1st line therapy as per NACO guidelines were included. The data analysis was carried out using Graph pad prism version 5.0. P value <0.01 considered as statistically significant. RESULTS It was observed that mean levels of CD4 after six months of therapy were elevated compared to the initial mean values. The observed difference was statistically significant (p<0.0001. Mean levels of viral load after six months of therapy were decreased compared to the initial mean values. The observed difference was not statistically significant (p=0.17 (Table 10. CONCLUSION Patients who were initiated on second line therapy after the failure of first line regimen had high rates of immunologic and virologic success and low rates of mortality. This is evident by the increase in CD4 count and decrease in viral load in our study.

  4. Revised National Tuberculosis Control Program regimens with and without directly observed treatment, short-course: A comparative study of therapeutic cure rate and adverse reactions

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    Rengaraj Sivaraj

    2014-01-01

    Full Text Available Objective: To compare the therapeutic cure rate and adverse reactions in the regimens of the Revised National Tuberculosis Control Program (RNTCP with directly observed treatment, short-course (DOTS and without DOTS. Materials and Methods: Fifty patients in the DOTS regimen and 50 patients in the non-DOTS regimen were enrolled in the study. All the participants were asked to come regularly for 3 consecutive days for sputum collection, and the sputum samples were examined for acid-fast bacilli. If tuberculosis (TB was confirmed, the disease status was confirmed through a chest X-ray (PA view. The participants were monitored for adverse events arising from the use of anti-TB drugs for the next 6 months. Results: The TB cure rates for RNTCP with DOTS and RNTCP with non-DOTS were 80% and 66%, respectively. The DOTS therapy had a better cure rate for radiologically positive, sputum-positive cases compared with the non-DOTS regimen group. The non-DOTS treatment regimen had significantly increased numbers of adverse events in the hepatic and hematinic systems. Conclusion: The DOTS regimen has higher cure rates and a lower incidence of adverse reactions compared with the non-DOTS regimen.

  5. Spinal Muscular Atrophy: Current Therapeutic Strategies

    Science.gov (United States)

    Kiselyov, Alex S.; Gurney, Mark E.

    Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord. SMA is caused by deletion and/or mutation of the survival motor neuron gene (SMN1) on chromosome 5q13. There are variable numbers of copies of a second, related gene named SMN2 located in the proximity to SMN1. Both genes encode the same protein (Smn). Loss of SMN1 and incorrect splicing of SMN2 affect cellular levels of Smn triggering death of motor neurons. The severity of SMA is directly related to the normal number of copies of SMN2 carried by the patient. A considerable effort has been dedicated to identifying modalities including both biological and small molecule agents that increase SMN2 promoter activity to upregulate gene transcription and produce increased quantities of full-length Smn protein. This review summarizes recent progress in the area and suggests potential target product profile for an SMA therapeutic.

  6. Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax: A systematic review and meta-analysis

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    Lina Marcela Zuluaga-Idarraga

    2015-12-01

    Full Text Available Objective:To compare efficacy and safety of primaquine regimens currently used to prevent relapses by P. vivax.Methods:A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg / kg / day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated.Results:For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow-up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423 were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477. High risk of bias and differences in handling of included studies were found.Conclusion:Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax.

  7. Neurocysticercosis: Diagnostic problems & current therapeutic strategies

    Science.gov (United States)

    Rajshekhar, Vedantam

    2016-01-01

    Neurocysticercosis (NCC) is the most common single cause of seizures/epilepsy in India and several other endemic countries throughout the world. It is also the most common parasitic disease of the brain caused by the cestode Taenia solium or pork tapeworm. The diagnosis of NCC and the tapeworm carrier (taeniasis) can be relatively inaccessible and expensive for most of the patients. In spite of the introduction of several new immunological tests, neuroimaging remains the main diagnostic test for NCC. The treatment of NCC is also mired in controversy although, there is emerging evidence that albendazole (a cysticidal drug) may be beneficial for patients by reducing the number of seizures and hastening the resolution of live cysts. Currently, there are several diagnostic and management issues which remain unresolved. This review will highlight some of these issues. PMID:28139530

  8. Neurocysticercosis: Diagnostic problems & current therapeutic strategies

    Directory of Open Access Journals (Sweden)

    Vedantam Rajshekhar

    2016-01-01

    Full Text Available Neurocysticercosis (NCC is the most common single cause of seizures/epilepsy in India and several other endemic countries throughout the world. It is also the most common parasitic disease of the brain caused by the cestode Taenia solium or pork tapeworm. The diagnosis of NCC and the tapeworm carrier (taeniasis can be relatively inaccessible and expensive for most of the patients. In spite of the introduction of several new immunological tests, neuroimaging remains the main diagnostic test for NCC. The treatment of NCC is also mired in controversy although, there is emerging evidence that albendazole (a cysticidal drug may be beneficial for patients by reducing the number of seizures and hastening the resolution of live cysts. Currently, there are several diagnostic and management issues which remain unresolved. This review will highlight some of these issues.

  9. A simple dose regimen of artesunate and amodiaquine based on age or body weight range for uncomplicated falciparum malaria in children: comparison of therapeutic efficacy with standard dose regimen of artesunate and amodiaquine and artemether-lumefantrine.

    Science.gov (United States)

    Gbotosho, Grace O; Sowunmi, Akintunde; Okuboyejo, Titilope M; Happi, Christian T; Folarin, Onikepe O; Adewoye, Elsie O

    2012-07-01

    A new dose regimen of artesunate and amodiaquine (NDRAA) based on age or body weight range was compared with standard dose regimen of artesunate and amodiaquine (SDRAA) calculated according to body weight and with fixed-dose artesunate-amodiaquine (FDAA) and artemether-lumefantrine (AL) in 304 children afflicted by malaria aged 15 years or younger. In initial comparison (n = 208), children on NDRAA received 1-3 times amodiaquine per kilogram of body weight and 1-1.5 times of artesunate per kilogram of body weight compared with those receiving SDRAA. Parasite but not fever clearance was significantly faster in children who received NDRAA (19.4 ± 8.4 hours vs. 24.6 ± 15.5 hours, P = 0.003). Polymerase chain reaction-uncorrected cure rates on days 28-42 were also significantly higher in children who received NDRAA (P < 0.02 in all cases). Therapeutic responses in children younger than 5 years (n = 96) treated with NDRAA, FDAA, and AL were similar. Changes in hematocrit values and reported adverse events after commencing therapy were similar in those who received NDRAA and SDRAA. All drug regimens were well tolerated. NDRAA based on age or body weight range is simple, is therapeutically superior to SDRAA calculated according to body weight, and is as efficacious as AL in children younger than 5 years.

  10. [Analysis of the therapeutic efficacy and prognosis for acute myeloid leukemia M2a patients treated by IA and DA regimens].

    Science.gov (United States)

    Wang, Fan; Yuan, Hai-Long; Duan, Xian-Lin; Wang, Lei; Cao, Hai-Zhou; Xu, Jian-Li; Qu, Jian-Hua

    2014-08-01

    This study was purposed to compare the therapeutic efficacy and prognosis of acute myeloid leukemia M2a (AML-M2a) patients treated by idarubicin (IDA) combined with cytarabine (Ara-C) (IA) and daunorubicin (DNR) combined cytarabine (Ara-C) (DA) regimens. The clinical data of 65 patients with AML-M2a in our hospital were collected from May 2009 to May 2013 and analyzed. The results indicated the complete remission in IA group was slightly higher than that in DA group, there was no statistically significant difference(P > 0.05); leukocyte minimum value in IA group [(0.58 ± 0.40)×10(9)/L] was obviously lower than that in DA group [(0.99 ± 0.67)×10(9)/L] (P DA group [(0.21 ± 0.16)×10(9)/L] (P DA group (9.17 ± 7.04)d (P DA group (21.45 months) (P DA regimen, the IA regimen can prolong the median survival time and has better long-term therapeutic efficacy, thus it can be used as the first chemotherapy regimen for treatment of AML-M2a.

  11. Current regimen of pulse therapy for pemphigus: Minor modifications, improved results

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    Pasricha J

    2008-01-01

    Full Text Available Background: If administered properly, dexamethasone cyclophosphamide pulse (DCP therapy has the potential to effect lifelong recovery from pemphigus. Aims: The objective of this paper is to highlight various parameters of DCP therapy and also, to report the effects of a few modifications in the regimen. Methods: An analysis of 123 patients treated with the DCP/DP regimen over a period of five years (1998 to 2002 is presented here. Seventeen patients who did not start/continue the treatment and three patients who died during the treatment have been excluded from the analysis. Twenty patients who had not yet started families were given only dexamethasone pulses (DPs while 103 patients received DCPs. Low dose (50 mg/day cyclophosphamide was used as in the standard regimen. The three modifications introduced into the regimen were: (1 an additional daily dose of oral betamethasone sufficient to control the disease activity during phase I, which was progressively tapered off completely as the patient recovered, (2 use of systemic antibiotics if the patient had skin lesions, and oral anti-candida drugs if the patient had oral ulcers until complete healing, and (3 insistence on thorough cleaning of the skin and scalp with a normal soap and shampoo, and proper maintenance of oral hygiene in spite of skin/mucosal lesions. The regimen consisted of DCP/DP repeated in exactly 28-day cycles, along with 50 mg cyclophosphamide per day, insistence on completing the treatment and avoiding irregular pulses in all patients. The number of DCPs/DPs during phase I varied in different patients depending upon the dose of betamethasone used and the rate of recovery, but phase II (nine DCPs/DPs in exactly 28-day cycles along with 50 mg cyclophosphamide per day and phase III (only 50 mg cyclophosphamide per day was fixed at nine months each. This was followed by posttreatment follow-up (phase IV. Results: At present, all the patients are in complete remission. The

  12. A rational quantitative approach to determine the best dosing regimen for a target therapeutic effect: a unified formalism for antibiotic evaluation.

    Science.gov (United States)

    Li, Jun; Nekka, Fahima

    2013-02-21

    The determination of an optimal dosing regimen is a critical step to enhance the drug efficacy and avoid toxicity. Rational dosing recommendations based on mathematical considerations are increasingly being adopted in the process of drug development and use. In this paper, we propose a quantitative approach to evaluate the efficacy of antibiotic agents. By integrating both pharmacokinetic (PK) and pharmacodynamic (PD) information, this approach gives rise to a unified formalism able to measure the cause-effect of dosing regimens. This new pharmaco-metric allows to cover a whole range of antibiotics, including the two well known concentration and time dependent classes, through the introduction of the Hill-dependency concept. As a direct fallout, our formalism opens a new path toward the bioequivalence evaluation in terms of PK and PD, which associates the in vivo drug concentration and the in vitro drug effect. Using this new approach, we succeeded to reveal unexpected, but relevant behaviors of drug performance when different drug regimens and drug classes are considered. Of particular notice, we found that the doses required to reach the same therapeutic effect, when scheduled differently, exhibit completely different tendencies for concentration and time dependent drugs. Moreover, we theoretically confirmed the previous experimental results of the superiority of the once daily regimen of aminoglycosides. The proposed methodology is appealing for its computational features and can easily be applicable to design fair clinical protocols or rationalize prescription decisions.

  13. Current Progress in Therapeutic Gene Editing for Monogenic Diseases.

    Science.gov (United States)

    Prakash, Versha; Moore, Marc; Yáñez-Muñoz, Rafael J

    2016-03-01

    Programmable nucleases allow defined alterations in the genome with ease-of-use, efficiency, and specificity. Their availability has led to accurate and widespread genome engineering, with multiple applications in basic research, biotechnology, and therapy. With regard to human gene therapy, nuclease-based gene editing has facilitated development of a broad range of therapeutic strategies based on both nonhomologous end joining and homology-dependent repair. This review discusses current progress in nuclease-based therapeutic applications for a subset of inherited monogenic diseases including cystic fibrosis, Duchenne muscular dystrophy, diseases of the bone marrow, and hemophilia and highlights associated challenges and future prospects.

  14. MW PHARM, AN INTEGRATED SOFTWARE PACKAGE FOR DRUG-DOSAGE REGIMEN CALCULATION AND THERAPEUTIC DRUG-MONITORING

    NARCIS (Netherlands)

    PROOST, JH; MEIJER, DKF

    The pharmacokinetic software package MW/Pharm offers an interactive, user-friendly program which gives rapid answers in clinical practice. It comprises a database with pharmacokinetic parameters of 180 drugs, a medication history database, and procedures for an individual drug dosage regimen

  15. MW PHARM, AN INTEGRATED SOFTWARE PACKAGE FOR DRUG-DOSAGE REGIMEN CALCULATION AND THERAPEUTIC DRUG-MONITORING

    NARCIS (Netherlands)

    PROOST, JH; MEIJER, DKF

    1992-01-01

    The pharmacokinetic software package MW/Pharm offers an interactive, user-friendly program which gives rapid answers in clinical practice. It comprises a database with pharmacokinetic parameters of 180 drugs, a medication history database, and procedures for an individual drug dosage regimen calcula

  16. Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

    Directory of Open Access Journals (Sweden)

    Aloísio Sales da Cunha

    1987-10-01

    Full Text Available A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ and the quantitative Kato-Katz (K-K methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28% and K-K (80% became significative. When this number dropped to less than 2,000 the percentage of false negative

  17. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe.

    Science.gov (United States)

    Hofstra, L Marije; Sauvageot, Nicolas; Albert, Jan; Alexiev, Ivailo; Garcia, Federico; Struck, Daniel; Van de Vijver, David A M C; Åsjö, Birgitta; Beshkov, Danail; Coughlan, Suzie; Descamps, Diane; Griskevicius, Algirdas; Hamouda, Osamah; Horban, Andrzej; Van Kasteren, Marjo; Kolupajeva, Tatjana; Kostrikis, Leondios G; Liitsola, Kirsi; Linka, Marek; Mor, Orna; Nielsen, Claus; Otelea, Dan; Paraskevis, Dimitrios; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Van Laethem, Kristel; Zazzi, Maurizio; Zidovec Lepej, Snjezana; Boucher, Charles A B; Schmit, Jean-Claude; Wensing, Annemarie M J; Puchhammer-Stockl, E; Sarcletti, M; Schmied, B; Geit, M; Balluch, G; Vandamme, A-M; Vercauteren, J; Derdelinckx, I; Sasse, A; Bogaert, M; Ceunen, H; De Roo, A; De Wit, S; Echahidi, F; Fransen, K; Goffard, J-C; Goubau, P; Goudeseune, E; Yombi, J-C; Lacor, P; Liesnard, C; Moutschen, M; Pierard, D; Rens, R; Schrooten, Y; Vaira, D; Vandekerckhove, L P R; Van den Heuvel, A; Van Der Gucht, B; Van Ranst, M; Van Wijngaerden, E; Vandercam, B; Vekemans, M; Verhofstede, C; Clumeck, N; Van Laethem, K; Beshkov, D; Alexiev, I; Lepej, S Zidovec; Begovac, J; Kostrikis, L; Demetriades, I; Kousiappa, I; Demetriou, V; Hezka, J; Linka, M; Maly, M; Machala, L; Nielsen, C; Jørgensen, L B; Gerstoft, J; Mathiesen, L; Pedersen, C; Nielsen, H; Laursen, A; Kvinesdal, B; Liitsola, K; Ristola, M; Suni, J; Sutinen, J; Descamps, D; Assoumou, L; Castor, G; Grude, M; Flandre, P; Storto, A; Hamouda, O; Kücherer, C; Berg, T; Braun, P; Poggensee, G; Däumer, M; Eberle, J; Heiken, H; Kaiser, R; Knechten, H; Korn, K; Müller, H; Neifer, S; Schmidt, B; Walter, H; Gunsenheimer-Bartmeyer, B; Harrer, T; Paraskevis, D; Hatzakis, A; Zavitsanou, A; Vassilakis, A; Lazanas, M; Chini, M; Lioni, A; Sakka, V; Kourkounti, S; Paparizos, V; Antoniadou, A; Papadopoulos, A; Poulakou, G; Katsarolis, I; Protopapas, K; Chryssos, G; Drimis, S; Gargalianos, P; Xylomenos, G; Lourida, G; Psichogiou, M; Daikos, G L; Sipsas, N V; Kontos, A; Gamaletsou, M N; Koratzanis, G; Sambatakou, H; Mariolis, H; Skoutelis, A; Papastamopoulos, V; Georgiou, O; Panagopoulos, P; Maltezos, E; Coughlan, S; De Gascun, C; Byrne, C; Duffy, M; Bergin, C; Reidy, D; Farrell, G; Lambert, J; O'Connor, E; Rochford, A; Low, J; Coakely, P; O'Dea, S; Hall, W; Mor, O; Levi, I; Chemtob, D; Grossman, Z; Zazzi, M; de Luca, A; Balotta, C; Riva, C; Mussini, C; Caramma, I; Capetti, A; Colombo, M C; Rossi, C; Prati, F; Tramuto, F; Vitale, F; Ciccozzi, M; Angarano, G; Rezza, G; Kolupajeva, T; Vasins, O; Griskevicius, A; Lipnickiene, V; Schmit, J C; Struck, D; Sauvageot, N; Hemmer, R; Arendt, V; Michaux, C; Staub, T; Sequin-Devaux, C; Wensing, A M J; Boucher, C A B; van de Vijver, D A M C; van Kessel, A; van Bentum, P H M; Brinkman, K; Connell, B J; van der Ende, M E; Hoepelman, I M; van Kasteren, M; Kuipers, M; Langebeek, N; Richter, C; Santegoets, R M W J; Schrijnders-Gudde, L; Schuurman, R; van de Ven, B J M; Åsjö, B; Kran, A-M Bakken; Ormaasen, V; Aavitsland, P; Horban, A; Stanczak, J J; Stanczak, G P; Firlag-Burkacka, E; Wiercinska-Drapalo, A; Jablonowska, E; Maolepsza, E; Leszczyszyn-Pynka, M; Szata, W; Camacho, R; Palma, C; Borges, F; Paixão, T; Duque, V; Araújo, F; Otelea, D; Paraschiv, S; Tudor, A M; Cernat, R; Chiriac, C; Dumitrescu, F; Prisecariu, L J; Stanojevic, M; Jevtovic, Dj; Salemovic, D; Stanekova, D; Habekova, M; Chabadová, Z; Drobkova, T; Bukovinova, P; Shunnar, A; Truska, P; Poljak, M; Lunar, M; Babic, D; Tomazic, J; Vidmar, L; Vovko, T; Karner, P; Garcia, F; Paredes, R; Monge, S; Moreno, S; Del Amo, J; Asensi, V; Sirvent, J L; de Mendoza, C; Delgado, R; Gutiérrez, F; Berenguer, J; Garcia-Bujalance, S; Stella, N; de Los Santos, I; Blanco, J R; Dalmau, D; Rivero, M; Segura, F; Elías, M J Pérez; Alvarez, M; Chueca, N; Rodríguez-Martín, C; Vidal, C; Palomares, J C; Viciana, I; Viciana, P; Cordoba, J; Aguilera, A; Domingo, P; Galindo, M J; Miralles, C; Del Pozo, M A; Ribera, E; Iribarren, J A; Ruiz, L; de la Torre, J; Vidal, F; Clotet, B; Albert, J; Heidarian, A; Aperia-Peipke, K; Axelsson, M; Mild, M; Karlsson, A; Sönnerborg, A; Thalme, A; Navér, L; Bratt, G; Karlsson, A; Blaxhult, A; Gisslén, M; Svennerholm, B; Bergbrant, I; Björkman, P; Säll, C; Mellgren, Å; Lindholm, A; Kuylenstierna, N; Montelius, R; Azimi, F; Johansson, B; Carlsson, M; Johansson, E; Ljungberg, B; Ekvall, H; Strand, A; Mäkitalo, S; Öberg, S; Holmblad, P; Höfer, M; Holmberg, H; Josefson, P; Ryding, U

    2016-03-01

    Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected. © The Author 2015. Published by Oxford University Press for the Infectious

  18. Therapeutic Assessment of Chloroquine-Primaquine Combined Regimen in Adult Cohort of Plasmodium vivax Malaria from Primary Care Centres in Southwestern India

    Science.gov (United States)

    Saravu, Kavitha; Kumar, Rishikesh; Ashok, Herikudru; Kundapura, Premananda; Kamath, Veena; Kamath, Asha; Mukhopadhyay, Chiranjay

    2016-01-01

    Background Several reports of chloroquine treatment failure and resistance in Plasmodium vivax malaria from Southeast Asian countries have been published. Present study was undertaken to assess the efficacy of chloroquine-primaquine (CQ-PQ) combined regimen for the treatment of P. vivax malaria patients who were catered by the selected primary health centres (PHCs) of Udupi taluk, Udupi district, Karnataka, India. Method Five PHCs were selected within Udupi taluk based on probability proportional to size. In-vivo therapeutic efficacy assessment of CQ (1500 mg over three days) plus PQ (210 mg over 14 days) regimen was carried out in accordance with the World Health Organization’s protocol of 28 days follow-up among microscopically diagnosed monoinfection P. vivax cohort. Results In total, 161 participants were recruited in the study of which, 155 (96.3%) participants completed till day 28 follow-up, fully complied with the treatment regimen and showed adequate clinical and parasitological response. Loss to follow up was noted with 5 (3.1%) participants and non-compliance with treatment regimen occurred with one participant (0.6%). Glucose-6-phosphate dehydrogenase deficiency (G6PDd, <30% of normal mean activity) was noted among 5 (3.1%) participants and one of them did develop PQ induced dark-brown urination which subsided after PQ discontinuation. G6PDd patients were treated with PQ 45 mg/week for eight weeks while PQ was discontinued in one case with G6PD 1.4 U/g Hb due to complaint of reddish-brown coloured urine by 48 hours of PQ initiation. Nested polymerase chain reaction test revealed 45 (28%) cases as mixed (vivax and falciparum) malaria. Conclusions The CQ-PQ combined regimen remains outstandingly effective to treat uncomplicated P. vivax malaria in Udupi taluk and thus it should continue as first line regimen. For all P. vivax cases, G6PD screening before PQ administration must be mandatory and made available in all PHCs. PMID:27315280

  19. Therapeutic Assessment of Chloroquine-Primaquine Combined Regimen in Adult Cohort of Plasmodium vivax Malaria from Primary Care Centres in Southwestern India.

    Directory of Open Access Journals (Sweden)

    Kavitha Saravu

    Full Text Available Several reports of chloroquine treatment failure and resistance in Plasmodium vivax malaria from Southeast Asian countries have been published. Present study was undertaken to assess the efficacy of chloroquine-primaquine (CQ-PQ combined regimen for the treatment of P. vivax malaria patients who were catered by the selected primary health centres (PHCs of Udupi taluk, Udupi district, Karnataka, India.Five PHCs were selected within Udupi taluk based on probability proportional to size. In-vivo therapeutic efficacy assessment of CQ (1500 mg over three days plus PQ (210 mg over 14 days regimen was carried out in accordance with the World Health Organization's protocol of 28 days follow-up among microscopically diagnosed monoinfection P. vivax cohort.In total, 161 participants were recruited in the study of which, 155 (96.3% participants completed till day 28 follow-up, fully complied with the treatment regimen and showed adequate clinical and parasitological response. Loss to follow up was noted with 5 (3.1% participants and non-compliance with treatment regimen occurred with one participant (0.6%. Glucose-6-phosphate dehydrogenase deficiency (G6PDd, <30% of normal mean activity was noted among 5 (3.1% participants and one of them did develop PQ induced dark-brown urination which subsided after PQ discontinuation. G6PDd patients were treated with PQ 45 mg/week for eight weeks while PQ was discontinued in one case with G6PD 1.4 U/g Hb due to complaint of reddish-brown coloured urine by 48 hours of PQ initiation. Nested polymerase chain reaction test revealed 45 (28% cases as mixed (vivax and falciparum malaria.The CQ-PQ combined regimen remains outstandingly effective to treat uncomplicated P. vivax malaria in Udupi taluk and thus it should continue as first line regimen. For all P. vivax cases, G6PD screening before PQ administration must be mandatory and made available in all PHCs.

  20. Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Wojciech Szopa

    2017-01-01

    Full Text Available Glioblastoma (GBM is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis and only 3–5% of them survive for more than 5 years. The current GBM treatment standards include maximal resection followed by radiotherapy with concomitant and adjuvant therapies. Despite these aggressive therapeutic regimens, the majority of patients suffer recurrence due to molecular heterogeneity of GBM. Consequently, a number of potential diagnostic, prognostic, and predictive biomarkers have been investigated. Some of them, such as IDH mutations, 1p19q deletion, MGMT promoter methylation, and EGFRvIII amplification are frequently tested in routine clinical practice. With the development of sequencing technology, detailed characterization of GBM molecular signatures has facilitated a more personalized therapeutic approach and contributed to the development of a new generation of anti-GBM therapies such as molecular inhibitors targeting growth factor receptors, vaccines, antibody-based drug conjugates, and more recently inhibitors blocking the immune checkpoints. In this article, we review the exciting progress towards elucidating the potential of current and novel GBM biomarkers and discuss their implications for clinical practice.

  1. [Osteoarthrosis: implementation of current diagnostic and therapeutic algorithms].

    Science.gov (United States)

    Meza-Reyes, Gilberto; Aldrete-Velasco, Jorge; Espinosa-Morales, Rolando; Torres-Roldán, Fernando; Díaz-Borjón, Alejandro; Robles-San Román, Manuel

    2017-01-01

    In the modern world, among the different clinical presentations of osteoarthritis, gonarthrosis and coxarthrosis exhibit the highest prevalence. In this paper, the characteristics of osteoarthritis and the different scales of assessment and classification of this pathology are exposed, to provide an exhibition of current evidence generated around diagnostic algorithms and treatment of osteoarthritis, with emphasis set out in the knee and hip, as these are the most frequent; a rational procedure for monitoring patients with osteoarthritis based on characteristic symptoms and the severity of the condition is also set. Finally, reference is made to the therapeutic benefits of the recent introduction of viscosupplementation with Hylan GF-20.

  2. Therapeutic strategies for Leber's hereditary optic neuropathy: A current update.

    Science.gov (United States)

    Gueven, Nuri; Faldu, Dharmesh

    2013-11-01

    Leber's hereditary optic neuropathy (LHON) is a rare mitochondrial retinopathy, caused by mutations in subunits of complex I of the respiratory chain, which leads to elevated levels of oxidative stress and an insufficient energy supply. This molecular pathology is thought to be responsible for the dysfunction and eventual apoptotic loss of retinal ganglion cells in the eye, which ultimately results in blindness. Many strategies, ranging from neuroprotectants, antioxidants, anti-apoptotic- and anti-inflammatory compounds have been tested with mixed results. Currently, the most promising compounds are short-chain quinones that have been shown to protect the vision of LHON patients during the early stages of the disease. This commentary gives a brief overview on the current status of tested therapeutics and also addresses future developments such as the use of gene therapy that hopefully will provide safe and efficient therapy options for all LHON patients.

  3. Current protein-based anti-angiogenic therapeutics.

    Science.gov (United States)

    Chakrabarti, Sanjukta; Barrow, Colin J; Kanwar, Rupinder K; Ramana, Venkata; Kanwar, Jagat R

    2014-01-01

    Angiogenesis is a multistep process for the formation of new blood vessels. Interactions between several cellular factors including growth factors, cytokines and hematopoietic factors lead to activation of various cellular pathways finally resulting in the extracellular matrix (ECM) degradation, endothelial cell proliferation, survival and migration. Normally, angiogenesis is an essential requirement for vascular development in growing embryos as well as in adult tissues where this process depends on the intricate balance between the activities of the pro- and anti-angiogenic factors. Abnormal angiogenesis results in aberrant vasculature leading to various pathological conditions. The most important factor implicated in angiogenic processes is vascular endothelial growth factor (VEGF) and its family of ligands and receptors. Several anti-angiogenic drugs have been developed and many more are currently in different phases of clinical trials, which target various angiogenesis-inducing agents including VEGF, VEGF receptors, angiopoietins and ECM components such as integrins. Anti-angiogenic therapy can be divided into gene-based therapy and protein-based therapy. Gene-based therapies include the use of antisense oligonucleotides, siRNA, aptamers, catalytic oligonucleotides including ribozymes and DNAzymes and transcription decoys. Protein-based therapeutics includes monoclonal antibodies, peptidomimetics, fusion proteins and decoy receptors. The later class of therapeutics has several advantages over gene-based and small molecule drugs, including specificity and complexity in functions, better tolerability, less interference with normal biological processes and lesser adverse effects due to decreased immune response by virtue of being mostly body's natural proteins. This review provides a comprehensive overview of angiogenesis and on the current protein-based anti-angiogenic therapeutics under research and in the clinic.

  4. Neuropsychiatric involvement in systemic lupus erythematosus: current therapeutic approach.

    Science.gov (United States)

    Sanna, Giovanni; Bertolaccini, Maria Laura; Khamashta, Munther A

    2008-01-01

    The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of controlled randomized trials, current therapeutic approach is still empirical and based on clinical experience. The therapeutic choice depends on accurate diagnosis, identification of underlying pathogenic mechanism, severity of the presenting neuropsychiatric symptoms, and on prompt identification and management of contributing causes of CNS disease. Mild neuropsychiatric manifestations may need symptomatic treatment only. In more severe CNS disease it is important to distinguish between thrombotic and non-thrombotic mechanisms. Focal CNS manifestations, particularly TIA and stroke, are associated with the presence of antiphospholipid antibodies (aPL). Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid (Hughes) syndrome (APS). Other CNS manifestations, such as demyelinating syndrome, transverse myelitis, chorea, seizures, migraine and/or cognitive dysfunction, when associated with persistent positivity for aPL, may also benefit from anticoagulation in selected patients. Severe diffuse CNS manifestations, such as acute confusional state, generalised seizures, mood disorders and psychosis, generally require corticosteroids in the first instance. Pulse intravenous cyclophosphamide therapy may help when more severe manifestations are refractory to corticosteroids and other immunosuppressive agents, generally when response is not seen in 3-5 days. Plasmapheresis may also be added in severe cases of symptoms refractory to conventional treatment. Intravenous immunoglobulins, mycophenolate mofetil, rituximab, intratecal methotrexate and dexametasone deserve further studies to confirm their

  5. Current developments in pharmacological therapeutics for chronic constipation

    Directory of Open Access Journals (Sweden)

    Chunhuan Jiang

    2015-07-01

    Full Text Available Chronic constipation is a common gastrointestinal disease severely affecting the patient׳s quality of life. The traditional treatment of constipation is the use of laxatives. Recently, several new drugs including lubiprostone, linaclotide and prucalopride have been approved for treatment of chronic constipation. However, a significant unmet medical need still remains, particularly among those patients achieving poor results by current therapies. The 5-HT4 receptor modulators velusetrag and naronapride, the guanylate cyclase C agonist plecanatide and the ileal bile acid transporter inhibitor elobixibat are recognized as the most promising drugs under investigation. Herein, we give a comprehensive review on the pharmacological therapeutics for the treatment of chronic constipation, with the purpose of reflecting the drug development trends in this field.

  6. Therapeutic drug monitoring for imatinib: Current status and Indian experience.

    Science.gov (United States)

    Arora, Brijesh; Gota, Vikram; Menon, Hari; Sengar, Manju; Nair, Reena; Patial, Pankaj; Banavali, S D

    2013-07-01

    Imatinib is the current gold standard for treatment of chronic myeloid leukemia (CML). Recent pharmacokinetic studies have shown considerable variability in trough concentrations of imatinib due to variations in its metabolism, poor compliance, or drug-drug interactions and highlighted its impact on clinical response. A trough level close to 1000 ng/mL, appears to be correlated with better cytogenetic and molecular responses. Therapeutic Drug Monitoring (TDM) for imatinib may provide useful added information on efficacy, safety and compliance than clinical assessment alone and help in clinical decision making. It may be particularly helpful in patients with suboptimal response to treatment or treatment failure, severe or rare adverse events, possible drug interactions, or suspected nonadherence. Further prospective studies are needed to confirm relationship between imatinib plasma concentrations with response, and to define effective plasma concentrations in different patient populations.

  7. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

    NARCIS (Netherlands)

    L.M. Hofstra (L. Marije); N. Sauvageot (Nicolas); J. Albert (Jan); I. Alexiev (Ivailo); F. Garcia (Federico); D. Struck (Daniel); D.A.M.C. van de Vijver (David); B. Asjö (Birgitta); D. Beshkov (Danail); S. Coughlan (Suzie); D. Descamps (Diane); A. Griskevicius (Algis); O. Hamouda (Osamah); A. Horban (Andrzej); M.E.E. van Kasteren (Marjo); T. Kolupajeva (Tatjana); L.G. Kostrikis (Leondios); K. Liitsola (Kirsi); M. Linka (Marek); O. Mor (Orna); C. Nielsen (Claus); D. Otelea (Dan); D. Paraskevis (Dimitrios); R. Paredes (Roger); M. Poljak (Mario); E. Puchhammer-Stockl E. (E.); A. Sonnerborg (Anders); D. Stanekova (Danica); M. Stanojevic (Maja); K. Van Laethem (Kristel); M. Zazzi (Maurizio); S. Zidovec Lepej (Snjezana); C.A.B. Boucher (Charles A. B.); J.-C. Schmit (Jean-Claude); A.M.J. Wensing (Annemarie); E. Puchhammer-Stöckl (Elisabeth); M. Sarcletti (M.); B. Schmied (B.); M. Geit (M.); G. Balluch (G.); A.-M. Vandamme; J. Vercauteren (Jurgen); I. Derdelinckx; A. Sasse; M. Bogaert; H. Ceunen (H.); A. de Roo (Annie); S. De Wit; F. Echahidi (F.); K. Fransen; J.-C. Goffard (J.); P. Goubau; E. Goudeseune (E.); J.-C. Yombi (J.); P. Lacor; C. Liesnard (C.); M. Moutschen; L.A. Pierard; R. Rens (R.); J. Schrooten; D. Vaira; L.P.R. Vandekerckhove; A. van den Heuvel (A.); B. van der Gucht (B.); M. Van Ranst; E. Van Wijngaerden; B. Vandercam; M. Vekemans; C. Verhofstede; N. Clumeck (N.); K. van Laethem (Kristel); D. Beshkov; I. Alexiev; S.Z. Lepej (Snjezana); J. Begovac; L.G. Kostrikis (Leondios); I. Demetriades (I.); I. Kousiappa (Ioanna); V.L. Demetriou (Victoria); J. Hezka (Johana); M. Linka; M. Maly; L. MacHala; C. Nielsen; L.B. Jørgensen; J. Gerstoft (J.); L. Mathiesen (L.); C. Pedersen (Court); H. Nielsen; A. Laursen (A.); B. Kvinesdal (B.); K. Liitsola (Kirsi); M. Ristola (M.); J. Suni; J. Sutinen (J.); D. Descamps; L. Assoumou; G. Castor; M. Grude; P. Flandre; A. Storto; O. Hamouda (Osamah); C. K̈ucherer (C.); T. Berg; P. Braun; G. Poggensee; M. Daumer (Martin); J. Eberle; H. Heiken; R. Kaiser; H. Knechten (H.); K. Korn; H. Müller; S. Neifer; B. Schmidt; H. Walter; B. Gunsenheimer-Bartmeyer (B.); T. Harrer (T.); D. Paraskevis (Dimitrios); A. Hatzakis (Angelos); A. Zavitsanou (A.); A. Vassilakis; M. Lazanas; L. Chini; A. Lioni; V. Sakka (V.); S. Kourkounti (S.); V. Paparizos (V.); A. Antoniadou (A.); A. Papadopoulos; G. Poulakou; I. Katsarolis; K. Protopapas; G. Chryssos (G.); S. Drimis (S.); P. Gargalianos; G. Xylomenos; G. Lourida; M. Psichogiou (M.); G.L. Daikos (G.); N.V. Sipsas; A. Kontos (Angelos); M.N. Gamaletsou; G. Koratzanis (G.); H. Sambatakou; H. Mariolis; A. Skoutelis; V. Papastamopoulos; O. Georgiou; P. Panagopoulos (P.); E. Maltezos; S. Coughlan (Suzie); C. de Gascun (Cillian); C. Byrne; M. Duffy; P. Bergin; D. Reidy; G. Farrell; J. Lambert; E. O'Connor; A. Rochford; J. Low; P. Coakely (P.); S. O'Dea; W. Hall; O. Mor; I. Levi (I.); D. Chemtob (D.); Z. Grossman (Zehava); M. Zazzi; A. de Luca (Andrea); C. Balotta (Claudia); C. Riva (Chiara); C. Mussini (C.); I. Caramma (I.); A. Capetti (A.); M. Colombo (Massimo); C. Rossi; F. Prati (Francesco); F. Tramuto; F. Vitale (F.); M. Ciccozzi; G. Angarano (Guiseppe); G. Rezza (G.); T. Kolupajeva; O. Vasins; A. Griskevicius (Algis); V. Lipnickiene; J.C. Schmit; D. Struck (Daniel); N. Sauvageot; R. Hemmer (R.); V. Arendt (V.); C. Michaux; T. Staub (T.); C. Sequin-Devaux; A.M.J. Wensing (Annemarie); C.A. Boucher (Charles); D.A.M.C. van de Vijver (David); A. Van Kessel; P.H.M. Van Bentum; K. Brinkman; B.J. Connell; M.E. van der Ende (Marchina); I.M. Hoepelman (Ilja Mohandas); M.E.E. van Kasteren (Marjo); M. Kuipers; N. Langebeek (Nienke); C. Richter; R.M.W.J. Santegoets (R. M W J); L. Schrijnders-Gudde (L.); R. Schuurman (Rob); B.J.M. van de Ven (B. J M); B. Åsjö (Birgitta); A.-M.B. Kran (A.-M. Bakken); V. Ormaasen (Vidar); P. Aavitsland (P.); A. Horban (Andrzej); J. Stanczak (J.); G.P. Stanczak (G.); E. Firlag-Burkacka (E.); A. Wiercinska-Drapalo; E. Jablonowska (E.); E. Maolepsza; M. Leszczyszyn-Pynka (M.); W. Szata (W.); R.J. Camacho (Ricardo Jorge); A. de Palma (Andre); F. Borges (F.); T. Paixão; V. Duque (V.); F. Araújo; D. Otelea; C. Paraschiv (Corina); A.M. Tudor; R. Cernat; C. Chiriac; F. Dumitrescu; L.J. Prisecariu; M. Stanojevic (Maja); D.J. Jevtovic (D.); D. Salemovic (D.); D. Stanekova; M. Habekova (M.); Z. Chabadová; T. Drobkova; P. Bukovinova; A. Shunnar; P. Truska; M. Poljak (Mario); M.M. Lunar (Maja M.); D. Babic; J. Tomazic (J.); S. Vidmar (Suzanna); T. Vovko; P. Karner (P.); F. Garcia; R. Paredes (Roger); S. Monge; S. Moreno; J. Del Amo; V. Asensi; J.L. Sirvent; C. de Mendoza (Carmen); R. Delgado; F. Gutiérrez; J. Berenguer; S. Garcia-Bujalance; N. Stella; I. De Los Santos; J.R. Blanco; D. Dalmau; M. Rivero; F. Segura; M.J.P. Elías (M. J. Pcrossed); M. Alvarez; N. Chueca; C. Rodríguez-Martín; C. Vidal; J.C. Palomares; I. Viciana; P. Viciana; J. Cordoba; A. Aguilera; P. Domingo; M.J. Galindo; C. Miralles; M.A. Del Pozo; E. Ribera; C. Iribarren (Carlos); L. Ruiz; J. De La Torre; F. Vidal; B. Clotet (Bonaventura); J. Albert; A. Heidarian; K. Aperia-Peipke (K.); M. Axelsson; M. Mild; A. Karlsson; A. Sonnerborg (Anders); A. Thalme; L. Navénr; G. Bratt (G.); A. Karlsson; A. Blaxhult; M. Gisslénn; B. Svennerholm; I.-M. Bergbrant (I.); P. Bj̈orkman (P.); C. Säll; A. Mellgren; A. Lindholm; N. Kuylenstierna; R. Montelius; F. Azimi; B. Johansson; M. Carlsson; E. Johansson; B. Ljungberg; H. Ekvall; A. Strand; S. Mäkitalo; S. Öberg; P. Holmblad; M. Höfer; H. Holmberg; P. Josefson; U. Ryding

    2016-01-01

    textabstractBackground. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, the

  8. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

    NARCIS (Netherlands)

    Hofstra, L. Marije; Sauvageot, Nicolas; Albert, Jan; Alexiev, Ivailo; Garcia, Federico; Struck, Daniel; Van De Vijver, David A M C; Åsjö, Birgitta; Beshkov, Danail; Coughlan, Suzie; Descamps, Diane; Griskevicius, Algirdas; Hamouda, Osamah; Horban, Andrzej; Van Kasteren, Marjo; Kolupajeva, Tatjana; Kostrikis, Leontios G.; Liitsola, Kirsi; Linka, Marek; Mor, Orna; Nielsen, Claus; Otelea, Dan; Paraskevis, Dimitrios; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Van Laethem, Kristel; Zazzi, Maurizio; Lepej, Snjezana Zidovec; Boucher, Charles A B; Schmit, Jean Claude; Wensing, Annemarie M J; Puchhammer-Stockl, E.; Sarcletti, M.; Schmied, B.; Geit, M.; Balluch, G.; Vandamme, A. M.; Vercauteren, J.; Derdelinckx, I.; Sasse, A.; Bogaert, M.; Ceunen, H.; De Roo, A.; De Wit, S.; Echahidi, F.; Fransen, K.; Goffard, J. C.; Goubau, P.; Goudeseune, E.; Yombi, J. C.; Lacor, P.; Liesnard, C.; Moutschen, M.; Pierard, D.; Rens, R.; Schrooten, Y.; Vaira, D.; Vandekerckhove, L. P R; Van Den Heuvel, A.; Van Der Gucht, B.; Van Ranst, M.; Van Wijngaerden, E.; Vandercam, B.; Vekemans, M.; Verhofstede, C.; Clumeck, N.; Van Laethem, K.; Beshkov, D.; Alexiev, I.; Lepej, S. Zidovec; Begovac, J.; Kostrikis, Leontios G.; Demetriades, I.; Kousiappa, I.; Demetriou, V.; Hezka, J.; Linka, M.; Maly, M.; Machala, L.; Nielsen, C.; Jørgensen, L. B.; Gerstoft, J.; Mathiesen, L.; Pedersen, C.; Nielsen, H.; Laursen, A.; Kvinesdal, B.; Liitsola, K.; Ristola, M.; Suni, J.; Sutinen, J.; Descamps, D.; Assoumou, L.; Castor, G.; Grude, M.; Flandre, P.; Storto, A.; Hamouda, O.; Kücherer, C.; Berg, T.; Braun, P.; Poggensee, G.; Däumer, M.; Eberle, J.; Heiken, H.; Kaiser, R.; Knechten, H.; Korn, K.; Müller, H.; Neifer, S.; Schmidt, B.; Walter, H.; Gunsenheimer-Bartmeyer, B.; Harrer, T.; Paraskevis, D.; Hatzakis, A.; Zavitsanou, A.; Vassilakis, A.; Lazanas, M.; Chini, M.; Lioni, A.; Sakka, V.; Kourkounti, S.; Paparizos, V.; Antoniadou, A.; Papadopoulos, A.; Poulakou, G.; Katsarolis, I.; Protopapas, K.; Chryssos, G.; Drimis, S.; Gargalianos, P.; Xylomenos, G.; Lourida, G.; Psichogiou, M.; Daikos, G. L.; Sipsas, N. V.; Kontos, A.; Gamaletsou, M. N.; Koratzanis, G.; Sambatakou, E.; Mariolis, H.; Skoutelis, A.; Papastamopoulos, V.; Georgiou, O.; Panagopoulos, P.; Maltezos, E.; Coughlan, S.; De Gascun, C.; Byrne, C.; Duffy, M.; Bergin, C.; Reidy, D.; Farrell, G.; Lambert, J.; O'Connor, E.; Rochford, A.; Low, J.; Coakely, P.; O'Dea, S.; Hall, W.; Mor, O.; Levi, I.; Chemtob, D.; Grossman, Z.; Zazzi, M.; De Luca, A.; Balotta, C.; Riva, C.; Mussini, C.; Caramma, I.; Capetti, A.; Colombo, M. C.; Rossi, C.; Prati, F.; Tramuto, F.; Vitale, F.; Ciccozzi, M.; Angarano, G.; Rezza, G.; Kolupajeva, T.; Kolupajeva, T.; Vasins, O.; Griskevicius, A.; Lipnickiene, V.; Schmit, J. C.; Struck, D.; Sauvageot, N.; Hemmer, R.; Arendt, V.; Michaux, C.; Staub, T.; Sequin-Devaux, C.; Wensing, A. M J; Boucher, C. A B; Van Kessel, A.; Van Bentum, P. H M; Brinkman, K.; Connell, B. J.; Van Der Ende, M. E.; Hoepelman, I. M.; Van Kasteren, M.; Kuipers, M.; Langebeek, N.; Richter, C.; Santegoets, R. M W J; Schrijnders-Gudde, L.; Schuurman, R.; Van De Ven, B. J M; Åsjö, B.; Kran, A. M Bakken; Ormaasen, V.; Aavitsland, P.; Horban, A.; Stanczak, J. J.; Stanczak, G. P.; Firlag-Burkacka, E.; Wiercinska-Drapalo, A.; Jablonowska, E.; Maolepsza, E.; Leszczyszyn-Pynka, M.; Szata, W.; Camacho, R.; Palma, C.; Borges, F.; Paixão, T.; Duque, V.; Araújo, F.; Otelea, D.; Paraschiv, S.; Tudor, A. M.; Cernat, R.; Chiriac, C.; Dumitrescu, F.; Prisecariu, L. J.; Stanojevic, M.; Jevtovic, Dj; Salemovic, D.; Stanekova, D.; Habekova, M.; Chabadová, Z.; Drobkova, T.; Bukovinova, P.; Shunnar, A.; Truska, P.; Poljak, M.; Lunar, M.; Babic, D.; Tomazic, J.; Vidmar, L.; Vovko, T.; Karner, P.; Garcia, F.; Paredes, R.; Monge, S.; Moreno, S.; Del Amo, J.; Asensi, V.; Sirvent, J. L.; De Mendoza, C.; Delgado, R.; Gutiérrez, F.; Berenguer, J.; Garcia-Bujalance, S.; Stella, N.; De Los Santos, I.; Blanco, J. R.; Dalmau, D.; Rivero, M.; Segura, F.; Elías, M. J Pérez; Alvarez, M.; Chueca, N.; Rodríguez-Martín, C.; Vidal, C.; Palomares, J. C.; Viciana, I.; Viciana, P.; Cordoba, J.; Aguilera, A.; Domingo, P.; Galindo, M. J.; Miralles, C.; Del Pozo, M. A.; Ribera, E.; Iribarren, J. A.; Ruiz, L.; De La Torre, J.; Vidal, F.; Clotet, B.; Albert, J.; Heidarian, A.; Aperia-Peipke, K.; Axelsson, M.; Mild, M.; Karlsson, A.; Sönnerborg, A.; Thalme, A.; Navér, L.; Bratt, G.; Karlsson, A.; Blaxhult, A.; Gisslén, M.; Svennerholm, B.; Bergbrant, I.; Björkman, P.; Säll, C.; Lindholm, A.; Kuylenstierna, N.; Montelius, R.; Azimi, F.; Johansson, B.; Carlsson, M.; Johansson, E.; Ljungberg, B.; Ekvall, H.; Strand, A.; Mäkitalo, S.; Öberg, S.; Holmblad, P.; Höfer, M.; Holmberg, H.; Josefson, P.; Ryding, U.

    2016-01-01

    Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline

  9. Self-reported adherence supports patient preference for the single tablet regimen (STR in the current cART era

    Directory of Open Access Journals (Sweden)

    Sterrantino G

    2012-06-01

    Full Text Available Gaetana Sterrantino,1 Lucia Santoro,1 Dario Bartolozzi1,1 Michele Trotta,1 Mauro Zaccarelli21SOD Malattie Infettive, Azienda Ospedaliera Universitaria Careggi, Firenze, 2Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani," Roma, ItalyObjective: To analyze self-reported adherence to antiretroviral regimens containing ritonavir-boosted protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTI, raltegravir, and maraviroc.Methods: Overall, 372 consecutive subjects attending a reference center for HIV treatment in Florence, Italy, were enrolled in the study, from December 2010 to January 2012 (mean age 48 years. A self-report questionnaire was filled in. Patients were defined as "nonadherent" if reporting one of the following criteria: <90% of pills taken in the last month, ≥1 missed dose in the last week, spontaneous treatment interruptions reported, or refill problems in the last 3 months. Gender, age, CD4, HIV-RNA, years of therapy, and type of antiretroviral regimen were analyzed with respect to adherence.Results: At the time of the questionnaire, 89.8% of patients had <50 copies/mL HIV-RNA and 14.2% were on their first combined antiretroviral therapy. 57% of patients were prescribed a regimen containing ritonavir boosted protease inhibitors (boosted PI, 41.7% NNRTI, 17.2% raltegravir, and 4.8% maraviroc; 49.5% of the subjects were on bis-in-die regimens, while 50.5% were on OD regimens, with 23.1% of these on the single tablet regimen (STR: tenofovir/emtricitabine/efavirenz. The nonadherence proportion was lower in NNRTI than in boosted-PI treatments (19.4% vs 30.2%, and even lower in STR patients (17.4%. In multivariable logistic regression, patients with the NNRTI regimen (OR: 0.56, 95% CI: 0.34–0.94 and the STR (OR: 0.45, 95% CI: 0.22–0.92 reported lower nonadherence. Efavirenz regimens were also associated with lower nonadherence (OR: 0.42, 95% CI: 0.21–0.83, while atazanavir/ritonavir regimens were

  10. Searching for synergistic bronchodilators and novel therapeutic regimens for chronic lung diseases from a traditional Chinese medicine, Qingfei Xiaoyan Wan.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Hou

    Full Text Available Classical Chinese pharmacopeias describe numerous excellent herbal formulations, and each prescription is an outstanding pool of effective compounds for drug discovery. Clarifying the bioactivity of the combined mechanisms of the ingredients in complex traditional Chinese medicine formulas is challenging. A classical formula known as Qingfei Xiaoyan Wan, used clinically as a treatment for prevalent chronic lung disease, was investigated in this work. A mutually enhanced bioactivity-guided ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS characterization system was proposed, coupled with a dual-luciferase reporter assay for β2AR-agonist cofactor screening. Arctiin, arctigenin, descurainoside and descurainolide B, four lignin compounds that showed synergistic bronchodilation effects with ephedrine, were revealed. The synergistic mechanism of arctigenin with the β2ARagonist involved with the reduction of free Ca2+ was clarified by a dual-luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo-4/AM to monitor changes in the fluorescence. The relaxant and contractile responses of airway smooth muscle are regulated by crosstalk between the intracellular cAMP and calcium signaling pathways. Our data indicated the non-selective βAR agonist ephedrine as the principal bronchodilator of the formula, whereas the lignin ingredients served as adjuvant ingredients. A greater understanding of the mechanisms governing the control of these pathways, based on conventional wisdom, could lead to the identification of novel therapeutic targets or new agents for the treatment of asthma and COPD.

  11. DW-MRI as a biomarker to compare therapeutic outcomes in radiotherapy regimens incorporating temozolomide or gemcitabine in glioblastoma.

    Directory of Open Access Journals (Sweden)

    Stefanie Galbán

    Full Text Available The effectiveness of the radiosensitizer gemcitabine (GEM was evaluated in a mouse glioma along with the imaging biomarker diffusion-weighted magnetic resonance imaging (DW-MRI for early detection of treatment effects. A genetically engineered murine GBM model [Ink4a-Arf(-/- Pten(loxP/loxP/Ntv-a RCAS/PDGF(+/Cre(+] was treated with gemcitabine (GEM, temozolomide (TMZ +/- ionizing radiation (IR. Therapeutic efficacy was quantified by contrast-enhanced MRI and DW-MRI for growth rate and tumor cellularity, respectively. Mice treated with GEM, TMZ and radiation showed a significant reduction in growth rates as early as three days post-treatment initiation. Both combination treatments (GEM/IR and TMZ/IR resulted in improved survival over single therapies. Tumor diffusion values increased prior to detectable changes in tumor volume growth rates following administration of therapies. Concomitant GEM/IR and TMZ/IR was active and well tolerated in this GBM model and similarly prolonged median survival of tumor bearing mice. DW-MRI provided early changes to radiosensitization treatment warranting evaluation of this imaging biomarker in clinical trials.

  12. Searching for Synergistic Bronchodilators and Novel Therapeutic Regimens for Chronic Lung Diseases from a Traditional Chinese Medicine, Qingfei Xiaoyan Wan

    Science.gov (United States)

    Hou, Yuanyuan; Cheng, Binfeng; Zhou, Mengge; Fang, Runping; Jiang, Min; Hou, Wenbin; Bai, Gang

    2014-01-01

    Classical Chinese pharmacopeias describe numerous excellent herbal formulations, and each prescription is an outstanding pool of effective compounds for drug discovery. Clarifying the bioactivity of the combined mechanisms of the ingredients in complex traditional Chinese medicine formulas is challenging. A classical formula known as Qingfei Xiaoyan Wan, used clinically as a treatment for prevalent chronic lung disease, was investigated in this work. A mutually enhanced bioactivity-guided ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) characterization system was proposed, coupled with a dual-luciferase reporter assay for β2AR-agonist cofactor screening. Arctiin, arctigenin, descurainoside and descurainolide B, four lignin compounds that showed synergistic bronchodilation effects with ephedrine, were revealed. The synergistic mechanism of arctigenin with the β2ARagonist involved with the reduction of free Ca2+ was clarified by a dual-luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo-4/AM to monitor changes in the fluorescence. The relaxant and contractile responses of airway smooth muscle are regulated by crosstalk between the intracellular cAMP and calcium signaling pathways. Our data indicated the non-selective βAR agonist ephedrine as the principal bronchodilator of the formula, whereas the lignin ingredients served as adjuvant ingredients. A greater understanding of the mechanisms governing the control of these pathways, based on conventional wisdom, could lead to the identification of novel therapeutic targets or new agents for the treatment of asthma and COPD. PMID:25397687

  13. Self-reported adherence supports patient preference for the single tablet regimen (STR in the current cART era

    Directory of Open Access Journals (Sweden)

    G Sterrantino

    2012-11-01

    Full Text Available Objective: To analyze self-reported adherence to antiretroviral regimens containing ritonavir-boosted protease inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTI, raltegravir, and maraviroc. Methods: Overall, 372 consecutive subjects attending a reference center for HIV treatment in Florence, Italy, were enrolled in the study, from December 2010 to January 2012 (mean age 48 years. A self-report questionnaire was filled in. Patients were defined as “non-adherent” if reporting one of the following criteria:<90% of pills taken in the last month, ≥1 missed dose in the last week, spontaneous treatment interruptions reported, or refill problems in the last 3 months. Gender, age, CD4, HIV-RNA, years of therapy, and type of antiretroviral regimen were analyzed with respect to adherence. Results: At the time of the questionnaire, 89.8% of patients had <50 copies/mL HIV-RNA and 14.2% were on their first combined antiretroviral therapy. 57% of patients were prescribed a regimen containing ritonavir boosted protease inhibitors (boosted PI, 41.7% NNRTI, 17.2% raltegravir, and 4.8% maraviroc; 49.5% of the subjects were on bis-in-die regimens, while 50.5% were on once-daily regimens, with 23.1% of these on the single tablet regimen (STR: tenofovir/emtricitabine/efavirenz. The non-adherence proportion was lower in NNRTI than in boosted-PI treatments (19.4% vs 30.2%, and even lower in STR patients (17.4%. In multivariable logistic regression, patients with the NNRTI regimen (OR: 0.56, 95% CI: 0.34–0.94 and the STR (OR: 0.45, 95% CI: 0.22–0.92 reported lower non-adherence. Efavirenz regimens were also associated with lower non-adherence (OR: 0.42, 95% CI: 0.21–0.83, while atazanavir/ritonavir regimens were associated with higher non-adherence. No other relation to specific antiretroviral drugs was found. A higher CD4 count, lower HIV-RNA, and older age were also found to be associated with lower non-adherence, while a longer time on

  14. Current and novel therapeutic molecules and targets in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ashwini Kumar

    2016-01-01

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline, i.e., dementia. The disease starts with mild symptoms and gradually becomes severe. AD is one of the leading causes of mortality worldwide. Several different hallmarks of the disease have been reported such as deposits of β-amyloid around neurons, hyperphosphorylated tau protein, oxidative stress, dyshomeostasis of bio-metals, low levels of acetylcholine, etc. AD is not simple to diagnose since there is no single diagnostic test for it. Pharmacotherapy for AD currently provides only symptomatic relief and mostly targets cognitive revival. Computational biology approaches have proved to be reliable tools for the selection of novel targets and therapeutic ligands. Molecular docking is a key tool in computer-assisted drug design and development. Docking has been utilized to perform virtual screening on large libraries of compounds, and propose structural hypotheses of how the ligands bind with the target with lead optimization. Another potential application of docking is optimization stages of the drug-discovery cycle. This review summarizes the known drug targets of AD, in vivo active agents against AD, state-of-the-art docking studies done in AD, and future prospects of the docking with particular emphasis on AD.

  15. Current practice of therapeutic drug monitoring of biopharmaceuticals in spondyloarthritis.

    Science.gov (United States)

    Medina, Frédéric; Placensia, Chamaida; Goupille, Philippe; Paintaud, Gilles; Balsa, Alejandro; Mulleman, Denis

    2017-04-04

    Treatment of spondyloarthritis (SpA) has greatly improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor (TNF) inhibitors, are effective, but some patients may show poor response, sometimes due to the presence of anti-drug antibodies (ADAs). In some instances, clinicians may increase or taper the dose, depending on the clinical response. Besides the current clinical practice, a tailored strategy based on drug monitoring is emerging as a way to improve the use of these drugs. However, the relevance of this therapeutic drug monitoring (TDM) of biopharmaceuticals for SpA is still unknown. In this literature review, we examined the most relevant articles dealing with the concentration-response relation, ADA detection, and pharmacokinetics in SpA treated with biopharmaceuticals. ADAs were associated with low or undetectable concentration of monoclonal antibodies. The relation between drug concentration and clinical response in SpA is debated, some studies showing an association and others not. Therefore, TDM of biopharmaceuticals for SpA requires a better understanding of the association among the pharmacokinetics, pharmacodynamics, and immunogenicity of these drugs.

  16. Prophylaxis and therapeutic potential of ozone in buiatrics: Current knowledge.

    Science.gov (United States)

    Đuričić, Dražen; Valpotić, Hrvoje; Samardžija, Marko

    2015-08-01

    Ozone therapy has been in use since 1896 in the USA. As a highly reactive molecule, ozone may inactivate bacteria, viruses, fungi, yeasts and protozoans, stimulate the oxygen metabolism of tissue, treat diseases, activate the immune system, and exhibit strong analgesic activity. More recently, ozone has been used in veterinary medicine, particularly in buiatrics, but still insufficiently. Medical ozone therapy has shown effectiveness as an alternative to the use of antibiotics, which are restricted to clinical use and have been withdrawn from non-clinical use as in-feed growth promoters in animal production. This review is an overview of current knowledge regarding the preventive and therapeutic effects of ozone in ruminants for the treatment of puerperal diseases and improvement in their fertility. In particular, ozone preparations have been tested in the treatment of reproductive tract lesions, urovagina and pneumomovagina, metritis, endometritis, fetal membrane retention and mastitis, as well as in the functional restoration of endometrium in dairy cows and goats. In addition, the preventive use of the intrauterine application of ozone has been assessed in order to evaluate its effectiveness in improving reproductive efficiency in dairy cows. No adverse effects were observed in cows and goats treated with ozone preparations. Moreover, there is a lot of evidence indicating the advantages of ozone preparation therapy in comparison to the application of antibiotics. However, there are certain limitations on ozone use in veterinary medicine and buiatrics, such as inactivity against intracellular microbes and selective activity against the same bacterial species, as well as the induction of tissue inflammation through inappropriate application of the preparation.

  17. Mitochondrial dysfunction in psychiatric morbidity: current evidence and therapeutic prospects

    Directory of Open Access Journals (Sweden)

    Toker L

    2015-09-01

    Full Text Available Lilach Toker,1 Galila Agam2,3 1Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada; 2Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva, Israel; 3Mental Health Center, Beer-Sheva, Israel Abstract: Cumulating evidence for the involvement of mitochondrial dysfunction in psychiatric disorders leaves little to no doubt regarding the involvement of this pathology in mood disorders. However, mitochondrial abnormalities are also observed in a wide range of disorders spanning from cancer and diabetes to various neurodegenerative and neurodevelopmental disorders such as Parkinson’s, Alzheimer’s, Huntington’s, autism, and amyotrophic lateral sclerosis. The apparent lack of specificity questions the role of mitochondrial dysfunction in psychiatric disorders, in general, and in mood disorders, in particular. Is mitochondrial dysfunction a general phenomenon, simplistically rendering brain cells to be more vulnerable to a variety of disease-specific perturbations? Or is it an epiphenomenon induced by various disease-specific factors? Or possibly, the severity and the anatomical region of the dysfunction are the ones responsible for the distinct features of the disorders. Whichever of the aforementioned ones, if any, is correct, “mitochondrial dysfunction” became more of a cliché than a therapeutic target. In this review, we summarize current studies supporting the involvement of mitochondrial dysfunction in different psychiatric disorders. We address the question of specificity and causality of the different findings and provide an alternative explanation for some of the aforementioned questions. Keywords: bipolar disorder, psychiatric disorders, schizophrenia, Stanley Foundation Brain Collection

  18. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

    DEFF Research Database (Denmark)

    Hofstra, L Marije; Sauvageot, Nicolas; Albert, Jan

    2016-01-01

    BACKGROUND:  Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these basel...

  19. Current trends in the clinical development of peptide therapeutics.

    Science.gov (United States)

    Saladin, Pauline M; Zhang, Bodi D; Reichert, Janice M

    2009-12-01

    The development of peptides as drugs is attracting increasing attention from the pharmaceutical industry. This interest is at least partially a consequence of the widespread acceptance of therapeutic proteins by physicians and patients, and because of improvements to problems such as a short half-life and delivery issues. The markets for peptide-based compounds can be substantial, with six peptide drugs attaining global sales of more than US $750 million in 2008. To track trends in the clinical development and marketing approval of peptides, Tufts Center for the Study of Drug Development and Ferring Research Institute compiled publically available data for peptides that entered clinical trials sponsored by commercial firms, with a focus on peptide therapeutics, but also including peptide vaccines and diagnostics. The results provide an historical overview of the development of peptide therapeutics, and may inform strategic planning in this area.

  20. Salmon calcitonin: a review of current and future therapeutic indications.

    Science.gov (United States)

    Chesnut, C H; Azria, M; Silverman, S; Engelhardt, M; Olson, M; Mindeholm, L

    2008-04-01

    Salmon calcitonin, available as a therapeutic agent for more than 30 years, demonstrates clinical utility in the treatment of such metabolic bone diseases as osteoporosis and Paget's disease, and potentially in the treatment of osteoarthritis. This review considers the physiology and pharmacology of salmon calcitonin, the evidence based research demonstrating efficacy and safety of this medication in postmenopausal osteoporosis with potentially an effect on bone quality to explain its abilities to reduce the risk of spine fracture, the development of an oral salmon calcitonin preparation, and the therapeutic rationale for this preparation's chondroprotective effect in osteoarthritis.

  1. Current and novel therapeutic strategies in celiac disease.

    Science.gov (United States)

    Kurada, Satya; Yadav, Abhijeet; Leffler, Daniel A

    2016-09-01

    A gluten free diet (GFD) is the only available treatment for celiac disease (CD). However many patients fail to respond fully clinically or histologically. Several surveys highlight the psychosocial implications of adherence to a GFD. Hence, efforts are ongoing to develop therapeutic strategies beyond a GFD. We conducted a search of PubMed and clinicaltrials.gov to extract articles on CD using keywords including 'celiac disease' and 'refractory celiac disease' (RCD) and focused on articles conducting pathophysiologic and therapeutic research in/ex-vivo models and human trials. We highlight novel therapeutics that manipulate these mechanisms including tight junction regulators, glutenases, gluten sequestrants and immunotherapy using vaccines, nanoparticles that may serve as adjuncts to a GFD or more ambitiously to allow for gluten consumption. We also highlight the role of anti-inflammatories, immunosuppressants and monoclonal antibodies in RCD. Expert commentary: Therapeutics including tight junction regulators, glutenases have the potential to be approved for non-responsive CD or as gluten adjuncts. We expect results of various phase 1/2 trials using AMG 714, BL 7010, IgY antibodies to be published. In the interim, off-label use of 5 amino-salicylates, budesonide, nucleoside analogues and newer biologics developed for other inflammatory diseases will be used in RCD.

  2. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...... diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin...... variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides...

  3. Breast Cancer: Current Molecular Therapeutic Targets and New Players.

    Science.gov (United States)

    Nagini, Siddavaram

    2017-01-01

    Breast cancer is the most common cancer and the most frequent cause of cancer death among women worldwide. Breast cancer is a complex, heterogeneous disease classified into hormone-receptor-positive, human epidermal growth factor receptor-2 overexpressing (HER2+) and triple-negative breast cancer (TNBC) based on histological features. Endocrine therapy, the mainstay of treatment for hormone-responsive breast cancer involves use of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs) and aromatase inhibitors (AIs). Agents that target estrogen receptor (ER) and HER2 such as tamoxifen and trastuzumab have been the most extensively used therapeutics for breast cancer. Crosstalk between ER and other signalling networks as well as epigenetic mechanisms have been envisaged to contribute to endocrine therapy resistance. TNBC, a complex, heterogeneous, aggressive form of breast cancer in which the cells do not express ER, progesterone receptor or HER2 is refractory to therapy. Several molecular targets are being explored to target TNBC including androgen receptor, epidermal growth factor receptor (EGFR), poly(ADP-ribose) polymerase (PARP), and vascular endothelial growth factor (VEGF). Receptors, protein tyrosine kinases, phosphatases, proteases, PI3K/Akt signalling pathway, microRNAs (miRs) and long noncoding RNAs (lncRNAs) are potential therapeutic targets. miR-based therapeutic approaches include inhibition of oncomiRs by antisense oligonucleotides, restoration of tumour suppressors using miR mimics, and chemical modification of miRs. The lnRNAs HOTAIR, SPRY4-IT1, GAS5, and PANDAR, new players in tumour development and prognosis may have theranostic applications in breast cancer. Several novel classes of mechanism-based drugs have been designed and synthesised for treatment of breast cancer. Integration of nucleic acid sequencing studies with mass spectrometry-based peptide sequencing and posttranslational modifications as

  4. [The therapeutic problem of current drug addiction in Italy].

    Science.gov (United States)

    De Caro, D

    1980-04-28

    Psicosocial factors which are of main importance for drug-dependences, especially in young people, are examined. Then the most important elements of the therapy of drug-dependences are indicated, which first of all consists in the necessary treatment in the hospital and farmacological therapy (particularly during acute and over-dose states), and also psicotherapeutic--generally speaking--and social approaches. Among those therapeutic Communities seem to be extremely significant, whose most important patterns are described.

  5. RECURRENT ORAL CANCER: CURRENT AND EMERGING THERAPEUTIC APPROACHES

    Directory of Open Access Journals (Sweden)

    Sabrina Daniela Silva

    2012-07-01

    Full Text Available Oral cancer cavity (OCC is associated with high incidence of loco-regional recurrences, which account for the majority of treatment failures post-surgery and radiotherapy. The time-course of relapse manifestation and metastasis are unpredictable. Relapsed OCC represents a major clinical challenge in part due to their aggressive and invasive behaviors. Chemotherapy remains the only option for advanced OCC whenever salvage surgery or re-irradiation is not feasible, but its efficacy is limited as a result of the drug resistance development. Alternatives to use of different permutations of standard cytotoxic drugs or combinations with modulators of drug resistance have led to incremental therapeutic benefits. The introduction of targeted agents and biologics against selective targets that drive cancer progression has opened-up optimism to achieve superior therapeutic activity and overcome drug resistance because, unlike the non-selective cytotoxic, the target can be monitored at molecular levels to identify patients who can benefit from the drug. This review discusses the multifactorial aspects of clinical drug resistance and emerging therapeutic approaches in recurrent OCC, emphasizing recent advances in targeted therapies, immunotherapy, and potential relevance of new concepts such as epithelial-mesenchymal transition and cancer stem cell hypothesis to drug resistance.

  6. The microbiota in inflammatory bowel disease: current and therapeutic insights

    Directory of Open Access Journals (Sweden)

    Lane ER

    2017-06-01

    Full Text Available Erin R Lane,1 Timothy L Zisman,2 David L Suskind1 1Division of Gastroenterology and Hepatology, Seattle Children’s Hospital, 2Division of Gastroenterology, University of Washington, Seattle, WA, USA Abstract: Inflammatory bowel disease is a heterogeneous group of chronic disorders that result from the interaction of the intestinal immune system with the gut microbiome. Until recently, most investigative efforts and therapeutic breakthroughs were centered on understanding and manipulating the altered mucosal immune response that characterizes these diseases. However, more recent studies have highlighted the important role of environmental factors, and in particular the microbiota, in disease onset and disease exacerbation. Advances in genomic sequencing technology and bioinformatics have facilitated an explosion of investigative inquiries into the composition and function of the intestinal microbiome in health and disease and have advanced our understanding of the interplay between the gut microbiota and the host immune system. The gut microbiome is dynamic and changes with age and in response to diet, antibiotics and other environmental factors, and these alterations in the microbiome contribute to disease onset and exacerbation. Strategies to manipulate the microbiome through diet, probiotics, antibiotics or fecal microbiota transplantation may potentially be used therapeutically to influence modulate disease activity. This review will characterize the factors involved in the development of the intestinal microbiome and will describe the typical alterations in the microbiota that are characteristic of inflammatory bowel disease. Additionally, this manuscript will summarize the early but promising literature on the role of the gut microbiota in the pathogenesis of inflammatory bowel disease with implications for utilizing this data for diagnostic or therapeutic application in the clinical management of patients with these diseases. Keywords

  7. Current Status of Dengue Therapeutics Research and Development.

    Science.gov (United States)

    Low, Jenny G H; Ooi, Eng Eong; Vasudevan, Subhash G

    2017-03-01

    Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  8. Pharmacogenomics: current applications and future prospects towards personalized therapeutics.

    Science.gov (United States)

    Vaiopoulou, A; Gazouli, M; Karikas, G A

    2013-01-01

    Personalized Medicine is more than just a metabolic activity of a person. Pharmacogenomics, pharmacogenetics, pharmacoproteomics, and metabolomics play an important role in the development of personalized medicines. Personalized medicine uses information about a person's genes, proteins, enzyme activities, and cellular environment to diagnose and treat disease, cancer included. A major problem of personalized medicine is the fact that there is no portable bedside and low-cost bioanalytical technology that can be used in close proximity to the patient. This technology could play a significant role in defining the dosage setting for subsets of the population. The success of the personalized therapy is possible through the application of technology, which can provide a bridge between metabolism status and an individual's response to a particular drug and therapeutic modality.

  9. Viral vectors for gene transfer: current status of gene therapeutics.

    Science.gov (United States)

    Heilbronn, Regine; Weger, Stefan

    2010-01-01

    Gene therapy for the correction of inherited or acquired disease has gained increasing importance in recent years. Successful treatment of children suffering from severe combined immunodeficiency (SCID) was achieved using retrovirus vectors for gene transfer. Encouraging improvements of vision were reported in a genetic eye disorder (LCA) leading to early childhood blindness. Adeno-associated virus (AAV) vectors were used for gene transfer in these trials. This chapter gives an overview of the design and delivery of viral vectors for the transport of a therapeutic gene into a target cell or tissue. The construction and production of retrovirus, lentivirus, and AAV vectors are covered. The focus is on production methods suitable for biopharmaceutical upscaling and for downstream processing. Quality control measures and biological safety considerations for the use of vectors in clinical trials are discussed.

  10. [Coronary artery fistulas, a current problem: Clinical and therapeutic considerations].

    Science.gov (United States)

    Tiritilli, A; Iaria, P; Viard, P; Sayah, S; Benali, T; Detienne, J-P; Martis, S; Tchatchum, F; Aouate, P

    2016-02-01

    The coronary fistula is a link between one or more of the coronary arteries and cardiac cavity or great vessel. The exact occurrence is unknown. The majority of these fistulas are congenital in origin. However, they may occasionally be detected after cardiac surgery. For a long time, fistulas are asymptomatic, especially if they are small; the frequency of the symptoms and especially the complications rise with age. The potential complications are: cardiac failure, endocarditis, endarteritis, atrial fibrillation, ventricular arrhythmias, rupture, and thrombosis. The main differential diagnosis is patent arterial duct, while other congenital arteriovenous shunts need to be excluded. Even though echocardiography Doppler can help to differentiate shunts, the coronary angiography remains the main diagnostic tool for the description of the anatomy. For a long time, the surgery was the only therapeutic means, up till now, percutaneous occlusion is the first line therapy of coronary fistulas and that the different devices can be tailored to meet different anatomic and functional characteristics.

  11. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    Science.gov (United States)

    Ando, Kosei; Heymann, Marie-Françoise; Stresing, Verena; Mori, Kanji; Rédini, Françoise; Heymann, Dominique

    2013-01-01

    Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi-agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies. PMID:24216993

  12. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Kosei, E-mail: andokercgv@gmail.com [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Heymann, Marie-Françoise [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Nantes University Hospital, Nantes 44035 (France); Stresing, Verena [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Nantes University Hospital, Nantes 44035 (France); Mori, Kanji [Department of Orthopaedic Surgery, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga 520-2192 (Japan); Rédini, Françoise; Heymann, Dominique [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Nantes University Hospital, Nantes 44035 (France)

    2013-05-24

    Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi-agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies.

  13. Therapeutic radionuclides in nuclear medicine: current and future prospects.

    Science.gov (United States)

    Yeong, Chai-Hong; Cheng, Mu-hua; Ng, Kwan-Hoong

    2014-10-01

    The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 ((131)I), phosphorous-32 ((32)P), strontium-90 ((90)Sr), and yttrium-90 ((90)Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.

  14. Physiological Proteins in Therapeutics: A Current Review on Interferons.

    Science.gov (United States)

    Ghosh, Debosree; Ghosh, Debjani; Parida, Pratap

    2016-01-01

    Interferons are produced in vivo and are one of the prime components of natural defense system of animals. They are released by the viral infected cells and provide protection to the neighboring cells against viral infection. The cyto-protective property of the proteins ignited the thought of their pharmaceutical adaptation for therapeutic use against viral diseases in individuals in whom the interferons released naturally are not sufficient to combat the situation. Interferon supplements have been found to complement various antiviral drugs. Considering the efficacy of interferons in regulating angiogenesis and immunomodulation, they can be adapted for therapy of the killer diseases like cancer and AIDS. We have come ahead more than twenty five years after the approval of clinical use of interferon as drugs and are today really in a position to promise a disease free life to our present and next generation. Interferon therapy will be contributing a big share to the upcoming remedies for the new diseases and we are thus armed to fight back the deadly viral threats. Interferons have been modified [pegylated etc.] and have already been adapted to some extent in certain diseases and are in regular use in some. Thus interferons if modified as per need and used in combination with either antiviral drugs, antibiotics, antioxidants may strengthen our defense system effectively to bring about a strong protection against wide range of diseases.

  15. Current therapeutic strategies for invasive and metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Vishnu P

    2011-07-01

    Full Text Available Prakash Vishnu, Jacob Mathew, Winston W TanDivision of Hematology Oncology, Mayo Clinic, Jacksonville, FL, USABackground: Bladder cancer is one of the most common cancers in Europe, the United States, and Northern African countries. Muscle-invasive bladder cancer is an aggressive epithelial tumor, with a high rate of early systemic dissemination. Superficial, noninvasive bladder cancer can most often be cured; a good proportion of invasive cases can also be cured by a combined modality approach of surgery, chemotherapy, and radiation. Recurrences are common and mostly manifest as metastatic disease. Those with distant metastatic disease can sometime achieve partial or complete remission with combination chemotherapy.Recent developments: Better understanding of the biology of the disease has led to the incorporation of molecular and genetic features along with factors such as tumor grade, lympho-vascular invasion, and aberrant histology, thereby allowing identification of ‘favorable’ and ‘unfavorable’ cancers which helps a more accurate informed and objective selection of patients who would benefit from neoadjuvant and adjuvant chemotherapy. Gene expression profiling has been used to find molecular signature patterns that can potentially be predictive of drug sensitivity and metastasis. Understanding the molecular pathways of invasive bladder cancer has led to clinical investigation of several targeted therapeutics such as anti-angiogenics, mTOR inhibitors, and anti-EGFR agents.Conclusion: With improvements in the understanding of the biology of bladder cancer, clinical trials studying novel and targeted agents alone or in combination with chemotherapy have increased the armamentarium for the treatment of bladder cancer. Although the novel biomarkers and gene expression profiles have been shown to provide important predictive and prognostic information and are anticipated to be incorporated in clinical decision-making, their exact utility

  16. Obesity and asthma in children: current and future therapeutic options.

    Science.gov (United States)

    Lang, Jason E

    2014-06-01

    With the childhood prevalence of obesity and asthma increasing, it is important for pediatric professionals to appreciate that obesity modifies the diagnosis and management of asthma. These disease modifications present challenges to clinical management, including decreased responsiveness to controller therapy and decreased quality of life compared with normal-weight asthmatic children. While consensus guidelines do not currently suggest specific changes in asthma management for obese patients, management of some patients may be improved with consideration of the latest evidence. This article briefly summarizes what is known regarding the complex relationship between obesity and asthma in children, and discusses practical issues associated with the diagnosis and effective clinical management of asthma in obese children. On average, obese patients with asthma do not respond as well to inhaled corticosteroid therapy. Management approaches including weight loss and routine exercise are safe, and may improve important asthma outcomes. Asthma providers should learn to facilitate weight loss for their obese patients. In addition, pharmacologic interventions for weight loss in obese asthma, though not currently recommended, may soon be considered.

  17. Therapeutic Management of Familial Hypercholesterolemia: Current and Emerging Drug Therapies.

    Science.gov (United States)

    Patel, Roshni S; Scopelliti, Emily M; Savelloni, Julie

    2015-12-01

    Familial hypercholesterolemia (FH) is a genetic disorder characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) concentrations that result from mutations of the LDL receptor, apolipoprotein B (apo B-100), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Early and aggressive treatment can prevent premature atherosclerotic cardiovascular disease in these high-risk patients. Given that the cardiovascular consequences of FH are similar to typical hypercholesterolemia, traditional therapies are utilized to decrease LDL-C levels. Patients with FH should receive statins as first-line treatment; high-potency statins at high doses are often required. Despite the use of statins, additional treatments are often necessary to achieve appropriate LDL-C lowering in this patient population. Novel drug therapies that target the pathophysiologic defects of the condition are continuously emerging. Contemporary therapies including mipomersen (Kynamro, Genzyme), an oligonucleotide inhibitor of apo B-100 synthesis; lomitapide (Juxtapid, Aegerion), a microsomal triglyceride transfer protein inhibitor; and alirocumab (Praluent, Sanofi-Aventis/Regeneron) and evolocumab (Repatha, Amgen), PCSK9 inhibitors, are currently approved by the U.S. Food and Drug Administration for use in FH. This review highlights traditional as well as emerging contemporary therapies with supporting clinical data to evaluate current recommendations and discuss the future direction of FH management.

  18. Current therapeutic agents and anesthetic considerations for diabetes mellitus.

    Science.gov (United States)

    Kang, Hyoseok

    2012-09-01

    As the incidence of diabetes mellitus (DM) continues to increase worldwide, more diabetic patients will be presented for surgery and anesthesia. This increase of DM is a consequence of the rise in new patients of type 2 DM, and is likely attributable to rapid economic development, improved living standards, aging population, obesity, and lack of exercise. The primary goal of management in DM is to delay, or prevent the macro- and microvascular complications by achieving good glycemic control. More understanding of the pathophysiology of DM has contributed to the advance of new pharmacological approaches. In addition to the conventional therapy for DM, glucagon-like peptide-1 (GLP-1) mimetics, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones (TZDs), and insulin analogues are currently available effective hypoglycemic agents for the management of the patients with DM in the perioperative period and also consider the adverse effects of newly introduced agents that need more clinical observations.

  19. A systematic review of antibiotic dosing regimens for septic patients receiving continuous renal replacement therapy: do current studies supply sufficient data?

    Science.gov (United States)

    Li, A M M Y; Gomersall, C D; Choi, G; Tian, Q; Joynt, G M; Lipman, J

    2009-11-01

    Drug dosing for septic patients with acute renal failure receiving continuous renal replacement therapy (CRRT) is complicated, and failure to correctly dose may result in either drug toxicity or treatment failure and development of antibiotic resistance. The aim of this study was to establish an ideal dataset that needs to be reported when presenting pharmacokinetic data for these patients and review current literature for completeness of this dataset. An ideal dataset was established of the parameters that should be reported when calculating a drug dosing regimen from first principles. A Medline search was performed of relevant literature producing 64 citations from which completeness of the specified criteria was examined. None of the studies analysed presented the full dataset that we established as necessary. Of concern, basic pharmacokinetic parameters such as volume of distribution (V(d)) and clearance (CL) were specified in only 79% and 81% of studies, respectively. A large proportion of current studies do not report key information necessary to devise a rational dosing regimen for patients with acute renal failure receiving CRRT, and we hope this dataset will be a useful guide when reporting future pharmacokinetic data.

  20. Current Research Therapeutic Strategies for Alzheimer's Disease Treatment

    Science.gov (United States)

    Folch, Jaume; Petrov, Dmitry; Ettcheto, Miren; Abad, Sonia; Sánchez-López, Elena; García, M. Luisa; Olloquequi, Jordi; Beas-Zarate, Carlos; Auladell, Carme; Camins, Antoni

    2016-01-01

    Alzheimer's disease (AD) currently presents one of the biggest healthcare issues in the developed countries. There is no effective treatment capable of slowing down disease progression. In recent years the main focus of research on novel pharmacotherapies was based on the amyloidogenic hypothesis of AD, which posits that the beta amyloid (Aβ) peptide is chiefly responsible for cognitive impairment and neuronal death. The goal of such treatments is (a) to reduce Aβ production through the inhibition of β and γ secretase enzymes and (b) to promote dissolution of existing cerebral Aβ plaques. However, this approach has proven to be only modestly effective. Recent studies suggest an alternative strategy centred on the inhibition of the downstream Aβ signalling, particularly at the synapse. Aβ oligomers may cause aberrant N-methyl-D-aspartate receptor (NMDAR) activation postsynaptically by forming complexes with the cell-surface prion protein (PrPC). PrPC is enriched at the neuronal postsynaptic density, where it interacts with Fyn tyrosine kinase. Fyn activation occurs when Aβ is bound to PrPC-Fyn complex. Fyn causes tyrosine phosphorylation of the NR2B subunit of metabotropic glutamate receptor 5 (mGluR5). Fyn kinase blockers masitinib and saracatinib have proven to be efficacious in treating AD symptoms in experimental mouse models of the disease. PMID:26881137

  1. Ocular Behçet disease: current therapeutic approaches.

    Science.gov (United States)

    Evereklioglu, Cem

    2011-11-01

    To alert physician to timely recognition and current treatment of recurrent hypopyon iridocyclitis or panuveitis in ocular Behçet disease (OBD). Interferon-α, rituximab, intravitreal triamcinolone, and biological response modifiers by tumor necrosis factor inhibitors such as infliximab and adalimumab are being used increasingly for the treatment of severe sight-threatening ocular inflammation including retinal vasculitis and cystoid macular edema (CME). Biological agents offer tremendous potential in the treatment of OBD. Given that OBD predominantly afflicts the younger adults in their most productive years, dermatologist, rheumatologist, internist, or general practitioners supervising patients with oculo-articulo-oromucocutaneous syndromes should be aware of systemic Behçet disease. Early recognition of ocular involvement is important and such patients should strongly be instructed to visit immediately an ophthalmologist, as uveitis management differs from extraocular involvements with high ocular morbidity from sight-threatening complications due to relapsing inflammatory attacks in the posterior segment of the eye. A single infliximab infusion should be considered for the control of acute panuveitis, whereas repeated long-term infliximab infusions were proved to be more effective in reducing the number of episodes in refractory uveoretinitis with faster regression and complete remission of CME.

  2. Current Research Therapeutic Strategies for Alzheimer’s Disease Treatment

    Directory of Open Access Journals (Sweden)

    Jaume Folch

    2016-01-01

    Full Text Available Alzheimer’s disease (AD currently presents one of the biggest healthcare issues in the developed countries. There is no effective treatment capable of slowing down disease progression. In recent years the main focus of research on novel pharmacotherapies was based on the amyloidogenic hypothesis of AD, which posits that the beta amyloid (Aβ peptide is chiefly responsible for cognitive impairment and neuronal death. The goal of such treatments is (a to reduce Aβ production through the inhibition of β and γ secretase enzymes and (b to promote dissolution of existing cerebral Aβ plaques. However, this approach has proven to be only modestly effective. Recent studies suggest an alternative strategy centred on the inhibition of the downstream Aβ signalling, particularly at the synapse. Aβ oligomers may cause aberrant N-methyl-D-aspartate receptor (NMDAR activation postsynaptically by forming complexes with the cell-surface prion protein (PrPC. PrPC is enriched at the neuronal postsynaptic density, where it interacts with Fyn tyrosine kinase. Fyn activation occurs when Aβ is bound to PrPC-Fyn complex. Fyn causes tyrosine phosphorylation of the NR2B subunit of metabotropic glutamate receptor 5 (mGluR5. Fyn kinase blockers masitinib and saracatinib have proven to be efficacious in treating AD symptoms in experimental mouse models of the disease.

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

    Directory of Open Access Journals (Sweden)

    Couldwell DL

    2015-05-01

    Full Text Available Deborah L Couldwell,1,2 David A Lewis1,21Western Sydney Sexual Health Centre, Parramatta, 2Centre for Infectious Diseases and Microbiology and Marie Bashir Institute for Infectious Diseases and Biosecurity, Westmead Clinical School, University of Sydney, Sydney, NSW, Australia Abstract: Mycoplasma genitalium is an important cause of non-gonococcal urethritis, cervicitis, and related upper genital tract infections. The efficacy of doxycycline, used extensively to treat non-gonococcal urethritis in the past, is relatively poor for M. genitalium infection; azithromycin has been the preferred treatment for several years. Research on the efficacy of azithromycin has primarily focused on the 1 g single-dose regimen, but some studies have also evaluated higher doses and longer courses, particularly the extended 1.5 g regimen. This extended regimen is thought to be more efficacious than the 1 g single-dose regimen, although the regimens have not been directly compared in clinical trials. Azithromycin treatment failure was first reported in Australia and has subsequently been documented in several continents. Recent reports indicate an upward trend in the prevalence of macrolide-resistant M. genitalium infections (transmitted resistance, and cases of induced resistance following azithromycin therapy have also been documented. Emergence of antimicrobial-resistant M. genitalium, driven by suboptimal macrolide dosage, now threatens the continued provision of effective and convenient treatments. Advances in techniques to detect resistance mutations in DNA extracts have facilitated correlation of clinical outcomes with genotypic resistance. A strong and consistent association exists between presence of 23S rRNA gene mutations and azithromycin treatment failure. Fluoroquinolones such as moxifloxacin, gatifloxacin, and sitafloxacin remain highly active against most macrolide-resistant M. genitalium. However, the first clinical cases of moxifloxacin treatment

  4. Subcutaneous Immunoglobulin-G Replacement Therapy with Preparations Currently Available in the United States for Intravenous or Intramuscular Use: Reasons and Regimens

    Directory of Open Access Journals (Sweden)

    Chouksey Akhilesh

    2005-09-01

    Full Text Available Abstract For patients who require replacement therapy for primary immunodeficiency, subcutaneous infusions of immunoglobulin G (IgG may be preferable to intravenous infusions for several reasons. However, at present, there is no preparation marketed for use by this route in North America. In this article, we describe the reasons patients have selected this route of therapy and the range of treatment regimens used. Approximately 20% of our patients have chosen the subcutaneous route, mainly because of adverse effects from intravenous (IV infusions or difficulties with venous access. Unit dose regimens using whole bottles of currently available 16% intramuscular preparations or sucrose-containing lyophilized preparations intended for IV use but reconstituted to 15% IgG for subcutaneous administration were individually tailored to each patient. In most cases, self-infusions or home infusions were administered once or twice a week, most commonly requiring two subcutaneous sites and 2 to 3 hours per infusion. On average, patients took 0.18 mL of IgG per kilogram of body weight per site per hour. There were no systemic adverse effects. In patients for whom comparative data were available, trough serum IgG levels were higher with subcutaneous therapy than with IV therapy.

  5. Therapeutic use of prebiotics, probiotics, and postbiotics to prevent necrotizing enterocolitis: what is the current evidence?

    Science.gov (United States)

    Patel, Ravi Mangal; Denning, Patricia Wei

    2013-03-01

    Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality, and preventive therapies that are both effective and safe are urgently needed. Current evidence from therapeutic trials suggests that probiotics are effective in decreasing NEC in preterm infants, and probiotics are currently the most promising therapy for this devastating disease. However, concerns regarding safety and optimal dosing have limited the widespread adoption of routine clinical use of probiotics in preterm infants. This article summarizes the current evidence regarding the use of probiotics, prebiotics, and postbiotics in the preterm infant, including their therapeutic role in preventing NEC.

  6. Comparison of bacillary index on slit skin smear with bacillary index of granuloma in leprosy and its relevance to present therapeutic regimens

    Directory of Open Access Journals (Sweden)

    Sendhil M Kumaran

    2015-01-01

    Full Text Available Background: As the world moves toward elimination of leprosy, persistence of infective cases in endemic pockets remains a significant problem. The use of clinical criteria to decide the paucibacillary (PB versus multibacillary (MB regimens has greatly simplified therapy at the field setting. However, a small but significant risk of under-treatment of so-called "PB" cases which actually have significant bacillary load exists. This study was undertaken to assess this risk and compare two methods of assessment of bacillary load, namely bacillary index on slit skin smear (BIS versus bacillary index of granuloma (BIG. Aims: To compare BIS with BIG on skin biopsy in consecutive untreated cases of leprosy. Materials and Methods: This prospective study was conducted over a period of 12 months, wherein new untreated patients with leprosy were consecutively recruited. After a thorough clinical examination, each patient underwent slit skin smear (SSS where the BIS was calculated. The same patient also underwent a skin biopsy from a clinical lesion where, the BIG was calculated. SSS and skin biopsy for BIS and BIG respectively were repeated for all patients at the end of therapy for comparison. All patients received therapy according to World Health Organization-Multidrug Therapy Guidelines. Results: The BIG was positive in all cases where the BIS was positive. Significantly, BIG was positive in three cases of borderline tuberculoid leprosy with <5 lesions who received PB regimen, whereas the BIS was negative in all three cases. Conclusion: This study suggests that BIG may be a better indicator of the true bacillary load in leprosy as compared to BIS. Its role in management is significant, at least in tertiary care centers to prevent "under-treatment" of so called PB cases, which may actually warrant MB regimens.

  7. Pretreatment platelet count improves the prognostic performance of the TNM staging system and aids in planning therapeutic regimens for nasopharyngeal carcinoma: a single-institutional study of 2,626 patients.

    Science.gov (United States)

    Chen, Yu-Pei; Zhao, Bing-Cheng; Chen, Chen; Shen, Lu-Jun; Gao, Jin; Mai, Zhuo-Yao; Chen, Meng-Kun; Chen, Gang; Yan, Fang; Liu, Su; Xia, Yun-Fei

    2015-03-05

    Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer. This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the TNM staging system and therapeutic regimens in patients with nasopharyngeal carcinoma (NPC). A total of 2,626 patients with NPC were retrospectively analyzed. Platelet count >300 × 10(9)/L was defined as thrombocytosis. Matched-pair analysis was performed between patients receiving chemoradiotherapy and radiotherapy. Multivariate analysis showed that platelet count was an independent unfavorable prognostic factor for overall survival (OS) [hazard ratio (HR) = 1.810, 95% confidence interval (CI) = 1.531-2.140, P TNM classification (all P ≤ 0.001). Receiver operating characteristic (ROC) curves verified that the predictive value of TNM classification for OS was improved when combined with pretreatment platelet count (P = 0.030). Matched-pair analysis showed that chemoradiotherapy significantly improved OS only in advanced-stage NPC with thrombocytosis (HR = 0.416, 95% CI = 0.226-0.765, P = 0.005). Pretreatment platelet count, when combined with TNM classification, is a useful indicator for metastasis and survival in patients with NPC. It may improve the predictive value of the TNM classification and help to identify patients likely to benefit from more aggressive therapeutic regimens.

  8. Favorable therapeutic response with an antiretroviral salvage regimen in an HIV-1-positive subject infected with a CRF11-cpx virus.

    Science.gov (United States)

    Tau, Pamela; Mancon, Alessandro; Mileto, Davide; Di Nardo Stuppino, Silvia; Bottani, Giulia; Gismondo, Maria Rita; Galli, Massimo; Micheli, Valeria; Rusconi, Stefano

    2014-05-01

    HIV drug resistance still represents a crucial problem in antiretroviral therapy. We report a case of a naive patient, harboring a CRF11-cpx virus, which showed drug resistance mutations in the reverse transcriptase. A drug resistance genotyping test was performed for the pol (protease, reverse transcriptase, and integrase) and V3 regions. The initial clinical parameter results showed a 4 log level of HIV-RNA (12,090 cp/ml) and a very low CD4(+) cell count (35 cells/μl). We designed an initial highly active antiretroviral therapy (HAART) regimen including lamivudine (3TC)+abacavir (ABC)+booster ritonavir (DRV/r). The virus was highly resistant to all nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) except for ABC, tenofovir (TDF), and efavirenz (EFV) and was susceptible to all protease inhibitors (PIs) and integrase inhibitors (INIs). A salvage regimen including raltegravir (RAL)+DRV/r was started. Ten months later, the immunovirological status shows CD4(+) 142/μl and HIV-RNA <37 cp/ml. Our results demonstrate the effectiveness of a treatment combination that includes RAL+DRV/r in a patient infected with a complex X4-tropic CRF11-cpx virus.

  9. Therapeutic Use of Prebiotics, Probiotics, and Postbiotics to Prevent Necrotizing Enterocolitis: What is the Current Evidence?

    OpenAIRE

    2013-01-01

    Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality and preventative therapies that are both effective and safe are urgently needed. Current evidence from therapeutic trials suggests that probiotics are effective in decreasing NEC in preterm infants and probiotics are currently the most promising therapy on the horizon for this devastating disease. However, concerns regarding safety and optimal dosing have limited the widespread adoption of routine clinical ...

  10. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Faezeh Ghasemi

    2016-07-01

    Full Text Available Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus(HBV is mainly due to its ability to debilitate host's immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host's immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far.

  11. Therapeutic Use of Prebiotics, Probiotics, and Postbiotics to Prevent Necrotizing Enterocolitis: What is the Current Evidence?

    Science.gov (United States)

    Patel, Ravi Mangal; Denning, Patricia Wei

    2013-01-01

    Synopsis Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality and preventative therapies that are both effective and safe are urgently needed. Current evidence from therapeutic trials suggests that probiotics are effective in decreasing NEC in preterm infants and probiotics are currently the most promising therapy on the horizon for this devastating disease. However, concerns regarding safety and optimal dosing have limited the widespread adoption of routine clinical use of probiotics in preterm infants. In addition, prebiotics and postbiotics may be potential alternatives or adjunctive therapies to the administration of live microorganisms, although studies demonstrating their clinical efficacy in preventing NEC are lacking. This review summarizes the current evidence regarding the use of probiotics, prebiotics and postbiotics in the preterm infant, including its therapeutic role in preventing NEC. PMID:23415261

  12. Clinical observation and therapeutic evaluation of intravenous pump of recombinant human endostatin combined with TP regimen in treating patients with advanced ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Chi Zhang; Wen-Ying Deng; Ning Li; Su-Xia Luo

    2015-01-01

    Objectives: To observe the curative effects and adverse reactions of recombinant human (rh)-endostatin injection combined with a TP regimen for treating patients with advanced ovarian cancer.Methods: Fifty-four patients with pathologically confirmed ovarian cancer were randomly divided into a combined treatment (intravenous pump of rh-endostatin + TP regimen) group and a control (single chemotherapy) group, twenty-seven patients in each group.All patients were given a conventional CT examination.The level of vascular endothelial growth factor (VEGF), the size of tumor before treatment, after 2 cycles and after 4 cycles of treatment were determined for the comparison of curative effects and adverse reactions.Results: The effective rate was 37.0% (10/27) and disease control rate was 63.0% (17/27) in the combined treatment group after 2 cycles of treatment.The effective rate was 25.9% (7/27) and disease control rate was 63.0% (17/27) in the control group.The comparison between these two groups showed no significant differences (P > 0.05).The effective rate was 63.0% (17/27) and disease control rate was 92.6% (25/27) in the combined treatment group after 4 cycles of treatment.The effective rate was 29.6% (8/27) and disease control rate was 63.0% (17/27) in the control group.The effective rate and disease control rate between these two groups after 4 cycles of treatment showed significant differences (P < 0.05).The incidences of cardiovascular toxicity, myelosuppression, sore muscles and joints, alopecia and gastrointestinal reaction was not significantly different between two groups (P > 0.05).Conclusion: The pump delivery of rh-endostatin can down-regulate the expression of VEGF in ovarian cancer and has the better curative effect and slighter adverse reactions.Copyright 2015, Chinese Medical Association Production.Production and hosting by Elsevier B.V.on behalf of KeAi Communications Co., Ltd.This is an open access article under the CC BY

  13. Heterotopic ossifications following implant surgery--epidemiology, therapeutical approaches and current concepts.

    Science.gov (United States)

    Zeckey, Christian; Hildebrand, Frank; Frink, Michael; Krettek, Christian

    2011-05-01

    The pathophysiology of heterotopic ossification (HO) is still ill-understood. Several risk factors such as osteoarthritis, male gender and injury patterns like traumatic brain injury and severe soft tissue damage have been described. Furthermore, the pathophysiology of local and systemic factors has been investigated leading to an extended knowledge especially on the molecular level. Knowledge of the involved cell types and mediators led to the now widely used prophylactic and therapeutic strategies to prevent heterotopic ossifications. Out of these findings, the beneficial effects of NSAIDs and radiotherapy on HO prophylaxis have been proven for a number of indications such as total hip arthroplasty and acetabular surgery. However, there is little information about the potential effects on heterotopic ossifications around the elbow. Surgical treatment may be considered in some cases, but there are only limited indications. Generally, only clinically relevant bone formations should be resected. Following surgical resection, beneficial effects on range of motion and pain relief has been described. An accurate perioperative regimen is crucial and includes prophylactic medication. In combination with radiotherapy, low recurrence rates were described but there are still controversies about the optimal timing for surgical resection.

  14. Human Papillomavirus: Current and Future RNAi Therapeutic Strategies for Cervical Cancer

    Science.gov (United States)

    Jung, Hun Soon; Rajasekaran, Nirmal; Ju, Woong; Shin, Young Kee

    2015-01-01

    Human papillomaviruses (HPVs) are small DNA viruses; some oncogenic ones can cause different types of cancer, in particular cervical cancer. HPV-associated carcinogenesis provides a classical model system for RNA interference (RNAi) based cancer therapies, because the viral oncogenes E6 and E7 that cause cervical cancer are expressed only in cancerous cells. Previous studies on the development of therapeutic RNAi facilitated the advancement of therapeutic siRNAs and demonstrated its versatility by siRNA-mediated depletion of single or multiple cellular/viral targets. Sequence-specific gene silencing using RNAi shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, siRNA-based targeting requires further validation of its efficacy in vitro and in vivo, for its potential off-target effects, and of the design of conventional therapies to be used in combination with siRNAs and their drug delivery vehicles. In this review we discuss what is currently known about HPV-associated carcinogenesis and the potential for combining siRNA with other treatment strategies for the development of future therapies. Finally, we present our assessment of the most promising path to the development of RNAi therapeutic strategies for clinical settings. PMID:26239469

  15. Human Papillomavirus: Current and Future RNAi Therapeutic Strategies for Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Hun Soon Jung

    2015-05-01

    Full Text Available Human papillomaviruses (HPVs are small DNA viruses; some oncogenic ones can cause different types of cancer, in particular cervical cancer. HPV-associated carcinogenesis provides a classical model system for RNA interference (RNAi based cancer therapies, because the viral oncogenes E6 and E7 that cause cervical cancer are expressed only in cancerous cells. Previous studies on the development of therapeutic RNAi facilitated the advancement of therapeutic siRNAs and demonstrated its versatility by siRNA-mediated depletion of single or multiple cellular/viral targets. Sequence-specific gene silencing using RNAi shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, siRNA-based targeting requires further validation of its efficacy in vitro and in vivo, for its potential off-target effects, and of the design of conventional therapies to be used in combination with siRNAs and their drug delivery vehicles. In this review we discuss what is currently known about HPV-associated carcinogenesis and the potential for combining siRNA with other treatment strategies for the development of future therapies. Finally, we present our assessment of the most promising path to the development of RNAi therapeutic strategies for clinical settings.

  16. Initial dosing regimen of vancomycin to achieve early therapeutic plasma concentration in critically ill patients with MRSA infection based on APACHE II score.

    Science.gov (United States)

    Imaura, Masaharu; Yokoyama, Haruko; Kohata, Yuji; Kanai, Riichiro; Kohyama, Tomoki; Idemitsu, Wataru; Maki, Yuichi; Igarashi, Takashi; Takahashi, Hiroyuki; Kanno, Hiroshi; Yamada, Yasuhiko

    2016-06-01

    It is essential to assure the efficacy of antimicrobials at the initial phase of therapy. However, increasing the volume of distribution (Vd) of hydrophilic antimicrobials in critically ill patients leads to reduced antimicrobial concentration in plasma and tissue, which may adversely affect the efficacy of that therapy. The aim of the present study was to establish a theoretical methodology for setting an appropriate level for initial vancomycin therapy in individual patients based on Acute Physiology and Chronic Health Evaluation (APACHE) II score. We obtained data from patients who received intravenous vancomycin for a suspected or definitively diagnosed Gram-positive bacterial infection within 72 h after admission to the intensive care unit. The Vd and elimination half-life (t 1/2) of vancomycin values were calculated using the Bayesian method, and we investigated the relationship between them and APACHE II score. There were significant correlations between APACHE II scores and Vd/actual body weight (ABW), as well as t 1/2 (r = 0.58, p < 0.05 and r = 0.74, p < 0.01, respectively). Our results suggested that the Vd and t 1/2 of vancomycin could be estimated using the following regression equations using APACHE II score.[Formula: see text] [Formula: see text]We found that APACHE II score was a useful index for predicting the Vd and t 1/2 of vancomycin, and used that to establish an initial vancomycin dosing regimen comprised of initial dose and administration interval for individual patients.

  17. Pretreatment platelet count improves the prognostic performance of the TNM staging system and aids in planning therapeutic regimens for nasopharyngeal carcinoma:a single-institutional study of 2,626 patients

    Institute of Scientific and Technical Information of China (English)

    Yu-Pei Chen; Su Liu; Yun-Fei Xia; Bing-Cheng Zhao; Chen Chen; Lu-Jun Shen; Jin Gao; Zhuo-Yao Mai; Meng-Kun Chen; Gang Chen; Fang Yan

    2015-01-01

    Introduction:Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer. This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the TNM staging system and therapeutic regimens in patients with nasopharyngeal carcinoma (NPC). Methods:A total of 2,626 patients with NPC were retrospectively analyzed. Platelet count>300 × 109/L was defined as thrombocytosis. Matched-pair analysis was performed between patients receiving chemoradiotherapy and radiotherapy. Results:Multivariate analysis showed that platelet count was an independent unfavorable prognostic factor for overal survival (OS) [hazard ratio (HR)=1.810, 95%confidence interval (CI)=1.531–2.140, P<0.001] and distant metastasis–free survival (DMFS) (HR=1.873, 95%CI=1.475–2.379, P<0.001) in the entire patient cohort. Further subgroup analysis revealed that increased platelet count was an independent unfavorable prognostic factor for OS and DMFS in patients with NPC stratified by early and advanced T category, N category, or TNM classification (al P≤0.001). Receiver operating characteristic (ROC) curves verified that the predictive value of TNM classification for OS was improved when combined with pretreatment platelet count (P=0.030). Matched-pair analysis showed that chemoradiotherapy significantly improved OS only in advanced-stage NPC with thrombocytosis (HR=0.416, 95%CI=0.226–0.765, P=0.005). Conclusions:Pretreatment platelet count, when combined with TNM classification, is a useful indicator for metastasis and survival in patients with NPC. It may improve the predictive value of the TNM classification and help to identify patients likely to benefit from more aggressive therapeutic regimens.

  18. Single-tablet regimens (STRs enhance patients’ acceptability of HAART

    Directory of Open Access Journals (Sweden)

    F Maggiolo

    2012-11-01

    Full Text Available Patients’ acceptability of HAART is a subjective variable that may deeply influence therapeutic outcome. The feeling of the patient may alter adherence and lead to virologic failure. Acceptability may depend on various variables often difficulty evaluated by the care-giver. In a clinical setting the evaluation of acceptability is difficult, too, as patients may feel a judgement and be less sincere. Aim of this study was to asses adherence and acceptability of HAART. To limit reporting biases, the study was performed in five different non-clinic settings covering North and Central Italy. A total of 230 patients on stable HAART were asked to complete a semi-structured, anonymous questionnaire reporting their attitude toward HAART, their adherence and the acceptability of their regimen. In these notes we focus on this last patient-oriented outcome. Most of the subjects were males (66% with a mean age of 46 years, with higher education level (72% and a long history of HIV infection (mean 13.6 years. Consequently only 17% of patients were on a first-line regimen. Patients reporting a high or very high acceptability of HAART were 60% compared to a 31% reporting a fair grade of satisfaction and a 9% indicating low or null acceptability. However the type of the regimen significantly influenced patients’ acceptability. Single-tablet regimens (STRs, OD regimens with more than one tablet/day or BID regimens were scored as highly acceptable in 84%; 61%; and 53% of cases, respectively (P < 0.0001 (Figure. Statistical significance was retained when the dosing schedule was entered in a multivariate logistic model. When the analysis was restricted to experienced patients 62% of them were currently on a regimen based on a reduced number of pills compared to the previous one. Patients scored the previous regimen as more difficult to comply with in 72% of cases; as difficult in 22% and less difficult in 6%. The eventuality of AEs (40%; respect of timing of

  19. Therapeutic targeting of microRNAs: current status and future challenges.

    Science.gov (United States)

    Li, Zhonghan; Rana, Tariq M

    2014-08-01

    MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that have crucial roles in regulating gene expression. Increasing evidence supports a role for miRNAs in many human diseases, including cancer and autoimmune disorders. The function of miRNAs can be efficiently and specifically inhibited by chemically modified antisense oligonucleotides, supporting their potential as targets for the development of novel therapies for several diseases. In this Review we summarize our current knowledge of the design and performance of chemically modified miRNA-targeting antisense oligonucleotides, discuss various in vivo delivery strategies and analyse ongoing challenges to ensure the specificity and efficacy of therapeutic oligonucleotides in vivo. Finally, we review current progress on the clinical development of miRNA-targeting therapeutics.

  20. The impact of antiretroviral therapy in resource-limited settings and current HIV therapeutics.

    Science.gov (United States)

    Kumarasamy, N

    2016-04-01

    Four million people of the global total of 35 million with HIV infection are from South-East Asia. ART is currently utilized by 15 million people and has led to a dramatic decline in the mortality rate, including those in low- and middle-income countries. A reduction in sexually transmitted HIV and in comorbidities including tuberculosis has also followed. Current recommendations for the initiation of antiretroviral therapy in people who are HIV+ are essentially to initiate ART irrespective of CD4 cell count and clinical stage. The frequency of HIV testing should be culturally specific and based on the HIV incidence in different key populations but phasing in viral load technology in LMIC is an urgent priority and this needs resources and capacity. With the availability of simplified potent ART regimens, persons with HIV now live longer. The recent WHO treatment guidelines recommending routine HIV testing and earlier initiation of treatment should be the stepping stone for ending the AIDS epidemic and to meet the UNAIDS mission of 90*90*90.

  1. Liver Toxicity of Current Antiretroviral Regimens in HIV-Infected Patients with Chronic Viral Hepatitis in a Real-Life Setting: The HEPAVIR SEG-HEP Cohort

    Science.gov (United States)

    Neukam, Karin; Mira, José A.; Collado, Antonio; Rivero-Juárez, Antonio; Monje-Agudo, Patricia; Ruiz-Morales, Josefa; Ríos, María José; Merino, Dolores; Téllez, Francisco; Pérez-Camacho, Inés; Gálvez-Contreras, María Carmen; Rivero, Antonio; Pineda, Juan A.

    2016-01-01

    Objective To assess the current frequency of ART-associated grade 3–4 transaminase elevations (TE) and grade 4 total bilirubin elevations (TBE) in HIV-infected patients with chronic hepatitis B and/or C, who start a new regimen of ART. Patients and Methods A total of 192 pre-treated or treatment-naive HIV infected patients with HBV and/or HCV-coinfection who started ART in eight Southern Spanish centers from July/2011-December/2013, were followed for 12 months in this prospective study. Results Forty-one (21.4%) subjects had been naïve to ART, median (IQR) follow-up was 11.6 (5.6–12.9) months. The most frequently initiated NRTI were tenofovir/emtricitabine [49 patients (25.5%)]. Eighty-nine (46.4%) patients started a ritonavir-boosted protease inhibitor and 77 (40.1%) individuals a NNRTI. Raltegravir and maraviroc were initiated in 24 (12.5%) and 9 (4.7%) individuals. Ten [5.21%; 95% confidence interval (CI): 2.53%-9.37%] patients presented grade 3 TE, while 8 (4.17%; 95%CI: 1.82%-8.04%) subjects showed grade 4 TBE. No episodes of grade 4 TE or ART discontinuation due to hepatotoxic events were observed. The use of ritonavir-boosted atazanavir was the only independent predictor for grade 4 TBE [adjusted odds ratio: 7.327 (95%CI: 1.417–37.89); p = 0.018] in an analysis adjusted for age, sex and baseline HIV-RNA levels, while no factor could be independently associated with grade 3–4 TE. Conclusions Currently, the frequency of severe ART-associated TE and TBE under real-life conditions in patients with chronic viral hepatitis is similar to what has been reported previously. However, episodes of grade 4 TE are less frequent and severe TE appears to be of lesser concern. PMID:26848975

  2. Therapeutic antibodies: current state and future trends--is a paradigm change coming soon?

    Science.gov (United States)

    Dimitrov, Dimiter S; Marks, James D

    2009-01-01

    Antibody-based therapeutics currently enjoy unprecedented success, growth in research and revenues, and recognition of their potential. It appears that the promise of the "magic bullet" has largely been realized. There are currently 22 monoclonal antibodies (mAbs) approved by the United States Food and Drug Administration (FDA) for clinical use and hundreds are in clinical trials for treatment of various diseases including cancers, immune disorders, and infections. The revenues from the top five therapeutic antibodies (Rituxan, Remicade, Herceptin, Humira, and Avastin) nearly doubled from $6.4 billion in 2004 to $11.7 billion in 2006. During the last several years major pharmaceutical companies raced to acquire antibody companies, with a recent example of MedImmune being purchased for $15.6 billion by AstraZeneca. These therapeutic and business successes reflect the major advances in antibody engineering which have resulted in the generation of safe, specific, high-affinity, and non-immunogenic antibodies during the last three decades. Currently, second and third generations of antibodies are under development, mostly to improve already existing antibody specificities. However, although the refinement of already known methodologies is certainly of great importance for potential clinical use, there are no conceptually new developments in the last decade comparable, for example, to the development of antibody libraries, phage display, domain antibodies (dAbs), and antibody humanization to name a few. A fundamental question is then whether there will be another change in the paradigm of research as happened 1-2 decades ago or the current trend of gradual improvement of already developed methodologies and therapeutic antibodies will continue. Although any prediction could prove incorrect, it appears that conceptually new methodologies are needed to overcome the fundamental problems of drug (antibody) resistance due to genetic or/and epigenetic alterations in cancer and

  3. Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies.

    Science.gov (United States)

    Wang, S Z; Rui, Y F; Lu, J; Wang, C

    2014-10-01

    Intervertebral disc degeneration (IDD) is a chronic, complex process associated with low back pain; mechanisms of its occurrence have not yet been fully elucidated. Its process is not only accompanied by morphological changes, but also by systematic changes in its histological and biochemical properties. Many cellular and molecular mechanisms have been reported to be related with IDD and to reverse degenerative trends, abnormal conditions of the living cells and altered cell phenotypes would need to be restored. Promising biological therapeutic strategies still rely on injection of active substances, gene therapy and cell transplantation. With advanced study of tissue engineering protocols based on cell therapy, combined use of seeding cells, bio-active substances and bio-compatible materials, are promising for IDD regeneration. Recently reported progenitor cells within discs themselves also hold prospects for future IDD studies. This article describes the background of IDD, current understanding and implications of potential therapeutic strategies.

  4. Current Pathophysiological Aspects and Therapeutic Modalities for Pemphigus Vulgaris : A Review

    Directory of Open Access Journals (Sweden)

    J Raviraj

    2007-01-01

    Full Text Available Pemphigus vulgaris (PV is an autoimmune disorder manifesting primarily as blisters involving the mucocutaneous systems. The current medical literature indicates many breakthroughs in the research of pathophysiology and treatment aspects of PV. This article tries to describe some of the novel aspects briefing the role of nondesmoglein antibodies and the role of TNF-alpha in the etiopathogenesis of pemphigus vulgaris and the role of newer therapeutic modalities like Rituximab, Etanercept, intravenous Immunoglobulins, cholinergic drugs, arid the like in the treatment of PV.

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

    Directory of Open Access Journals (Sweden)

    Vajro Pietro

    2012-10-01

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

  6. 3种联合用药方案治疗急性脑梗死的成本-效果分析%Cost-effectiveness Analysis on Three Combination Therapeutic Regimens for Acute Cerebral Infarction

    Institute of Scientific and Technical Information of China (English)

    耿国民

    2012-01-01

    目的:评价不同药物治疗方案在急性脑梗死治疗中的疗效及经济学效果.方法:114例急性脑梗死患者随机分成A、B、C组,每组38例,分别给予丹参注射液+胞磷胆碱注射液、丹参川芎嗪注射液+胞磷胆碱注射液、曲克芦丁脑蛋白水解物注射液+丹参川芎嗪注射液+胞磷胆碱注射液静滴,运用成本-效果分析法比较3种方案的疗效和成本.结果:A、B、C组成本分别为6 037.66元、6 575.95元、15 388.42元,总有效率分别为34.2%、65.8%、76.3%,成本-效果比分别为17 653.98、9 993.84、20 168.31,A、C组各出现1例消化道出血,经治疗痊愈,未见颅内出血者.结论:B组治疗方案较佳.%Objective: To evaluate the clinical efficacy and economic effect of different combination therapeutic regimens in the treatment of acute cerebral infarction. Method: Totally 114 cases with acute cerebral infarction were randomly divided into group A, B and C, 38 cases in each group with Danshen injections and citicoline sodium injections for group A, Danshen Chuanxiongqin injections and citicoline sodium injections for group B, and troxerutin cerebroprotein hydrolysate injections, Danshen Chuanxiongqin injections and citicoline sodium injections for group C. The clinical efficacy and economic effect of the three groups were analyzed using cost-effectiveness analysis method. Result: The cost of group A, B and C was 6 037.66, 6 575.95 and 15 388.42 yuan with the total efficiency of 34. 2% , 65. 8% and 76. 3% , and cost-effectiveness ratio was 17 653. 98 , 9 993. 84 and 20 168. 31, respectively. One case in group A and C showed gastrointestinal bleeding, and recovered after the treatment. No intracranial hemorrhage was shown among the patients. Conclusion: Among the three groups, group B is the best combination therapeutic regimen.

  7. Leveraging Cancer Therapeutics for the HIV Cure Agenda: Current Status and Future Directions.

    Science.gov (United States)

    Polizzotto, Mark N; Chen, Grace; Tressler, Randall L; Godfrey, Catherine

    2015-09-01

    Despite effective antiretroviral therapy (ART) and undetectable HIV RNA in the plasma, latent replication-competent HIV persists indefinitely in long-lived cells. Cessation of ART results in rebound of HIV from these persistent reservoirs. While this was thought to be an insurmountable obstacle to viral eradication, recent cases suggest otherwise. To date one patient has been "cured" of HIV and several others have been able to interrupt ART without viral rebound for prolonged periods. These events have sparked renewed interest in developing strategies that will allow eradication of HIV in infected individuals. We review the current knowledge of HIV latency and the viral reservoir, describe the potential utility of emerging cancer therapeutics in HIV cure research with an emphasis on pathways implicated in reservoir persistence, and outline opportunities and challenges in the context of the current clinical trial and regulatory environment.

  8. Potassium currents in the heart: functional roles in repolarization, arrhythmia and therapeutics.

    Science.gov (United States)

    Chiamvimonvat, Nipavan; Chen-Izu, Ye; Clancy, Colleen E; Deschenes, Isabelle; Dobrev, Dobromir; Heijman, Jordi; Izu, Leighton; Qu, Zhilin; Ripplinger, Crystal M; Vandenberg, Jamie I; Weiss, James N; Koren, Gideon; Banyasz, Tamas; Grandi, Eleonora; Sanguinetti, Michael C; Bers, Donald M; Nerbonne, Jeanne M

    2016-11-03

    This is the second of the two White Papers from the fourth UC Davis Cardiovascular Symposium Systems Approach to Understanding Cardiac Excitation-Contraction Coupling and Arrhythmias (3-4 March 2016), a biennial event that brings together leading experts in different fields of cardiovascular research. The theme of the 2016 symposium was 'K(+) channels and regulation', and the objectives of the conference were severalfold: (1) to identify current knowledge gaps; (2) to understand what may go wrong in the diseased heart and why; (3) to identify possible novel therapeutic targets; and (4) to further the development of systems biology approaches to decipher the molecular mechanisms and treatment of cardiac arrhythmias. The sessions of the Symposium focusing on the functional roles of the cardiac K(+) channel in health and disease, as well as K(+) channels as therapeutic targets, were contributed by Ye Chen-Izu, Gideon Koren, James Weiss, David Paterson, David Christini, Dobromir Dobrev, Jordi Heijman, Thomas O'Hara, Crystal Ripplinger, Zhilin Qu, Jamie Vandenberg, Colleen Clancy, Isabelle Deschenes, Leighton Izu, Tamas Banyasz, Andras Varro, Heike Wulff, Eleonora Grandi, Michael Sanguinetti, Donald Bers, Jeanne Nerbonne and Nipavan Chiamvimonvat as speakers and panel discussants. This article summarizes state-of-the-art knowledge and controversies on the functional roles of cardiac K(+) channels in normal and diseased heart. We endeavour to integrate current knowledge at multiple scales, from the single cell to the whole organ levels, and from both experimental and computational studies.

  9. Therapeutic efficacy of TCI chemotherapy regimen for epithelial ovarian cancer and its long- term prognosis%卵巢上皮癌TCI化疗方案的疗效研究及远期预后探讨

    Institute of Scientific and Technical Information of China (English)

    燕纪林

    2012-01-01

    目的 探讨TCI联合化疗方案对于卵巢上皮癌的疗效及远期预后.方法 2000年2月~2010年12月在本院进行规范治疗的卵巢上皮癌158例,运用TCI治疗方案为88例,其化疗方案为TP和值CAP和/或IAP(简称TCI方案);对照组治疗70例,方案选择为PC(环磷酰胺与顺铂),比较两组的临床缓解情况、毒性反应及远期预后,并且对TCI组进行OOX系统回归因素分析.结果 TCI治疗组总体缓解率明显高于对照组,毒性反应方面TCI治疗组的血液系统及神经系统不良反应均显著低于PC组,胃肠道不良反应与心血管系统反应则无显著差异;TCI组5年平均生存率为31.2%,病理分期Ⅰ、Ⅱ、Ⅲ、Ⅳ期中位生存时间分别是79、56、22、18个月,残留灶小于2cm者和治疗次数大于6次者远期预后明显好与相对应者.结论 TCI化疗方案显著优于PC方案,且不良反应相对较少,但胃肠道反应应引起重视,在预后各种因素方面病理分期、术后残留及疗程多少均具有一定相关意义.%Objective To explore the therapeutic efficacy of TCI combined chemotherapy regimen for and its long - term prognosis of epithelial ovarian cancer. Methods A total of 159 patients with epithelial ovarian cancer who received treatments from February 2000 to December 2010 in our hospital were included in the study. Among them, 88 patients were administered with TP and/or CAP and/or IAP regimen (TCI regimen). The control group included 70 patients who were administered with PC (cyclophosphamide and cisplatin). The clinical remission, toxic reactions and long - term prognosis were compared between the two groups. Cox system was applied to the TCI group for regression factor analysis. Results The overall remission was significantly higher in the TCI group than in the control group. In terms of toxic reactions, the adverse reactions of hemato- logical system and nerve system in the TCI group were significantly lower than those in the PC

  10. Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis.

    Science.gov (United States)

    Guptill, Jeffrey T; Soni, Madhu; Meriggioli, Matthew N

    2016-01-01

    Myasthenia gravis (MG) is an autoimmune disease associated with the production of autoantibodies against 1) the skeletal muscle acetylcholine receptor; 2) muscle-specific kinase, a receptor tyrosine kinase critical for the maintenance of neuromuscular synapses; 3) low-density lipoprotein receptor-related protein 4, an important molecular binding partner for muscle-specific kinase; and 4) other muscle endplate proteins. In addition to the profile of autoantibodies, MG may be classified according the location of the affected muscles (ocular vs generalized), the age of symptom onset, and the nature of thymic pathology. Immunopathologic events leading to the production of autoantibodies differ in the various disease subtypes. Advances in our knowledge of the immunopathogenesis of the subtypes of MG will allow for directed utilization of the ever-growing repertoire of therapeutic agents that target distinct nodes in the immune pathway relevant to the initiation and maintenance of autoimmune disease. In this review, we examine the pathogenesis of MG subtypes, current treatment options, and emerging new treatments and therapeutic targets.

  11. Therapeutic monoclonal antibodies for respiratory diseases: Current challenges and perspectives, March 31 - April 1, 2016, Tours, France.

    Science.gov (United States)

    Desoubeaux, Guillaume; Reichert, Janice M; Sleeman, Matthew; Reckamp, Karen L; Ryffel, Bernhard; Adamczewski, Jörg P; Sweeney, Theresa D; Vanbever, Rita; Diot, Patrice; Owen, Caroline A; Page, Clive; Lerondel, Stéphanie; Le Pape, Alain; Heuze-Vourc'h, Nathalie

    2016-01-01

    Monoclonal antibody (mAb) therapeutics have tremendous potential to benefit patients with lung diseases, for which there remains substantial unmet medical need. To capture the current state of mAb research and development in the area of respiratory diseases, the Research Center of Respiratory Diseases (CEPR-INSERM U1100), the Laboratory of Excellence "MAbImprove," the GDR 3260 "Antibodies and therapeutic targeting," and the Grant Research program ARD2020 "Biotherapeutics" invited speakers from industry, academic and government organizations to present their recent research results at the Therapeutic Monoclonal Antibodies for Respiratory Diseases: Current challenges and perspectives congress held March 31 - April 1, 2016 in Tours, France.

  12. ['I'm worthless' and other forms of self-criticism: Current knowledge and therapeutic interventions].

    Science.gov (United States)

    Maillard, Pauline; Kramer, Ueli

    2015-01-01

    Self-criticism is considered as a harsh or punitive evaluation of the self. It is omnipresent in culture, in daily life as well as in psychotherapy. Self-criticism can lead to question oneself but can also open new perspectives and guide us. However, it can become excessive, rigid, and might turn out to be deleterious. This present article focuses on the concept of self-criticism in clinical psychology and psychotherapy and aims to review current knowledge about this topic. First, its definition and the reasons for its development in individuals will be presented. Second, a description of the links between self-criticism and psychopathology will be made, in particular regarding depression. Finally, the third part of this article will be dedicated to the therapeutic interventions that can reduce self-criticism.

  13. Immunopathogenesis of neurodegenerative diseases: current therapeutic models of neuroprotection with special reference to natural products.

    Science.gov (United States)

    Magrone, T; Marzulli, G; Jirillo, E

    2012-01-01

    Parkinson disease (PD) and Alzheimer disease (AD) are neurodegenerative processes whose frequency is dramatically increasing in the western world. Both diseases share a common pathogenic denominator characterized by an exaggerated activation of the systemic and cerebral immune system, respectively. For instance, lipopolysaccharides in PD and amyloid beta in AD trigger microglia and astrocytes to release reactive oxygen species (ROS) and proinflammatory cytokines. Infiltrating peripheral T cells once activated in the central nervous system also contribute to the neurodegenerative process. Besides innovative biotherapy, nutraceuticals or functional foods are currently investigated for their neuroprotective activities. Especially, vitamin D and polyphenols, seem to be promising therapeutic tools for inhibiting ROS formation and arresting cytokine-mediated neuroinflammation in PD and AD.

  14. History and current use of mild therapeutic hypothermia after cardiac arrest.

    Science.gov (United States)

    Bonaventura, Jiří; Alan, David; Vejvoda, Jiri; Honek, Jakub; Veselka, Josef

    2016-10-01

    In spite of many years of development and implementation of pre-hospital advanced life support programmes, the survival rate of out-of-hospital cardiac arrest (OHCA) used to be very poor. Neurologic injury from cerebral hypoxia is the most common cause of death in patients with OHCA. In the past two decades, post-resuscitation care has developed many new concepts aimed at improving the neurological outcome and survival rate of patients after cardiac arrest. Systematic post-cardiac arrest care after the return of spontaneous circulation, including induced mild therapeutic hypothermia (TH) in selected patients, is aimed at significantly improving rates of long-term neurologically intact survival. This review summarises the history and current knowledge in the field of mild TH after OHCA.

  15. Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Tom J. Burdon

    2011-01-01

    Full Text Available During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

  16. µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission: A Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Elisabetta Tosti

    2017-09-01

    Full Text Available The Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins (CTX. Each species is able to produce up to 200 different biological active peptides. Common structure of CTX is the low number of amino acids stabilized by disulfide bridges and post-translational modifications that give rise to different isoforms. µ and µO-CTX are two isoforms that specifically target voltage-gated sodium channels. These, by inducing the entrance of sodium ions in the cell, modulate the neuronal excitability by depolarizing plasma membrane and propagating the action potential. Hyperexcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and neuropathic pain states. In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the mechanism of action and their potential therapeutic use as analgesic compounds in the clinical management of pain conditions.

  17. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS).

    Science.gov (United States)

    Lefaucheur, Jean-Pascal; Antal, Andrea; Ayache, Samar S; Benninger, David H; Brunelin, Jérôme; Cogiamanian, Filippo; Cotelli, Maria; De Ridder, Dirk; Ferrucci, Roberta; Langguth, Berthold; Marangolo, Paola; Mylius, Veit; Nitsche, Michael A; Padberg, Frank; Palm, Ulrich; Poulet, Emmanuel; Priori, Alberto; Rossi, Simone; Schecklmann, Martin; Vanneste, Sven; Ziemann, Ulf; Garcia-Larrea, Luis; Paulus, Walter

    2017-01-01

    A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson's disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer's disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10-24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform t

  18. Pathogenesis of metastatic disease: implications for current therapy and for the development of new therapeutic strategies.

    Science.gov (United States)

    Poste, G

    1986-01-01

    Different tumor cell subpopulations coexisting within the same tumor exhibit varied susceptibilities to antineoplastic agents. Tumor cell heterogeneity is now recognized as the principal cause of treatment failure in cancer, and is a formidable obstacle to effective therapy and to the development of drug delivery systems for selective targeting of antineoplastic agents to tumor cells. Recent insights into the genesis of tumor cell heterogeneity during progressive tumor growth reveal new complexities that raise challenging questions about the adequacy of certain approaches to the current therapy of metastatic disease and impose challenging criteria for the development of improved therapeutic strategies. Many of the experimental approaches used in the search for new antineoplastic agents and targeted drug delivery systems ignore the pathogenesis of metastasis and the problem of tumor cell heterogeneity. The adoption of more relevant assay systems is an urgent priority. These include the greater use of metastatic tumor models and the increased use of human tumor cells to replace rodent cell systems which have been of limited predictive value in identifying effective anticancer agents. In contrast to current strategies for the development of new antineoplastic drugs which seek to identify agents with activity against a broad range of histologically diverse tumors, greater success may be achieved by seeking agents active only against specific cell lineages. Many established human tumor cell lines may not be suitable for this purpose because of extensive phenotypic change produced by prolonged passage ex vivo. Development of histiotype-specific human tumor cell screens will require an extensive research effort to identify target cells that display demonstrable phenotypic relatedness to tumor cells in neoplastic lesions. Major advances in the therapy of metastatic disease are considered unlikely in the next few years, and progress will stem from improved use of existing

  19. Non-adherence to medication regimens among older African-American adults.

    Science.gov (United States)

    Bazargan, Mohsen; Smith, James; Yazdanshenas, Hamed; Movassaghi, Masoud; Martins, David; Orum, Gail

    2017-07-25

    Despite concerns about racial differences on adherence to prescribed medication rigimens among older adults, current information about nonadherence among underserved elderly African Americans with co-morbidities is limited. This study examines the association between adherence to drug regimens and an array of medication-related factors, including polypharmacy, medication regimen complexity, use of Potentially Inappropriate Medications (PIM), and knowledge about the therapeutic purpose and instructions of medication use. Four-hundred African Americans, aged 65 years and older, were recruited from South Los Angeles. Structured, face-to-face interviews and visual inspection of participants' medications were conducted. From the medication container labels, information including strength of the drug, expiration date, instructions, and special warnings were recorded. The Medication Regimen Complexity Index (MRCI) was measured to quantify multiple features of drug regimen complexity. The Beers Criteria was used to measure the PIM use. Participants reported taking an average of 5.7 prescription drugs. Over 56% could not identify the purpose of at least one of their medications. Only two-thirds knew dosage regimen of their medications. Thirty-five percent of participants indicated that they purposely had skipped taking at least one of their medications within last three days. Only 8% of participants admitted that they forgot to take their medications. The results of multivariate analysis showed that co-payment for drugs, memory deficits, MRCI, and medication-related knowledge were all associated with adherence to dosage regimen of medications. Participants with a higher level of knowledge about therapeutic purpose and knowledge about dosage regimen of their medications were seven times (CI: 4.2-10.8) more likely to adhere to frequency and dose of medications. Participants with a low complexity index were two times (CI: 1.1-3.9) more likely to adhere to the dosage regimen

  20. Neonatal infections due to multi-resistant strains: Epidemiology, current treatment, emerging therapeutic approaches and prevention.

    Science.gov (United States)

    Tzialla, Chryssoula; Borghesi, Alessandro; Pozzi, Margherita; Stronati, Mauro

    2015-12-07

    Severe infections represent the main cause of neonatal mortality accounting for more than one million neonatal deaths worldwide every year. Antibiotics are the most commonly prescribed medications in neonatal intensive care units. The benefits of antibiotic therapy when indicated are clearly enormous, but the continued and widespread use of antibiotics has generated over the years a strong selective pressure on microorganisms, favoring the emergence of resistant strains. Health agencies worldwide are galvanizing attention toward antibiotic resistance in gram-positive and gram-negative bacteria. Infections in neonatal units due to multidrug and extensively multidrug resistant bacteria are rising and are already seriously challenging antibiotic treatment options. While there is a growing choice of agents against multi-resistant gram-positive bacteria, new options for multi-resistant gram-negative bacteria in the clinical practice have decreased significantly in the last 20 years making the treatment of infections caused by multidrug-resistant pathogens challenging mostly in neonates. Treatment options are currently limited and will be some years before any new treatment for neonates become available for clinical use, if ever. The aim of the review is to highlight the current knowledge on antibiotic resistance in the neonatal population, the possible therapeutic choices, and the prevention strategies to adopt in order to reduce the emergency and spread of resistant strains.

  1. Late sodium current is a new therapeutic target to improve contractility and rhythm in failing heart.

    Science.gov (United States)

    Undrovinas, Albertas; Maltsev, Victor A

    2008-10-01

    Most cardiac Na+ channels open transiently within milliseconds upon membrane depolarization and are responsible for the excitation propagation. However, some channels remain active during hundreds of milliseconds, carrying the so-called persistent or late Na+ current (I(NaL)) throughout the action potential plateau. I(NaL) is produced by special gating modes of the cardiac-specific Na+ channel isoform. Experimental data accumulated over the past decade show the emerging importance of this late current component for the function of both normal and especially failing myocardium, where I(NaL) is reportedly increased. Na+ channels represent a multi-protein complex and its activity is determined not only by the pore-forming alpha subunit but also by its auxiliary beta subunits, cytoskeleton, and by Ca2+ signaling and trafficking proteins. Remodeling of this protein complex and intracellular signaling pathways may lead to alterations of I(NaL) in pathological conditions. Increased I(NaL) and the corresponding Na+ influx in failing myocardium contribute to abnormal repolarization and an increased cell Ca2+ load. Interventions designed to correct I(NaL) rescue normal repolarization and improve Ca2+ handling and contractility of the failing cardiomyocytes. New therapeutic strategies to target both arrhythmias and deficient contractility in HF may not be limited to the selective inhibition of I(NaL) but also include multiple indirect, modulatory (e.g. Ca(2+)- or cytoskeleton- dependent) mechanisms of I(NaL) function.

  2. Galeazzi fractures: our modified classification and treatment regimen.

    Science.gov (United States)

    Fayaz, H C; Jupiter, J B

    2014-02-01

    While diaphyseal fractures of the forearm are a common orthopedic injury, Galeazzi fractures are difficult to treat. The current knowledge on pathobiomechanics and modified therapeutic decisions implicate the need to devise an updated classification and treatment regimen of Galeazzi fractures. We challenge the concept that isolated fractures of the radius should be considered as a Galeazzi fractures as long as stability of the distal radioulnar joint is not proven. Contrary to others we demonstrate that the fracture location alone is not sufficient to determine the stability of the distal radioulnar joint. © Georg Thieme Verlag KG Stuttgart · New York.

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

    Science.gov (United States)

    Haque, Azizul; Hober, Didier; Blondiaux, Joel

    2015-10-01

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

  4. Current Status of Pharmaceutical and Genetic Therapeutic Approaches to Treat DMD

    Science.gov (United States)

    Pichavant, Christophe; Aartsma-Rus, Annemieke; Clemens, Paula R; Davies, Kay E; Dickson, George; Takeda, Shin'ichi; Wilton, Steve D; Wolff, Jon A; Wooddell, Christine I; Xiao, Xiao; Tremblay, Jacques P

    2011-01-01

    Duchenne muscular dystrophy (DMD) is a genetic disease affecting about one in every 3,500 boys. This X-linked pathology is due to the absence of dystrophin in muscle fibers. This lack of dystrophin leads to the progressive muscle degeneration that is often responsible for the death of the DMD patients during the third decade of their life. There are currently no curative treatments for this disease but different therapeutic approaches are being studied. Gene therapy consists of introducing a transgene coding for full-length or a truncated version of dystrophin complementary DNA (cDNA) in muscles, whereas pharmaceutical therapy includes the use of chemical/biochemical substances to restore dystrophin expression or alleviate the DMD phenotype. Over the past years, many potential drugs were explored. This led to several clinical trials for gentamicin and ataluren (PTC124) allowing stop codon read-through. An alternative approach is to induce the expression of an internally deleted, partially functional dystrophin protein through exon skipping. The vectors and the methods used in gene therapy have been continually improving in order to obtain greater encapsidation capacity and better transduction efficiency. The most promising experimental approaches using pharmaceutical and gene therapies are reviewed in this article. PMID:21468001

  5. Classifying insulin regimens--difficulties and proposal for comprehensive new definitions.

    Science.gov (United States)

    Neu, A; Lange, K; Barrett, T; Cameron, F; Dorchy, H; Hoey, H; Jarosz-Chobot, P; Mortensen, H B; Robert, J-J; Robertson, K; de Beaufort, C

    2015-09-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1 diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin regimens reflecting current diabetes management in childhood and adolescence. The HSG--founded in 1994--is an international group representing 24 highly experienced pediatric diabetes centers, from Europe, Japan, North America and Australia. Different benchmarking studies of the HSG revealed a broad variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the concepts 'conventional' and 'intensified', several other terms for the characterization of insulin regimens are in use: Basal Bolus Concept (BBC), multiple daily injections (MDI), and flexible insulin therapy (FIT) are most frequently used, although none of these expressions is clearly or consistently defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen.

  6. From mechanisms of action to therapeutic application: A review on current therapeutic approaches and future directions in systemic sclerosis.

    Science.gov (United States)

    Del Papa, Nicoletta; Zaccara, Eleonora

    2015-12-01

    Systemic sclerosis (SSc) is one of the most complex connective tissue diseases. Although the pathogenesis of SSc still remains elusive, it is generally accepted that initial vascular injury due to autoimmunity might result in the constitutive activation of fibroblasts and fibrosis. All of these three processes interact and affect one another resulting in a polymorphous spectrum of clinical and pathologic manifestations of SSc. The disease pleomorphism poses numerous difficulties in defining the ideal outcomes to be used in clinical trials. Despite significant progress over the past decades, the clinical management of patients with SSc remains a challenge. Novel therapies are currently being tested in the treatment of SSc and have the potential for modifying the disease process and improving the clinical outcomes. However, the evaluation of the studies is still difficult, due to either the small size of included patients or the different types and phases of the scleroderma disease under scrutiny.

  7. Therapy of Human African Trypanosomiasis: Current Situation

    Directory of Open Access Journals (Sweden)

    Jorge Atouguia

    1999-03-01

    Full Text Available This paper is a review of the current situation of the treatment of human African trypanosomiasis. The existing approved drugs are old, toxic and/or expensive. Therapeutic failures are common. Several factors may contribute to the problems of chemotherapy, including differences in the epidemiology of the disease, difficulties in the diagnosis and staging of the infection, availability, distribution and pharmacologic properties of drugs, standardization of treatment regimens, response to therapy, follow-up period, and relapses and clinical trials. The new therapeutic approaches include the development and approval of new drugs, the use of new therapeutic regimens, the study of drug combinations, and the development of new formulations.

  8. Current progress of siRNA/shRNA therapeutics in clinical trials.

    Science.gov (United States)

    Burnett, John C; Rossi, John J; Tiemann, Katrin

    2011-09-01

    Through a mechanism known as RNA interference (RNAi), small interfering RNA (siRNA) molecules can target complementary mRNA strands for degradation, thus specifically inhibiting gene expression. The ability of siRNAs to inhibit gene expression offers a mechanism that can be exploited for novel therapeutics. Indeed, over the past decade, at least 21 siRNA therapeutics have been developed for more than a dozen diseases, including various cancers, viruses, and genetic disorders. Like other biological drugs, RNAi-based therapeutics often require a delivery vehicle to transport them to the targeted cells. Thus, the clinical advancement of numerous siRNA drugs has relied on the development of siRNA carriers, including biodegradable nanoparticles, lipids, bacteria, and attenuated viruses. Most therapies permit systemic delivery of the siRNA drug, while others use ex vivo delivery by autologous cell therapy. Advancements in bioengineering and nanotechnology have led to improved control of delivery and release of some siRNA therapeutics. Likewise, progress in molecular biology has allowed for improved design of the siRNA molecules. Here, we provide an overview of siRNA therapeutics in clinical trials, including their clinical progress, the challenges they have encountered, and the future they hold in the treatment of human diseases.

  9. Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

    NARCIS (Netherlands)

    Zuur, Marlanka A.; Bolhuis, Mathieu S.; Anthony, Richard; den Hertog, Alice; van der Laan, Tridia; Wilffert, Bob; Lange, de Wiel; van Soolingen, Dick; Alffenaar, Jan-Willem C.

    Introduction: Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order

  10. Is the current therapeutic armamentarium in diabetes enough to control the epidemic and its consequences? What are the current shortcomings?

    DEFF Research Database (Denmark)

    Giugliano, Dario; Standl, Eberhard; Vilsbøll, Tina;

    2009-01-01

    glycated haemoglobin targets, trial data show that such interventions reduce the incidence of macrovascular events; however, intensive lowering may be detrimental in patients with existing cardiovascular disease. Currently available oral drugs do not address the key driver of type 2 diabetes...

  11. Effect observation and mechanism of low - dose decitabine combined with modified CAG therapeutic regimen in the treatment of patients with myelodysplastic syndrome(MDS)%低剂量地西他滨序贯改良 CAG 方案对治疗骨髓增生异常综合征的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    陈喜填; 夏维林; 林东; 王楚林; 张淳嘉; 吴桂香

    2016-01-01

    目的:探究低剂量地西他滨序贯改良 CAG 方案对治疗中高危骨髓增生异常综合征(Myelodysplastic syn-drome,MDS)的临床疗效。方法:随机抽取收治的中高危 MDS 患者96例,分为观察组46例及对照组患者50例,其中观察组患者采用低剂量地西他滨序贯 CAG 方案进行治疗,而对照组患者均采用 CAG 方案进行治疗,观察两组患者的临床疗效、不良反应的发生情况及处理结果。结果:观察组比对照组患者的疾病缓解率更高、疗效更显著,且两组比较差异具有统计学意义(P ﹤0.05)。结论:低剂量地西他滨序贯改良 CAG 方案治疗高危 MDS 比单用 CAG 方案疗效更明显、确切。%Objective The objection of the study was to investigate the clinical efficiencies and adverse reactions of treating the myelodysplastic syndrome(MDS)by using low - does decitabine combined with modified CAG therapeutic regimen. Method 96 high - risk MDS patients were randomly selected,they were divided into observation group with 46 cases and control group with 50 cases. The observation group was treated with low - dose decitabine combined with modified CAG therapeutic regimen, while the control group was treated with CAG therapeutic regimen. Clinical efficacy,adverse reactions and treatment results of each group were observed and analyzed. Results The remission rate was higher and the curative effect was more significant of ob-servation group when compared with control group,the difference between two groups has statistical significance( P ﹤ 0. 05) . Conclusion The effect of high risk MDS in treatment with low dose of decitabine combined with modified CAG therapeutic regi-ment is more significance than treated with CAG therapeutic regimen.

  12. Multiple, sclerosis: clinical feature, pathogenesis and current therapeutical approaches; Encephalomyelitis disseminata: Klinik, Pathogenese und aktuelle Therapiekonzepte

    Energy Technology Data Exchange (ETDEWEB)

    Merkelbach, S.; Koelmel, C.; Schimrigk, K. [Universitaet des Saarlandes, Homburg/Saar (Germany). Neurologische Klinik

    2000-11-01

    Multiple sclerosis (MS) is considered as a T-cell mediated autoimmune disease. Caused by central nervous system demyelination and axonal damage varying clinical signs do occur either with relapsing-remitting or with chronic progressive course. Based on pathogenetic considerations immunomodulative and immunosuppressive therapeutical approaches are used to limit the disease progression. Clinical symptoms, diagnostic criteria, pathogenetical considerations, and consecutive therapeutical interventions are summarized. (orig.) [German] Die Encephalomyelitis disseminata oder Multiple Sklerose (ED oder MS) gilt als T-Zell-vermittelte Autoimmunerkrankung. Schubfoermig oder chronisch progredient kommt es im Zentralnervensystem infolge einer Demyelinisierung der weissen Substanz und axonaler Schaedigungen zu einer Vielzahl neurologischer Symptome. Basierend auf pathogenetischen Erkenntnissen werden derzeit immunmodulative und immunsuppressive Therapien eingesetzt, die den Krankheitsverlauf zumindest bremsen. Klinische Symptome, diagnostische Kriterien, pathogenetische Ueberlegungen und sich daraus ableitende Therapiekonzepte werden zusammenfassend dargestellt. (orig.)

  13. Therapeutic options in papillary thyroid carcinoma: current guidelines and future perspectives.

    Science.gov (United States)

    Scott, Emma; Learoyd, Diana; Clifton-Bligh, Roderick J

    2016-11-01

    The treatment of papillary thyroid cancer is now based on individual patient risk and response to therapies. Molecular techniques are increasingly being used to risk stratify and to guide therapeutic decisions. There have been advances in the treatment of local disease through surgery or radioiodine. Directed techniques can target metastatic disease including bisphosphonates, radiofrequency ablation or radiotherapy. Systemic therapies such as tyrosine kinase inhibitors show great promise although such treatment must be individualized. Future therapies will target treating radioiodine refractory disease.

  14. [Therapeutic strategies. Evolution and current status of the European Guidelines on Cardiovascular disease prevention].

    Science.gov (United States)

    Guijarro, Carlos; García-Díaz, Juan de Dios

    2013-01-01

    The European Guidelines on Dyslipidaemias (2011) and Cardiovascular Prevention (2012) have incorporated important changes. Firstly, it highlights the identification of a group of "very high risk" patients: patients with atherosclerotic disease in any vascular area, diabetes with associated risk factors, advanced chronic renal failure, or a SCORE estimate >10%. Patients with diabetes and no other risk factors, moderate renal failure, severe hypertension, genetic dyslipidaemias, or a SCORE estimate 5-10%, are considered as "high risk". The HDL cholesterol and triglycerides levels are considered as modulators of risks, but not therapeutic objectives per se. The therapeutic objectives are set at LDL cholesterol levels < 70 mg/dl (or at least a reduction of at least 50%) for patients at very high risk, and an LDL < 100 mg/dl for high risk patients. As well as the changes in lifestyle, pharmacological treatment with statins is the focal point of lipid lowering treatments. Other pharmacological options may be considered if the treatment with the maximum tolerable doses of statins do not achieve the therapeutic objectives. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

  15. Past and current perspective on new therapeutic targets for Type-II diabetes.

    Science.gov (United States)

    Patil, Pradip D; Mahajan, Umesh B; Patil, Kalpesh R; Chaudhari, Sandip; Patil, Chandragouda R; Agrawal, Yogeeta O; Ojha, Shreesh; Goyal, Sameer N

    2017-01-01

    Loss of pancreatic β-cell function is a hallmark of Type-II diabetes mellitus (DM). It is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Recently, United Kingdom Prospective Diabetes Study reported that Type-II DM is a progressive disorder. Although, DM can be treated initially by monotherapy with oral agent; eventually, it may require multiple drugs. Additionally, insulin therapy is needed in many patients to achieve glycemic control. Pharmacological approaches are unsatisfactory in improving the consequences of insulin resistance. Single therapeutic approach in the treatment of Type-II DM is unsuccessful and usually a combination therapy is adopted. Increased understanding of biochemical, cellular and pathological alterations in Type-II DM has provided new insight in the management of Type-II DM. Knowledge of underlying mechanisms of Type-II DM development is essential for the exploration of novel therapeutic targets. Present review provides an insight into therapeutic targets of Type-II DM and their role in the development of insulin resistance. An overview of important signaling pathways and mechanisms in Type-II DM is provided for the better understanding of disease pathology. This review includes case studies of drugs that are withdrawn from the market. The experience gathered from previous studies and knowledge of Type-II DM pathways can guide the anti-diabetic drug development toward the discovery of clinically viable drugs that are useful in Type-II DM.

  16. Current perspectives on therapeutic ultrasound in the management of chronic wounds: a review of evidence

    Directory of Open Access Journals (Sweden)

    Conner-Kerr T

    2017-07-01

    Full Text Available Teresa Conner-Kerr,1 Mary Ellen Oesterle2 1College of Health Sciences & Professions, 2Department of Physical Therapy, University of North Georgia, Dahlonega, GA, USA Abstract: Although therapeutic ultrasound has been in existence since the 1930s, questions remain as to its effectiveness in promoting tissue healing in various injured tissues. These tissues include soft tissues such as skin, tendons, ligaments, bursae, joint capsules and muscles. Limited evidence exists to support a role for therapeutic ultrasound in closed, soft tissue lesions. However, an evolving literature provides support for the role of therapeutic ultrasound in the treatment of chronic wounds, acute injuries such as fractures and split thickness graft donor sites as well as in the modulation of wound-related pain. Modern technology that uses low-frequency (kilohertz, long wave ultrasound appears promising compared to older, higher frequency ultrasound (megahertz devices. These newer devices appear to have positive effects on healing rates in various wound types, pain levels and the modulation of proinflammatory cytokines. Keywords: low-frequency ultrasound, non-contact ultrasound, KHz, acoustic, healing, cavitation

  17. Current status of temporomandibular joint disorders and the therapeutic system derived from a series of biomechanical, histological, and biochemical studies

    OpenAIRE

    Kazuo Tanne; Yuki Okamoto; Shao-Ching Su; Tomomi Mitsuyoshi; Yuki Asakawa-Tanne; Kotaro Tanimoto

    2015-01-01

    This article was designed to report the current status of temporomandibular joint disorders (TMDs) and the therapeutic system on the basis of a series of clinical, biomechanical, histological and biochemical studies in our research groups. In particular, we have focused on the association of degenerative changes of articular cartilage in the mandibular condyle and the resultant progressive condylar resorption with mechanical stimuli acting on the condyle during the stomatognathic function. In...

  18. Anti-hypertensive treatment in pheochromocytoma and paraganglioma: current management and therapeutic features.

    Science.gov (United States)

    Mazza, Alberto; Armigliato, Michela; Marzola, Maria Cristina; Schiavon, Laura; Montemurro, Domenico; Vescovo, Giorgio; Zuin, Marco; Chondrogiannis, Sotirios; Ravenni, Roberta; Opocher, Giuseppe; Colletti, Patrick M; Rubello, Domenico

    2014-04-01

    Pheochromocytoma (PH) and paraganglioma (PG) are neuroendocrine neoplasms arising from chromaffin cells of the adrenal medulla and the sympathetic ganglia, respectively. Although are unusual cause of hypertension (HT) accounting for at most 0.1-0.2 % of cases, they may lead to severe and potentially lethal hypertensive crisis due to the effects of the released catecholamines. However, both PH and PG may be asymptomatic as ~30 % of subjects are normotensive or have orthostatic hypotension and in these cases the 24 h ambulatory blood pressure (BP) monitoring is an important toll to diagnose and treat HT. HT treatment may be difficult when PH or PG occurs in pregnancy or in the elderly subjects and in these cases a multidisciplinary team is required. When surgical excision is mandatory the perioperative management requires the administration of selective α1-adrenergic blocking agents (i.e., doxazosin, prazosin or terazosin) followed by a β-adrenergic blockade (i.e., propranolol, atenolol). This latter should never be started first because blockade of vasodilatory peripheral β-adrenergic receptors with unopposed α-adrenergic receptor stimulation can lead to a further elevation of BP. Although labetalol is traditionally considered the ideal agent due to its α- and β-adrenergic antagonism, experimental studies do not support its use in this clinical setting. As second regimen, the administration of vasodilators as calcium channel blockers (i.e., nicardipine, nifedipine) may be required to control BP. Oral and sublingual short-acting nifedipine are potentially dangerous in patients with hypertensive emergencies and are not recommend. The latest evidences into the diagnosis and treatment of hypertensive crisis due to PH and PG are reviewed here.

  19. [Infection-induced urinary calculi in children; current therapeutic schedule and prevention of recurrence].

    Science.gov (United States)

    Bach, D; Brühl, P; Hesse, A

    1988-01-01

    Infection stones have an outstanding position in childhood urolithiasis. In non-infection stones one can mostly find a certain--for example metabolic--causes of stone formation. In infection stones, the urease-producing and thus urea-cleaving properties of some gram-negative bacteria are responsible for alkalization of the urine and lead especially in combination with disturbances of urine transport to the staghorn calculi. Therefore in such children early diagnosis, adequate therapy and consequent maintenance is the crucial point for good life quality in future. Preliminary condition for therapeutic success is a close coworking between pediatric nephrologist, pediatric urologist, family doctor and parents.

  20. Current understanding of dystrophin-related muscular dystrophy and therapeutic challenges ahead

    Institute of Scientific and Technical Information of China (English)

    ZHOU Guang-qian; XIE Hui-qi; ZHANG Su-zhen; YANG Zhi-ming

    2006-01-01

    Objective To review the recent research progress in dystrophin-related muscular dystrophy includes X-linked hereditary Duchenne and Becker muscular dystrophies (DMD and BMD).Data sources Information included in this article was identified by searches of PUBMED and other online resources using the key terms DMD, dystrophin, mutations, animal models, pathophysiology, gene expression, stem cells, gene therapy, cell therapy, and pharmacological.Study selection Mainly original milestone articles and timely reviews written by major pioneer investigators of the field were selected.Results The key issues related to the genetic basis and pathophysiological factors of the diseases were critically addressed. The availabilities and advantages of various animal models for the diseases were described. Major molecular and cellular therapeutic approaches were also discussed, many of which have indeed exhibited some success in pre-clinical studies but at the same time encountered a number of technical hurdles, including the efficient and systemic delivery of a functional gene and myogenic precursor/stem cells to repair genetic defects.Conclusions Further understanding of pathophysiological mechanisms at molecular levels and regenerative properites of myogenic precursor/stem cells will promote the development of multiple therapeutic strategies. The combined use of multiple strategies may represent the major challenge as well as the greatest hope for the therapy of these diseases in coming years.

  1. Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis.

    Science.gov (United States)

    Zuur, Marlanka A; Bolhuis, Mathieu S; Anthony, Richard; den Hertog, Alice; van der Laan, Tridia; Wilffert, Bob; de Lange, Wiel; van Soolingen, Dick; Alffenaar, Jan-Willem C

    2016-05-01

    Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order to tailor the dose to the individual patient, in tuberculosis treatment. Literature on pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs was explored to evaluate the effect of drug exposure in relation to drug susceptibility, toxicity and efficacy. New, down-sized strategies, like dried blood spot analysis and limited sampling strategies are reviewed. In addition, molecular resistance testing of Mycobacteria tuberculosis, combining a short turn-around time with relevant information on drug susceptibility of the causative pathogen was explored. Newly emerging host biomarkers provide information on the response to treatment. Therapeutic drug monitoring can minimize toxicity and increase efficacy of tuberculosis treatment and prevent the development of resistance. Dried blood spot analysis and limited sampling strategies, can be combined to provide us with a more patient friendly approach. Furthermore, rapid information on drug susceptibility by molecular testing, and information from host biomarkers on the bacteriological response, can be used to further optimize tuberculosis treatment.

  2. Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases.

    Science.gov (United States)

    Skeate, Joseph G; Woodham, Andrew W; Einstein, Mark H; Da Silva, Diane M; Kast, W Martin

    2016-06-01

    Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed.

  3. Forced degradation studies: current trends and future perspectives for protein-based therapeutics.

    Science.gov (United States)

    Chan, Christine P

    2016-07-01

    Forced degradation (FD) studies (stress testing) are an integral part of pharmaceutical product development. The design and execution of these studies require thorough planning and coordination through the various stages of development as well as post-approval commercial operations. This is particularly crucial in the case for protein-based therapeutics due to complexity of the molecular structure as well as the potential influence of the manufacturing process on product attributes. Often, FD study applications are linked to specific product development in a phase-specific and case-by-case manner with differing purposes and focus. Expert commentary: This paper summarizes some key FD approaches commonly employed in the industry and provides considerations on study design strategies and database management through the course of the product lifecycle.

  4. [Stem cells in adult retina--current state of research, future therapeutic prospects].

    Science.gov (United States)

    Machalińska, Anna; Zuba-Surma, Ewa K

    2009-01-01

    The latest research reports revealed the presence of stem/progenitor cells located in different regions of matured eye. They are able to differentiate into retinal pigment epithelium cells as well as neural structure of retina. These cells were identified in neurosensory retina, pigment epithelium and within cilliary body and iris epithelium. Moreover, it has been proved that Muller glia possess the potential of differentiation into retinal cells. These findings indicate the presence of potential mechanisms enabling retinal cell repopulation and retinal tissue regeneration. In the present work, the recent reports documenting the presence of different stem cell populations in eye have been reviewed, particularly focusing on recently identified very small embryonic-like stem cells (VSEL-SCs). The potential clinical applications of the residing stem cells and limitations of such therapeutic strategies have been also discussed.

  5. Recent advances in tuberculosis: New drugs and treatment regimens.

    Science.gov (United States)

    Sloan, Derek J; Davies, Geraint R; Khoo, Saye H

    2013-06-01

    The current treatment regimen against drug susceptible tuberculosis (DS-TB) was defined by the 1980s. Since then the emergence of the global HIV pandemic and the escalation of drug resistant (DR-) forms of TB have presented new challenges for therapeutic research. Priority goals include shortening DS-TB treatment, improving DR-TB treatment and making combined TB-HIV therapy easier. To help achieve these goals, a range of new drugs and treatment strategies are currently being evaluated. Phase IIb and III clinical trials are ongoing to assess combinations involving the high-dose rifamycins, the 8-methoxyquinolones, a diarylquinoline (bedaquiline) and the nitroimidazoles. Other compounds (e.g. novel oxazolidinones and ethylenediamines) are at earlier stages of clinical development. Overall, there are grounds for optimism that recent advances will contribute towards achievement of new treatment regimens in the foreseeable future. However, long-term investment, political commitment and scientific endeavour are crucial to ensure that progress is sustained and the benefits of recent advances reach those in the greatest need.

  6. Therapeutic Mechanisms of Lithium in Bipolar Disorder: Recent Advances and Current Understanding.

    Science.gov (United States)

    Malhi, Gin S; Outhred, Tim

    2016-10-01

    Lithium is the most effective and well established treatment for bipolar disorder, and it has a broad array of effects within cellular pathways. However, the specific processes through which therapeutic effects occur and are maintained in bipolar disorder remain unclear. This paper provides a timely update to an authoritative review of pertinent findings that was published in CNS Drugs in 2013. A literature search was conducted using the Scopus database, and was limited by year (from 2012). There has been a resurgence of interest in lithium therapy mechanisms, perhaps driven by technical advancements in recent years that permit the examination of cellular mechanisms underpinning the effects of lithium-along with the reuptake of lithium in clinical practice. Recent research has further cemented glycogen synthase kinase 3β (GSK3β) inhibition as a key mechanism, and the inter-associations between GSK3β-mediated neuroprotective, anti-oxidative and neurotransmission mechanisms have been further elucidated. In addition to highly illustrative cellular research, studies examining higher-order biological systems, such as circadian rhythms, as well as employing innovative animal and human models, have increased our understanding of how lithium-induced changes at the cellular level possibly translate to changes at behavioural and clinical levels. Neural circuitry research is yet to identify clear mechanisms of change in bipolar disorder in response to treatment with lithium, but important structural findings have demonstrated links to the modulation of cellular mechanisms, and peripheral marker and pharmacogenetic studies are showing promising findings that will likely inform the exploration for predictors of lithium treatment response. With a deeper understanding of lithium's therapeutic mechanisms-from the cellular to clinical levels of investigation-comes the opportunity to develop predictive models of lithium treatment response and identify novel drug targets, and

  7. A review of current knowledge of the complement system and the therapeutic opportunities in inflammatory arthritis.

    Science.gov (United States)

    Mizuno, M

    2006-01-01

    The complement activation system, a key component of the innate immune system, protects the host from microorganisms such as bacteria, and other foreign threats including abnormal cells. However, it is also double-edged in that it can have negative effects in the host; excessive complement activation damages the host and can even kill in anaphylactic shock and septic shock. Regulation of the complement system is a useful strategy to control inflammatory diseases, including inflammatory arthritis. Rheumatoid arthritis is a common inflammatory disease worldwide. Many medicines are developed to control inflammation, including recently developed biological response modifiers such as anti-TNF and IL-6 agents. Nevertheless, in some patients disease remains difficult to control because of complications, side effects and tolerance of medicines. In inflammatory arthritis, including rheumatoid arthritis, there is abundant evidence implicating complement activation in humans and animal models. Therefore, anti-complement agents might be beneficial as part of clinical treatment. However, at present, there are still no applicable agents for therapeutic regulation of excessive complement activation in chronic disease. Novel agents in development might be useful as a strategy to control complement activation. Here I describe recent knowledge of the complement system in inflammatory arthritis, the recent developments in anti-complement agents and their considerable potential for the future.

  8. Therapeutic Approach in the Improvement of Endothelial Dysfunction: The Current State of the Art

    Directory of Open Access Journals (Sweden)

    Miroslav Radenković

    2013-01-01

    Full Text Available The endothelium has a central role in the regulation of blood flow through continuous modulation of vascular tone. This is primarily accomplished by balanced release of endothelial relaxing and contractile factors. The healthy endothelial cells are essential for maintenance of vascular homeostasis involving antioxidant, anti-inflammatory, pro-fibrinolytic, anti-adhesive, or anticoagulant effects. Oppositely, endothelial dysfunction is primarily characterized by impaired regulation of vascular tone as a result of reduced endothelial nitric oxide (NO synthase activity, lack of cofactors for NO synthesis, attenuated NO release, or increased NO degradation. So far, the pharmacological approach in improving/reversal of endothelial dysfunction was shown to be beneficial in clinical trials that have investigated actions of different cardiovascular drugs. The aim of this paper was to summarize some of the latest clinical findings related to therapeutic possibilities for improving endothelial dysfunction in different pathological conditions. In the majority of presented clinical investigations, the assessment of improvement or reversal of endothelial dysfunction was performed through the flow-mediated dilatation measurement, and in some of those endothelial progenitor cells’ count was used for the same purpose. Still, given the fast and continuous development of this field, the evidence acquisition included the MEDLINE data base screening and the selection of articles published between 2010 and 2012.

  9. Immunotherapy and therapeutic vaccines in prostate cancer:an update on current strategies and clinical implications

    Institute of Scientific and Technical Information of China (English)

    B Harpreet Singh; James L Gulley

    2014-01-01

    In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical beneift.

  10. Current understanding of BRAF alterations in diagnosis, prognosis and therapeutic targeting in paediatric low grade gliomas

    Directory of Open Access Journals (Sweden)

    Catherine Louise Penman

    2015-03-01

    Full Text Available The mitogen-activated protein kinase (MAPK pathway is known to play a key role in the initiation and maintenance of many tumours as well as normal development. This often occurs through mutation of the genes encoding RAS and RAF proteins which are involved in signal transduction in this pathway. BRAF is one of three RAF kinases which act as downstream effectors of growth factor signalling leading to cell cycle progression, proliferation and survival. Initially reported as a point mutation (V600E in the majority of metastatic melanomas, other alterations in the BRAF gene have now been reported in a variety of human cancers including papillary thyroid cancer, colon carcinomas, hairy cell leukaemia and more recently in gliomas. The identification of oncogenic mutations in the BRAF gene have led to a revolution in the treatment of metastatic melanoma using targeted molecular therapies that affect the MAPK pathway either directly through BRAF inhibition or downstream through inhibition of MEK. This review describes the molecular biology of BRAF in the context of paediatric low grade gliomas, the role of BRAF as a diagnostic marker, the prognostic implications of BRAF and evidence for therapeutic targeting of BRAF.

  11. The Role of Stem Cell Therapeutics in Wound Healing: Current Understanding and Future Directions.

    Science.gov (United States)

    Sorice, Sarah; Rustad, Kristine C; Li, Alexander Y; Gurtner, Geoffrey C

    2016-09-01

    Chronic wounds present unique challenges for healthcare providers as they place patients at increased risk for various morbidities and mortality. Advances in wound care technology have expanded the treatment options available for wound management, but few products fully address the underlying core deficiencies responsible for the development of poorly healing wounds. In the future, addressing these derangements will undoubtedly play a key role in the treatment of these patients. Broad enthusiasm has surrounded the field of stem cell biology, which has shown great promise in repairing damaged tissues across numerous disease phenotypes. In this review, we provide a comprehensive review of the literature and evaluate the present landscape of wound therapeutics while discussing the rationales and allure behind stem cell-based products. We further propose 2 challenges that remain as new stem cell-based therapies are being developed and as this technology moves toward clinical translation. Given the relatively young age of this newer technology in wound healing, numerous challenges continue to surround its effective use including identifying the ideal population of stem cells to use and determining the optimal cell delivery method. However, significant forward progress has been made, with several clinical trials beginning to demonstrate reliable clinical benefit. The upward trajectory of stem cell technologies provides an exciting opportunity to positively impact patient outcomes through the controlled application of regenerative cell-based therapy.

  12. Current therapeutic leads for the treatment of melanoma: targeted immunotherapy in the post-genomic era.

    Science.gov (United States)

    Papanastasiou, Anastasios D; Sirinian, Chaido; Kalofonos, Haralabos P; Repanti, Maria

    2014-01-01

    Metastatic melanoma has a poor prognosis and until today most therapeutic approaches are ineffective. Advances in molecular pathology and genome analysis technologies have led to the identification of genetic events and immune regulatory checkpoints that provide novel targets for pharmaceutical intervention in melanoma. Development of selective mitogen-activated kinase (MAPK) pathway inhibitors was the first major achievement coming from genetic studies that identified a constitutively active MAP kinase pathway and BRAF activating mutations in melanoma. At the same time, the manipulation of immune system checkpoints through monoclonal antibodies changed clinical practice and led to further improvement of patient outcomes. In an effort to further develop melanoma targeted therapies that depend on the genetic profile of a given patient, high-throughput genome wide approaches (next-generation sequencing [NGS], gene arrays, etc) have been employed for the characterization of genetic alterations in the patient's tumor. In the near future, the combined information from the genetic and immune background of an individual will provide the basis for a personalized, highly targeted approach in the treatment of melanoma.

  13. Current trends in diagnostic and therapeutic principles for prostate cancer in Japan.

    Science.gov (United States)

    Okihara, Koji; Shiraishi, Takumi; Ukimura, Osamu; Mizutani, Yoichi; Kawauchi, Akihiro; Miki, Tsuneharu

    2008-06-01

    This study aimed to clarify characteristics of the diagnosis and treatment of prostate cancer in Japan. In September 2005, questionnaire surveys were mailed to Japanese urologists (response rate, 43%; 474/1090) who were listed as voting members (VMs) of the Japanese Urological Association (JUA); the questionnaire surveys were also mailed to professors and chairmen (PCs) of urology departments at Japanese national, public, and private universities who were also VMs of the JUA (response rate, 76%; 68/90). The questionnaires asked about beliefs and practices regarding prostate cancer management. The answers of the VMs and PCs to the questionnaire were very similar. About 60% of these urologists answered that they did not set an age limit for prostate-specific antigen (PSA) testing, and about 40% answered that they did not set an age limit for prostate needle biopsy in individuals with an intermediately elevated PSA level. The age limit for radical prostatectomy (RP) was set at 75 years by 69% (322/470) of the VMs and 66% (45/68) of the PCs. The order of priority of factors considered for the selection of RP for early prostate cancer was radicality, including tumor grade (mean, 1.97); patient's wish for radical surgery (mean, 2.47); comorbidity (mean, 2.72); and age (mean, 2.81). There are trends in diagnostic and therapeutic principles for prostate cancer which are characteristic of Japan, and these trends are associated with the recent rapid extension of life expectancy in that country.

  14. Current Advances in the Biological Activity of Polysaccharides in Dendrobium with Intriguing Therapeutic Potential.

    Science.gov (United States)

    Lee, Chun-Ting; Kuo, Heng-Chun; Chen, Yung-Hsiang; Tsai, Ming-Yen

    2017-02-27

    The polysaccharides in many plants are attracting worldwide attention because of their biological activities and medical properties, such as anti-viral, anti-oxidative, anti-chronic inflammation, anti-hypertensive, immunomodulation, and neuron-protective effects, as well as anti-tumor activity. Denodrobium species, a genus of the family orchidaceae, have been used as herbal medicines for hundreds of years in China due to their pharmacological effects. These effects include nourishing the Yin, supplementing the stomach, increasing body fluids, and clearing heat. Recently, numerous researchers have investigated possible active compounds in Denodrobium species, such as lectins, phenanthrenes, alkaloids, trigonopol A, and polysaccharides. Unlike those of other plants, the biological effects of polysaccharides in Dendrobium are a novel research field. In this review, we focus on these novel findings to give readers an overall picture of the intriguing therapeutic potential of polysaccharides in Dendrobium, especially those of the four commonly-used Denodrobium species: D. huoshanense, D. offininale, D. nobile, and D. chrysotoxum. . Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Giant cell tumor of bone: current review of morphological, clinical, radiological, and therapeutic characteristics

    Directory of Open Access Journals (Sweden)

    Georgi P. Georgiev

    2014-09-01

    Full Text Available Giant cell tumor of bone accounts for about 5% of all primary bone tumors in adults and is still one of the most obscure and intensively examined tumors of bone. This largely results from the lack of uniform clinical, radiographic, histological or morphological aspects that allow prediction of recurrence. Classified by the World Health Organization as “an aggressive, potentially malignant lesion”, the giant cell tumor of bone could give lung metastases, could undergo malignant degeneration or could have multicentric localization. It usually develops in long bones but can also occur in unusual locations. The common presenting symptom is increasing pain at the tumor site. Standard treatment ranges from curettage to wide resection, with reports of varying oncological and functional results. The recurrence rate is high during the first 2-3 years after surgery regardless of pre-operative tumor stage. Herein, we discuss the morphological, clinical, radiological, and therapeutic characteristics of this pathologic entity as well as its differential diagnosis. J Clin Exp Invest 2014; 5 (3: 475-485

  16. [Relationships between diabetes mellitus and periodontal disease: current knowledges and therapeutic prospects].

    Science.gov (United States)

    Garofalo, G S

    2008-01-01

    Diabetes mellitus is a disorder of the endocrine system. An important pathology of dental interest to which the diabetic patient can go encounter, especially if not controlled from the metabolic point of view, is the periodontal disease. The aim of this review is to illustrate the relation between diabetes mellitus and periodontal disease estimating the several therapeutic options on hand in the clinical daily practice. Many studies show an important association between diabetes and the pathogenesis of periodontal disease. Vascular changes caused by hyper-glycemia are associated to the development of periodontal pathogens species. Moreover, diabetics show an exacerbate host response with hyperproduction of inflammatory mediators and polymorphonuclear dysfunction. Diabetics with good metabolic control and patients with good oral hygiene show a reduced risk of periodontitis. In conclusion, diabetes mellitus (of type 1 and type 2) is an important risk factor for periodontitis. Diabetes mellitus determines changes in bacterial population and production of inflammatory mediators, and reduces the efficacy of the host response. Good controlled diabetes do not cause a major risk of periodontitis and improve the results of the periodontal initial therapy and of the eventual surgical therapy. Moreover, periodontal therapy may reduce the request of insulin in diabetics. It is reasonable a reciprocal relation between diabetes and periodontal disease.

  17. Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics.

    Science.gov (United States)

    Pearn, Matthew L; Niesman, Ingrid R; Egawa, Junji; Sawada, Atsushi; Almenar-Queralt, Angels; Shah, Sameer B; Duckworth, Josh L; Head, Brian P

    2016-07-06

    Traumatic brain injury (TBI) is one of the leading causes of death of young people in the developed world. In the United States alone, 1.7 million traumatic events occur annually accounting for 50,000 deaths. The etiology of TBI includes traffic accidents, falls, gunshot wounds, sports, and combat-related events. TBI severity ranges from mild to severe. TBI can induce subtle changes in molecular signaling, alterations in cellular structure and function, and/or primary tissue injury, such as contusion, hemorrhage, and diffuse axonal injury. TBI results in blood-brain barrier (BBB) damage and leakage, which allows for increased extravasation of immune cells (i.e., increased neuroinflammation). BBB dysfunction and impaired homeostasis contribute to secondary injury that occurs from hours to days to months after the initial trauma. This delayed nature of the secondary injury suggests a potential therapeutic window. The focus of this article is on the (1) pathophysiology of TBI and (2) potential therapies that include biologics (stem cells, gene therapy, peptides), pharmacological (anti-inflammatory, antiepileptic, progrowth), and noninvasive (exercise, transcranial magnetic stimulation). In final, the review briefly discusses membrane/lipid rafts (MLR) and the MLR-associated protein caveolin (Cav). Interventions that increase Cav-1, MLR formation, and MLR recruitment of growth-promoting signaling components may augment the efficacy of pharmacologic agents or already existing endogenous neurotransmitters and neurotrophins that converge upon progrowth signaling cascades resulting in improved neuronal function after injury.

  18. Immunotherapy and therapeutic vaccines in prostate cancer: an update on current strategies and clinical implications

    Directory of Open Access Journals (Sweden)

    B Harpreet Singh

    2014-06-01

    Full Text Available In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical benefit.

  19. Prospective Multicentre Study on the Epidemiology and Current Therapeutic Management of Severe Bronchiolitis in Spain

    Directory of Open Access Journals (Sweden)

    Jose C. Flores-González

    2017-01-01

    Full Text Available Objective. To determine the epidemiology and therapeutic management of patients with severe acute bronchiolitis (AB admitted to paediatric intensive care units (PICUs in Spain. Design. Descriptive, prospective, multicentre study. Setting. Sixteen Spanish PICUs. Patients. Patients with severe AB who required admission to any of the participating PICUs over 1 year. Interventions. Both epidemiological variables and medical treatment received were recorded. Results. A total of 262 patients were recruited; 143 were male (54.6%, with median age of 1 month (0–23. Median stay in the PICU was 7 days (1–46. Sixty patients (23% received no nebuliser treatment, while the rest received a combination of inhalation therapies. One-quarter of patients (24.8% received corticosteroids and 56.5% antibiotic therapy. High-flow oxygen therapy was used in 14.3% and noninvasive ventilation (NIV was used in 75.6%. Endotracheal intubation was required in 24.4% of patients. Younger age, antibiotic therapy, and invasive mechanical ventilation (IMV were risk factors that significantly increased the stay in the PICU. Conclusions. Spanish PICUs continue to routinely use nebulised bronchodilator treatment and corticosteroid therapy. Despite NIV being widely used in this condition, intubation was required in one-quarter of cases. Younger age, antibiotic therapy, and IMV were associated with a longer stay in the PICU.

  20. Therapeutic trial of intensified conditioning regimen with high-dose cytosine arabinoside, cyclophosphamide and either total body irradiation or busulfan followed by allogeneic bone marrow transplantation for myelodysplastic syndrome in children

    Energy Technology Data Exchange (ETDEWEB)

    Nagatoshi, Yoshihisa; Okamura, Jun; Ikuno, Yoshiko; Akamatsu, Minoru; Tasaka, Hideko [National Kyushu Cancer Center, Fukuoka (Japan)

    1997-04-01

    Ten children with myelodysplastic syndrome underwent an allogeneic bone marrow transplantation (BMT) with an intensified conditioning regimen. The median age of the patients was 8 years (range 2-10), and included 6 males and 4 females. The subtype of the disease was refractory anemia (RA) in 4, RA with excess blasts (RAEB) in 4, RAEB in transformation (RAEB-T) in 1, and juvenile chronic myelogenous leukemia (JCML) in 1. All patients were conditioned with high-dose cytosine arabinoside (12000 mg/m{sup 2}), cyclophosphamide (120 mg/kg) and either total body irradiation (10-13.2 Gy) or busulfan (16 mg/kg or 560 mg/m{sup 2}). Cyclosporine A and/or methotrexate were used for the prophylaxis of graft-versus-host disease (GVHD). Engraftment was prompt in all but one patient. Severe acute GVHD (grade 3) (n=1), interstitial pneumonitis (n=1) and veno-occlusive disease of the liver (n=1) occurred. The disease relapsed in one patient with RAEB-T. Seven of the 10 patients were alive and disease free 2-74 months after BMT. The disease-free survival rate at 4 years was 69{+-}15%. All surviving patients were in the full performance status. The examined children with MDS tolerated this intensified conditioning regimen well. (author)

  1. AIDS-Related Non-Hodgkin's Lymphoma in Sub-Saharan Africa: Current Status and Realities of Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Peter M. Mwamba

    2012-01-01

    Full Text Available Today AIDS-related non-Hodgkin's lymphoma (AR-NHL is a significant cause of morbidity and mortality in HIV-infected patients the world over, and especially in sub-Saharan Africa. While the overall incidence of AR-NHL since the emergence of combination antiretroviral therapy (cART era has declined, the occurrence of this disease appears to have stabilized. In regions where access to cART is challenging, the impact on disease incidence is less clear. In the resource-rich environment it is clinically recognized that it is no longer appropriate to consider AR-NHL as a single disease entity and rather treatment of AIDS lymphoma needs to be tailored to lymphoma subtype. While intensive therapeutic strategies in the resource-rich world are clearly improving outcome, in AIDS epicenters of the world and especially in sub-Saharan Africa there is a paucity of data on treatment and outcomes. In fact, only one prospective study of dose-modified oral chemotherapy and limited retrospective studies with sufficient details provide a window into the natural history and clinical management of this disease. The scarcities and challenges of treatment in this setting provide a backdrop to review the current status and realities of the therapeutic approach to AR-NHL in sub-Saharan Africa. More pragmatic and risk-adapted therapeutic approaches are needed.

  2. Current and Emerging Therapeutic Strategies for the Treatment of Meibomian Gland Dysfunction (MGD).

    Science.gov (United States)

    Thode, Adam R; Latkany, Robert A

    2015-07-01

    Meibomian gland (MG) dysfunction (MGD) is a multifactorial, chronic condition of the eyelids, leading to eye irritation, inflammation and ocular surface disease. Initial conservative therapy often includes a combination of warm compresses in addition to baby shampoo or eyelid wipes. The practice of lid hygiene dates back to the 1950s, when selenium sulfide-based shampoo was first used to treat seborrhoeic dermatitis of the eyelids. Today, tear-free baby shampoo has replaced dandruff shampoo for MGD treatment and offers symptom relief in selected patients. However, many will not achieve significant improvement on this therapy alone; some may even develop an allergy to the added dyes and fragrances in these products. Other manual and mechanical techniques to treat MGD include MG expression and massage, MG probing and LipiFlow(®). While potentially effective in patients with moderate MGD, these procedures are more invasive and may be cost prohibitive. Pharmacological treatments are another course of action. Supplements rich in omega-3 fatty acids have been shown to improve both MGD and dry eye symptoms. Tea tree oil, specifically the terpenin-4-ol component, is especially effective in treating MGD associated with Demodex mites. Topical antibiotics, such as azithromycin, or systemic antibiotics, such as doxycycline or azithromycin, can improve MGD symptoms both by altering the ocular flora and through anti-inflammatory mechanisms. Addressing and treating concurrent ocular allergy is integral to symptom management. Topical N-acetylcysteine and topical cyclosporine can both be effective therapeutic adjuncts in patients with concurrent dry eye. A short course of topical steroid may be used in some severe cases, with monitoring for steroid-induced glaucoma and cataracts. While the standard method to treat MGD is simply warm compresses and baby shampoo, a more tailored approach to address the multiple aetiologies of the disease is suggested.

  3. Breast papillomas: current management with a focus on a new diagnostic and therapeutic modality

    Science.gov (United States)

    Al Sarakbi, W; Worku, D; Escobar, PF; Mokbel, K

    2006-01-01

    Breast papilloma is a term that describes an intraductal papillary configuration of the mammary epithelium on macroscopic or microscopic examination. It includes solitary intraductal papillomas, multiple papillomas, papillomatosis, and juvenile papillomatosis (JP). Recent advances in mammary ductoscopy (MD) have raised new possibilities in the diagnosis and treatment of breast papillomas. This technique represents an important diagnostic adjunct in patients with pathological nipple discharge (PND) by allowing direct visualisation and biopsy of intraductal lesions and guiding duct excision surgery. Treatment of breast papillomas often entails surgical duct excision for symptomatic relief and histopathological examination. Recently, more conservative approach has been adapted. MD-assisted microdochectomy should be considered the procedure of choice for a papilloma-related single duct discharge. Furthermore, there is increasing evidence that MD has the potential to reduce the number of duct excision procedures and minimise the extent of surgical resection. Imaging-guided vacuum-assisted core biopsy can be diagnostic and therapeutic for papillomas seen on mammography and/or ultrasound. Patients with multiple papillomas do have an increased risk of developing cancer and should be kept under annual review with regular mammography (preferably digital mammography) if treated conservatively. Magnetic resonance (MR) can be also used in surveillance in view of its high sensitivity. Because the risk is small, long term and affects both breasts, long-term follow-up is more appropriate than prophylactic mastectomy. Patients who prove to have solitary duct papilloma have insufficient increase in the risk of subsequent malignancy to justify routine follow-up. PMID:16417642

  4. Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis, and therapeutics

    Directory of Open Access Journals (Sweden)

    Dhanasekaran R

    2012-05-01

    Full Text Available Renumathy Dhanasekaran, Alpna Limaye, Roniel CabreraDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USAAbstract: Hepatocellular carcinoma (HCC is a common malignancy in developing countries and its incidence is on the rise in the developing world. The epidemiology of this cancer is unique since its risk factors, including hepatitis C and B, have been clearly established. The current trends in the shifting incidence of HCC in different regions of the world can be explained partly by the changing prevalence of hepatitis. Early detection offers the only hope for curative treatment for patients with HCC, hence effective screening strategies for high-risk patients is of utmost importance. Liver transplantation and surgical resection remains the cornerstone of curative treatment. But major advances in locoregional therapies and molecular-targeted therapies for the treatment of advanced HCC have occurred recently. In this review, current trends in the worldwide epidemiology, surveillance, diagnosis, standard treatments, and the emerging therapies for HCC are discussed.Keywords: liver cancer, sorafenib, hepatitis C, TACE

  5. Current status and regulatory perspective of chimeric antigen receptor-modified T cell therapeutics.

    Science.gov (United States)

    Kim, Mi-Gyeong; Kim, Dongyoon; Suh, Soo-Kyung; Park, Zewon; Choi, Min Joung; Oh, Yu-Kyoung

    2016-04-01

    Chimeric antigen receptor-modified T cells (CAR-T) have emerged as a new modality for cancer immunotherapy due to their potent efficacy against terminal cancers. CAR-Ts are reported to exert higher efficacy than monoclonal antibodies and antibody-drug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors. CAR-Ts are classified as first-, second- and third-generation, depending on the intracellular signaling domain number of T cell receptors. This review covers the current status of CAR-T research, including basic proof-of-concept investigations at the cell and animal levels. Currently ongoing clinical trials of CAR-T worldwide are additionally discussed. Owing to the lack of existing approved products, several unresolved concerns remain with regard to safety, efficacy and manufacturing of CAR-T, as well as quality control issues. In particular, the cytokine release syndrome is the major side-effect impeding the successful development of CAR-T in clinical trials. Here, we have addressed the challenges and regulatory perspectives of CAR-T therapy.

  6. Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others?

    Science.gov (United States)

    Maccarrone, Mauro; Maldonado, Rafael; Casas, Miguel; Henze, Thomas; Centonze, Diego

    2017-04-01

    The complexity of the endocannabinoid (eCB) system is becoming better understood and new drivers of eCB signaling are emerging. Modulation of the activities of the eCB system can be therapeutic in a number of diseases. Research into the eCB system has been paralleled by the development of agents that interact with cannabinoid receptors. In this regard it should be remembered that herbal cannabis contains a myriad of active ingredients, and the individual cannabinoids have quite distinct biological activities requiring independent studies. Areas covered: This article reviews the most important current data involving the eCB system in relation to human diseases, to reflect the present (based mainly on the most used prescription cannabinoid medicine, THC/CBD oromucosal spray) and potential future uses of cannabinoid-based therapy. Expert commentary: From the different therapeutic possibilities, THC/CBD oromucosal spray has been in clinical use for approximately five years in numerous countries world-wide for the management of multiple sclerosis (MS)-related moderate to severe resistant spasticity. Clinical trials have confirmed its efficacy and tolerability. Other diseases in which different cannabinoids are currently being investigated include various pain states, Alzheimer's disease, Parkinson's disease, Huntington's disease and epilepsy. The continued characterization of individual cannabinoids in different diseases remains important.

  7. Combining Upper Limb Robotic Rehabilitation with Other Therapeutic Approaches after Stroke: Current Status, Rationale, and Challenges

    Directory of Open Access Journals (Sweden)

    Stefano Mazzoleni

    2017-01-01

    Full Text Available A better understanding of the neural substrates that underlie motor recovery after stroke has led to the development of innovative rehabilitation strategies and tools that incorporate key elements of motor skill relearning, that is, intensive motor training involving goal-oriented repeated movements. Robotic devices for the upper limb are increasingly used in rehabilitation. Studies have demonstrated the effectiveness of these devices in reducing motor impairments, but less so for the improvement of upper limb function. Other studies have begun to investigate the benefits of combined approaches that target muscle function (functional electrical stimulation and botulinum toxin injections, modulate neural activity (noninvasive brain stimulation, and enhance motivation (virtual reality in an attempt to potentialize the benefits of robot-mediated training. The aim of this paper is to overview the current status of such combined treatments and to analyze the rationale behind them.

  8. Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus.

    Science.gov (United States)

    Tahrani, Abd A; Barnett, Anthony H; Bailey, Clifford J

    2016-10-01

    Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

  9. Current and Future Therapeutic Agents in the Management of Heart Failure

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Congestive heart failare is a disease in which initially compensutory changes in car-diac, vascular, and renal functions become detrimental over time. The changes are mediated by a largenamber of neurohormones and cytokines. Counter-regalutory hormones also play a role, but ave general-ly insuffwient to offset the adverse effects of the neurohormones or progression of the disease. Symp-toms of heart failure occurs in the presence of systolic dysfunction, usually documented by a decrease inejection fraction, or can present with impaired diastolic function occasionally labeled as heart failureuith preserved systolic function of the left ventricle. Heart failure and its treatment represent a medicalproblem of significant importance because of the high mortality associated with it despite the current ther-apy, which has substantial evidence of reduction in mortality and morbidity. Prevention or slowing of theprogressive deterioration in function of the heart and other organs involved through utilizing new agentsthat affect more or differentneurohormonal pathways may be beneficial and forms the focus of heartfailure research and drug development. However, the multiplicity of hormonal effects mandate the useof complex therapy in the management of congestive heart failure( CHF ). The new agents in addition tothe conventional therapy used in the management of heart failure are; Human B-type natriuretic peptide(in the treatment of decompensated CHF), endothelin receptor antagonists, calcium sensitizers, neutralendopeptidase ( NEP ) and vasopeptidase inhibitors, vasopressin antagonists and cytokine inhibitors.

  10. Facial seborrheic dermatitis: a report on current status and therapeutic horizons.

    Science.gov (United States)

    Bikowski, Joseph

    2009-02-01

    Seborrheic dermatitis, characterized by erythema and/or flaking or scaling in areas of high sebaceous activity, affects up to 5% of the US population and often appears in conjunction with other common skin disorders, such as rosacea and acne. Despite ongoing research, its etiology is puzzling. Increased sebaceous and hormonal (androgenic) activity is thought to play a part. Recent evidence suggests an important role for individual susceptibility to irritant metabolites of the skin commensal Malassezia, most probably M globosa. Current approaches thus include agents with antifungal as well as antikeratinizing, and anti-inflammatory activity. Azelaic acid, which has all 3 properties, may be a useful addition to first-line management, which now comprises of topical steroids, the immunosuppressant agents tacrolimus and pimecrolimus, azoles and other antifungals, and keratolytic agents. A recent exploratory study supports the efficacy and safety of azelaic acid 15% gel in seborrheic dermatitis. Azelaic acid may be especially valuable in this application because of its efficacy in treating concomitant rosacea and acne.

  11. Use of novel proteosome inhibitors as a therapeutic strategy in lymphomas current experience and emerging concepts.

    Science.gov (United States)

    Abayomi, Emmanuel Akinola; Sissolak, Gerhard; Jacobs, Peter

    2007-08-01

    Precedent from preclinical experiments coupled with two pivotal phase 2 studies in myeloma has focused attention on a potential role for ubiquitin-proteasome pathway in modulating a number of events that occur commonly in the neoplastic process involving proteins in the regulation of cells cycling, growth and differentiation. This influence is vested in the proteasomes which are large complexes of proteolytic enzymes responsible for degradation of many of these intracellular messengers. Logically interest has centred on molecules having the capacity to influence, by degradation, such molecules and although a number of agents are in development bortezomib is the only one currently in clinical use. Velcade, formerly PS-341, is a novel dipeptide boronic acid capable of reversibly inhibiting the 26S proteasome through a range of activities. The latter are anti-proliferative and proapoptotic with the latter blocking nuclear transcription via NF-kappa B in addition to down regulating adhesion and inhibiting angiogenesis. Additional changes are mediated in protein folding within the endoplasmic reticulum and contribute to cell death. These concepts are given focus by considering their introduction into treatment of lymphoreticular malignancy.

  12. Does hemispheric lateralization inlfuence therapeutic effects of transcranial direct current stimulation?

    Institute of Scientific and Technical Information of China (English)

    Yong Hyun Kwon; Kyung Woo Kang; Na Kyung Lee; Sung Min Son

    2016-01-01

    This study investigated the effect of transcranial direct current stimulation (tDCS) polarity depending on lat-eralized function of task property in normal individuals performing visuomotor and simple repetitive tasks. Thirty healthy participants with no neurological disorders were recruited to participate in this study. Partici-pants were randomly allocated into active or control condition. For the active condition, tDCS intensity was 2 mA with stimulation applied for 15 minutes to the right hemisphere (tDCS condition). For the sham control, electrodes were placed in the same position, but the stimulator was turned off after 30 seconds (sham con-dition). The tapping and tracking task tests were performed before and after for both conditions. Univariate analysis revealed signiifcant difference only in the tracking task. For direct comparison of both tasks within each group, the tracking task had signiifcantly higher Z score than the tapping task in the tDCS group (P < 0.05). Thus, our study indicates that stimulation of the right hemisphere using tDCS can effectively improve visuomotor (tracking) task over simple repetitive (tapping) task.

  13. [Current antibiotic resistance profile of uropathogenic Escherichia coli strains and therapeutic consequences].

    Science.gov (United States)

    El Bouamri, M C; Arsalane, L; Kamouni, Y; Yahyaoui, H; Bennouar, N; Berraha, M; Zouhair, S

    2014-12-01

    Urinary tract infections (UTI) are a very common reason for consultation and prescription in current practice. Excessive or inappropriate use of antibiotics in treating urinary tract infections is responsible for the emergence and spread of multiresistant uropathogenic bacteria. To evaluate the isolation frequency and antibiotic resistance of uropathogenic Escherichia coli strains isolated at the Marrakech region. We conducted a retrospective study over a period of three years (from 1st January 2010 to 31 December 2012). It included all non-redundant uropathogenic E. coli strains isolated in the microbiology laboratory of the Avicenne hospital of Marrakech, Morocco. During this study, 1472 uropathogenic enterobacteriaceae were isolated including 924 non-repetitive E. coli strains, an overall isolation frequency of 63%. Antibiotic resistance of isolated E. coli strains showed resistance rates to amoxicillin (65%), sulfamethoxazole-triméthropime (55%), amoxicillin-clavulanic acid (43%), ciprofloxacin (22%), gentamicin (14%), nitrofurans (11%), amikacin (8%) and fosfomycin (7%). The number of E. coli strains resistant to C3G by ESBL production was 67, an average frequency of 4.5% of all isolated uropathogenic enterobacteria. The associated antibiotic resistance in the case of ESBL-producing E. coli were 82% for ciprofloxacin, 76% for sulfamethozole trimethoprim, 66% for gentamicin and 56% for amikacin. No resistance to imipenem was recorded for the isolated E. coli strains, which represents an imipenem sensitivity of 100%. Antibiotic resistance of uropathogenic E. coli strains limits treatment options and therefore constitutes a real public health problem. The regular updating of antibiotic susceptibility statistics of E. coli strains allows a better adaptation of the probabilistic antibiotic therapy to local epidemiological data. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents.

    Science.gov (United States)

    Miyamoto, S; Miyake, N; Jarskog, L F; Fleischhacker, W W; Lieberman, J A

    2012-12-01

    Since the introduction of chlorpromazine and throughout the development of the new-generation antipsychotic drugs (APDs) beginning with clozapine, the D(2) receptor has been the target for the development of APDs. Pharmacologic actions to reduce neurotransmission through the D(2) receptor have been the only proven therapeutic mechanism for psychoses. A number of novel non-D(2) mechanisms of action of APDs have been explored over the past 40 years but none has definitively been proven effective. At the same time, the effectiveness of treatments and range of outcomes for patients are far from satisfactory. The relative success of antipsychotics in treating positive symptoms is limited by the fact that a substantial number of patients are refractory to current medications and by their lack of efficacy for negative and cognitive symptoms, which often determine the level of functional impairment. In addition, while the newer antipsychotics produce fewer motor side effects, safety and tolerability concerns about weight gain and endocrinopathies have emerged. Consequently, there is an urgent need for more effective and better-tolerated antipsychotic agents, and to identify new molecular targets and develop mechanistically novel compounds that can address the various symptom dimensions of schizophrenia. In recent years, a variety of new experimental pharmacological approaches have emerged, including compounds acting on targets other than the dopamine D(2) receptor. However, there is still an ongoing debate as to whether drugs selective for singe molecular targets (that is, 'magic bullets') or drugs selectively non-selective for several molecular targets (that is, 'magic shotguns', 'multifunctional drugs' or 'intramolecular polypharmacy') will lead to more effective new medications for schizophrenia. In this context, current and future drug development strategies can be seen to fall into three categories: (1) refinement of precedented mechanisms of action to provide drugs

  15. 非霍奇金淋巴瘤应用CHVP和CHOP治疗方案的临床实验观察%Comparision of the Therapeutic Effects of CHVP and CHOP Regimens For Non-Hodgkin'Lymphoma

    Institute of Scientific and Technical Information of China (English)

    徐丽; 吐尔逊江·司拉木; 杜春辉; 田刚

    2011-01-01

    Objective To compare efficacy and toxicity of CHVP (with VDS) and CHOP (with VCR) regimens for NonHodgkin lymphoma. Methods 60 NHL patients were devided into two groups including 30 cases CHVP and 30 cases CHOP. The rate of response and toxicity for 2 regimens were detected by the standard method. Results The rate of response for CHVP and CHOP were 76. 67 % and 70. 00% (x2 = 0. 34,P> 0. 05), the clinical benefit rates were 93. 33% and 90. 00 % , respectively(x2 = 0.01,P> 0. 05). Major toxicity was alopecia ,disorder of stomache and intestine , hepatic fuction,neurotoxieity( x2 = 0. 01 , P > 0. 05 ; x2 = 0. 29, P > 0. 05 ; x2 = 0.00 , P > 0. 05). Incidence neurotoxicity was lower in the CHVP group than in the CHOP group(16. 67% vs 46. 67 % , x2 = 6. 24,P<0. 05). Conclusion CHVP(with VDS) regimes may more effective for Non-Hodgkin lymphoma with lower toxicity. It should be used generally in clinic.%目的 比较含长春地辛(VDS)的CHVP方案和含长春新碱(VCR)的CHOP方案治疗非霍奇金淋巴瘤(NHL)的疗效和不良反应.方法 两种方案治疗患者各30例.结果 两组患者的有效率分别为76.67%和70.00%(χ2=0.34,P>0.05).临床受益率分别为93.33%和90.00%(χ2=0.01,P>0.05).两组血小板减少、胃肠功能紊乱和肝功异常比较差异均无统计学意义(χ2=0.01,P>0.05;χ2=0.29,P>0.05;χ2=0.00,P>0.05).外周神经毒性为主要不良反应.CHVP组和CHOP组外周神经毒性的发生率分别为16.67%和46.67%(χ2=6.24,P<0.05).结论 应用含长春地辛(VDS)的CHVP方案治疗NHL疗效好,神经毒性低,值得临床推广.

  16. Medical Management of Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage: A Review of Current and Emerging Therapeutic Interventions.

    Science.gov (United States)

    Adamczyk, Peter; He, Shuhan; Amar, Arun Paul; Mack, William J

    2013-01-01

    Cerebral vasospasm is a major source of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Evidence suggests a multifactorial etiology and this concept remains supported by the assortment of therapeutic modalities under investigation. The authors provide an updated review of the literature for previous and recent clinical trials evaluating medical treatments in patients with cerebral vasospasm secondary to aSAH. Currently, the strongest evidence supports use of prophylactic oral nimodipine and initiation of triple-H therapy for patients in cerebral vasospasm. Other agents presented in this report include magnesium, statins, endothelin receptor antagonists, nitric oxide promoters, free radical scavengers, thromboxane inhibitors, thrombolysis, anti-inflammatory agents and neuroprotectants. Although promising data is beginning to emerge for several treatments, few prospective randomized clinical trials are presently available. Additionally, future investigational efforts will need to resolve discrepant definitions and outcome measures for cerebral vasospasm in order to permit adequate study comparisons. Until then, definitive recommendations cannot be made regarding the safety and efficacy for each of these therapeutic strategies and medical management practices will continue to be implemented in a wide-ranging manner.

  17. Medical Management of Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage: A Review of Current and Emerging Therapeutic Interventions

    Directory of Open Access Journals (Sweden)

    Peter Adamczyk

    2013-01-01

    Full Text Available Cerebral vasospasm is a major source of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH. Evidence suggests a multifactorial etiology and this concept remains supported by the assortment of therapeutic modalities under investigation. The authors provide an updated review of the literature for previous and recent clinical trials evaluating medical treatments in patients with cerebral vasospasm secondary to aSAH. Currently, the strongest evidence supports use of prophylactic oral nimodipine and initiation of triple-H therapy for patients in cerebral vasospasm. Other agents presented in this report include magnesium, statins, endothelin receptor antagonists, nitric oxide promoters, free radical scavengers, thromboxane inhibitors, thrombolysis, anti-inflammatory agents and neuroprotectants. Although promising data is beginning to emerge for several treatments, few prospective randomized clinical trials are presently available. Additionally, future investigational efforts will need to resolve discrepant definitions and outcome measures for cerebral vasospasm in order to permit adequate study comparisons. Until then, definitive recommendations cannot be made regarding the safety and efficacy for each of these therapeutic strategies and medical management practices will continue to be implemented in a wide-ranging manner.

  18. Current Status of Poly(ADP-ribose Polymerase Inhibitors as Novel Therapeutic Agents for Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    David J. Hiller

    2012-01-01

    Full Text Available Triple-negative breast cancer (TNBC is an aggressive type of breast cancer that is clinically defined as lacking estrogen and progesterone receptors, as well as being ERBB2 (HER-2 negative. Without specific therapeutic targets, TNBC carries a worse prognosis than other types of breast cancer in the absence of therapy. Research has now further differentiated breast cancer into subtypes based on genetic expression patterns. One of these subtypes, basal-like, frequently overlaps with the clinical picture of TNBC. Additionally, both TNBC and basal-like breast cancer link to BRCA mutations. Recent pharmaceutical advances have created a class of drugs, poly(ADP-ribose polymerase (PARP inhibitors, which are showing potential to effectively treat these patients. The aim of this paper is to summarize the basis behind PARP inhibitors and update the current status of their development in clinical trials for the treatment of TNBC.

  19. Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Berg, Lise Charlotte; Betts, Dean H.

    2009-01-01

    This paper provides a bird's-eye perspective of the general principles of stem-cell therapy and tissue engineering; it relates comparative knowledge in this area to the current and future status of equine regenerative medicine.The understanding of equine stem cell biology, biofactors, and scaffolds...... mesenchymal stromal cells, unless there is proof that they exhibit the fundamental in vivo characteristics of pluripotency and the ability to self-renew. That said, these cells from various tissues hold great promise for therapeutic use in horses. The 3 components of tissue engineering - cells, biological...... factors, and biomaterials - are increasingly being applied in equine medicine, fuelled by better scaffolds and increased understanding of individual biofactors and cell sources.The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently...

  20. Amyloid Beta and Tau Proteins as Therapeutic Targets for Alzheimer’s Disease Treatment: Rethinking the Current Strategy

    Directory of Open Access Journals (Sweden)

    Siddhartha Mondragón-Rodríguez

    2012-01-01

    Full Text Available Alzheimer’s disease (AD is defined by the concurrence of accumulation of abnormal aggregates composed of two proteins: Amyloid beta (Aβ and tau, and of cellular changes including neurite degeneration and loss of neurons and cognitive functions. Based on their strong association with disease, genetically and pathologically, it is not surprising that there has been a focus towards developing therapies against the aggregated structures. Unfortunately, current therapies have but mild benefit. With this in mind we will focus on the relationship of synaptic plasticity with Aβ and tau protein and their role as potential targets for the development of therapeutic drugs. Finally, we will provide perspectives in developing a multifactorial strategy for AD treatment.

  1. Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Berg, Lise Charlotte; Betts, Dean H.

    2009-01-01

    This paper provides a bird's-eye perspective of the general principles of stem-cell therapy and tissue engineering; it relates comparative knowledge in this area to the current and future status of equine regenerative medicine.The understanding of equine stem cell biology, biofactors, and scaffolds......, and their potential therapeutic use in horses are rudimentary at present. Mesenchymal stem cell isolation has been proclaimed from several equine tissues in the past few years. Based on the criteria of the International Society for Cellular Therapy, most of these cells are more correctly referred to as multipotent...... factors, and biomaterials - are increasingly being applied in equine medicine, fuelled by better scaffolds and increased understanding of individual biofactors and cell sources.The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently...

  2. Current Status of Therapeutic Strategies for Patent Ductus Arteriosus in Very-Low-Birth-Weight Infants in Korea.

    Science.gov (United States)

    Lee, Jin A; Kim, Myo-Jing; Oh, Sohee; Choi, Byung Min

    2015-10-01

    This study aimed to investigate current therapeutic strategies for patent ductus arteriosus (PDA) in very-low-birth-weight (VLBW) infants in Korea. A total of 2,254 VLBW infants among 2,386 from Korean Neonatal Network cohort born from January 2013 to June 2014 were included. No PDA was seen for 1,206 infants (53.5%) and the infants diagnosed or treated for PDA were 1,048 infants (46.5%). The proportion of infants with PDA was decreased according to the increase in gestational age (GA) and birthweight. Infants with PDA were divided into groups according to the therapeutic strategies of PDA: prophylactic treatment (PT, n = 69, 3.1%), pre-symptomatic treatment (PST, n = 212, 9.4%), symptomatic treatment (ST, n = 596, 26.4%), and conservative treatment (CT, n = 171, 7.6%). ST was the most preferred treatment modality for preterm PDA and the proportion of the patients was decreased in the order of PST, CT, and PT. Although ST was still the most favored treatment in GA < 24 weeks group, CT was more preferred than PST or ST when compared with GA ≥ 32 weeks group [CT vs. PST, OR 5.3, 95% CI 1.56-18.18; CT vs. ST, OR 2.9, 95% CI 1.03-8.13]. A total of 877 infants (38.9%) received pharmacological or surgical treatment about PDA, and 35.5% (801 infants) received pharmacological treatment, mostly with ibuprofen. Seventy-six infants (3.4%) received primary ligation and 8.9% (201 infants) received secondary ligation. Diverse treatment strategies are currently used for preterm PDA in Korea. Further analyses of neonatal outcomes according to the treatment strategies are necessary to obtain a standardized treatment guideline for preterm PDA.

  3. 含莫西沙星强化期抗结核方案用于初治肺结核的效果评价%Therapeutic effect of the regimen containing Moxifloxacin in intensive phase for pulmonary tuberculosis patients

    Institute of Scientific and Technical Information of China (English)

    贾维

    2011-01-01

    Objective To explore the effect and safety of the regimen containing Moxifloxacin in intensive phase for pulmonary tuberculosis patients. Methods 88 cases with initial tuberculosis(each group of 44 cases) were studied in comparison in the same period. The treatment group contained isoniazid, rifampicin and moxifloxacin of antituberculosis regime and the control group contained isoniazid,rifampicin and pyrazineamide. Results After 2 months intensive phase anti-tubercular treatment ,the sputum negative conversion rates was 95.0% and control's was 94.4%(P > 0.05); the absorb rate of lesions: the treatment group 77.3 % and the control group 79.5%; the liver damage rate: the treatment group and control group was 68.2% ,34.1% respectively(P < 0.05). Conclusion Anti-tuberculosis intensive phase regimes containing moxifloxacin for tuberculosis treatment was safe and effective in initial treatment of pulmonary tuberculose.%目的 探讨强化期含莫西沙星用于初治肺结核的有效性和安全性.方法 对88例初治肺结核进行了同期对照配对研究(每组44例).其中治疗组为含莫西沙星(异烟肼、利福平、莫西沙星)的抗结核方案,对照组为异烟肼、利福平、吡嗪酰胺的治疗方案.结果 抗结核治疗2个月,治疗组与对照组痰菌阴转率(95.0%与94.4%)、病灶吸收好转率(77.3%与79.5%)差异均无统计学意义(均P>0.05));肝损率治疗组34.1%,对照组68.2%,差异有统计学意义(P<0.05).结论 含莫西沙星的强化期联合抗结核方案用于初治肺结核的治疗安全有效.

  4. Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time

    Science.gov (United States)

    Lee, Bai-Yu; Clemens, Daniel L.; Silva, Aleidy; Dillon, Barbara Jane; Masleša-Galić, Saša; Nava, Susana; Ding, Xianting; Ho, Chih-Ming; Horwitz, Marcus A.

    2017-01-01

    The current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. Previously, using an output-driven optimization platform and an in vitro macrophage model of Mycobacterium tuberculosis infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. Here we use this platform to optimize the in vivo drug doses of two of these regimens in a mouse model of pulmonary tuberculosis. The experimental regimens kill M. tuberculosis much more rapidly than the standard regimen and reduce treatment time to relapse-free cure by 75%. Thus, these regimens have the potential to provide a markedly shorter course of treatment for tuberculosis in humans. As these regimens omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, they would be suitable for treating many cases of multidrug and extensively drug-resistant tuberculosis. PMID:28117835

  5. Ataxin-3 protein and RNA toxicity in spinocerebellar ataxia type 3: current insights and emerging therapeutic strategies.

    Science.gov (United States)

    Evers, Melvin M; Toonen, Lodewijk J A; van Roon-Mom, Willeke M C

    2014-06-01

    Ataxin-3 is a ubiquitously expressed deubiqutinating enzyme with important functions in the proteasomal protein degradation pathway and regulation of transcription. The C-terminus of the ataxin-3 protein contains a polyglutamine (PolyQ) region that, when mutationally expanded to over 52 glutamines, causes the neurodegenerative disease spinocerebellar ataxia 3 (SCA3). In spite of extensive research, the molecular mechanisms underlying the cellular toxicity resulting from mutant ataxin-3 remain elusive and no preventive treatment is currently available. It has become clear over the last decade that the hallmark intracellular ataxin-3 aggregates are likely not the main toxic entity in SCA3. Instead, the soluble PolyQ containing fragments arising from proteolytic cleavage of ataxin-3 by caspases and calpains are now regarded to be of greater influence in pathogenesis. In addition, recent evidence suggests potential involvement of a RNA toxicity component in SCA3 and other PolyQ expansion disorders, increasing the pathogenic complexity. Herein, we review the functioning of ataxin-3 and the involvement of known protein and RNA toxicity mechanisms of mutant ataxin-3 that have been discovered, as well as future opportunities for therapeutic intervention.

  6. An Official American Thoracic Society Research Statement: Current Challenges Facing Research and Therapeutic Advances in Airway Remodeling.

    Science.gov (United States)

    Prakash, Y S; Halayko, Andrew J; Gosens, Reinoud; Panettieri, Reynold A; Camoretti-Mercado, Blanca; Penn, Raymond B

    2017-01-15

    Airway remodeling (AR) is a prominent feature of asthma and other obstructive lung diseases that is minimally affected by current treatments. The goals of this Official American Thoracic Society (ATS) Research Statement are to discuss the scientific, technological, economic, and regulatory issues that deter progress of AR research and development of therapeutics targeting AR and to propose approaches and solutions to these specific problems. This Statement is not intended to provide clinical practice recommendations on any disease in which AR is observed and/or plays a role. An international multidisciplinary group from within academia, industry, and the National Institutes of Health, with expertise in multimodal approaches to the study of airway structure and function, pulmonary research and clinical practice in obstructive lung disease, and drug discovery platforms was invited to participate in one internet-based and one face-to-face meeting to address the above-stated goals. Although the majority of the analysis related to AR was in asthma, AR in other diseases was also discussed and considered in the recommendations. A literature search of PubMed was performed to support conclusions. The search was not a systematic review of the evidence. Multiple conceptual, logistical, economic, and regulatory deterrents were identified that limit the performance of AR research and impede accelerated, intensive development of AR-focused therapeutics. Complementary solutions that leverage expertise of academia and industry were proposed to address them. To date, numerous factors related to the intrinsic difficulty in performing AR research, and economic forces that are disincentives for the pursuit of AR treatments, have thwarted the ability to understand AR pathology and mechanisms and to address it clinically. This ATS Research Statement identifies potential solutions for each of these factors and emphasizes the importance of educating the global research community as to the

  7. STUDY OF EFFICACY OF LOW DOSE MAGNESIUM SULPHATE REGIMEN (DHAKA REGIMEN AS COMPARED TO STANDARD REGIMEN (PRITCHARD IN THE MANAGEMENT OF ECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Prosun

    2015-07-01

    Full Text Available BACKGROUND : Eclampsia is one of the most important cause of maternal mortality and morbidity worldwide Dr . J . A . Pritchard in 1955 , introduced magnesium sulphate for control of convulsions in eclampsia and now magnesium sulfate is the anticonvulsant drug of choice for both prevention and treatment of eclampsia , but due to its narrow therapeutic window its dose - related toxicity is a major concern . Considering the lower body weight of Indian women than wes tern counter part , different low dose magnesium sulphate regime has been formulated in different parts of India and Bangladesh and these modifications appeared to reduce drug toxicity . The Objective was to compare the efficacy of low dose magnesium sulphat e regimen ( Dhaka regimen with standard Pritchard’s regimen for management of eclampsia . METHODS: This was a hospital based prospective study conducted in the Dept . of O & G of VSSMCH , Burla from Oct . 2012 to S ept . 2014 . Total 300 patients with eclampsia were included in study and randomly distributed into two groups containing 150 patients each in both Dhaka & Pritchard groups . The statistical software SPSS version 20 has been used for the analysis . An alpha error of 5% has been taken as significant . RESU LTS: In the present study , there is no recurrence of convulsion among both the groups . The Dhaka regimen was associated with significantly lower deep tendon reflex loss ( 2 . 67% vs 8 . 0%; P =0 . 040 , significantly lower total amount of Mgso4 requirement , and lower maternal mortality ( 3 . 33% vs 6 . 67%; P = 0 . 185 as compared with the standerd Pritchard regimen . CONCLUSIONS : The maternal morbidity and mortality in the present study were comparable to those of standard Pritchard’s regimen . The Dhaka regimen was equ ally effective and more safe for the management of eclampsia in a region where most women are of low body weight KEYWORDS: Antepartum E clampsia ; Magnesium S ulphate; Dhaka R egimen; Pritchard R

  8. Metronomic chemotherapy regimens in oncology

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2016-01-01

    Full Text Available Metronomic chemotherapy implies the regular use of cytotoxic agents in doses much smaller than the maximum tolerable doses for a long time. Preclinical experiments show that this treatment option has a many-sided (antiangiogenic, immunostimulating, and direct cytotoxic effect on tumor. Moreover, this approach has gained the widest acceptance in treating patients with metastatic breast cancer in clinical practice. By taking into account the high activity of angiogenesis in colon cancer progression, it is interesting to study the impact of metronomic chemotherapy regimens for this nosological entity as well. This literature review considers not only the history of metronomic chemotherapy, the mechanisms of action, and a range of drugs having an antitumor effect in the metronomic regimens, but also analyzes clinical trials of metronomic chemotherapy regimens in patients with metastatic colon cancer.

  9. Measurement and simulation of ionic current as a means of quantifying effects of therapeutic millimeter wave radiation

    Science.gov (United States)

    Slovinsky, William Stanley

    A "millimeter wave" (MMW) is an electromagnetic oscillation with a wavelength between 1 and 10 mm, and a corresponding frequency of 30 to 300 GHz. In the spectrum of electromagnetic radiation, this band falls above the frequencies of radio waves and microwaves, and below that of infrared radiation. Since the 1950s, frequencies in this regime have been used for short range communications and beginning in the 1970s, a form of therapy known as "millimeter wave therapy" (MWT) , or microwave resonance therapy, in some publications. This form of therapy has been widely used in the republics of the former Soviet Union (FSU). As of 1995, it is estimated that more than one thousand medical centers in the FSU have performed MWT and more than three million patients have received this method of treatment. Despite the abundant use of this form of medicine, very little is known about the mechanisms by which it works. Early accounts of use are limited to Soviet government documents, largely unavailable to the scientific public, and limited translations and oral accounts from FSU scientists and literature reviews . This anecdotal body of evidence lacks the scrutiny of peer-reviewed journal publications. In order to gain more widespread acceptance in Western medicine, the pathway through which this regime of the electromagnetic radiation spectrum affects the human body must be rigorously mapped and quantified. Despite the anecdotal nature of a large portion of the existing research on biological MMW effects, a common link is the idea of an interaction occurring at the skin level, which is transduced into a signal used at a remote location in the body. This study explores a possible mechanism for the generation of this signal. The effects of therapeutic frequency MMW on the ionic currents through two different types of ion transport channels were studied, and the results are discussed with emphasis on how they relate to possible changes in nerve signals used by the body for

  10. "Rescue" regimens after Helicobacter pylori treatment failure

    Institute of Scientific and Technical Information of China (English)

    Javier P Gisbert

    2008-01-01

    Helicobacter pylori (H pylori)infection is the main cause of gastritis,gastroduodenal ulcer disease,and gastric cancer.After more than 20 years of experience in Hpylori treatment,in my opinion,the ideal regimen to treat this infection is still to be found.Currently,apart from having to know first-line eradication regimens well,we must also be prepared to face lyeatment failures.Therefore,in designing a treatment strategy we should not focus on the results of primary therapy alone,but also on the final (overall) eradication rate.The choice of a "rescue" treatment depends on which treatment is used initially.If a clarithromycinbased regimen was used initially,a subsequent metronidazole-based treatment (quadruple therapy)may be used afterwards,and then a levofloxacinbased combination would be a third "rescue" option.Alternatively,it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging second-line strategy,representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure,with the advantage of efficacy,simplicity and safety.In this case,a quadruple regimen may be reserved as a third-line rescue option.Finally,rifabutin-based rescue therapy constitutes an encouraging empirical fourthline strategy after multiple previous eradication failures with key antibiotics such as amoxicillin,clarithromycin,metronidazole,tetracycline,and levofloxacin.Even after two consecutive failures,several studies have demonstrated that H pylor/eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given.Therefore,the attitude in H pylori eradication therapy failure,even after two or more unsuccessful attempts,should be to fight and not to surrender.

  11. Does chronic alcohol use by HIV-infected patients on d4T/3TC/NVP drug regimen effect the HIV viral load and what is the therapeutic window of the drugs, CD4+ count and WBC count in patients with high viral load during the 9 months period of follow up?

    Directory of Open Access Journals (Sweden)

    Godfrey S. Bbosa

    2013-10-01

    Full Text Available The study investigated the effects of chronic alcohol use on HIV viral load in HIV-infected patients on d4T/3TC/NVP drug regimen during 9 months follow up period. It also determined plasma drug concentrations of d4T, 3TC and NVP; CD4+ and WBC counts for patients with high HIV viral load. A case-control study using repeated measures with serial measurements was used. A total of 41 patients (20 alcohol group and 21 control group were screened for alcohol use using WHO AUDIT tool and chronic alcohol use biomarkers. Blood sampling was done at 3 month intervals for a period of 9 months. HIV viral load was determined using Roche Amplicor HIV-1 monitor test, version 1.5 (Amplicor. The d4T, 3TC and NVP concentrations were determined by Shimadzu Class-VPTM HPLC Chromatography data system version 6.1. The CD4+ cell count was determined using FACSCalibur flow cytometer. The WBC was determined using automated hematological Coulter CBC-5 Hematology Analyzer system. Results show that % patients with HIV viral load ≥400 copies/ml in control group was highest (23.8%, n=5 at 3 month while in chronic alcohol use group, it was at 0 month (35%, n=7 for both WHO AUDIT tool and chronic alcohol-use biomarkers groups. Generally patients with high viral load ≥400 copies/ml was observed in chronic alcohol use as compared to control group in both WHO AUDIT tool and biomarkers group despite of patients having high steady state d4T, 3TC and NVP plasma drug concentrations in circulation that is available to suppress HIV virus. The high viral load could be associated with the emergence of resistance of the HIV virus and these patients generally had a low CD4+ cell count. Some of these patients had no detectable d4T plasma drug concentrations in circulation and most of them with high viral load had sub-therapeutic NVP plasma drug concentrations in their blood circulation. Chronic ethanol use by HIV-infected patients on d4T/3TC/NVP drug regimen increased HIV viral load and

  12. Controlled-protein dietary regimens for Parkinson's disease.

    Science.gov (United States)

    Cereda, Emanuele; Barichella, Michela; Pezzoli, Gianni

    2010-02-01

    Continuous levodopa replacement still is the most efficacious treatment for patients with Parkinson's disease. Unfortunately, the neutral aromatic amino acids contained in dietary proteins may compete with this drug for intestinal absorption and transport across the blood-brain barrier, thus limiting its efficacy and being responsible for the occurrence of motor fluctuations. Current guidelines recommend low-protein dietary regimens with protein redistribution, as shifting protein intake to the evening has proved to ameliorate the response to levodopa. However, adherence to this dietary regimen does not seem to be satisfactory and response is variable. Recent studies have shown that low-protein products designed for chronic renal failure patients are safe, tasty, well-tolerated and useful in improving both adherence to low-protein dietary regimens and levodopa-related motor fluctuations. However, there still is the need to define the selection criteria for the patients who may benefit the most from adherence to this regimen.

  13. Current status of temporomandibular joint disorders and the therapeutic system derived from a series of biomechanical, histological, and biochemical studies

    Directory of Open Access Journals (Sweden)

    Kazuo Tanne

    2015-01-01

    Full Text Available This article was designed to report the current status of temporomandibular joint disorders (TMDs and the therapeutic system on the basis of a series of clinical, biomechanical, histological and biochemical studies in our research groups. In particular, we have focused on the association of degenerative changes of articular cartilage in the mandibular condyle and the resultant progressive condylar resorption with mechanical stimuli acting on the condyle during the stomatognathic function. In a clinical aspect, the nature and prevalence of TMDs, association of malocclusion with TMDs, association of condylar position with TMDs, association of craniofacial morphology with TMDs, and influences of TMDs, TMJ-osteoarthritis (TMJ-OA in particular, were examined. In a biomechanical aspect, the nature of stress distribution in the TMJ from maximum clenching was analyzed with finite element method. In addition, the pattern of stress distribution was examined in association with varying vertical discrepancies of the craniofacial skeleton and friction between the articular disk and condyle. The results demonstrated an induction of large compressive stresses in the anterior and lateral areas on the condyle by the maximum clenching and the subsequent prominent increases in the same areas of the mandibular condyle as the vertical skeletal discrepancy became more prominent. Increase of friction at the articular surface was also indicated as a cause of larger stresses and the relevant disk displacement, which further induced an increase in stresses in the tissues posterior to the disks, indicating an important role of TMJ disks as a stress absorber. In a histological or biological aspect, increase in TMJ loading simulated by vertical skeletal discrepancy, which has already been revealed by the preceding finite element analysis or represented by excessive mouth opening, produced a decrease in the thickness of cartilage layers, an increase in the numbers of

  14. Cyber stalking victimisation of women: Evaluating the effectiveness of current laws in India from restorative justice and therapeutic jurisprudential perspectives

    Directory of Open Access Journals (Sweden)

    Halder Debarati

    2015-01-01

    Full Text Available Victimisation of women through cyber stalking is one of the most serious crimes against women. Many countries including India have developed laws regulating cyber stalking. This article argues that since both, restorative justice (RJ and therapeutic jurisprudence (TJ are victim oriented, the issue of cyber stalking of women may be dealt with by RJ process and the laws in this regard must be analysed by the legal actors with a background in RJ and TJ philosophy. India had earlier taken up therapeutic punishment policy to enforce rights of the accused. But the modern principles of TJ have still not been considered in the RJ background in cyber stalking cases. This article therefore examines whether RJ and TJ principles can replace retributive principles for cyber stalking victimisation. It also examines the Indian cyber stalking law from RJ and TJ perspectives to assess its effectiveness for victims.

  15. Cytokines in common variable immunodeficiency as signs of immune dysregulation and potential therapeutic targets - a review of the current knowledge.

    Science.gov (United States)

    Varzaneh, Farnaz Najmi; Keller, Bärbel; Unger, Susanne; Aghamohammadi, Asghar; Warnatz, Klaus; Rezaei, Nima

    2014-07-01

    Common variable immunodeficiency (CVID) is characterized by low levels of circulating immunoglobulins and compromised specific antibody response leading to frequent infections. Cytokines play an important role in the orchestration of the antibody response. Several previous studies have attempted to identify distinct cytokines responsible for the inflammatory changes and different manifestations of CVID, but there are conflicting results regarding the cytokine profiles in CVID patients. In light of this, an extensive review regarding the level of various cytokines and their potential therapeutic role in CVID patients was performed. This review delineates the contribution of interleukin (IL)-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-21, interferons, tumor necrosis factor (TNF)-α, IL-17, APRIL (a proliferation inducing ligand) and BAFF (B cell activating factor) in CVID disease and outline their potential therapeutic implications in these patients.

  16. Current Opinion on the Role of Neurogenesis in the Therapeutic Strategies for Alzheimer Disease, Parkinson Disease, and Ischemic Stroke; Considering Neuronal Voiding Function

    Science.gov (United States)

    Lee, Eun-Hye

    2016-01-01

    Neurological diseases such as Alzheimer, Parkinson, and ischemic stroke have increased in occurrence and become important health issues throughout the world. There is currently no effective therapeutic strategy for addressing neurological deficits after the development of these major neurological disorders. In recent years, it has become accepted that adult neural stem cells located in the subventricular and subgranular zones have the ability to proliferate and differentiate in order to replace lost or damaged neural cells. There have been many limitations in the clinical application of both endogenous and exogenous neurogenesis for neurological disorders. However, many studies have investigated novel mechanisms in neurogenesis and have shown that these limitations can potentially be overcome with appropriate stimulation and various approaches. We will review concepts related to possible therapeutic strategies focused on the perspective of neurogenesis for the treatment of patients diagnosed with Alzheimer disease, Parkinson disease, and ischemic stroke based on current reports. PMID:28043116

  17. Current Opinion on the Role of Neurogenesis in the Therapeutic Strategies for Alzheimer Disease, Parkinson Disease, and Ischemic Stroke; Considering Neuronal Voiding Function.

    Science.gov (United States)

    Han, Myung-Hoon; Lee, Eun-Hye; Koh, Seong-Ho

    2016-12-01

    Neurological diseases such as Alzheimer, Parkinson, and ischemic stroke have increased in occurrence and become important health issues throughout the world. There is currently no effective therapeutic strategy for addressing neurological deficits after the development of these major neurological disorders. In recent years, it has become accepted that adult neural stem cells located in the subventricular and subgranular zones have the ability to proliferate and differentiate in order to replace lost or damaged neural cells. There have been many limitations in the clinical application of both endogenous and exogenous neurogenesis for neurological disorders. However, many studies have investigated novel mechanisms in neurogenesis and have shown that these limitations can potentially be overcome with appropriate stimulation and various approaches. We will review concepts related to possible therapeutic strategies focused on the perspective of neurogenesis for the treatment of patients diagnosed with Alzheimer disease, Parkinson disease, and ischemic stroke based on current reports.

  18. Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions

    OpenAIRE

    Catherine Tomaro-Duchesneau; Shyamali Saha; Meenakshi Malhotra; Imen Kahouli; Satya Prakash

    2013-01-01

    Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of ...

  19. Efficacy of combination of glycolic acid peeling with topical regimen in treatment of melasma.

    Science.gov (United States)

    Chaudhary, Savita; Dayal, Surabhi

    2013-10-01

    Various treatment modalities are available for management of melasma, ranging from topical and oral to chemical peeling, but none is promising alone. Very few studies are available regarding efficacy of combination of topical treatment with chemical peeling. Combination of chemical peeling and topical regimen can be a good treatment modality in the management of this recalcitrant disorder. To assess the efficacy of combination of topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling in the treatment of melasma in Indian patients. Forty Indian patients of moderate to severe epidermal variety melasma were divided into two groups of 20 each. One Group i.e. peel group received topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling and other group i.e. control group received topical regimen (2% hydroquinone, 1% hydrocortisone, 0.05% tretinoin). There was an overall decrease in MASI from baseline in 24 weeks of therapy in both the groups (P value glycolic acid peel with topical regimen showed early and greater improvement than the group which was receiving topical regimen only. This study concluded that combining topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling significantly enhances the therapeutic efficacy of glycolic acid peeling. The combination of glycolic acid peeling with the topical regimen is a highly effective, safe and promising therapeutic option in treatment of melasma.

  20. Therapeutic Targets for Management of Periodontitis and Diabetes

    Science.gov (United States)

    Sima, Corneliu; Van Dyke, Thomas E.

    2016-01-01

    The increasing incidence of diabetes mellitus (DM) and chronic periodontitis (CP) worldwide imposes a rethinking of individualized therapy for patients with both conditions. Central to bidirectional links between DM and CP is deregulated systemic inflammation and dysfunctional immune responses to altered-self and non-self. Control of blood glucose levels and metabolic imbalances associated with hyperglycemia in DM, and disruption of pathogenic subgingival biofilms in CP are currently the main therapeutic approaches for these conditions. Mounting evidence suggests the need to integrate immune modulatory therapeutics in treatment regimens that address the unresolved inflammation associated with DM and CP. The current review discusses the pathogenesis of DM and CP with emphasis on deregulated inflammation, current therapeutic approaches and the novel pro-resolution lipid mediators derived from Ω-3 polyunsaturated fatty acids.

  1. Therapeutic Targets for Management of Periodontitis and Diabetes

    Science.gov (United States)

    Sima, Corneliu; Van Dyke, Thomas E.

    2016-01-01

    The increasing incidence of diabetes mellitus (DM) and chronic periodontitis (CP) worldwide imposes a rethinking of individualized therapy for patients with both conditions. Central to bidirectional links between DM and CP is deregulated systemic inflammation and dysfunctional immune responses to altered-self and non-self. Control of blood glucose levels and metabolic imbalances associated with hyperglycemia in DM, and disruption of pathogenic subgingival biofilms in CP are currently the main therapeutic approaches for these conditions. Mounting evidence suggests the need to integrate immune modulatory therapeutics in treatment regimens that address the unresolved inflammation associated with DM and CP. The current review discusses the pathogenesis of DM and CP with emphasis on deregulated inflammation, current therapeutic approaches and the novel pro-resolution lipid mediators derived from n-3 polyunsaturated fatty acids. PMID:26881443

  2. Current state of pharmacology and therapeutics in irritable bowel syndrome with special reference to brain-gut axis

    Directory of Open Access Journals (Sweden)

    Suryaprakash Mishra

    2013-04-01

    Full Text Available Irritable bowel syndrome (IBS, principal morbidity being visceral hypersensitivity, consumes significant speciality gastroenterologic and general practitioner’s care. The complex etiology perhaps varying among the patients makes therapeutic address very challenging. Continuous researches on neurophysiological aberrations in IBS have continued. The drugs and the neurophysiological understanding with regard to addressing visceral hypersensitivity are relevant to be appraised. The translation of research wisdom into clinical practice may be facilitated by gastroenterology experts. The issues of effectiveness of the options in general and in particular patients may thus be addressed. [Int J Basic Clin Pharmacol 2013; 2(2.000: 122-129

  3. Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions

    Directory of Open Access Journals (Sweden)

    Catherine Tomaro-Duchesneau

    2013-01-01

    Full Text Available Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of microencapsulation and its latest developments in the field. It provides a comprehensive overview of the technology and primary goals of microencapsulation and discusses various processes and techniques involved in microencapsulation including physical, chemical, physicochemical, and other methods involved. It also summarizes the state-of-the-art successes of microencapsulation, specifically with regard to the encapsulation of microorganisms, mammalian cells, drugs, and other biopharmaceutics in various diseases. The limitations and future directions of microencapsulation technologies are also discussed.

  4. Are calcineurin inhibitors-free regimens ready for prime time?

    Science.gov (United States)

    Vincenti, Flavio

    2012-11-01

    The goal of research in transplant therapeutics is to achieve safe and effective immunosuppression strategies that allow durable engraftment free of toxicities. The calcineurin inhibitors (CNIs) regimens, because of their inherent toxicities (including nephrotoxicity), have been unable to meet these promises. Over the past decade acute cellular rejection decreased dramatically with a concomitant robust increase in 1-year graft survival; however, long-term graft outcome showed only modest improvement. This is due in part to the toxicities of the immunosuppressive drugs. The quest for a toxicity-free-CNI-free regimen has been both intense and frustrating. A turning point in CNIs-free therapy may have occurred with the recent approval of belatacept, which represents a new paradigm in immunosuppression: biological therapy for chronic immunosuppression devoid of the usual toxicities associated with the CNIs. Belatacept, a fusion receptor protein, blocks costimulation signals necessary for the activation of T cells. Although costimulation blockade has not been shown to induce tolerance, it can provide safe and effective immunosuppression without renal or cardiovascular toxicities. The approval of belatacept in both the United States and Europe for use in renal transplantation will finally push CNI-free regimens into prime time. Novel biologics such as ASKP1240 (a human anti-CD40 monoclonal antibody) and one small molecule, tofacitinib, may advance further the use of CNI-free regimens in organ transplantation.

  5. 2011 Update in Gastrointestinal Cancer Therapeutics

    Science.gov (United States)

    Sahai, Vaibhav; Nimeiri, Halla

    2012-01-01

    ABSTRACT This discussion highlights key investigational findings of existing cytotoxic and novel biological therapeutics, combination regimens, and predictive and prognostic biomarkers in the field of gastrointestinal oncology during the past year. PMID:23077682

  6. Pharmacogenomics: road to anticancer therapeutics nirvana?

    Science.gov (United States)

    Desai, Apurva A; Innocenti, Federico; Ratain, Mark J

    2003-09-29

    Interindividual differences in the toxicity and response to anticancer therapies are currently observed for essentially all available treatment regimens. Such 'unpredictable' drug responses are particularly dangerous in the context of anticancer agents that have narrow therapeutic indices. Pharmacogenomics attempts to elucidate the inherited basis of interindividual differences in drug response, with the eventual goal of minimizing such variability through the use of 'individualized' treatments. There are several emerging examples of genetic polymorphisms of drug-metabolizing enzymes, DNA repair genes and drug targets that have been shown to influence the toxicity and efficacy of anticancer treatment. This review discusses the role of genetic variants of UGT1A1, TS and EGFR to exemplify the potential impact of phramacogenomics on the field of anticancer therapeutics.

  7. Acurácia das características definidoras do diagnóstico controle familiar ineficaz do regime terapêutico Perfeccionamiento de las características definidoras del diagnóstico control familiar ineficaz del régimen terapéutico Accuracy of diagnosis of the defining characteristics of ineffective family therapeutic regimen management

    Directory of Open Access Journals (Sweden)

    Lanuza Celes Mendes

    2011-01-01

    necesidad de trabajar la adhesión con una perspectiva volcada a la familia, sobre todo considerándose la complejidad del tratamiento para la diabetes.OBJECTIVE: To investigate the accuracy of diagnosis, ineffective family therapeutic regimen management, based on the assessment of defining characteristics. METHODS: Cross-sectional study with 68 diabetic patients seen in a family health center. Measures of sensitivity were calculated, specificity and predictive values of the defining characteristics were identified. RESULTS: The diagnosis was present in 36.8% of these patients, and all defining characteristics showed statistical significance, except for "difficulty in following the prescribed regimen". The characteristic "inappropriate family activities for meeting health goals" was the most sensitive, while "acceleration of illness symptoms of a family member" and "lack of attention to illness" were the most specific. CONCLUSION: The results call attention to the need to work with a family-focused adherence perspective, especially considering the complexity of treatment for individuals with diabetes.

  8. An Official American Thoracic Society Research Statement : Current Challenges Facing Research and Therapeutic Advances in Airway Remodeling

    NARCIS (Netherlands)

    Prakash, Y S; Halayko, Andrew J; Gosens, Reinoud; Panettieri Jr., Reynold A; Camoretti-Mercado, Blanca; Penn, Raymond B; Burgess, Janette K

    2017-01-01

    BACKGROUND: Airway remodeling (AR) is a prominent feature of asthma and other obstructive lung diseases that is minimally affected by current treatments. The goals of this Official American Thoracic Society (ATS) Research Statement are to discuss the scientific, technological, economic, and

  9. An Official American Thoracic Society Research Statement : Current Challenges Facing Research and Therapeutic Advances in Airway Remodeling

    NARCIS (Netherlands)

    Prakash, Y S; Halayko, Andrew J; Gosens, Reinoud; Panettieri Jr., Reynold A; Camoretti-Mercado, Blanca; Penn, Raymond B; Burgess, Janette K

    2017-01-01

    BACKGROUND: Airway remodeling (AR) is a prominent feature of asthma and other obstructive lung diseases that is minimally affected by current treatments. The goals of this Official American Thoracic Society (ATS) Research Statement are to discuss the scientific, technological, economic, and regulato

  10. Modulation of the activity of N-methyl-d-aspartate receptors as a novel treatment option for depression: current clinical evidence and therapeutic potential of rapastinel (GLYX-13)

    Science.gov (United States)

    Vasilescu, Andrei-Nicolae; Schweinfurth, Nina; Borgwardt, Stefan; Gass, Peter; Lang, Undine E; Inta, Dragos; Eckart, Sarah

    2017-01-01

    Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD). Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13), a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive–compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment of MDD from the US Food and Drug Administration, representing one of the most promising alternative antidepressants under current investigation.

  11. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease

    Science.gov (United States)

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E.; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C.; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-01-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions. PMID:26342919

  12. Sedation regimens for gastrointestinal endoscopy.

    Science.gov (United States)

    Moon, Sung-Hoon

    2014-03-01

    Sedation allows patients to tolerate unpleasant endoscopic procedures by relieving anxiety, discomfort, or pain. It also reduces a patient's risk of physical injury during endoscopic procedures, while providing the endoscopist with an adequate setting for a detailed examination. Sedation is therefore considered by many endoscopists to be an essential component of gastrointestinal endoscopy. Endoscopic sedation by nonanesthesiologists is a worldwide practice and has been proven effective and safe. Moderate sedation/analgesia is generally accepted as an appropriate target for sedation by nonanesthesiologists. This focused review describes the general principles of endoscopic sedation, the detailed pharmacology of sedatives and analgesics (focused on midazolam, propofol, meperidine, and fentanyl), and the multiple regimens available for use in actual practice.

  13. A Disease-Modifying Approach for Advanced Hidradenitis Suppurativa (Regimen with Metformin, Liraglutide, Dapsone, and Finasteride: A Case Report

    Directory of Open Access Journals (Sweden)

    Birgit N. Khandalavala

    2017-07-01

    Full Text Available Hidradenitis suppurativa (HS is a challenging skin disease with limited therapeutic options. Obesity and metabolic syndrome are being increasingly implicated and associated with younger ages and greater metabolic severity. A 19-year-old female with an 8-year history of progressively debilitating cicatricial HS disease presented with obesity, profound anemia, leukocytosis, increased platelet count, hypoalbuminemia, and elevated liver enzymes. A combination of metformin, liraglutide, levonorgestrel-ethinyl estradiol, dapsone, and finasteride was initiated. Acute antibiotic use for recurrences and flares could be slowly discontinued. Over the course of 3 years on this regimen, the liver enzymes normalized in 1 year, followed in2 years by complete resolution of the majority of the hematological and metabolic abnormalities. The sedimentation rate reduced from over 120 to 34 mm/h. She required 1 surgical intervention for perianal disease after 9 months on the regimen. Flares greatly diminished in intensity and duration, with none in the past 6 months. Right axillary lesions have completely healed with residual disease greatly reduced. Chiefly abdominal lesions are persistent. She was able to complete high school from home, start a job, and resume a normal life. Initial weight loss of 40 pounds was not maintained. The current regimen is being well tolerated and continued.

  14. Genetics-based pediatric warfarin dosage regimen derived using pharmacometric bridging.

    Science.gov (United States)

    Lala, Mallika; Burckart, Gilbert J; Takao, Cheryl M; Pravica, Vera; Momper, Jeremiah D; Gobburu, Jogarao V S

    2013-07-01

    Warfarin dosage regimens using CYP2C9 and VKORC1 polymorphisms have been extensively studied in adults and is included in US Food and Drug Administration-approved warfarin labeling. However, no dosage algorithm is available for pediatric patients. To derive a genetics-based pediatric dosge regimen for warfarin, including starting dose and titration scheme. A model-based approach was developed based on a previously validated warfarin dosage model in adults, with subsequent comparison to pediatric data from pediatric warfarin dose, genotyping, and international normalized ratio (INR) results. The adult model was based on a previously established model from the CROWN (CReating an Optimal Warfarin dosing Nomogram) trial. Pediatric warfarin data were obtained from a study conducted at the Children's Hospital of Los Angeles with 26 subjects. Variant alleles of CYP2C9 (rs1799853 or *2, and rs1057910 or *3) and the VKORC1 single nucleotide polymorphism (SNP) rs9923231 (-1639 G>A) were assessed, where the rs numbers are reference SNP identification tags assigned by the National Center for Biotechnology Information. A pediatric warfarin model was derived using the previously validated model and clinical pharmacology considerations. The model was validated, and clinical trial simulation and stochastic modeling were used to optimize pediatric dosage and titration. The final dosage regimen was optimized based on simulations targeting a high (≥60%) proportion of INRs within the therapeutic range by week 2 of warfarin therapy while minimizing INRs >3.5 or A) genotypes may offer improved dosage compared to current treatment strategies, especially in patients with variant CYP2C9 and VKORC1 alleles. This pilot study provides the foundation for a larger prospective evaluation of genetics-based warfarin dosage in pediatric patients.

  15. Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential.

    Science.gov (United States)

    Capel, Rebecca A; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J; Terrar, Derek A; Burton, Rebecca-Ann B

    2015-10-01

    Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the "funny" current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1-30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). In mouse atria, spontaneous beating rate was significantly (P rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  16. Are current disease-modifying therapeutics in multiple sclerosis justified on the basis of studies in experimental autoimmune encephalomyelitis?

    Science.gov (United States)

    Farooqi, Nasr; Gran, Bruno; Constantinescu, Cris S

    2010-11-01

    The precise aetio-pathology of multiple sclerosis remains elusive. However, important recent advances have been made and several therapies have been licensed for clinical use. Many of these were developed, validated or tested in the animal model, experimental autoimmune encephalomyelitis (EAE). This systematic review aims to assess whether the current disease modifying treatments and those that are the closest to the clinic are justified on the basis of the results of EAE studies. We discuss some aspects of the utility and caveats of EAE as a model for multiple sclerosis drug development.

  17. Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice?

    Directory of Open Access Journals (Sweden)

    Renato De Vecchis

    2016-10-01

    Full Text Available In the congestive heart failure (CHF setting, chronic hyponatremia is very common. The present review aims at addressing topics relevant to the pathophysiology of hyponatremia in the course of CHF as well as its optimal treatment, including the main advantages and the limitations resulting from the use of the available dietary and pharmacological measures approved for the treatment of this electrolytic trouble. A narrative review is carried out in order to represent the main modalities of therapy for chronic hyponatremia that frequently complicates CHF. The limits of usual therapies implemented for CHF-related chronic hyponatremia are outlined, while an original analysis of the main advancements achieved with the use of vasopressin receptor antagonists (VRAs is also executed. The European regulatory restrictions that currently limit the use of VRAs in the management of CHF are substantially caused by financial concerns, i.e., the high costs of VRA therapy. A thoughtful reworking of current restrictions would be warranted in order to enable VRAs to be usefully associated to loop diuretics for decongestive treatment of CHF patients with hyponatremia.

  18. [Impact of early benefit assessment on patients with epilepsy in Germany: Current healthcare provision and therapeutic needs].

    Science.gov (United States)

    Strzelczyk, A; Hamer, H M

    2016-04-01

    Epilepsy is one of the most common chronic neurological diseases and represents a significant burden for patients, their families and society. In more than 75 % of patients anticonvulsant therapy consists of valproate, carbamazepine, lamotrigine or levetiracetam. There is a need for polytherapy in drug-refractory patients and they suffer from negative effects on quality of life and employment that is associated with high indirect costs. To allow a comprehensive treatment in this patient group, access to new anticonvulsants with novel modes of action is needed; however, all applications for new antiepileptic drugs failed to prove added benefits during the Pharmaceutical Market Restructuring Act (AMNOG) in Germany. One of the main reasons is the mandatory definition of a standard comparative therapy. It remains unclear whether there will be studies in the future which will fulfill the requirements of the current version of AMNOG. Observational studies after approval and marketing of new antiepileptic drugs could be better alternatives to prove added benefits for individual patients in the current German healthcare system.

  19. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia.

    OpenAIRE

    Schneider, Constanze; Oellerich, Thomas; Baldauf, Hanna-Mari; Schwarz, Sarah-Marie; Thomas, Dominique; Flick, Robert; Bohnenberger, Hanibal; Kaderali, Lars; Stegmann, Lena; Cremer, Anjali; Martin, Margarethe; Lohmeyer, Julian; Michaelis, Martin; Hornung, Veit; Schliemann, Christoph

    2016-01-01

    The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the th...

  20. INVASIVE CANDIDA INFECTIONS IN PATIENTS WITH HAEMATOLOGICAL MALIGNANCIES AND HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: CURRENT EPIDEMIOLOGY AND THERAPEUTIC OPTIONS.

    Directory of Open Access Journals (Sweden)

    Corrado Girmenia

    2011-03-01

    Full Text Available In the last decades, the global epidemiological impact of invasive candidiasis (IC in patients with hematologic malignancies (HM and in hematopoietic stem cell transplant (HSCT recipients has decreased and the incidence of invasive aspergillosis  exceeded that of Candida infections. The use of prevention strategies, first of all antifungal prophylaxis with triazoles,  contributed to the reduction of IC in these populations as demonstrated by several  epidemiological studies. However, relatively little is known about the current epidemiological patterns of IC in HM and HSCT populations, because recent epidemiological data almost exclusively derive from retrospective experiences and few prospective data are available. Several prospective, controlled studies in the prophylaxis of invasive fungal diseases have been conducted in both the HM and HSCT setting. On the contrary, most of the prospective controlled trials that demonstrated the efficacy of the antifungal drugs echinocandins and voriconazole in the treatment of candidemia and invasive candidiasis mainly involved  patients with underlying conditions other than HM or  HSCT.  For these reasons, international guidelines provided specific indications for the prophylaxis strategies in HM and HSCT patients, whereas the  recommendations on therapy of documented Candida infections are based on the results observed in the general population and should be considered with caution.

  1. Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer.

    Science.gov (United States)

    Haque, Absarul; Alam, Qamre; Alam, Mohammad Zubair; Azhar, Esam I; Sait, Khalid Hussain Wali; Anfinan, Nisrin; Mushtaq, Gohar; Kamal, Mohammad Amjad; Rasool, Mahmood

    2016-01-01

    Heat Shock Protein 90 (HSP90) is a ubiquitous molecular chaperone that is considered to be the most abundantly expressed protein in various human cancers such as breast, lung, colon, prostate, leukemia and skin. The master regulator, HSP90 plays a pivotal role in the conformational stabilization, maturation and activity of its various labile oncogenic client proteins such as p53, ErbB2, Bcr-Abl, Akt, Her-2, Cdk4, Cdk6, Raf-1 and v-Src in altered cells. Hence, making a guaranteed attempt to inhibit such a master regulator for cancer therapy appears to be a potential approach for combinatorial inhibition of numerous oncogenic signaling pathways simultaneously. Considerable efforts are being under way to develop novel molecular targets and its inhibitors that may block key signaling pathways involved in the process of tumorigenesis and metastasis. In this regards, HSP90 has acquired immense interest as a potent anticancer drug-target due to its key functional link with multiple signaling pathways involved in the process of cell proliferation and cell survival. Notably, geldanamycin and its derivatives (17-AAG, 17-DMAG) have shown quite encouraging results in inhibiting HSP90 function in several cancers and currently almost 17 drug candidates known to be target HSP90 are being under clinical trials either as single agents or combinatorial therapy. Hence, this review is an attempt to get new insight into novel drug target therapy by focusing on recent advances made in understanding HSP90 chaperone structure-function relationships, identification of new HSP90 client proteins and, more importantly, on the advancements of HSP90 targeted therapy based on various existing and emerging classical inhibitors.

  2. Modulation of the activity of N-methyl-D-aspartate receptors as a novel treatment option for depression: current clinical evidence and therapeutic potential of rapastinel (GLYX-13

    Directory of Open Access Journals (Sweden)

    Vasilescu AN

    2017-03-01

    Full Text Available Andrei-Nicolae Vasilescu,1,* Nina Schweinfurth,2,* Stefan Borgwardt,2,* Peter Gass,1 Undine E Lang,2,* Dragos Inta,1,2,* Sarah Eckart2,* 1Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; 2Department of Psychiatry (Universitäre Psychiatrische Kliniken, University of Basel, Basel, Switzerland *These authors contributed equally to this work Abstract: Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD. Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13, a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive–compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment

  3. Corticosteroid and calcineurin inhibitor sparing regimens in kidney transplantation.

    Science.gov (United States)

    Cortazar, Frank; Diaz-Wong, Roque; Roth, David; Isakova, Tamara

    2013-11-01

    Chronic kidney disease is a major public health problem that is associated with increased risks of kidney disease progression, cardiovascular disease and death. Kidney transplantation remains the renal replacement therapy of choice for patients with end-stage kidney disease. Despite impressive strides in short-term allograft survival, there has been little improvement in long-term kidney graft survival, and rates of death with a functioning allograft remain high. Long-term safety profiles of existing immunosuppressive regimens point to a need for continued search for alternative agents. This overview discusses emerging evidence on a few promising therapeutic approaches, juxtaposes conflicting findings and highlights remaining knowledge gaps.

  4. A comparison of the therapeutic and reactivating efficacy of newly developed bispyridinium compounds (K206, K269) with currently available oximes against tabun in rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana; Bajgar, Jiri; Kuca, Kamil; Musilek, Kamil

    2008-12-01

    The potency of newly developed bispyridinium compounds (K206, K269) in reactivating tabun-inhibited acetylcholinesterase and eliminating tabun-induced lethal toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies which determined percentage of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats showed that the reactivating efficacy of both newly developed oximes is comparable with obidoxime and trimedoxime in blood but lower than the reactivating potency of trimedoxime and obidoxime in the diaphragm and brain. Nevertheless, the differences in reactivating efficacy of obidoxime, trimedoxime and K206 was not significant while the potency of K269 to reactivate tabun-inhibited acetylcholinesterase was significantly lower. Both newly developed oximes were also found to be relatively efficacious in elimination of the lethal toxic effects in tabun-poisoned mice. Their therapeutic efficacy corresponds to the therapeutic potency of obidoxime. The oxime HI-6, relatively efficacious against soman, did not seem to be an adequately effective oxime in reactivation of tabun-inhibited AChE and to counteract lethal effects of tabun. Both newly developed oximes (K206, K269) are significantly more efficacious in reactivating tabun-inhibited AChE in rats and to eliminate lethal toxic effects of tabun in mice than the oxime HI-6 but their reactivating and therapeutic potency does not prevail over the effectiveness of currently available obidoxime and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute tabun poisoning.

  5. 腹主动脉瘤的内科治疗现状%Current Medical Therapeutic Prospect of Abdominal Aortic Aneurysms

    Institute of Scientific and Technical Information of China (English)

    邹雨珮; 杨轶; 赵纪春

    2012-01-01

    OBJECTIVE To investigate the medical therapeutic prospect of abdominal aortic aneurysm (AAA). METHODS Relevant literatures about medical treatment for AAA in recent years were reviewed. RESULTS Therapeutic strategies of current interest included exercise, smoking cessation, statins, beta blockers, MMPs inhibition, macrolides, angiotensin pathway inhibition, and -platelet drugs, NSAIDs and genetic therapy. CONCLUSION Medical treatment is an important supplement of surgical treatment for AAAs and needed further research.%目的 探讨小腹主动脉瘤的内科治疗进展.方法 复习近几年有关腹主动脉瘤内科治疗的文献,进行综述.结果 腹主动脉瘤的内科治疗主要包括:锻炼和戒烟的非药物治疗以及他汀类药物、β受体阻滞剂、基质金属蛋白酶抑制剂、大环内酯类抗生素、肾素血管紧张素系统抑制剂、抗血小板药物、非甾体类抗炎药以及基因治疗等治疗方式.结论 内科治疗是外科治疗的重要补充,仍需进一步的研究.

  6. Evaluation of the adverse reactions of antiretroviral drug regimens in a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    Zahoor A Rather

    2013-01-01

    Conclusion: The most common adverse effects associated with currently used ART regimens are anemia, hepatic toxicity, itching, skin rash, elevated triglycerides, and peripheral neuropathy. Gender differences were seen mainly with skin rash, which was significantly more in females.

  7. New drugs targeting the cardiac ultra-rapid delayed-rectifier current (I Kur): rationale, pharmacology and evidence for potential therapeutic value.

    Science.gov (United States)

    Ford, John W; Milnes, James T

    2008-08-01

    There is a clear unmet medical need for new pharmacologic therapies for the treatment of atrial fibrillation (AF) with improved efficacy and safety. This article reviews the development of new and novel Kv1.5/ultra-rapid delayed-rectifier current (I Kur) inhibitors and presents evidence that Kv1.5 modulation provides an atrial-selective mechanism for treating AF. Academia and industry have invested heavily in Kv1.5 (>500 scientific publications and >50 patents published since 1993); however, to realize the full value of this therapeutic drug target, clinical efficacy and safety data are required for a selective Kv1.5 modulator. The reward for demonstrating clinical efficacy and safety in a pivotal Phase 3 trial, on regulatory approval, is "first in class" status.

  8. Therapeutic effect of different dosing regimens of rmlL-12 on acute radiation sickness in mice%白介素12不同给药方案对急性放射病小鼠的治疗作用

    Institute of Scientific and Technical Information of China (English)

    王利; 王松雷; 曹务锐; 耿斌; 翟瑞仁; 逄朝霞; 张超; 余长林

    2013-01-01

    Objective: To study the therapeutic effect of different dosing regimens of recombinant murine interleu-kin 12(rmIL - 12) on the mice irradiated by γ -rays. Methods: Forty -two BALB/c mice were given 6.0Gy 60Co γ - rays total body irradiation and randomly assigned into irradiation control group,rmIL - 12 one dose and five doses treatment group. 20μg/kg of rmIL - 12 was administrated intraperitoneally 1 hour following irradiation in one dose treatment group, and was administrated every 3 days after irradiation for four times additionally in five doses treatment group. The general conditions of mice were observed twice a day, the changes in body weight, peripheral blood cell counts were examined once every three days, bone marrow cells were collected to perform colony cultivation on the 14th and 28th day after irradiation. Results: The general conditions of mice in rmIL - 12 treatment group were better than those of irradiation control group. The decline speed of platelet in rmIL - 12 one and five doses treatment group was significantly slower than that of control group. rmIL - 12 treatment significantly promoted platelet recovery, resulting in less profound nadirs(18.9% vs 8. 1% ,22.5% vs 8. 1% ,P0. 05). The white blood cell recovery speed in two treatment groups was faster than that of the irradiation control group(P<0.05) ,but there was no significant difference between two treatment groups. Semi - solid bone marrow cell culture also demonstrated that rmIL - 12 could stimulate bone marrow cells to form more CFU - Mix than those of the irradiation control group on 14th after irradiation(P <0. 01) ,and there were more CFU - GM and CFU - Mix in two rmIL - 12 treatment group than those of the irradiation control group on 28th after irradiation (P < 0.05, P< 0.01). Conclusion: 1 and 5 dosing regimens of rmIL - 12 can significantly accelerate the recovery of hematopoietic function , especially the recovery of megakaryocyte in acute radiation sickness mice.%目的:

  9. The impact of therapeutic regimen on the depression in type 2 diabetes mellitus: A cross-sectional study%治疗方案对2型糖尿病患者抑郁情绪影响的调查研究

    Institute of Scientific and Technical Information of China (English)

    吴冰; 陈璇; 杨莉; 周方圆; 陈娜; 吴静

    2015-01-01

    To explore the depression in type 2 diabetic patients treated with insulin and compared to those treated with oral anti-diabetic drugs.283 type 2 diabetics were seclected randomly from outpatient and inpatient departments of endocrionology in Jiangsu Province Hospital of Traditional Chinese Medicine,with the self-designed questionnaire and Zung self-rating depression scale to conduct the survey.Comparisons between the two groups were carried out with t-test or x2 test for quantitative and qualitative data,respectively.Logistic regression were used for the analysis of the relationship between the therapeutic regimen and depression.Overall,43.1% of the type 2 diabetic subjects showed depressive symptoms in different degrees.Compared to the oral drug group,the insulin group showed a significantly higher prevalence of depressive symptoms (insulin group,53.5%,oral drug group,30.5%;P<0.01)and higher self-rating depression scale scores (insulin group,51.7 ± 12.4,oral drug group,44.8 ± 10.6;P<0.01).Moreover,after an adjustment for age,sex,body mass index,diabetic duration,complications,HbA1Cand so on,the insulin group showed a significantly higher frequency of depression (OR=4.218,95% CI 1.764-13.285,P=0.004),compared to the oral drug group.The data showed that insulin treatment is an independent risk factor to the presence of depressive symptoms in type 2 diabetics,and it is necessary to pay more attention to their psychological support.%探讨胰岛素与口服降糖药物治疗对2型糖尿病患者抑郁情绪的影响.随机抽取江苏省中医院内分泌科门诊及住院的2型糖尿病患者283例,使用自行设计的问卷和Zung抑郁自评量表(SDS)开展横断面调查.利用t检验或x2比较不同治疗方案组患者的基本情况.应用logistic回归分析治疗方案与抑郁情绪的关系.结果显示43.1%的2型糖尿病患者存在不同程度的抑郁症状.与口服药物组相比,胰岛素组存在抑

  10. Host-directed therapeutics as novel angle for tuberculosis treatment.

    Science.gov (United States)

    Kim, Ye-Ram; Yang, Chul-Su

    2017-07-07

    Despite significant efforts to improve tuberculosis (TB) treatment, it remains a worldwide infectious disease due to the limitations of current TB regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors is beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs are more beneficial than existed TB drugs, which are limited the long durations of treatment and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune check points, immune cell functions, and essential enzyme activities. This article includes examples of potentially applicable HDTs and introduces novel approaches for their development.

  11. Comparison of different anthelminthic drug regimens against Mansonella perstans filariasis.

    Science.gov (United States)

    Bregani, Enrico Rino; Rovellini, Angelo; Mbaïdoum, Narassem; Magnini, Maria Giovanna

    2006-05-01

    Mansonella perstans filariasis is widely present in Africa and equatorial America and its pathogenicity has recently been reconsidered. Effective treatment is lacking and there is no consensus on the optimal therapeutic approach. The aim of this study was to compare the effects of different drug regimens on M. perstans infection. Six different anthelminthic therapeutic protocols were undertaken on 165 subjects with M. perstans infection and their effects on microfilariae burden were evaluated. Diethylcarbamazine (DEC) was able to reduce microfilariae density in the majority of cases, but it seldom eliminated infection after a single treatment. Mebendazole appeared to be more active than DEC in eliminating the infection, with a comparable rate of overall responses. Ivermectin and praziquantel showed no modification of microfilariae concentration. Thiabendazole showed a small but significant activity against the infection. Combination treatments (DEC plus mebendazole) resulted in a significantly higher activity than the single drugs.

  12. Switching regimens in virologically suppressed HIV-1-infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)-containing regimens.

    Science.gov (United States)

    Raffi, F; Esser, S; Nunnari, G; Pérez-Valero, I; Waters, L

    2016-10-01

    In an era when most individuals with treated HIV infection can expect to live into old age, clinicians should proactively review their patients' current and future treatment needs and challenges. Clinical guidelines acknowledge that, in the setting of virological suppression, treatment switch may yield benefits in terms of tolerability, regimen simplification, adherence, convenience and long-term health considerations, particularly in the context of ageing. In this paper, we review evidence from six key clinical studies on switching virologically suppressed patients to regimens based on integrase strand transfer inhibitors (INSTIs), the antiretroviral class increasingly preferred as initial therapy in clinical guidelines. We review these studies and focus on the virological efficacy, safety, and tolerability of switching to INSTI-based regimens in suppressed HIV-positive individuals. We review the early switch studies SWITCHMRK and SPIRAL [assessing a switch from a ritonavir-boosted protease inhibitor (PI/r) to raltegravir (RAL)-containing regimens], together with data from STRATEGY-PI [assessing a switch to elvitegravir (EVG)-containing regimens; EVG/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) vs. remaining on a PI/r-containing regimen], STRATEGY-NNRTI [assessing a switch to EVG/COBI/FTC/TDF vs. continuation of a nonnucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs)], STRIIVING [assessing a switch to a dolutegravir (DTG)-containing regimen (abacavir (ABC)/lamivudine (3TC)/DTG) vs. staying on the background regimen], and GS study 109 [assessing a switch to EVG/COBI/FTC/tenofovir alafenamide fumarate (TAF) vs. continuation of FTC/TDF-based regimens]. Switching to INSTI-containing regimens has been shown to support good virological efficacy, with evidence from two studies demonstrating superior virological efficacy for a switch to EVG-containing regimens. In addition, switching

  13. ON THE SELECTION OF DRUGS DOSAGE REGIMEN

    Directory of Open Access Journals (Sweden)

    E. N. Bochanova

    2015-09-01

    Full Text Available A complex system of hemostasis regulation, insufficient data on drugs pharmacokinetics, multiple factors effecting treatment, including patient’s adherence to therapy, that can lead to the need for the dosage regimen specification are presented.

  14. A Clinical Study of Melasma and a Comparison of the Therapeutic Effect of Certain Currently Available Topical Modalities for its Treatment

    Science.gov (United States)

    Sardesai, Vidyadhar R; Kolte, Jennifer N; Srinivas, Babu N

    2013-01-01

    Background: Melasma is a common acquired facial hypermelanosis. Conventional treatment of melasma includes a sunscreen and hypopigmenting agents. The treatment of this recalcitrant disorder is often difficult and unsatisfactory. Aims: The objective is to carry out a detailed clinical study of melasma and to assess the therapeutic effect and side effects of certain currently available topical modalities for the treatment of melasma. Materials and Methods: 160 patients of all age groups and both sexes were treated sequentially with five different combination regimes for 3 months. Assessment of the response was done subjectively as well as by melasma area and severity index (MASI). Results: Out of the five modalities studied, the modified Kligman's formula was the most effective. However, it had comparatively higher incidence of side effects. Conclusions: Among the currently available topical modalities for the treatment of melasma, the most effective combination is the modified Kligman's formula. However, in view of the side effects it causes, it must be used with caution and proper counseling. PMID:23723484

  15. A clinical study of melasma and a comparison of the therapeutic effect of certain currently available topical modalities for its treatment

    Directory of Open Access Journals (Sweden)

    Vidyadhar R Sardesai

    2013-01-01

    Full Text Available Background: Melasma is a common acquired facial hypermelanosis. Conventional treatment of melasma includes a sunscreen and hypopigmenting agents. The treatment of this recalcitrant disorder is often difficult and unsatisfactory. Aims: The objective is to carry out a detailed clinical study of melasma and to assess the therapeutic effect and side effects of certain currently available topical modalities for the treatment of melasma. Materials and Methods: 160 patients of all age groups and both sexes were treated sequentially with five different combination regimes for 3 months. Assessment of the response was done subjectively as well as by melasma area and severity index (MASI. Results: Out of the five modalities studied, the modified Kligman′s formula was the most effective. However, it had comparatively higher incidence of side effects. Conclusions: Among the currently available topical modalities for the treatment of melasma, the most effective combination is the modified Kligman′s formula. However, in view of the side effects it causes, it must be used with caution and proper counseling.

  16. [Achievement of therapeutic objectives].

    Science.gov (United States)

    Mantilla, Teresa

    2014-07-01

    Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk. Copyright © 2014 Sociedad Española de Arteriosclerosis y Elsevier España, S.L. All rights reserved.

  17. Therapeutic evaluation of cisplatin, etoposide, and bleomycin chemotherapy regimen in high-risk gestational trophoblastic neoplasia%BEP方案治疗高危型妊娠滋养细胞肿瘤的疗效及安全性评价

    Institute of Scientific and Technical Information of China (English)

    宋水勤; 张国楠

    2012-01-01

    Objective To evaluate the effectiveness and safety of combination chemotherapy with bleomycin,etoposide and cisplatin (BEP) regimen on the patients with high-risk gestational trophoblastic neoplasia (GTN).Methods Forty-two patients with high-risk GTN admitted in Sichuan Cancer Hospital between Jan.1997 and Oct.2011 were analyzed retrospectively.The International Federation of Gynecology and Obstetrics (FIGO) prognostic score of all patients was more than 7.The mean age of patients was 30.2years (range 20 -49 years).All patients were treated with more than two cycles BEP regimen and followed up to the patients' death or at the end of Feb.2012.The clinical response,toxicity and the occurrence of secondary tumors were investigated.Results Forty-two high-risk GTN patients received the total of 251courses of the BEP regimen,the average number of courses for each patient was 6.0 courses.Thirty-seven patients achieved complete remission and 5 patients showed drug-resistant.The total complete remission rate of BEP regimen was 88% ( 37/42 ).Among the complete remission patients,the total courses of BEP regimen of cases getting normal serum β-hCG level was 129 courses ( average 3.5 courses),and the total courses of cases achieving complete remission was 227 courses (average 6.1 courses ).Among the 37 complete remission patients,31 cases were treated with BEP regimen chemotherapy alone,4 patients with BEP regimen chemotherapy combined with surgical treatment (1 case had no cancer after surgery) and 2 cases with BEP regimen chemotherapy combined with radiation therapy.Therefore,the complete remission rate of BEP regimen chemotherapy alone was 74% (31/42 ).There were 5 patients who showed drug-resistance after 24 courses of BEP regimen chemotherapy (average 4.8 courses),then received etoposide,methotrexate and dactinomycin( EMA )/cyclophosphamide and vincristine sulfate ( CO ) regimen chemotherapy after drugresistance,2 cases combined with radiation therapy,1 case combined

  18. Evaluation of various gentamicin dosage regimens in geriatric patients: a simulation study.

    Science.gov (United States)

    Bourguignon, Laurent; Goutelle, Sylvain; De Saint-Martin, Julie Burdin; Maire, Pascal; Ducher, Michel

    2010-02-01

    The aim of this simulation study was to evaluate the ability of three regimens proposed in official French recommendations for gentamicin to hit defined pharmacokinetic (PK) and pharmacodynamic targets in a population of elderly patients. The first drug regimen tested consisted of a loading dose of 1 mg/kg and a maintenance dose weighted by creatininemia, every 8 h. The second regimen consisted of a fixed dose of 1 mg/kg at various intervals of time, calculated from creatinine clearance. The last regimen was a fixed dose of 3 mg/kg once a day. All regimens were for 5 days. We used a bicompartmental PK model and implemented a Monte Carlo simulation to generate a large sample of geriatric subjects. The analysis examined three ranges of creatinine clearance. Simulations showed that for the two regimens using multiple doses per day, neither was able to reach an efficacy level without significant toxicity after 5 days of treatment, regardless of the level of renal function. The use of creatininemia or creatinine clearance to adjust the drug dose did not alter these findings. The once-a-day dosing regimen gave better results both in efficacy and toxicity, except for patients with creatinine clearance lower than 60 mL/min, where the incidence of potential toxicity was above 25%. These results strongly suggest that official French recommendations about aminoglycoside dosage regimens in elderly patients with renal impairment should be updated, and that the frequent need for therapeutic drug monitoring and dosage individualization should be clearly stated.

  19. Current progresses of experimental models of amblyopia and clinical therapeutic%弱视的实验研究及临床治疗展望

    Institute of Scientific and Technical Information of China (English)

    李少敏(综述)

    2014-01-01

    弱视是一种儿童早期由于异常的视觉经历如斜视,屈光参差,视觉剥夺等导致的皮层性视觉损害,因而,只有理解了其发病的神经机制,才可能提出有效的治疗。一般观念认为弱视只有在儿童期治疗才有效,而成人的弱视基本无法治愈,但是近年来随着对弱视发病机制的分子生物学及神经电生理的研究,尤其是对视觉皮层发育可塑性的细胞间交流及细胞内分子信号通路的认识,拓展了人们对弱视病理的知识,因而也成功地通过恢复成年期的可塑性改善了成年弱视的视力。本文介绍了视觉发育可塑性的进展,就近年在增强成年可塑性途径如改变神经兴奋性与抑制性的平衡、细胞外基质、丰富环境及表观遗传学修饰等作了介绍,以其对弱视的病理机制,尤其对成人弱视的治疗有更深入的认识。%Amblyopia is a form of cerebral visual impairment caused by abnormal visual experience ( e.g., strabismus, anisometropia, deprivation) during early childhood. It is essential to understand the neural mechanism of amblyopia in order to devise novel therapeutic strategies. Although previous concepts of amblyopia is an untreatable pathology in adults, recent data deepen our knowledge of the factors involved in the intercellular communication and intracellular signaling that mediate experience-dependent plasticity in the developing visual cortex. Successful en-hancement of adult plasticity has been achieved by altering the excitation to inhibition balance;extracellular matrices;environmental enrichment and epigenetic modification. In this review, I describe current concepts of brain plasticity and the established mechanisms of amblyopia, and their implications for novel therapeutic strategies, these may hold the best hope for success in the fight against amblyopia.

  20. Antiretroviral therapy in HIV-infected patients: a proposal to assess the economic value of the single-tablet regimen

    Directory of Open Access Journals (Sweden)

    Colombo GL

    2013-02-01

    cost-effectiveness ratio per QALY versus the multipill regimen, with a 17% lower cost in favor of the single-tablet regimen. The value determined could be used to identify a maximum potential "premium price" of 29% to be assigned to therapeutic regimens proposing a single-tablet regimen for HIV-infected patients.Keywords: tenofovir, emtricitabine, efavirenz, single-tablet regimen, highly active antiretroviral therapy, quality of life, pharmacoeconomics, adherence

  1. Care of Patients With HIV Infection: Antiretroviral Drug Regimens.

    Science.gov (United States)

    Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H

    2016-04-01

    The advent of combination antiretroviral drug regimens has transformed HIV infection from a fatal illness into a manageable chronic condition. All patients with HIV infection should be considered for antiretroviral therapy, regardless of CD4 count or HIV viral load, for individual benefit and to prevent HIV transmission. Antiretroviral drugs affect HIV in several ways: entry inhibitors block HIV entry into CD4 T cells; nucleotide and nucleoside reverse transcriptase inhibitors prevent reverse transcription from RNA to DNA via chain-terminating proteins; nonnucleoside reverse transcriptase inhibitors prevent reverse transcription through enzymatic inhibition; integrase strand transfer inhibitors block integration of viral DNA into cellular DNA; protease inhibitors block maturation and production of the virus. Current guidelines recommend six combination regimens for initial therapy. Five are based on tenofovir and emtricitabine; the other uses abacavir and lamivudine. Five include integrase strand transfer inhibitors. HIV specialists should assist with treating patients with complicated HIV infection, including patients with treatment-resistant HIV infection, coinfection with hepatitis B or C virus, pregnancy, childhood infections, severe opportunistic infections, complex drug interactions, significant drug toxicity, or comorbidities. Family physicians can treat most patients with HIV infection effectively by choosing appropriate treatment regimens, monitoring patients closely, and retaining patients in care.

  2. Prophylactic antibiotic regimens in tumour surgery (PARITY)

    DEFF Research Database (Denmark)

    Petersen, Michael Mørk; Hettwer, Werner H; Grum-Schwensen, Tomas

    2015-01-01

    -day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. METHODS: We performed a pilot international multi-centre RCT. We used central randomisation......% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. CONCLUSIONS: It is feasible to conduct a definitive multi-centre RCT of post-operative...... to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. RESULTS: We screened 96 patients and enrolled 60 participants...

  3. Beneficial Effects of an Alternating High- Fat Dietary Regimen on Systemic Insulin Resistance, Hepatic and Renal Inflammation and Renal Function

    NARCIS (Netherlands)

    Yakala, Gopala K.; van der Heijden, Roel; Molema, Grietje; Schipper, Martin; Wielinga, Peter Y.; Kleemann, Robert; Kooistra, Teake; Heeringa, Peter

    2012-01-01

    Background: An Alternating high-cholesterol dietary regimen has proven to be beneficial when compared to daily high-cholesterol feeding. In the current study we explored whether the same strategy is applicable to a high-fat dietary regimen. Objective: To investigate whether an alternating high-fat d

  4. Beneficial Effects of an Alternating High- Fat Dietary Regimen on Systemic Insulin Resistance, Hepatic and Renal Inflammation and Renal Function

    NARCIS (Netherlands)

    Yakala, G.K.; Heijden, R. van der; Molema, G.; Schipper, M.; Wielinga, P.Y.; Kleemann, R.; Kooistra, T.; Heeringa, P.

    2012-01-01

    Background: An Alternating high- cholesterol dietary regimen has proven to be beneficial when compared to daily high- cholesterol feeding. In the current study we explored whether the same strategy is applicable to a high- fat dietary regimen. Objective: To investigate whether an alternating high- f

  5. Beneficial Effects of an Alternating High- Fat Dietary Regimen on Systemic Insulin Resistance, Hepatic and Renal Inflammation and Renal Function

    NARCIS (Netherlands)

    Yakala, Gopala K.; van der Heijden, Roel; Molema, Grietje; Schipper, Martin; Wielinga, Peter Y.; Kleemann, Robert; Kooistra, Teake; Heeringa, Peter

    2012-01-01

    Background: An Alternating high-cholesterol dietary regimen has proven to be beneficial when compared to daily high-cholesterol feeding. In the current study we explored whether the same strategy is applicable to a high-fat dietary regimen. Objective: To investigate whether an alternating high-fat d

  6. Beneficial Effects of an Alternating High- Fat Dietary Regimen on Systemic Insulin Resistance, Hepatic and Renal Inflammation and Renal Function

    NARCIS (Netherlands)

    Yakala, G.K.; Heijden, R. van der; Molema, G.; Schipper, M.; Wielinga, P.Y.; Kleemann, R.; Kooistra, T.; Heeringa, P.

    2012-01-01

    Background: An Alternating high- cholesterol dietary regimen has proven to be beneficial when compared to daily high- cholesterol feeding. In the current study we explored whether the same strategy is applicable to a high- fat dietary regimen. Objective: To investigate whether an alternating high- f

  7. Beneficial Effects of an Alternating High- Fat Dietary Regimen on Systemic Insulin Resistance, Hepatic and Renal Inflammation and Renal Function

    NARCIS (Netherlands)

    Yakala, G.K.; Heijden, R. van der; Molema, G.; Schipper, M.; Wielinga, P.Y.; Kleemann, R.; Kooistra, T.; Heeringa, P.

    2012-01-01

    Background: An Alternating high- cholesterol dietary regimen has proven to be beneficial when compared to daily high- cholesterol feeding. In the current study we explored whether the same strategy is applicable to a high- fat dietary regimen. Objective: To investigate whether an alternating high-

  8. Beneficial Effects of an Alternating High- Fat Dietary Regimen on Systemic Insulin Resistance, Hepatic and Renal Inflammation and Renal Function

    NARCIS (Netherlands)

    Yakala, Gopala K.; van der Heijden, Roel; Molema, Grietje; Schipper, Martin; Wielinga, Peter Y.; Kleemann, Robert; Kooistra, Teake; Heeringa, Peter

    2012-01-01

    Background: An Alternating high-cholesterol dietary regimen has proven to be beneficial when compared to daily high-cholesterol feeding. In the current study we explored whether the same strategy is applicable to a high-fat dietary regimen. Objective: To investigate whether an alternating high-fat

  9. Transfusion regimens in thalassemia intermedia

    Directory of Open Access Journals (Sweden)

    Z. Karakas

    2011-12-01

    Full Text Available Thalassemia intermedia (TI is a heterogeneous disease, in terms of both clinical manifestations and underlying molecular defects. Some TI patients are asymptomatic until adult life, whereas others are symptomatic from early childhood. In contrast with patients with Thalassemia major (TM, the severity of anemia is less and the patients do not require transfusions during at least the first few years of life. Many patients with TI, especially older ones, have been exposed to the multiple long-term effects of chronic anemia and tissue hypoxia and their compensatory reactions, including enhanced erythropoiesis and increased iron absorption. Bone marrow expansion and extramedullary hematopoiesis lead to bone deformities and liver and spleen enlargement. Therapeutic strategies in TI are not clear and different criteria are used to decide the initiation of transfusion and chelation therapy, modulation of fetal hemoglobin production, and hematopoietic stem cell transplantation on an individual basis. The clinical picture of well-treated TM patients with regular transfusionchelation therapy is better from TI patients who have not received adequate transfusion therapy. There is a significant role of early blood transfusion to prevent and treat complications commonly associated with TI, such as extramedullary erythropoiesis and bone deformities, autoimmune hemolytic anemia, leg ulcers, gallstones, pseudoxantoma elasticum, hyperuricosuria, gout and pulmonary hypertension, which are rarely seen in thalassemia major. Nowadays, indications of transfusion in patients with TI are chronic anemia (Hb < 7 g/dL, bone deformities, growth failure, extramedullary erythropoiesis, heart failure, pregnancy and preparation for surgical procedures. Conclusion: Adequate (regular or tailored transfusion therapy is an important treatment modality for increasing the quality of life in patients with thalassemia intermedia during childhood. 就临床表象和潜在的分子缺

  10. Prophylactic antibiotic regimens in tumor surgery (PARITY survey

    Directory of Open Access Journals (Sweden)

    Hasan Khaled

    2012-06-01

    Full Text Available Abstract Background Deep infection following endoprosthetic limb reconstruction for sarcoma of the long bones is a devastating complication occurring in 15% of sarcoma patients. Optimizing infection protocols and conducting definitive surgical trials are critical to improving outcomes. In this study, the PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery investigators aimed to examine surgeon preferences in antibiotic prophylaxis and perceptions about current evidence, as well as to ascertain interest in resolving uncertainty in the evidence with clinical trials. Methods We used a cross-sectional survey to examine current practice in the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery. The survey was approved by our institution’s Ethics Board and emailed to all Active Members of the Musculoskeletal Tumor Society (MSTS and Canadian Orthopaedic Oncology Society (CANOOS. Survey answers were collected using an anonymous online survey tool. Results Of the 96 surgeons who received the questionnaire, 72 responded (75% response rate (% CI: 65.5, 82.5%. While almost all respondents agreed antibiotic regimens were important in reducing the risk of infection, respondents varied considerably in their choices of antibiotic regimens and dosages. Although 73% (95% CI: 61, 82% of respondents prescribe a first generation cephalosporin, 25% favor additional coverage with an aminoglycoside and/or Vancomycin. Of those who prescribe a cephalosporin, 33% prescribe a dosage of one gram for all patients and the reminder prescribe up to 2 grams based on body weight. One in three surgeons (95% CI: 25, 48% believes antibiotics could be discontinued after 24 hours but 40% (95% CI: 30, 53% continue antibiotics until the suction drain is removed. Given the ongoing uncertainty in evidence to guide best practices, 90% (95% CI: 81, 95% of respondents agreed that they would change their practice if a large randomized controlled trial showed

  11. Intravenous and intramuscular magnesium sulphate regimens in ...

    African Journals Online (AJOL)

    1993-09-03

    Sep 3, 1993 ... Pritchard' and a continuous intravenous (IV) infusion described by Zuspan! ... in the treatment of severe pre-eclampsia with the IM regimen of ..... people under the age of 50 years and more men died than women. In 40% of ...

  12. Interferon-free regimens in patients with hepatitis C infection and renal dysfunction or kidney transplantation

    Science.gov (United States)

    Cholongitas, Evangelos; Pipili, Chrysoula; Papatheodoridis, George V

    2017-01-01

    Treatment of patients with chronic kidney disease (CKD) and chronic hepatitis C (CHC) differs from that used in the general CHC population mostly when glomerular filtration rate (GFR) is below 30 mL/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvir-based regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response (SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current management of CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice. PMID:28217256

  13. Pharmacology and therapeutics of bronchodilators.

    Science.gov (United States)

    Cazzola, Mario; Page, Clive P; Calzetta, Luigino; Matera, M Gabriella

    2012-07-01

    regimens as much as possible. This review will describe the pharmacology and therapeutics of old, new, and emerging classes of bronchodilator.

  14. New Treatment Regimen for Latent Tuberculosis Infection

    Centers for Disease Control (CDC) Podcasts

    2012-03-15

    In this podcast, Dr. Kenneth Castro, Director of the Division of Tuberculosis Elimination, discusses the December 9, 2011 CDC guidelines for the use of a new regimen for the treatment of persons with latent tuberculosis infection.  Created: 3/15/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 3/15/2012.

  15. Assessment of adherence to tuberculosis drug regimen

    Directory of Open Access Journals (Sweden)

    Khalili H.

    2008-03-01

    Full Text Available Background and the purpose of the study: Tuberculosis is curable if patients take sufficient uninterrupted therapy. Most experts acknowledge importance of patient adherence in efforts to control of the disease. This cross-sectional study was designed to evaluate the rate of compliance to anti-tuberculosis regimens by means of urine tests in newly diagnosed tuberculosis patients.Method: Investigation was carried out in Tehran University of Medical Sciences Teaching Hospitals, Tehran, IRAN. Fifty patients completed the study. The patients' urine samples were obtained at 0, 1, 2, 4 and 6 months of the study. Simple chemical methods were used to detect Isoniazid, Rifampin, and pyrazinamide, the three main drugs in tuberculosis treatment regimens. Urine tests at months of 0 and l of the study were considered as control tests.Results: After the first month, the patients' compliance was about 96%. At months of second, fourth and sixth, the whole adherence rates were 56 %, 76% and 81% respectively. Conclusion: About 30% of patients were non-compliant with treatment regimen which was more frequent than presumed; therefore detection of non-adherent patients is an essential subject in developing countries.

  16. Therapeutic drug monitoring of aminoglycosides in neonates

    NARCIS (Netherlands)

    Touw, Daniël J; Westerman, Elsbeth M; Sprij, Arwen J

    2009-01-01

    The efficacy and toxicity of aminoglycosides show a strong direct positive relationship with blood drug concentrations, therefore, therapy with aminoglycosides in adults is usually guided by therapeutic drug monitoring. Dosing regimens in adults have evolved from multiple daily dosing to extended-in

  17. Improving adherence to medical regimens for juvenile rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Lindsley Carol B

    2007-05-01

    Full Text Available Abstract Poor adherence to medical regimens can compromise the efficacy of treatments for children and adolescents with juvenile rheumatoid arthritis (JRA. The purpose of this review is to describe medical regimens for the treatment of JRA and the rates of adherence to these regimens. We also summarize and critically the few research studies aimed at improving adherence to regimens for JRA. Finally, we summarize strategies for enhancing adherence in clinical practice.

  18. Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model

    Science.gov (United States)

    Cohen, Ted; Nuermberger, Eric; Dooley, Kelly E.; Gonzalez-Angulo, Lice; Churchyard, Gavin J.; Nahid, Payam; Rich, Michael L.; Bansbach, Cathy; Forissier, Thomas; Dowdy, David W.

    2017-01-01

    Background Novel drug regimens are needed for tuberculosis (TB) treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen’s ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective. Methods and Findings We developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis), South Africa, the Philippines, and Brazil. We modeled the introduction of various novel rifampicin-susceptible (RS) or rifampicin-resistant (RR) TB regimens that differed on six characteristics, identified in consultation with a team of global experts: (1) efficacy, (2) duration, (3) ease of adherence, (4) medical contraindications, (5) barrier to resistance, and (6) baseline prevalence of resistance to the novel regimen. We compared scale-up of these regimens to a baseline reflective of continued standard of care. For our primary analysis situated in India, our model generated baseline TB incidence and mortality of 157 (95% uncertainty range [UR]: 113–187) and 16 (95% UR: 9–23) per 100,000 per year at the time of novel regimen introduction and RR TB incidence and mortality of 6 (95% UR: 4–10) and 0.6 (95% UR: 0.3–1.1) per 100,000 per year. An optimal RS TB regimen was projected to reduce 10-y TB incidence and mortality in the India-like scenario by 12% (95% UR: 6%–20%) and 11% (95% UR: 6%–20%), respectively, compared to current-care projections. An optimal RR TB regimen reduced RR TB incidence by an estimated 32% (95% UR: 18%–46%) and RR TB mortality by 30% (95% UR: 18%–44%). Efficacy was the greatest determinant of impact; compared to a novel regimen meeting all minimal targets only, increasing RS TB treatment efficacy from 94% to 99

  19. Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

    Directory of Open Access Journals (Sweden)

    Joana R. Viola

    2013-01-01

    Full Text Available Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed.

  20. The role of expectation in the therapeutic outcomes of alcohol and drug addiction treatments.

    Science.gov (United States)

    Spagnolo, Primavera A; Colloca, Luana; Heilig, Markus

    2015-05-01

    Throughout history, patient-physician relationships have been acknowledged as an important component of the therapeutic effects of any pharmacological treatment. Here, we discuss the role of physicians' expectations in influencing the therapeutic outcomes of alcohol and drug addiction pharmacological treatments. As largely demonstrated, such expectations and attitudes may contribute to produce placebo and nocebo effects that in turn affect the course of the disease and the response to the therapy. This article is aimed at discussing the current insights into expectations, placebo and nocebo mechanisms and their impact on the therapeutic outcomes of alcohol and drug addiction treatments; with the goal of informing physicians and other health care providers about the potentially widespread implications for clinical practice and for a successful treatment regimen. Published by Oxford University Press on behalf of Medical Council on Alcohol 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Xu, Xu Steven; Yan, Xiaoyu; Puchalski, Thomas

    2017-01-01

    New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first-in-class, CD38 human immunoglobulin G1κ monoclonal antibody approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen...

  2. Clinical roundtable monograph. Current treatment options for metastatic breast cancer: what now?

    Science.gov (United States)

    Rugo, Hope S; O'Shaughnessy, Joyce A; Perez, Edith A

    2011-11-01

    Approximately 30% of patients with breast cancer will develop metastatic breast disease. Metastatic breast cancer is considered an incurable disease, with complete remission rarely achieved after treatment. The goal of treatment for metastatic breast cancer patients is to increase overall survival time and delay disease progression while ameliorating symptoms and improving or maintaining quality of life. Single-agent therapeutic regimens are appropriate for most metastatic breast cancer patients. Patients with the luminal A subtype of breast cancer, which is more indolent in nature and tends to be more sensitive to treatment in general, often respond well to single-agent therapy. Several chemotherapy regimens are recommended for the treatment of metastatic breast cancer. Compared with single-agent regimens, these combination regimens often produce a greater improvement in the rate of objective response as well as a prolongation of progression-free survival. There is little evidence, however, of improvement in overall survival. Combination chemotherapy regimens are often associated with a greater degree of toxicity depending on schedules and doses used. The use of bevacizumab in metastatic breast cancer is currently a topic of controversy. It is hoped that forthcoming trial data will enable the identification of a group of patients, based on tumor biology, who could benefit from bevacizumab-based therapy.

  3. Material properties and electrical stimulation regimens through polycaprolactone fumarate-polypyrrole scaffolds as potential conductive nerve conduits

    Science.gov (United States)

    Moroder, Philipp; Wang, Huan; Ruesink, Terry; Lu, Lichun; Windebank, Anthony J.; Yaszemski, Michael J.; Runge, M. Brett

    2010-01-01

    Mechanical and electrical properties of polycaprolactone fumarate-polypyrrole (PCLF-PPy) scaffolds were studied under physiological conditions to evaluate their ability to maintain material properties necessary for application as conductive nerve conduits. PC12 cells cultured on PCLF-PPy scaffolds were stimulated with regimens of 10 μA of constant or 20 Hz frequency current passed through the scaffolds for 1 h/day. PC12 cellular morphologies were analyzed by fluorescence microscopy after 48 h. PCLF-PPy scaffolds exhibited excellent mechanical properties at 37°C which would allow suturing and flexibility. The surface resistivity of the scaffolds was 2kΩ and the scaffolds were electrically stable during application of electrical stimulation (ES). In vitro studies showed significant increases in percentage of neurite bearing cells, number of neurites per cell and neurite length in the presence of ES compared to no ES. Additionally, extending neurites were observed to align in the direction of the applied current. This study shows that electrically conductive PCLF-PPy scaffolds possess material properties necessary for application as nerve conduits. Additionally, the capability to significantly enhance and direct neurite extension by passing electrical current through PCLF-PPy scaffolds renders them even more promising as future therapeutic treatments for severe nerve injuries. PMID:20965280

  4. Current situation of evaluation and application with alternative dosing regimens for piperacillin sodium-tazobactam sodium%哌拉西林钠-他唑巴坦钠优选给药方案的评估及应用的研究现状

    Institute of Scientific and Technical Information of China (English)

    李园园; 于锋

    2014-01-01

    Objective To offer reference to reasonable clinical use of piperacillin sodium sodium-tazobactam sodium .Methods We reviewed pharmacokinetic/pharmacodynamic studies , clinical trails and implementation of piperacillin sodium-tazobactam sodi-um alternative dosing regimen in recent .Results The alternative dosing regimens , prolonged and continuous infusion , could maximise the likelihood of achieving desirable pharmacodynamic targets and improve clinical effectiveness .Conclusion It’ s needed to improve the strategies of alternative dosing regimens for clinical practice .%目的:为哌拉西林钠-他唑巴坦钠的临床合理用药提供参考。方法对哌拉西林钠-他唑巴坦钠的优选给药方案的药动/药效学研究、临床试验及具体实施情况进行综述。结果哌拉西林钠-他唑巴坦钠的优选给药方案(延长输注或持续输注)可最大化地达到药效学目标,改善临床有效性。结论需积极完善优化方案用于临床实践的策略。

  5. Plasma concentrations of caspofungin at two different dosage regimens in a patient with hepatic dysfunction

    NARCIS (Netherlands)

    Elst, K.C. van der; Bruggemann, R.J.M.; Rodgers, M.G.; Alffenaar, J.W.C.

    2012-01-01

    The currently recommended dosage regimen of caspofungin (50 mg/day) was developed for patients with invasive candidiasis. With invasive aspergillosis, successful outcomes occur in less than half the patients. We evaluate the pharmacokinetics in a patient with elevated liver enzyme levels after liver

  6. Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: A modelling study

    NARCIS (Netherlands)

    M.A. Irvine (Michael A.); W.A. Stolk (Wilma); Smith, M.E. (Morgan E); S.V. Subramanian; B.K. Singh (Brajendra K.); G.J. Weil (Gary); E. Michael (Edwin); T.D. Hollingsworth (T. Déirdre)

    2017-01-01

    textabstractBackground: Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen (ivermectin

  7. Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: A modelling study

    NARCIS (Netherlands)

    M.A. Irvine (Michael A.); W.A. Stolk (Wilma); Smith, M.E. (Morgan E); S.V. Subramanian; B.K. Singh (Brajendra K.); G.J. Weil (Gary); E. Michael (Edwin); T.D. Hollingsworth (T. Déirdre)

    2017-01-01

    textabstractBackground: Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen

  8. Therapeutic Options in High-risk Non-muscle-invasive Bladder Cancer During the Current Worldwide Shortage of Bacille Calmette-Guerin

    NARCIS (Netherlands)

    Mostafid, A.H.; Redorta, J. Palou; Sylvester, R.; Witjes, J.A.

    2015-01-01

    Optimal management of high-risk non-muscle-invasive bladder cancer during the current bacillus Calmette-Guerin (BCG) shortage is challenging. Although no evidence-based guidelines exist for this specific situation, current management options can be adapted for when BCG supplies are limited or when

  9. Positioning end-of-life care education within the pre-registration therapeutic radiography curriculum: A survey of current practices amongst UK higher education institutions.

    Science.gov (United States)

    White, N

    2017-09-01

    It is essential that all health professionals who come into contact with patients with terminal diagnoses are equipped to effectively and competently provide end of life care. This study aims to investigate the manner in which Higher Education Institutions address this requirement with their programmes of pre-registration therapeutic radiography education. A structured survey was administered electronically to all UK universities with responsibility for therapeutic radiography education. The scope of the survey addressed mode and duration of end of life care education, its location, curricular assessment, identifiable barriers and best practice. All respondents confirmed the presence of dedicated end of life care education within their curriculum. Variation in the duration and location of this education is reported as are approaches to assessment of associated skills and knowledge. Analysis of respondent commentary has identified three themes-preparedness for the clinical role, dissonance between technology and care, and holistic approaches to course design. Respondents have highlighted the importance of end of life care instruction with their programmes of study and identified aspects of the mode and duration of its delivery. Inclusion of this aspect of study may be problematic in the face of competing demands arising from the volume and complexity of the curriculum. Practical experience of end of life care predominantly occurs within the radiotherapy department, although there is scope to explore opportunities within the hospice and community care setting. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  10. Retrospective analysis of the therapeutic efficacy of four chemotherapy regimens for newly diagnosed smear-positive outpatients with pulmonary tuberculosis in Shijingshan District of Beijing during 1985-2008%北京市石景山区1985-2008年新涂阳肺结核非住院患者4种化疗方案疗效回顾性分析

    Institute of Scientific and Technical Information of China (English)

    王珏; 唐桂琴; 张亚敬

    2013-01-01

    Objective To evaluate the effect of directly observed chemotherapy on newly diagnosed smear-positive outpatients with pulmonary tuberculosis (TB) in Shijingshan District, Beijing, during 1985-2008. Methods Totally 1133 newly diagnosed smear-positive pulmonary TB outpatients in Shijingshan District during 1985-2008 were given 4 chemotherapy regimens, one-year course of standard chemotherapy regimen, short-course (half a year) intermittent chemotherapy regimen 1, short-course (half a year) intermittent chemotherapy regimen 2 and short-course daily chemotherapy regimen. The treatment success rates, incidence of adverse reactions and the three-year recurrence rates of the different treatment groups were compared and analyzed. Results The treatment success rate was the highest in short-course daily chemotherapy regimen group (97.2%) and the lowest in standard chemotherapy regimen group (84.3%). The three-year recurrence rates and adverse reaction rates were the lowest in short-course daily chemotherapy regimen group and short-course intermittent chemotherapy regimen 1 group. Conclusion To take the treatment success rates, three-year recurrence rates and adverse reaction rates into account, shortcourse daily chemotherapy regimen is superior to short-course intermittent chemotherapy regimens and standard chemotherapy regimen.%目的 评价北京市石景山区1985-2008年新涂阳肺结核病例非住院全面督导化疗效果.方法 石景山区1985-2008年管理的1133例新涂阳肺结核患者在不同时期分别采用了12个月疗程的标准化疗方案、2种6个月疗程的短程化疗间歇方案和6个月疗程的短程化疗每日方案4种治疗方案.通过收集这1133例新涂阳肺结核患者资料,对不同治疗方案组的治疗成功率、3年复发率和不良反应发生率等资料进行比较分析.结果 治疗成功率方面,短程化疗每日方案最高(97.2%),标准化疗方案最低(84.3%);短程化疗每日方案

  11. Esomeprazole regimens for reflux symptoms in Chinese patients with chronic gastritis.

    Science.gov (United States)

    Sun, Jing; Yuan, Yao-Zong; Hou, Xiao-Hua; Zou, Duo-Wu; Lu, Bin; Chen, Min-Hu; Liu, Fei; Wu, Kai-Chun; Zou, Xiao-Ping; Li, Yan-Qing; Zhou, Li-Ya

    2015-06-14

    To compare symptom control with esomeprazole regimens for non-erosive reflux disease and chronic gastritis in patients with a negative endoscopy. This randomized, open-label study was designed in line with clinical practice in China. Patients with typical reflux symptoms for ≥ 3 mo and a negative endoscopy who had a Gastroesophageal Reflux Disease Questionnaire score ≥ 8 were randomized to initial treatment with esomeprazole 20 mg once daily either for 8 wk or for 2 wk. Patients with symptom relief could enter another 24 wk of maintenance/on-demand treatment, where further courses of esomeprazole 20 mg once daily were given if symptoms recurred. The primary endpoint was the symptom control rate at week 24 of the maintenance/on-demand treatment period. Secondary endpoints were symptom relief rate, success rate (defined as patients who had symptom relief after initial treatment and after 24 wk of maintenance treatment), time-to-first-relapse and satisfaction rate. Based on the data collected in the modified intention-to-treat population (MITT; patients in the ITT population with symptom relief after initial esomeprazole treatment, n = 262), the symptom control rate showed a small but statistically significant difference in favor of the 8-wk regimen (94.9% vs 87.3%, P = 0.0473). Among the secondary endpoints, based on the data collected in the ITT population (n = 305), the 8-wk group presented marginally better results in symptom relief after initial esomeprazole treatment (88.3% vs 83.4%, P = 0.2513) and success rate over the whole study (83.8% vs 72.8%, P = 0.0258). The 8-wk regimen was found to provide a 46% reduction in risk of relapse vs the 2-wk regimen (HR = 0.543; 95%CI: 0.388-0.761). In addition, fewer unscheduled visits and higher patient satisfaction supported the therapeutic benefits of the 8-wk regimen over the 2-wk regimen. Safety was comparable between the two groups, with both regimens being well tolerated. Chinese patients diagnosed with chronic

  12. Virological and immunological outcomes at 3 years after starting antiretroviral therapy with regimens containing non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or both in INITIO: open-label randomised trial

    DEFF Research Database (Denmark)

    Yeni, P; Cooper, DA; Aboulker, J-P

    2006-01-01

    BACKGROUND: Antiretroviral therapy has greatly reduced HIV mortality and morbidity. However, the best sequence of regimens and implications of initial regimen for long-term therapeutic success are not well defined. METHODS: In INITIO, a large international randomised trial, we compared antiretrov...

  13. Characterization of HIV-1 from patients with virological failure to a boosted protease inhibitor regimen

    DEFF Research Database (Denmark)

    Lillemark, Marie Rathcke; Gerstoft, Jan; Obel, Niels

    2011-01-01

    The use of highly active antiretroviral treatment (HAART) regimens with unboosted protease inhibitors (PIs) has resulted in a high level of virological failure primarily due to the development of resistant virus. Current boosted PI regimens combine successfully low-dose ritonavir (r) with a second...... PI. The aim of the study was to estimate the proportion of patients, in a population based setting, who develop virological failure on a PI/r regimen. Through The Danish HIV Cohort Study 1,007 patients who received PI/r based treatment between 1995 and 2008 were identified. Twenty-three (2.......3%) experienced virological failure, of whom 19 (83%) started PI/r treatment before 2001. Patients from Copenhagen (n=19) were selected to study the development of protease (PR) and gag cleavage site (CS) mutations during PI/r treatment and PI plasma levels at the time of virological failure. Three patients (16...

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

    Science.gov (United States)

    Cossu, Giulia

    2014-04-01

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

  15. Complicaciones respiratorias de la tetraplejia: Una mirada a las alternativas terapéuticas actuales Respiratory complications in tetraplegia: Overview to current therapeutic alternatives

    Directory of Open Access Journals (Sweden)

    DANIELA GARCÍA P

    2007-06-01

    Full Text Available Las complicaciones respiratorias son la principal causa de muerte en los pacientes con tetraplejia, tanto en el período agudo como crónico. En esta categoría se incluyen diversas alteraciones como neumonías recurrentes, atelectasias, mal manejo de las secreciones, insuficiencia respiratoria e hipoventilación. Además, son frecuentes patologías más complejas como el tromboembolismo pulmonar y la apnea obstructiva del sueño. Se postula que las causas principales de los problemas respiratorios son la debilidad de los músculos intercostales y abdominales, y la disfunción parcial o total del diafragma. Hoy en día existen múltiples alternativas terapéuticas para prevenir, manejar y tratar en forma específica las diversas complicaciones. El propósito de este artículo es revisar las opciones terapéuticas actualmente vigentes y despertar el interés entre los clínicos para profundizar más en este importante temaRespiratory complications are the first cause of death in patients with tetraplegia, including both the acute and chronic stage of the disease. They include a wide variety of respiratory problems, such as repeated pneumonias, atelectasis, unsatisfactory secretions manage, respiratory failure, hypoventilation, and other complex pathologies such as pulmonary embolism and sleep apnea syndrome. It has been postulated that the main cause of all these respiratory complications is weakness of inter costáis and abdominal muscles, and partial or complete dysfunction of the diaphragm. Today we have multiple therapeutic alternatives to prevent, manage and specifically treat the multiple types of complications. The main objective of this article is to review the different therapeutical alternatives and encourage the study of this important topic

  16. A comparison of the therapeutic and reactivating efficacy of newly developed oximes (K117, K127) and currently available oximes (obidoxime, trimedoxime, HI-6) in tabun-poisoned rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana; Musilek, Kamil; Kuca, Kamil; Jung, Young-Sik

    2008-01-01

    The potency of newly developed bispyridinium compounds (K117, K127) to reactivate tabun-inhibited acetylcholinesterase and reduce tabun-induced lethal toxic effects was compared with currently available oximes (obidoxime, trimedoxime, oxime HI-6) by using in vivo methods. A study that determined the percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of newly developed oxime K127 is comparable with obidoxime and trimedoxime in blood but lower than the reactivating potency of trimedoxime and obidoxime in the diaphragm and brain. The potency of another newly developed K117 to reactivate tabun-inhibited acetylcholinesterase is comparable with obidoxime or trimedoxime in the diaphragm, but it is significantly lower than the reactivating potency of trimedoxime and obidoxime in the blood and brain. The oxime, K127, was also found to be relatively effective in reducing lethal toxic effects in tabun-poisoned mice. Its therapeutic efficacy is consistent with the therapeutic potency of obidoxime. On the other hand, the potency of the oxime, K117, to reduce acute toxicity of tabun is significantly lower compared to trimedoxime and obidoxime. The therapeutic efficacy of K117 and K127 corresponds to their potency to reactivate tabun-inhibited acetylcholinesterase, especially in the diaphragm and brain. Contrary to obidoxime and trimedoxime, the oxime, HI-6, is not an effective oxime in the reactivation of tabun-inhibited acetycholinesterase and in reducing the lethal effects of tabun. The reactivating and therapeutic potency of both newly developed oximes does not prevail over the effectiveness of currently available obidoxime and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute tabun poisoning.

  17. Mesenteric panniculitis: Various presentations and treatment regimens

    Institute of Scientific and Technical Information of China (English)

    Iyad Issa; Hassan Baydoun

    2009-01-01

    Mesenteric panniculitis is a rare, benign and chronic fibrosing inflammatory disease that affects the adipose tissue of the mesentery of the small intestine and colon. The specific etiology of the disease is unknown. The diagnosis is suggested by computed tomography and is usually confirmed by surgical biopsies. Treatment is empirical and based on a few selected drugs. Surgical resection is sometimes attempted for definitive therapy, although the surgical approach is often limited. We report two cases of mesenteric panniculitis with two different presentations and subsequently varying treatment regimens. Adequate response was obtained in both patients. We present details of these cases as well as a literature review to compare various presentations, etiologies and potential treatment modalities.

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

    Science.gov (United States)

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

    2016-05-01

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

  19. Antiviral Polymer Therapeutics

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford

    2014-01-01

    The field of drug delivery is in essence an exercise in engineered pharmacokinetics. Methods of doing so have been developed through the introduction of a vehicle carrying the drug, either by encapsulation or covalent attachment. The emergence of polymer therapeutics in anticancer therapy has...... the examples of polymer therapeutics being applied as an antiviral treatment are few and far in-between. This work aims to explore antiviral therapeutics, specifically in context of hepatitis virus C (HCV) and HIV. The current treatment of hepatitis C consists of a combination of drugs, of which ribavirin....... Curiously, the therapeutic window of ribavirin was vastly improved in several of these polymers suggesting altered pharmacodynamics. The applicability of liver-targeting sugar moieties is likewise tested in a similarly methodical approach. The same technique of synthesis was applied with zidovudine to make...

  20. Current therapeutic status for generalized status epilepticus%全面性癫痫持续状态的治疗现状

    Institute of Scientific and Technical Information of China (English)

    黎黎; 张洪

    2013-01-01

    全面性癫痫持续状态是癫痫持续状态中最严重的类型,是神经科一种急诊。本文就近年来有关全面性癫痫持续状态的流行病学、病因、药物治疗的研究现状进行阐述。%Generalized status epilepticus is one of the most serious types of status epilepticus, and it is an emergency condition in neurology department. This article reviewed currently research about epidemiology, etiology, and drug treatment of generalized status epilepticus.

  1. Taking Sides: An Integrative Review of the Impact of Laterality and Polarity on Efficacy of Therapeutic Transcranial Direct Current Stimulation for Anomia in Chronic Poststroke Aphasia

    Directory of Open Access Journals (Sweden)

    Margaret Sandars

    2016-01-01

    Full Text Available Anomia is a frequent and persistent symptom of poststroke aphasia, resulting from damage to areas of the brain involved in language production. Cortical neuroplasticity plays a significant role in language recovery following stroke and can be facilitated by behavioral speech and language therapy. Recent research suggests that complementing therapy with neurostimulation techniques may enhance functional gains, even amongst those with chronic aphasia. The current review focuses on the use of transcranial Direct Current Stimulation (tDCS as an adjunct to naming therapy for individuals with chronic poststroke aphasia. Our survey of the literature indicates that combining therapy with anodal (excitatory stimulation to the left hemisphere and/or cathodal (inhibitory stimulation to the right hemisphere can increase both naming accuracy and speed when compared to the effects of therapy alone. However, the benefits of tDCS as a complement to therapy have not been yet systematically investigated with respect to site and polarity of stimulation. Recommendations for future research to help determine optimal protocols for combined therapy and tDCS are outlined.

  2. Taking Sides: An Integrative Review of the Impact of Laterality and Polarity on Efficacy of Therapeutic Transcranial Direct Current Stimulation for Anomia in Chronic Poststroke Aphasia.

    Science.gov (United States)

    Sandars, Margaret; Cloutman, Lauren; Woollams, Anna M

    2016-01-01

    Anomia is a frequent and persistent symptom of poststroke aphasia, resulting from damage to areas of the brain involved in language production. Cortical neuroplasticity plays a significant role in language recovery following stroke and can be facilitated by behavioral speech and language therapy. Recent research suggests that complementing therapy with neurostimulation techniques may enhance functional gains, even amongst those with chronic aphasia. The current review focuses on the use of transcranial Direct Current Stimulation (tDCS) as an adjunct to naming therapy for individuals with chronic poststroke aphasia. Our survey of the literature indicates that combining therapy with anodal (excitatory) stimulation to the left hemisphere and/or cathodal (inhibitory) stimulation to the right hemisphere can increase both naming accuracy and speed when compared to the effects of therapy alone. However, the benefits of tDCS as a complement to therapy have not been yet systematically investigated with respect to site and polarity of stimulation. Recommendations for future research to help determine optimal protocols for combined therapy and tDCS are outlined.

  3. [Therapeutic drug monitoring of rufinamide].

    Science.gov (United States)

    Bentué-Ferrer, Danièle; Tribut, Olivier; Verdier, Marie-Clémence

    2012-01-01

    Rufinamide is a third-generation antiepileptic drug, available since early 2010 in France. It is indicated in combination therapy in the Lennox-Gastaut syndrome from the age of 4. It has orphan drug status. The bioavailability of rufinamide is high, but decreases with the dose and increases with food intake. Rufinamide is not metabolized by cytochromes but hydrolyzed by a carboxylesterase in an inactive carboxylic derivative. Elimination is mainly renal. The half-life varies from 6 to 10h. Although established from relatively few studies, exposure efficacy and exposure toxicity relationships are argued. A plasma concentration of 15 mg/L, obtained with a standard regimen, reduces the number of seizures of 25%. Few factors of intrinsic variability are described. There are few clinically significant pharmacokinetic interactions and they concern combinations with other antiepileptic drugs, especially valproate. Although there is no validated therapeutic range, the level of evidence for this therapeutic drug monitoring has been estimated at "possibly useful".

  4. Treatment-time regimen of hypertension medications significantly affects ambulatory blood pressure and clinical characteristics of patients with resistant hypertension.

    Science.gov (United States)

    Hermida, Ramón C; Ríos, María T; Crespo, Juan J; Moyá, Ana; Domínguez-Sardiña, Manuel; Otero, Alfonso; Sánchez, Juan J; Mojón, Artemio; Fernández, José R; Ayala, Diana E

    2013-03-01

    Patients with resistant hypertension (RH) are at greater risk for stroke, renal insufficiency, and cardiovascular disease (CVD) events than are those for whom blood pressure (BP) is responsive to and well controlled by therapeutic interventions. Although all chronotherapy trials have compared the effects on BP regulation of full daily doses of medications when ingested in the morning versus at bedtime, prescription of the same medications in divided doses twice daily (BID) is frequent. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and laboratory medicine parameters of RH patients evaluated by 48-h ambulatory BP monitoring (ABPM). This cross-sectional study evaluated 2899 such patients (1701 men/1198 women), 64.2 ± 11.8 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 1084 were ingesting all hypertension medications upon awakening (upon-awakening regimen), 1436 patients were ingesting the full daily dose of ≥1 of them at bedtime (bedtime regimen), and 379 were ingesting split doses of ≥1 medications BID upon awakening and at bedtime (BID regimen). Patients of the bedtime regimen compared with the other two treatment-time regimens had lower likelihood of microalbuminuria and chronic kidney disease; significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; plus higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. The bedtime regimen was also significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than the upon-awakening and BID regimens. The sleep-time relative SBP and DBP decline was significantly attenuated by the upon-awakening and BID regimens (p pattern, associated with highest CVD risk, was much greater, 31.0% and 29.8%, respectively, among patients of the upon-awakening and BID

  5. The Sex Res Non Naturales and the Regimen of Health

    DEFF Research Database (Denmark)

    Agerholm, Frank Juul

    2013-01-01

    The paper discusses the ethical and social soundness of the classical idea of diaita/regimen vis-à-vis the contemporary focus on healthy lifestyle......The paper discusses the ethical and social soundness of the classical idea of diaita/regimen vis-à-vis the contemporary focus on healthy lifestyle...

  6. Study on therapeutic effect of anti-TB drugs and regimens for tuberculosis meningitis and PK /PD of these drugs%抗结核药物及方案对结核性脑炎治疗作用及药物的药代动力学/药效学研究

    Institute of Scientific and Technical Information of China (English)

    赵伟杰; 付雷; 李破; 王彬; 徐建

    2011-01-01

    Objective To determinte the concentrations of three anti -TB drugs are increased in the brain tissue of health and TB meningitis( MTB) model mice , study the pharmacokinetics/pharmacodynamics ( PK/PD) parameters of them in plasma and brain tissue using healthy and MTB model mice , evaluate the activities of these drugs respectively and combinations of them , provide information for the treatment of MTB based on their activities and parameters . Methods MTB mice model was developed through injecting H 37Rv into the tail vein of mice. After administrated RFP . Lfx. Mfx for 5 days , the plasma and brain tissue of healthy and MTB mice were gotten at different time points and the concentrations of these drugs were determined by HPLC , and then obtain the PK and PK/PD parameters.The mice were given Lfx. Mfx and other drugs usually used to therapy TB alone or combination , CFU in lungs and brain tissues were obtained after treatment for 8 weeks and these data together with the PK and PK/PD parameters were analyzed to evaluate the efficiency of treating pulmonaiy TB and MTB. Results The AUC0-24 of RFP, Lfx, Mfx were increased by 56. 0% , 148. 5% , 80. 4% , AUC0-24/MIC were 445. 0, 16. 5, 7. 4 respectively ; after treatment for 8 weeks, except PZA , Lfx that the CFU were decreased more . For MTB , every groups except Lfx were effective and INH , RHPto, RHLfx, RHMfx were more effective. Conclusions The amounts of drugs entering into the brain tissue increase while the hrain was infected by H 37Rv when compared with that of healthy mice ; RHPto, RHLfx, RHMfx are effective combinations to therapy MTB , so all of them can be choosed as therapeutic remedy for different patients.%目的 测定三种抗结核药在健康和结核性脑膜炎小鼠脑组织中的浓度,评价几种单药和联合方案抗肺结核和结核性脑膜炎的活性;评价其药代动力学/药效学(PK/PD)参数.方法 通过小鼠静脉感染H37Rv 建立结核性脑膜炎模型,健康和结核

  7. Phytochemical Modulators of Mitochondria: The Search for Chemopreventive Agents and Supportive Therapeutics

    Directory of Open Access Journals (Sweden)

    Maja M. Grabacka

    2014-09-01

    Full Text Available Mitochondria are crucially important for maintaining not only the energy homeostasis, but the proper cellular functions in a general sense. Impairment of mitochondrial functions is observed in a broad variety of pathological states such as neoplastic transformations and cancer, neurodegenerative diseases, metabolic disorders and chronic inflammation. Currently, in parallel to the classical drug design approaches, there is an increasing interest in the screening for natural bioactive substances, mainly phytochemicals, in order to develop new therapeutic solutions for the mentioned pathologies. Dietary phytochemicals such as resveratrol, curcumin and sulforaphane are very well tolerated and can effectively complement classical pharmacological therapeutic regimens. In this paper we disscuss the effect of the chosen phytochemicals (e.g., resveratrol, curcumin, sulforaphane on various aspects of mitochondrial biology, namely mitochondrial biogenesis, membrane potential and reactive oxygen species production, signaling to and from the nucleus and unfolded protein response.

  8. Daclatasvir-based Treatment Regimens for Hepatitis C Virus Infection: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Alavian

    2016-08-01

    Full Text Available Context Direct acting antivirals (DAAs have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus (HCV infection, which is a major public health problem. Among the known DAAs, daclatasvir (DCV, an inhibitor of the non-structural 5A protein, has been used in combination with several drugs for treatment of infection with HCV of different genotypes under different conditions. We conducted a systematic review and meta-analysis of combination therapy with DCV. Evidence Acquisition We performed a systematic search in PubMed, Scopus, Science Direct and Web of Science with appropriate keywords for DCV. Studies that evaluated any regimen containing DCV and reported the sustained virological response (SVR 12 weeks after therapy based on the HCV genotype, treatment duration and use of ribavirin (RBV were included. The selected studies were considered for meta-analysis using STATA 11.0. Results We found six different regimens containing DCV: DCV/asunaprevir (ASV, DCV/ASV/beclubavir, DCV/pegylated interferon lambda or alpha/RBV with or without ASV, DCV/simeprevir, DCV/VX-135 and DCV/sofosbuvir (SOF. Most of these regimens were used for the treatment of HCV genotype 1 infections, and in most cases, treatment failure was noted in subtype 1a infections. Among all these regimens, DCV/SOF with or without RBV for 12 or 24 weeks was found to be an efficacious approach for treatment of different types of patients with infections with different HCV genotypes. Conclusions Among the treatment regimens containing DCV, DCV/SOF has the highest SVR rate for the treatment of infection with different HCV genotypes in different patient contexts; thus, this regimen shows promise for the treatment of HCV infections.

  9. A review of the potential therapeutic role of statins in the treatment of Alzheimer’s disease: current research and opinion

    Directory of Open Access Journals (Sweden)

    Mitchell AJ

    2013-01-01

    Full Text Available Álvaro Sánchez-Ferro,1–4 Julián Benito-León,1–3 Alex J Mitchell,5 Félix Bermejo-Pareja1–31Department of Neurology, University Hospital 12 de Octubre, Madrid, Spain; 2Department of Medicine, Complutense University, Madrid, Spain; 3Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain; 4Instituto de Salud Carlos III, Madrid, Spain; 5Department of Psycho-oncology, Leicestershire Partnership NHS Trust and University of Leicester, Leicester, UKAbstract: Alzheimer’s disease is one of the most prevalent neurodegenerative disorders. However, there is no current treatment, which definitively influences disease progression over a sustained period. Numerous studies linking an increase in serum cholesterol, mainly during midlife, with the pathogenic process of Alzheimer’s disease have been published. Therefore, the role of statins as a therapy in this disorder may be of great interest. The aim of the present review is to summarize of the role of statins in the treatment of Alzheimer’s disease.Keywords: animal models, epidemiology, HMGCoA-inhibitors, clinical trials, prevention, cognitive function

  10. Opioid Addiction: Social Problems Associated and Implications of Both Current and Possible Future Treatments, including Polymeric Therapeutics for Giving Up the Habit of Opioid Consumption

    Directory of Open Access Journals (Sweden)

    M. Cristina Benéitez

    2017-01-01

    Full Text Available Background. Detoxification programmes seek to implement the most secure and compassionate ways of withdrawing from opiates so that the inevitable withdrawal symptoms and other complications are minimized. Once detoxification has been achieved, the next stage is to enable the patient to overcome his or her drug addiction by ensuring consumption is permanently and completely abandoned, only after which can the subject be regarded as fully recovered. Methods. A systematic search on the common databases of relevant papers published until 2016 inclusive. Results and Conclusion. Our study of the available oral treatments for opioid dependence has revealed that no current treatment can actually claim to be fully effective. These treatments require daily oral administration and, consequently, regular visits to dispensaries, which in most cases results in a lack of patient compliance, which causes fluctuations in drug plasma levels. We then reviewed alternative treatments in the available scientific literature on polymeric sustained release formulations. Research has been done not only on release systems for detoxification but also on release systems for giving up the habit of taking opioids. These efforts have obtained the recent authorization of polymeric systems for use in patients that could help them to reduce their craving for drugs.

  11. Adherence to asthma controller medication regimens.

    Science.gov (United States)

    Stempel, D A; Stoloff, S W; Carranza Rosenzweig, J R; Stanford, R H; Ryskina, K L; Legorreta, A P

    2005-10-01

    Improved adherence to inhaled corticosteroids (ICS) is recognized as an important factor in reduced morbidity, mortality and consumption of health care resources. The present study was designed to replicate previous reports of patient adherence with fluticasone/salmeterol in a single inhaler (FSC), fluticasone and salmeterol in separate inhalers (FP+SAL), fluticasone and montelukast (FP+MON), fluticasone alone (FP) and montelukast alone (MON). A 24-month observational retrospective study was conducted using administrative claims data. Subjects were 12 years old with 24 months of continuous enrollment; had 1 asthma claim (ICD-9: 493), 1 short-acting beta(2)-agonist claim, and 1 FSC, FP, SAL, or MON claim. Outcomes included asthma medication refill rates and persistence measured by treatment days. This study was designed with a unique population of patients with asthma from different health plans to validate previous findings. A total of 3,503 subjects were identified based on their index medication: FSC (996), FP+SAL (259), FP+MON (101), FP (1254) and MON (893). Mean number of prescription refills for FSC (3.98) was significantly higher than FP (2.29) and the FP component of FP+SAL (2.36), and FP+MON (2.15), P<0.05. No significant differences were observed between FSC and MON fill rates (4.33). Mean number of treatment days was greater for FSC compared to FP, FP+SAL, and FP+MON (P<0.0001). This study confirms a previous report that adherence profiles of fluticasone and salmeterol in a single inhaler are significantly better when compared to the controller regimens of fluticasone and salmeterol in separate inhalers, fluticasone and montelukast, or fluticasone alone and similar to montelukast alone.

  12. Among once-daily regimens, single tablet regimens (STRs are associated with better adherence

    Directory of Open Access Journals (Sweden)

    R Murri

    2012-11-01

    Full Text Available Previous published evidences showed that taking HAART once-daily (OD is associated to better adherence when compared to BID or TID regimens. However, no further studies investigated whether, among OD regimens, adherence levels can be differently influenced. Aim of the study was to evaluate levels of self-reported adherence in HIV+ people according to type of HAART dosing (STR, OD with more than one pill or BID. To limit reporting biases, the study was performed in five different non-clinic settings covering North and Central Italy. A total of 230 patients on stable HAART were asked to complete a semi-structured, anonymous questionnaire reporting their attitude toward HAART, their adherence and the acceptability of their regimen. Self-perception of adherence was also investigated with a single item for comparison with real adherence behavior. Most of the subjects were males (66% with a mean age of 46 years, with higher education level (72% and a long history of HIV infection (mean 13.6 years. 17% of patients were on a first-line regimen. 21% reported to miss at least one dose during the past week (STR: 6%; OD >1 pill 23% and BID 21%; p<0.05. People taking STR and BID tend to report less discontinuations (all the drug of the day for at least 3 times in a month compared to OD>1 pill (6 and 4% vs 11%. People taking therapies other than HAART reported similar adherence levels of people taking only HAART, even when stratified for dosing groups. Even people judging their adherence as ‘optimal’ or ‘very good’, 10 and 17% respectively, reported having missed a dose during the last week. At stepwise regression model, optimal adherence was correlated to being male (OR: 2.38; 95% CI: 1.19–4.74, younger (OR: 3.04; 95% CI: 1.01–9.13 and with a shorter HIV infection (OR: 3.58; 95% CI: 1.04–12.38. People taking simpler once-daily STR tend to report better adherence than people taking OD>1 pill or BID. Perception of optimal adherence is largely

  13. The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

    Directory of Open Access Journals (Sweden)

    Sonia A Tucci

    2010-05-01

    Full Text Available Sonia A Tucci, Emma J Boyland, Jason CG HalfordKissileff Laboratory for the Study of Human Ingestive Behaviour, School of Psychology, University of Liverpool, Liverpool, UKAbstract: Obesity is a global epidemic associated with significant morbidity and mortality in adults and ill health in children. A proven successful approach in weight management has been the disruption of nutrient digestion, with orlistat having been used to treat obesity for the last 10 years. Although orlistat-induced weight loss remains modest, it produces meaningful reductions in risk factors for obesity-related conditions such as diabetes and cardiovascular disease. Moreover, this lipase inhibitor is free of the serious side effects that have dogged appetite-suppressing drugs. This success had driven investigation into new generation nutraceuticals, supplements and pharmaceutical agents that inhibit the breakdown of complex carbohydrates and fats within the gut. This review focuses on agents purported to inhibit intestinal enzymes responsible for macronutrient digestion. Except for some synthetic products, the majority of agents reviewed are either botanical extracts or bacterial products. Currently, carbohydrate digestion inhibitors are under development to improve glycemic control and these may also induce some weight loss. However, colonic fermentation induced side effects, such as excess gas production, remain an issue for these compounds. The α-glucosidase inhibitor acarbose, and the α-amylase inhibitor phaseolamine, have been used in humans with some promising results relating to weight loss. Nonetheless, few of these agents have made it into clinical studies and without any clinical proof of concept or proven efficacy it is unlikely any will enter the market soon.Keywords: lipase, amylase, saccharidases, overweight, orlistat, Alli®, digestion, body weight

  14. Immediate therapeutic effect of interferential current therapy on spasticity, balance, and gait function in chronic stroke patients: a randomized control trial.

    Science.gov (United States)

    Suh, Hye Rim; Han, Hee Chul; Cho, Hwi-Young

    2014-09-01

    To determine whether a single trial of interferential current therapy (ICT) can immediately alleviate spasticity and improve balance and gait performance in patients with chronic stroke. Randomized, placebo-controlled clinical trial. Inpatient rehabilitation in a local center. A total of 42 adult patients with chronic stroke with plantar flexor spasticity of the lower limb. The ICT group received a single 60-minute ICT stimulation of the gastrocnemius in conjunction with air-pump massage. In the placebo-ICT group, electrodes were placed and air-pump massage performed without electrical stimulation. After a single ICT application, spasticity was measured immediately using the Modified Ashworth Scale (MAS), and balance and functional gait performance were assessed using the following clinical tools: Functional Reach Test (FRT), Berg Balance Scale (BBS), Timed Up and Go Test (TUG), and 10-m Walk Test (10MWT). Gastrocnemius spasticity significantly decreased in the ICT group than in the placebo-ICT group (MAS: ICT vs placebo-ICT: 1.55±0.76 vs 0.40±0.50). The ICT group showed significantly greater improvement in balance and gait abilities than the placebo-ICT group (FRT: 2.62±1.21 vs 0.61±1.34, BBS: 1.75±1.52 vs 0.40±0.88, TUG: 6.07±6.11 vs 1.68±2.39, 10MWT: 7.02±7.02 vs 1.96±3.13). Spasticity correlated significantly with balance and gait abilities (P stroke patients, but not for long-term effects. Further study on the effects of repeated ICT is needed. © The Author(s) 2014.

  15. Novel Kivexa-based regimens in early courses of treatment for HIV infection

    Directory of Open Access Journals (Sweden)

    B Conway

    2012-11-01

    Full Text Available Background: As the long-term efficacy of antiretroviral therapy regimens is confirmed, we need to identify additional combinations with long-term safety and potency, while also favoring simplicity of administration. In this light, we have undertaken a review of the use of abacavir/lamivudine (Kivexa, KVX-based regimens using integrase or CCR5 inhibitors as the third agent. Methods: A retrospective chart review was undertaken, with informed patient consent. We identified all the patients in whom KVX was prescribed (following appropriate HLA-B5701 screening with either raltegravir (RGV or maraviroc (MVC as initial therapy or as a switch from another regimen for reasons other than virologic failure. Virologic efficacy over 48 weeks was evaluated, along with specific drug-associated toxicity, adherence, and regimen modifications. Results: A total of 38 patients (5 women were evaluated, 24 on KVX/RGV, 13 on KVX/MVC, 1 on KVX/RGV/MVC. This was used as initial therapy in drug-naïve subjects in three cases, and was selected as a modification of previous (current or not therapy in 35 cases. Switches included replacement of the third agent with RGV or MVC (n=13, replacement of the NRTI backbone with KVX (n=13 or both. In all cases, the change was implemented to address a current or previous medication-associated toxicity, most commonly to address jaundice (n=8, diarrhea (n=5 or reduced renal function (n=5. Patients were predominantly MSMs (n=17 or IDUs (n=13 with a mean baseline CD4 cell count of 363 cells/mm3, and plasma viral load of 46407 copies/mL (20 with full suppression at time of study entry. At 48 weeks, 34/38 (89% achieved or maintained full suppression, with a mean CD4 count of 553 cells/mm3. Virologic failure with the development of the M184V mutation was observed in 3/4 non-suppressed patients, and a loss of CCR5 tropism and RGV resistance were observed in one case each, all in the context of reduced adherence. There were no treatment

  16. Food allergen selective thermal processing regimens may change oral tolerance in infancy.

    Science.gov (United States)

    Kosti, R I; Triga, M; Tsabouri, S; Priftis, K N

    2013-01-01

    Food allergy can be considered a failure in the induction of oral tolerance. Recently, great interest has been focused on understanding the mechanisms and the contributing factors of oral tolerance development, hoping for new definitive interventions in the prevention and treatment of food allergy. Given that food processing may modify the properties and the nature of dietary proteins, several food processing methods could affect the allergenicity of these proteins and consequently may favour oral tolerance induction to food allergic children. Indeed, effective thermal food processing regimens of altering food proteins to reduce allergenicity have been recently reported in the literature. This article is mainly focused on the effect of selective thermal processing regimens on the main infant allergenic foods, with a potential clinical relevance on their allergenicity and therefore on oral tolerance induction. In the light of recent findings, the acquisition of tolerance in younger age and consequently the ability of young children to "outgrow" food allergy could be achieved through the application of selective thermal processing regimens on certain allergenic foods. Therefore, the ability of processed foods to circumvent clinical disease and at the same time to have an impact on the immune system and facilitate tolerance induction could be invaluable as a component of a successful therapeutic strategy. The opening in the new avenues of research in the use of processed foods in clinical practice for the amelioration of the impact on the quality of life of patients and possibly in food allergy prevention is warranted.

  17. HIV-2 infection, end-stage renal disease and protease inhibitor intolerance: which salvage regimen?

    Science.gov (United States)

    Francisci, Daniela; Martinelli, Laura; Weimer, Liliana E; Zazzi, Maurizio; Floridia, Marco; Masini, Giulia; Baldelli, Franco

    2011-01-01

    Non-nucleoside reverse transcriptase inhibitors and enfuvirtide are ineffective against HIV-2 replication. These considerations may have particular significance in the formulation of second-line or salvage regimens for HIV-2 infection when resistance or toxicity precludes the use of protease inhibitors (PIs) or specific nucleoside analogues. We describe a case of a treatment-experienced patient with important limitations in therapeutic options dictated by the presence of HIV-2 infection, severe HIV nephropathy (requiring haemodialysis), intolerance to PIs and clinical contraindications to the use of some nucleoside analogues (anaemia, pancreatic toxicity and high cardiovascular risk). A three-drug regimen based on raltegravir, tenofovir disoproxil fumarate and lamivudine was given, with no major toxicity, good immunological response and complete viral suppression. Our case indicates that regimens based on integrase inhibitors could represent an effective alternative in PI-resistant or PI-intolerant patients with HIV-2, and that tenofovir disoproxil fumarate may be used in patients with end-stage renal disease requiring haemodialysis who cannot take other nucleoside analogues because of treatment-limiting adverse effects.

  18. TAC-TIC use of tacrolimus-based regimens in lupus nephritis

    Science.gov (United States)

    Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

    2016-01-01

    Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, pstudies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN. PMID:28123768

  19. Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen

    Energy Technology Data Exchange (ETDEWEB)

    Sharabi, Y.; Sachs, D.H.

    1989-02-01

    The use of allogeneic bone marrow transplantation as a means of inducing donor-specific tolerance across MHC barriers could provide an immunologically specific conditioning regimen for organ transplantation. However, a major limitation to this approach is the toxicity of whole body irradiation as currently used to abrogate host resistance and permit marrow engraftment. The present study describes methodology for abrogating host resistance and permitting marrow engraftment without lethal irradiation. Our preparative protocol involves administration of anti-CD4 and anti-CD8 mAbs in vivo, 300-rad WBI, 700-rad thymic irradiation, and unmanipulated fully MHC-disparate bone marrow. B10 mice prepared by this regimen developed stable mixed lymphohematopoetic chimerism without any clinical evidence of graft-vs.-host disease. Engraftment was accompanied by induction of specific tolerance to donor skin grafts (B10.D2), while third-party skin grafts (B10.BR) were promptly rejected. Mice treated with the complete regimen without bone marrow transplantation appeared healthy and enjoyed long-term survival. This study therefore demonstrates that stable mixed chimerism with donor-specific tolerance can be induced across an MHC barrier after a nonlethal preparative regimen, without clinical GVHD and without the risk of aplasia.

  20. Development of symptomatic brain metastases after chemoradiotherapy for stage III non-small cell lung cancer: Does the type of chemotherapy regimen matter?

    NARCIS (Netherlands)

    Hendriks, L.E.; Brouns, A.J.; Amini, M.; Uyterlinde, W.; Wijsman, R.; Bussink, J.; Biesma, B.; Oei, S.B.; Stigt, J.A.; Bootsma, G.P.; Belderbos, J.S.; Ruysscher, D.K. De; Heuvel, M.M. Van den; Dingemans, A.C.

    2016-01-01

    OBJECTIVES: Symptomatic brain metastases (BM) occur frequently after chemoradiotherapy (CRT) for stage III NSCLC. Aim of the current study was to determine whether the specific chemotherapy used in a CRT regimen influences BM development. MATERIALS AND METHODS: Retrospective multicenter study

  1. Radiotherapy of high-grade gliomas:current standards and new concepts, innovations in imaging and radiotherapy, and new therapeutic approaches

    Institute of Scientific and Technical Information of China (English)

    Frederic Dhermain

    2014-01-01

    The current standards in radiotherapy of high-grade gliomas (HGG) are based on anatomic imaging techniques, usually computed tomography (CT) scanning and magnetic resonance imaging (MRI). The guidelines vary depending on whether the HGG is a histological grade 3 anaplastic glioma (AG) or a grade 4 glioblastoma multiforme (GBM). For AG, T2-weighted MRI sequences plus the region of contrast enhancement in T1 are considered for the delineation of the gross tumor volume (GTV), and an isotropic expansion of 15 to 20 mm is recommended for the clinical target volume (CTV). For GBM, the Radiation Therapy Oncology Group favors a two-step technique, with an initial phase (CTV1) including any T2 hyperintensity area (edema) plus a 20 mm margin treated with up to 46 Gy in 23 fractions, followed by a reduction in CTV2 to the contrast enhancement region in T1 with an additional 25 mm margin. The European Organisation of Research and Treatment of Cancer recommends a single-phase technique with a unique GTV, which comprises the T1 contrast enhancement region plus a margin of 20 to 30 mm. A total dose of 60 Gy in 30 fractions is usual y delivered for GBM, and a dose of 59.4 Gy in 33 fractions is typical y given for AG. As more than 85% of HGGs recur in field, dose-escalation studies have shown that 70 to 75 Gy can be delivered in 6 weeks with relevant toxicities developing in60 Gy. Trials delivering a SIB into a biological GTV showed the feasibility of this treatment, but the final results, in terms of clinical benefits for HGG patients, are stil pending. Many issues have been identified: the variety of MRI and PET machines (and amino-acid tracers), the heterogeneity of the protocols used for image acquisition and post-treatment, the geometric distortion and the unreliable algorithms for co-registration of brain anatomy with functional maps, and the semi-quiescent but highly invasive HGG cells. These issues could be solved by the homogenization of the protocols and software

  2. Efficacy of traditional treatment regimen on Kati Shoola with special reference to lumbar spondylolisthesis

    OpenAIRE

    Ediriweera, E. R. H. S. S.; Gunathilka, H. D. P.; Weerasinghe, K. D. C. M.; Kalawana, O. T. M. R. K. S. B.

    2013-01-01

    According to Ayurveda, Kati Shoola is a disease with pain in lumbar region. Lumbar spondylolisthesis, anterior displacement of a vertebra or the vertebral column in relation to the vertebrae below, is one of the common causes. Current case study was carried out at Ayurveda Teaching hospital, Borella, to evaluate the efficacy of a treatment regimen used by Sri Lankan traditional physician family “Weerasinghe.” A 59-year-old female with a 9-month history of lumbar spondylolisthesis was treated ...

  3. New regimens for reducing the duration of the treatment of drug-susceptible pulmonary tuberculosis

    OpenAIRE

    Conde, Marcus B.; Lapa e Silva, José R.

    2011-01-01

    Tuberculosis (TB) remains an important health problem worlwide. The structure necessary for delivering TB treatment and implementing the directly observed treatment accounts for more than two-thirds of its final cost. Furthemore, although with efficacy greater than 90%, the effectiveness of present treatment regimens ranges from 55–85%, depending on the setting, mainly due to poor adherence. Duration of treatment with the current first-line anti-TB drugs is a minimum of 6 months. Reducing the...

  4. Hybrid Therapy Regimen for Helicobacter Pylori Eradication

    Institute of Scientific and Technical Information of China (English)

    Zhi-Qiang Song; Jian Liu; Li-Ya Zhou

    2016-01-01

    Objective:Helicobacterpylori (H.pylori) eradication remains a challenge with increasing antibiotic resistance.Hybrid therapy has attracted widespread attention because of initial report with good efficacy and safety.However,many issues on hybrid therapy are still unclear such as the eradication efficacy,safety,compliance,influencing factors,correlation with antibiotic resistance,and comparison with other regimens.Therefore,a comprehensive review on the evidence of hybrid therapy for H.pylori infection was conducted.Data Sources:The data used in this review were mainly from PubMed articles published in English up to September 30,2015,searching by the terms of"Helicobacterpylori" or "H.pylori",and "hybrid".Study Selection:Clinical research articles were selected mainly according to their level of relevance to this topic.Results:Totally,1871 patients of 12 studies received hybrid therapy.The eradication rates were 77.6-97.4% in intention-to-treat and 82.6-99.1% in per-protocol analyses.Compliance was 93.3-100.0%,overall adverse effects rate was 14.5-67.5%,and discontinued medication rate due to adverse effects was 0-6.7%.H.pylori culture and sensitivity test were performed only in 13.3% patients.Pooled analysis showed that the eradication rates with dual clarithromycin and metronidazole susceptible,isolated metronidazole or clarithromycin resistance,and dual clarithromycin and metronidazole resistance were 98.5%,97.6%,92.9%,and 80.0%,respectively.Overall,the efficacy,compliance,and safety of hybrid therapy were similar with sequential or concomitant therapy.However,hybrid therapy might be superior to sequential therapy in Asians.Conclusions:Hybrid therapy showed wide differences in the efficacy but consistently good compliance and safety across different regions.Dual clarithromycin and metronidazole resistance were the key factor to efficacy.Hybrid therapy was similar to sequential or concomitant therapy in the efficacy,safety,and compliance.

  5. Adherence in HIV-positive patients treated with single-tablet regimens and multi-pill regimens: findings from the COMPACT study

    Directory of Open Access Journals (Sweden)

    A Antinori

    2012-11-01

    on STR, 78% PI, 88% NNRTI, 87% RAL. Interruptions in cART refill remain a relevant problem across all cART regimens. Patients on STR displayed a higher adherence rate compared to multi-pill regimes (PI, NNRTI, and RAL, primarily due to lack of selective non-adherence. Patients on STR experienced also higher rates of VL < 50 and CD4 > 500. The use of an STR regimen appears an effective therapeutic option to avoid selective non-adherence and, consequently, to prevent virological failure and disease progression.

  6. A comparison of reactivating and therapeutic efficacy of the oxime K203 and its fluorinated analog (KR-22836) with currently available oximes (obidoxime, trimedoxime, HI-6) against tabun in rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Caisberger, Filip; Musilek, Kamil; Kuca, Kamil; Jung, Young-Sik

    2010-08-01

    The potency of newly developed bispyridinium compound K203 and its fluorinated analog KR-22836 in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determining the percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in rats showed that the reactivating efficacy of K203 is higher than the reactivating efficacy of its fluorinated analog KR-22836 as well as currently available oximes studied. The therapeutic efficacy of the oxime K203 and its fluorinated analog corresponds to their potency to reactivate tabun-inhibited acetylcholinesterase. According to the results, the oxime K203 is more suitable than KR-22836 for the replacement of commonly used oximes for the antidotal treatment of acute tabun poisoning due to its relatively high potency to counteract the acute toxicity of tabun.

  7. Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

    DEFF Research Database (Denmark)

    Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    PURPOSE: The present work focuses on the in vivo evaluation of tamoxifen and quercetin combination loaded into solid self-nanoemulsifying drug delivery system (s-Tmx-QT-SNEDDS). METHODS: Lyophilization was employed to prepare s-Tmx-QT-SNEDDS using Aerosil 200 as carrier. The developed formulation...

  8. Improved Therapeutic Regimens for Treatment of Post-Traumatic Ocular Infections

    Science.gov (United States)

    2011-05-01

    619-626, 1991. MORáN F41. J, PUENTE LF, PéREZ-GIRALDO C, BLANCO MT, HURTADO C, GóMEZ- GARCíA AC. Activity of vancomycin and teicoplanin against human...evaluation and management. Retina 27, 662–680 (2007). 52 García-Sáenz MC, Arias- Puente A, Rodríguez-Caravaca G, Bañuelos JB. Effectiveness of

  9. Clinical applications of therapeutic phlebotomy.

    Science.gov (United States)

    Kim, Kyung Hee; Oh, Ki Young

    2016-01-01

    Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program.

  10. Therapeutic ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Crum, Lawrence A [Center for Industrial and Medical Ultrasound, 1013 NE 40th Street, University of Washington, Seattle, WA 98105 (United States)

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  11. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Science.gov (United States)

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  12. What to Start: Selecting a First HIV Regimen

    Science.gov (United States)

    HIV Treatment What to Start: Choosing an HIV Regimen (Last updated 2/24/2016; last reviewed 2/24/ ... of HIV medicines used to treat HIV infection. HIV treatment (also called antiretroviral therapy or ART) begins with ...

  13. Comparison of MACT and 5Fu+ACT-D chemotherapy regimens in the treatment of low-risk gestational trophoblastic neoplasia.

    Science.gov (United States)

    Wang, Yu; Miao, Jin-Wei; Wang, Tong; Wang, Yan; Wu, Yu-Mei; Kong, Wei-Min; Su, Li; Duan, Wei

    2016-04-01

    The study aimed to compare the efficacy of methotrexate (MTX) cervical injections + actinomycin-D (ACT-D)(MACT) and 5-fluorouracil (5-Fu) + actinomycin-D (5-Fu plus ACT-D) chemotherapy regimens for low-risk gestational trophoblastic neoplasia (LR-GTN). Clinical data from 66 LR-GTN patients, admitted to the Beijing Obstetrics and Gynecology Hospital from January 2010 to April 2012, were analysed retrospectively. In total, 32 patients were treated with a MACT therapeutic regimen and the remaining 34 with a 5Fu + ACT-D therapeutic regimen. Complete remission rates (CR), duration of treatment, hospital stay and toxicity effects were compared. There was no statistical difference in CR for the MACT (90.63%) or the 5-Fu plus ACT-D (100%) therapeutic regimens (p = 0.0676) or in the duration of treatment [MACT (3.50) or 5-Fu plus ACT-D (3.71; p = 0.2021)]. Moreover, the hospital stay in the 5-Fu plus ACT-D group (32.88 days) was significantly longer than for the MACT group (22.09 days; p < 0.001). Furthermore, the degree of myelosuppression, nausea and vomiting, diarrhoea, stomatitis and alopecia was more severe in the 5Fu + ACT-D group (p < 0.01). However, there was no statistical difference in the severity of liver function damage between the two groups. A shorter hospital stay, lower hospitalization cost and slightly more toxic effects were observed in LR-GTN patients treated with the MACT therapeutic regimen. We suggest that the MACT regimen should be used as first-line chemotherapy for LR-GTN.

  14. Economic evaluation of 3-drug antiretroviral regimens for the prevention of mother-to-child HIV transmission in Thailand.

    Science.gov (United States)

    Werayingyong, Pitsaphun; Phanuphak, Nittaya; Chokephaibulkit, Kulkunya; Tantivess, Sripen; Kullert, Nareeluk; Tosanguan, Kakanang; Butchon, Rukmanee; Voramongkol, Nipunporn; Boonsuk, Sarawut; Pilasant, Songyot; Kulpeng, Wantanee; Teerawattananon, Yot

    2015-03-01

    The current program for prevention of mother-to-child HIV transmission in Thailand recommends a 2-drugs regimen for HIV-infected pregnant women with a CD4 count >200 cells/mm(3). This study assesses the value for money of 3 antiretroviral drugs compared with zidovudine (AZT)+single-dose nevirapine (sd-NVP). A decision tree was constructed to predict costs and outcomes using the governmental perspective for assessing cost-effectiveness of 3-drug regimens: (1) AZT, lamivudine, and efavirenz and (2) AZT, 3TC, and lopinavir/ritonavir, in comparison with the current protocol, AZT+sd-NVP. The 3-drug antiretroviral regimens yield lower costs and better health outcomes compared with AZT+sd-NVP. Although these 3-drug regimens offer higher program costs and health care costs for premature birth, they save money significantly in regard to pediatric HIV treatment and treatment costs for drug resistance in mothers. The 3-drug regimens are cost-saving interventions. The findings from this study were used to support a policy change in the national recommendation. © 2013 APJPH.

  15. Bacteriophage Procurement for Therapeutic Purposes.

    Science.gov (United States)

    Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

    2016-01-01

    Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented.

  16. [Current therapeutic indications of thalidomide and lenalidomide].

    Science.gov (United States)

    Ordi-Ros, Josep; Cosiglio, Francisco Javier

    2014-04-22

    Thalidomide is a synthetic glutamic acid derivative first introduced in 1956 in Germany as an over the counter medications. It was thought to be one of the safest sedatives ever produced as it was effective in small doses, was not addictive, and did not have acute side-effects such as motor impairment, but was quickly removed from market after it was linked to cases of severe birth defects. The Food and Drug Administration approved use in the treatment of erythema nodosum leprosum. Further, it was shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell hystiocytosis, aphthous stomatitis, Behçet syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and others. In May 2006, it was approved for the treating multiple myeloma. New thalidomide analogues have been developed but lack clinical experience. This paper is a review of the history, pharmacology, mechanism of action, clinical applications and side effects of thalidomide and its analogues.

  17. Nanomedicines as cancer therapeutics: Current status

    NARCIS (Netherlands)

    Akhter, S.; Ahmad, M; Ramzani, F.; Singh, A..; Ahmad, I.; Rahman, Z.; Ahmad, F.J.; Storm, G.; Kok, R.J.

    2013-01-01

    As of 21st century, cancer is arguably the most complex and challenging disease known to mankind and an inevitable public health concern of this millennium. Nanotechnology, suitably amalgamated with cancer research, has ushered an era of highly personalized and safer medicines which can improve canc

  18. Current therapeutic approaches for plantar fasciitis

    Directory of Open Access Journals (Sweden)

    Martinelli N

    2014-03-01

    Full Text Available Nicolò Martinelli, Carlo Bonifacini, Giovanni RomeoDepartment of Ankle and Foot Surgery, IRCCS Galeazzi Orthopaedic Institute, Milan, ItalyAbstract: Almost 1 million Americans are affected by plantar fasciitis (PF, which is the commonest cause of chronic heel pain. This condition is often managed conservatively, and many rehabilitation protocols, some with the aid of orthoses, have been adopted, with good-to-excellent clinical results. Although most cases of chronic PF can be successfully managed with a conservative approach, alternative treatments, including high-energy shock wave therapy and corticosteroid injections, are commonly accepted as second-line treatment when traditional conservative therapy fails. However, surgery is still an important mode of treatment. Recently, new minimally invasive surgical techniques that offer numerous advantages (faster recovery time, early weight-bearing, lower postoperative pain over standard surgical approaches have been proposed, with good results and low complication rates. The purpose of this review is to report new conservative and surgical techniques for the treatment of PF. A literature search for articles about plantar fasciitis was conducted on the PubMed database in order to identify publications addressing the treatments of PF. The literature suggests that, initially, traditional conservative treatments consisting of rest, oral nonsteroidal anti-inflammatory drugs, foot orthotics, and stretching exercises can be tried for several weeks. In patients with chronic recalcitrant PF, extracorporeal shock wave therapy or corticosteroid injection can be considered. Surgery (minimally invasive techniques should be considered only after failure of the conservative treatments.Keywords: heel pain, surgery, plantar fasciosis

  19. Current therapeutic approaches for plantar fasciitis

    OpenAIRE

    Martinelli N; Bonifacini C; Romeo G

    2014-01-01

    Nicolò Martinelli, Carlo Bonifacini, Giovanni RomeoDepartment of Ankle and Foot Surgery, IRCCS Galeazzi Orthopaedic Institute, Milan, ItalyAbstract: Almost 1 million Americans are affected by plantar fasciitis (PF), which is the commonest cause of chronic heel pain. This condition is often managed conservatively, and many rehabilitation protocols, some with the aid of orthoses, have been adopted, with good-to-excellent clinical results. Although most cases of chronic PF can be succ...

  20. Current guidelines in defining therapeutic strategies.

    Science.gov (United States)

    Ferrajoli, Alessandra; Keating, Michael J

    2004-08-01

    The past three decades have brought major changes in the approach toward chronic lymphocytic leukemia (CLL). This disease was considered a simple form of leukemia for which the only goal of treatment was control of the leukocytosis and of the symptoms related to disease expansion. Many biologic discoveries have increased our understanding of the disease process. New prognostic markers have been identified and are being incorporated into clinical practice. Now, CLL is considered a complex and challenging leukemia for which multiple treatment options are emerging, from chemotherapy to monoclonal antibodies, from vaccines to immunomodulatory strategies. The evaluation of treatment results also has been revolutionized: clones carrying genetic aberrations are monitored, and patients who have had a response are assessed for the presence of minimal residual disease.

  1. Lagophthalmos after facial palsy: current therapeutic options.

    Science.gov (United States)

    Vásquez, Luz María; Medel, Ramón

    2014-01-01

    As the facial nerve carries sensory, motor and parasympathetic fibres involved in facial muscle innervation, facial palsy results in functional and cosmetic impairment. It can result from a wide variety of causes like infectious processes, trauma, neoplasms, autoimmune diseases, and most commonly Bell's palsy, but it can also be of iatrogenic origin. The main ophthalmic sequel is lagophthalmos. The increased surface exposure increases the risk of keratitis, corneal ulceration, and potentially loss of vision. Treatment options are wide; some are temporary, some permanent. In addition to gold standard and traditional therapies and procedures, new options are being proposed aiming to improve not only lagophthalmos but also the quality of life of these patients. © 2014 S. Karger AG, Basel.

  2. [Combined treatment: regimens, indications and safety profile].

    Science.gov (United States)

    Muñiz Grijalvo, Ovidio; Villar Ortiz, Jose

    2013-01-01

    Statins are the current basis of lipid-lowering therapy, despite which may have limitations on efficacy and safety. In high risk patients who do not achieve current lipid goals, in those intolerant to statins or those with atherogenic dyslipidemia, it is possible combine two or more lipid lowering drugs, including statins, ezetimibe, bile acid sequestrants, fibrates, niacin and prescription omega-3 fatty acids. However, for most of these combination therapies pivotal data on clinical outcomes are still lacking. Copyright © 2013 Elsevier España, S.L. and SEA. All rights reserved.

  3. Review of therapeutic agents for burns pruritus and protocols for management in adult and paediatric patients using the GRADE classification

    Directory of Open Access Journals (Sweden)

    Goutos Ioannis

    2010-10-01

    Full Text Available To review the current evidence on therapeutic agents for burns pruritus and use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE classification to propose therapeutic protocols for adult and paediatric patients. All published interventions for burns pruritus were analysed by a multidisciplinary panel of burns specialists following the GRADE classification to rate individual agents. Following the collation of results and panel discussion, consensus protocols are presented. Twenty-three studies appraising therapeutic agents in the burns literature were identified. The majority of these studies (16 out of 23 are of an observational nature, making an evidence-based approach to defining optimal therapy not feasible. Our multidisciplinary approach employing the GRADE classification recommends the use of antihistamines (cetirizine and cimetidine and gabapentin as the first-line pharmacological agents for both adult and paediatric patients. Ondansetron and loratadine are the second-line medications in our protocols. We additionally recommend a variety of non-pharmacological adjuncts for the perusal of clinicians in order to maximise symptomatic relief in patients troubled with postburn itch. Most studies in the subject area lack sufficient statistical power to dictate a ′gold standard′ treatment agent for burns itch. We encourage clinicians to employ the GRADE system in order to delineate the most appropriate therapeutic approach for burns pruritus until further research elucidates the most efficacious interventions. This widely adopted classification empowers burns clinicians to tailor therapeutic regimens according to current evidence, patient values, risks and resource considerations in different medical environments.

  4. Reappraisal of the therapeutic role of celecoxib in cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Chun-Nan Yeh

    Full Text Available Cholangiocarcinoma (CCA, a lethal disease, affects many thousands worldwide yearly. Surgical resection provides the best chance for a cure; however, only one-third of CCA patients present with a resectable tumour at the time of diagnosis. Currently, no effective chemotherapy is available for advanced CCA. Cyclooxygenase-2 (COX-2 is a potential oncogene expressing in human CCA tissues and represents a candidate target for treatment; however, COX-2 inhibitors increase the risk of negative cardiovascular events as application for chemoprevention aim. Here, we re-evaluated the effectiveness and safety of celecoxib, one widely used COX-2 inhibitor, in treating CCA. We demonstrated that celecoxib exhibited an anti-proliferative effect on CGCCA cells via cell cycle arrest at G2 phase and apoptosis induction. Treatment for 5 weeks high dose celecoxib (160 mg/kg significantly repressed thioacetamide-induced CCA tumour growth in rats as monitored by animal positron emission tomography through apoptosis induction. No obviously observable side effects were noted during the therapeutic period. As retrospectively reviewing 78 intrahepatic mass-forming CCA patients, their survival was strongly and negatively associated with a positive resection margin and high COX-2 expression. Based on our result, we concluded that short-term high dose celecoxib may be a promising therapeutic regimen for CCA. Yet its clinical application still needs more studies to prove its safety.

  5. Metformin: A Potential Therapeutic Agent for Recurrent Colon Cancer

    Science.gov (United States)

    Nangia-Makker, Pratima; Yu, Yingjie; Vasudevan, Anita; Farhana, Lulu; Rajendra, Sindhu G.; Levi, Edi; Majumdar, Adhip P. N.

    2014-01-01

    Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties. However, most of the studies to evaluate therapeutic efficacy of metformin have been on primary cancer. No information is available whether metformin could be effectively used for recurrent cancer, specifically colorectal cancer (CRC) that affects up to 50% of patients treated by conventional chemotherapies. Although the reasons for recurrence are not fully understood, it is thought to be due to re-emergence of chemotherapy-resistant cancer stem/stem-like cells (CSCs/CSLCs). Therefore, development of non-toxic treatment strategies targeting CSCs would be of significant therapeutic benefit. In the current investigation, we have examined the effectiveness of metformin, in combination with 5-fluorouracil and oxaliplatin (FuOx), the mainstay of colon cancer therapeutics, on survival of chemo-resistant colon cancer cells that are highly enriched in CSCs/CSLCs. Our data show that metformin acts synergistically with FuOx to (a) induce cell death in chemo resistant (CR) HT-29 and HCT-116 colon cancer cells, (b) inhibit colonospheres formation and (c) enhance colonospheres disintegration. In vitro cell culture studies have further demonstrated that the combinatorial treatment inhibits migration of CR colon cancer cells. These changes were associated with increased miRNA 145 and reduction in miRNA 21. Wnt/β-catenin signaling pathway was also down-regulated indicating its pivotal role in regulating the growth of CR colon cancer cells. Data from SCID mice xenograft model of CR HCT-116 and CR HT-29 cells show that the combination of metformin and FuOX is highly effective in inhibiting the growth of colon tumors as evidenced by ∼50% inhibition in growth following 5 weeks of combination treatment, when compared with the vehicle treated controls. Our current data suggest that metformin together with conventional chemotherapy could be an effective treatment

  6. Metformin: a potential therapeutic agent for recurrent colon cancer.

    Directory of Open Access Journals (Sweden)

    Pratima Nangia-Makker

    Full Text Available Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties. However, most of the studies to evaluate therapeutic efficacy of metformin have been on primary cancer. No information is available whether metformin could be effectively used for recurrent cancer, specifically colorectal cancer (CRC that affects up to 50% of patients treated by conventional chemotherapies. Although the reasons for recurrence are not fully understood, it is thought to be due to re-emergence of chemotherapy-resistant cancer stem/stem-like cells (CSCs/CSLCs. Therefore, development of non-toxic treatment strategies targeting CSCs would be of significant therapeutic benefit. In the current investigation, we have examined the effectiveness of metformin, in combination with 5-fluorouracil and oxaliplatin (FuOx, the mainstay of colon cancer therapeutics, on survival of chemo-resistant colon cancer cells that are highly enriched in CSCs/CSLCs. Our data show that metformin acts synergistically with FuOx to (a induce cell death in chemo resistant (CR HT-29 and HCT-116 colon cancer cells, (b inhibit colonospheres formation and (c enhance colonospheres disintegration. In vitro cell culture studies have further demonstrated that the combinatorial treatment inhibits migration of CR colon cancer cells. These changes were associated with increased miRNA 145 and reduction in miRNA 21. Wnt/β-catenin signaling pathway was also down-regulated indicating its pivotal role in regulating the growth of CR colon cancer cells. Data from SCID mice xenograft model of CR HCT-116 and CR HT-29 cells show that the combination of metformin and FuOX is highly effective in inhibiting the growth of colon tumors as evidenced by ∼ 50% inhibition in growth following 5 weeks of combination treatment, when compared with the vehicle treated controls. Our current data suggest that metformin together with conventional chemotherapy could be an

  7. Editorial: advances in therapeutic glycopeptides.

    Science.gov (United States)

    Zeng, Wenbin; Chen, Yue-Lei

    2014-01-01

    Glycopeptides, peptides containing sugar β-amino acids, have significant impact on medicinal chemistry research and pharmaceutical industr. In 1956, the discovery of one classic glycopeptide, vancomycin, broke the dawn of a new age for antibacterial research. Employing glycopeptides for the therapeutic purposes used to be regarded as proposals. Owing largely to the recent improvements in separation practices, characterization techniques, synthetic methods, and biological research, these proposals have been transformed into ongoing research projects in many laboratories around the world. Previously known as antibiotics, glycopeptides have been used as chemotherapeutic, antiviral, antitubercular, antifungal, antiproliferative and apoptotic agents. Nowadays they are even considered for the development of HIV and cancer vaccines. While several of them are in clinical trials, it could be expected that in the near future, treatment regimen of such difficult diseases might be reformed accordingly. Many interesting preliminary results are being produced in this emerging area. As witnesses and practitioners in this exciting area, however, we notice that the related communication in public domain is still limited due to the relatively small number of researchers involved. Thus, we feel the necessity to compile a timely issue about the special topic "Advances in Therapeutic Glycopeptides", covering state-of-the-art research papers and expert reviews from this area. We are glad that Protein & Peptide Letters is willing to realize the idea with us. The opening paper of this issue by Dr. Voglmeir and coauthor discusses three types of PNGases in respect of their general properties and applications of the commercially available PNGases in glycopeptide and glycoprotein analysis. Dr. Liu and coauthors describe current techniques such as high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and mass spectrometry (MS), for the characterization of

  8. Therapeutic drug monitoring in neonates.

    Science.gov (United States)

    Pauwels, Steven; Allegaert, Karel

    2016-04-01

    Therapeutic drug monitoring (TDM) aims to integrate drug measurement results into clinical decision making. The basic rules apply when using TDM in neonates (aminoglycosides, vancomycin, phenobarbital, digoxin), but additional factors should also be taken into account. First, due to both pharmacokinetic variability and non-pharmacokinetic factors, the correlation between dosage and concentration is poor in neonates, but can be overcome with the use of more complex, validated dosing regimens. Second, the time to reach steady state is prolonged, especially when no loading dose is used. Consequently, the timing of TDM sampling is important in this population. Third, the target concentration may be uncertain (vancomycin) or depend on specific factors (phenobarbital during whole body cooling). Finally, because of differences in matrix composition (eg, protein, bilirubin), assay-related inaccuracies may be different in neonates. We anticipate that complex validated dosing regimens, with subsequent TDM sampling and Bayesian forecasting, are the next step in tailoring pharmacotherapy to individual neonates. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. The Technique, Resources and Costs of Stereotactic Body Radiotherapy of Prostate Cancer: A Comparison of Dose Regimens and Delivery Systems.

    Science.gov (United States)

    Sharieff, Waseem; Greenspoon, Jeffrey N; Dayes, Ian; Chow, Tom; Wright, James; Lukka, Himu

    2016-02-01

    Robotic system has been used for stereotactic body radiotherapy (SBRT) of prostate cancer. Arc-based and fixed-gantry systems are used for hypofractionated regimens (10-20 fractions) and the standard regimen (39 fractions); they may also be used to deliver SBRT. Studies are currently underway to compare efficacy and safety of these systems and regimens. Thus, we describe the technique and required resources for the provision of robotic SBRT in relation to the standard regimen and other systems to guide investment decisions. Using administrative data of resource volumes and unit prices, we computed the cost per patient, cost per cure and cost per quality adjusted life year (QALY) of four regimens (5, 12, 20 and 39 fractions) and three delivery systems (robotic, arc-based and fixed-gantry) from a payer's perspective. We performed sensitivity analyses to examine the effects of daily hours of operation and in-room treatment delivery times on cost per patient. In addition, we estimated the budget impact when a robotic system is preferred over an arc-based or fixed-gantry system. Costs of SBRT were $6333/patient (robotic), $4368/patient (arc-based) and $4443/patient (fixed-gantry). When daily hours of operation were varied, the cost of robotic SBRT varied from $9324/patient (2 hours daily) to $5250/patient (10 hours daily). This was comparable to the costs of 39 fraction standard regimen which were $5935/patient (arc-based) and $7992/ patient (fixed-gantry). In settings of moderate to high patient volume, robotic SBRT is cost effective compared to the standard regimen. If SBRT can be delivered with equivalent efficacy and safety, the arc-based system would be the most cost effective system.

  10. Reasons and Risk Factors for the Initial Regimen Modification in Chinese Treatment-Naive Patients with HIV Infection: A Retrospective Cohort Analysis.

    Directory of Open Access Journals (Sweden)

    Jianjun Sun

    Full Text Available To investigate the reasons and risk factors for modification of the first combined antiretroviral therapy (cART currently used for HIV infected patients who were treatment naïve in Shanghai China.Making a retrospective observational research on treatment naïve patients with HIV infection who initiated cART during the period of September 1st 2005---December 1st 2013. The demographic and clinical data were collected from the first visit to the time of the first regimen modification or the last visit in December 1st, 2014. The reasons of treatment modification were recorded. Survival analysis of modification was made by Kaplan-Meier curves analysis and log rank test, and a Cox multiple regression model was constructed to identify related factors of modification.A total number of the eligible participants were 3372 and 871(25.8% patients changed their first cART regimen. The median follow up was 22 months [interquartile range (IQR 14-39]. Among patients who modified the original regimen, drug toxicity occurred in 805(92.4% participants and 44(5.1% experienced treatment failure. In multiple regression analysis regimen modification was associated with patients' age more than 40 years old (aHR 1.224, 95%CI 1.051-1.426, P = 0.010, CD4 less than 200(aHR 1.218, 95%CI 1.044-1.421, P = 0.012 and the initial regimen they received. Compared with the regimen of TDF+3TC+EFV, patients with regimen of d4T+3TC+NVP, d4T+3TC+EFV, AZT+3TC+NVP or AZT+3TC+EFV were 10.4, 8.2, 6.4, 2.5 times more likely to modify their initial regimen, respectively.The main reason for the regimen switch was drug toxicity and main risk factors for regimen modification were age older than 40 years, CD4 cell counts less than 200 at baseline and regimen they received. Among the 2NRTI plus 1NNRTI regimens, the co-formulation of d4T+3TC+NVP had the highest risk for modification while the regimen of TDF+3TC+EFV was the most tolerable treatment regimen in first years' follow up.

  11. Hypofractionation regimens for stereotactic radiotherapy for large brain tumors.

    Science.gov (United States)

    Yuan, Jiankui; Wang, Jian Z; Lo, Simon; Grecula, John C; Ammirati, Mario; Montebello, Joseph F; Zhang, Hualin; Gupta, Nilendu; Yuh, William T C; Mayr, Nina A

    2008-10-01

    To investigate equivalent regimens for hypofractionated stereotactic radiotherapy (HSRT) for brain tumor treatment and to provide dose-escalation guidance to maximize the tumor control within the normal brain tolerance. The linear-quadratic model, including the effect of nonuniform dose distributions, was used to evaluate the HSRT regimens. The alpha/beta ratio was estimated using the Gammaknife stereotactic radiosurgery (GKSRS) and whole-brain radiotherapy experience for large brain tumors. The HSRT regimens were derived using two methods: (1) an equivalent tumor control approach, which matches the whole-brain radiotherapy experience for many fractions and merges it with the GKSRS data for few fractions; and (2) a normal-tissue tolerance approach, which takes advantages of the dose conformity and fractionation of HSRT to approach the maximal dose tolerance of the normal brain. A plausible alpha/beta ratio of 12 Gy for brain tumor and a volume parameter n of 0.23 for normal brain were derived from the GKSRS and whole-brain radiotherapy data. The HSRT prescription regimens for the isoeffect of tumor irradiation were calculated. The normal-brain equivalent uniform dose decreased as the number of fractions increased, because of the advantage of fractionation. The regimens for potential dose escalation of HSRT within the limits of normal-brain tolerance were derived. The designed hypofractionated regimens could be used as a preliminary guide for HSRT dose prescription for large brain tumors to mimic the GKSRS experience and for dose escalation trials. Clinical studies are necessary to further tune the model parameters and validate these regimens.

  12. Front-loaded linezolid regimens result in increased killing and suppression of the accessory gene regulator system of Staphylococcus aureus.

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    Tsuji, Brian T; Brown, Tanya; Parasrampuria, Ridhi; Brazeau, Daniel A; Forrest, Alan; Kelchlin, Pamela A; Holden, Patricia N; Peloquin, Charles A; Hanna, Debra; Bulitta, Jurgen B

    2012-07-01

    Front loading is a strategy used to optimize the pharmacodynamic profile of an antibiotic through the administration of high doses early in therapy for a short duration. Our aims were to evaluate the impact of front loading of linezolid regimens on bacterial killing and suppression of resistance and on RNAIII, the effector molecule of the accessory gene regulator system (encoded by agr) in methicillin-resistant Staphylococcus aureus (MRSA). Time-killing experiments over 48 h were utilized for linezolid against four strains of MRSA: USA100, USA300, USA400, and ATCC 29213. A hollow-fiber infection model simulated traditional and front-loaded human therapeutic regimens of linezolid versus USA300 at 10(6) CFU/ml over 240 h. Over 48 h in time-kill experiments, linezolid displayed bacteriostatic activity, with reductions of >1 log(10) CFU/ml for all strains. Front-loaded regimens that were administered over 5 days, 1,200 mg every 12 h (q12h) (total, 10 doses) and 2,400 mg q12h (total, 10 doses) followed by 300 mg q12h thereafter, resulted in sustained bactericidal activity, with reductions of the area under the CFU curve of -6.15 and -6.03, respectively, reaching undetectable limits at the 10-day study endpoint. All regimens displayed a reduction in RNAIII relative expression at 24 h and 240 h compared with that of the growth control. Monte Carlo simulations predicted a infections, where early aggressive therapy is necessary.

  13. Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB.

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    Tiberi, Simon; Payen, Marie-Christine; Sotgiu, Giovanni; D'Ambrosio, Lia; Alarcon Guizado, Valentina; Alffenaar, Jan Willem; Abdo Arbex, Marcos; Caminero, Jose A; Centis, Rosella; De Lorenzo, Saverio; Gaga, Mina; Gualano, Gina; Roby Arias, Aurora Jazmín; Scardigli, Anna; Skrahina, Alena; Solovic, Ivan; Sulis, Giorgia; Tadolini, Marina; Akkerman, Onno W; Alarcon Arrascue, Edith; Aleska, Alena; Avchinko, Vera; Bonini, Eduardo Henrique; Chong Marín, Félix Antonio; Collahuazo López, Lorena; de Vries, Gerard; Dore, Simone; Kunst, Heinke; Matteelli, Alberto; Moschos, Charalampos; Palmieri, Fabrizio; Papavasileiou, Apostolos; Spanevello, Antonio; Vargas Vasquez, Dante; Viggiani, Pietro; White, Veronica; Zumla, Alimuddin; Migliori, Giovanni Battista

    2016-04-01

    No large study has ever evaluated the efficacy, safety and tolerability of meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR- and XDR-TB cases.Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, pMDR-TB cohort and in the subgroups with and without the XDR-TB patients; in particular, sputum smear and culture conversion rates were similar in XDR-TB patients exposed to meropenem/clavulanate-containing regimens (88.0% versus 100.0%, p=1.00 and 88.0% versus 100.0%, p=1.00, respectively). Only six cases reported adverse events attributable to meropenem/clavulanate (four of them then restarting treatment).The nondifferent outcomes and bacteriological conversion rate observed in cases who were more severe than controls might imply that meropenem/clavulanate could be active in treating MDR- and XDR-TB cases.

  14. Rethinking therapeutic action.

    Science.gov (United States)

    Gabbard, Glen O; Westen, Drew

    2003-08-01

    Like other core psychoanalytic constructs, the theory of therapeutic action is currently in flux, as theorists of differing persuasions propose different mechanisms. In this article, the authors attempt to integrate developments within and without psychoanalysis to provide a working model of the multifaceted processes involved in producing change in psychoanalysis and psychoanalytic psychotherapy. A theory of therapeutic action must describe both what changes (the aims of treatment) and what strategies are likely to be useful in facilitating those changes (technique). The authors believe that single-mechanism theories of therapeutic action, no matter how complex, are unlikely to prove useful at this point because of the variety of targets of change and the variety of methods useful in effecting change in those targets (such as techniques aimed at altering different kinds of conscious and unconscious processes). Interventions that facilitate change may be classified into one of three categories: those that foster insight, those that make use of various mutative aspects of the treatment relationship and a variety of secondary strategies that can be of tremendous importance. They propose that, in all forms of psychoanalytic treatment, we would be more accurate to speak of the therapeutic actions, rather than action.

  15. Analysis of Efficacy of DICE (Dexamethasone, Ifosfamide,Cisplatin and Etoposide) Regimen on Recurrent and Refractory Intermediate and High Grade Non-Hodgkin's Lymphoma

    Institute of Scientific and Technical Information of China (English)

    Lei Yang; Zhucheng Song; Xiaohong Xu; Jinzhi Wei; Qinghe Tan; Zhirong Cong; Chunlei Peng

    2009-01-01

    OBJECTIVE Thus far there is no standard salvage regimen for patients with recurrent and refractory intermediate and high grade non-Hodgkin's lymphoma (NHL). This study intends to investigate the therapeutic efficacy of the DICE (dexamethasone, isofosfamide, cisplatin and etoposide) regimen on the recurrent and refractory NHL, and to observe the related adverse effects. METHODS Clinical records of 22 patients with recurrent and refractory NHL, who failed to achieve a remission from the CHOP [cyclophosphamide, hydroxydaunomycin/doxorubicin (adriamycin), oncovin, prednisone] regimen within 2 to 6 cycles of treatment, were reviewed. DICE, as a salvage regimen with a median course of treatment of 4 cycles (ranging from 2 to 7 cycles), was now used, and evaluation of the therapeutic efficacy and adverse effect of DICE was conducted in all the patients. Of the 22 NHL cases, 8 were of T-cell origin and the other 14 B-cell origin. Salvage treatment was performed in the patients, with appraisal, prevention and treatment of the toxic reactions. RESULTS Following DICE treatment in the 22 patients, the total effective rate of the regimen was 63.6%, and the complete remission (CR) rate was 40.9%. The effective rates of DICE on the T and B-cell sourced NHL were 75.0% and 57.1%, and the CR rate were 37.5%, 42.9%, respectively (P > 0.05). An increase of the lactate dehydrogenase (LDH) level accompanied by a giant lump was the short-term effect on patients with recurrence (mean P < 0.05) who were drug resistant. Myelosuppression, digestive system reaction and alopecia were the commonly-seen complications in the patients who Received DICE regimen. All patients recovered after treatment, and no chemotherapy-related death occurred. CONCLUSION DICE regimen is effective in treating refractory and recurrent NHL.

  16. Oxytocin regimen for labor augmentation, labor progression, and perinatal outcomes.

    Science.gov (United States)

    Zhang, Jun; Branch, D Ware; Ramirez, Mildred M; Laughon, S Katherine; Reddy, Uma; Hoffman, Mathew; Bailit, Jennifer; Kominiarek, Michelle; Chen, Zhen; Hibbard, Judith U

    2011-08-01

    To examine the effects and safety of high-dose (compared with low-dose) oxytocin regimen for labor augmentation on perinatal outcomes. Data from the Consortium on Safe Labor were used. A total of 15,054 women from six hospitals were eligible for the analysis. Women were grouped based on their oxytocin starting dose and incremental dosing of 1, 2, and 4 milliunits/min. Duration of labor and a number of maternal and neonatal outcomes were compared among these three groups stratified by parity. Multivariable logistic regression and generalized linear mixed model were used to adjust for potential confounders. Oxytocin regimen did not affect the rate of cesarean delivery or other perinatal outcomes. Compared with 1 milliunit/min, the regimens starting with 2 milliunits/min and 4 milliunits/min reduced the duration of first stage by 0.8 hours (95% confidence interval 0.5-1.1) and 1.3 hours (1.0-1.7), respectively, in nulliparous women. No effect was observed on the second stage of labor. Similar patterns were observed in multiparous women. High-dose regimen was associated with a reduced risk of meconium stain, chorioamnionitis, and newborn fever in multiparous women. High-dose oxytocin regimen (starting dose at 4 milliunits/min and increment of 4 millliunits/min) is associated with a shorter duration of first-stage of labor for all parities without increasing the cesarean delivery rate or adversely affecting perinatal outcomes. II.

  17. Development of antibiotic regimens using graph based evolutionary algorithms.

    Science.gov (United States)

    Corns, Steven M; Ashlock, Daniel A; Bryden, Kenneth M

    2013-12-01

    This paper examines the use of evolutionary algorithms in the development of antibiotic regimens given to production animals. A model is constructed that combines the lifespan of the animal and the bacteria living in the animal's gastro-intestinal tract from the early finishing stage until the animal reaches market weight. This model is used as the fitness evaluation for a set of graph based evolutionary algorithms to assess the impact of diversity control on the evolving antibiotic regimens. The graph based evolutionary algorithms have two objectives: to find an antibiotic treatment regimen that maintains the weight gain and health benefits of antibiotic use and to reduce the risk of spreading antibiotic resistant bacteria. This study examines different regimens of tylosin phosphate use on bacteria populations divided into Gram positive and Gram negative types, with a focus on Campylobacter spp. Treatment regimens were found that provided decreased antibiotic resistance relative to conventional methods while providing nearly the same benefits as conventional antibiotic regimes. By using a graph to control the information flow in the evolutionary algorithm, a variety of solutions along the Pareto front can be found automatically for this and other multi-objective problems.

  18. Clinical applications of therapeutic phlebotomy

    Directory of Open Access Journals (Sweden)

    Kim KH

    2016-07-01

    Full Text Available Kyung Hee Kim,1 Ki Young Oh,2 1Department of Laboratory Medicine, Gachon University Gil Medical Center, Incheon, 2Department of Physical Medicine and Rehabilitation, Soonchunhyang University, Cheonan Hospital, Cheonan, South Korea Abstract: Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. Keywords: therapeutic phlebotomy, hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, nonalcoholic fatty liver disease

  19. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.

    Science.gov (United States)

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-03-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.

  20. Helicobacter pylori:Effect of coexisting diseases and update on treatment regimens

    Institute of Scientific and Technical Information of China (English)

    Shen-Shong; Chang; Hsiao-Yun; Hu

    2015-01-01

    The presence of concomitant diseases is an independentpredictive factor for non-Helicobacter pylori(H. pylori) peptic ulcers. Patients contracting concomitant diseases have an increased risk of developing ulcer disease through pathogenic mechanisms distinct from those of H. pylori infections. Factors other than H. pylori seem critical in peptic ulcer recurrence in end stage renal disease(ESRD) and cirrhotic patients. However, early H. pylori eradication is associated with a reduced risk of recurrent complicated peptic ulcers in patients with ESRD and liver cirrhosis. Resistances to triple therapy are currently detected using culture-based and molecular methods. Culture susceptibility testing before first- or second-line therapy is unadvisable. Using highly effective empiric first-line and rescue regimens can yield acceptable results. Sequential therapy has been included in a recent consensus report as a valid first-line option for eradicating H. pylori in geographic regions with high clarithromycin resistance. Two novel eradication regimens, namely concomitant and hybrid therapy, have proven more effective in patients with dual-(clarithromycin- and metronidazole-) resistant H. pylori strains. We aim to review the prevalence of and eradication therapy for H. pylori infection in patients with ESRD and cirrhosis. Moreover, we summarized the updated H. pylori eradication regimens.

  1. Carbohydrates in therapeutics.

    Science.gov (United States)

    Kilcoyne, Michelle; Joshi, Lokesh

    2007-07-01

    Awareness of the importance of carbohydrates in living systems and medicine is growing due to the increasing understanding of their biological and pharmacological relevance. Carbohydrates are ubiquitous and perform a wide array of biological roles. Carbohydrate-based or -modified therapeutics are used extensively in cardiovascular and hematological treatments ranging from inflammatory diseases and anti-thrombotic treatments to wound healing. Heparin is a well-known and widely used example of a carbohydrate-based drug but will not be discussed as it has been extensively reviewed. We will detail carbohydrate-based and -modified therapeutics, both those that are currently marketed or in various stages of clinical trials and those that are potential therapeutics based on promising preclinical investigations. Carbohydrate-based therapeutics include polysaccharide and oligosaccharide anti-inflammatory, anti-coagulant and anti-thrombotic agents from natural and synthetic sources, some as an alternative to heparin and others which were designed based on known structure-functional relationships. Some of these compounds have multiple biological effects, showing anti-adhesive, anti-HIV and anti-arthrithic activities. Small molecules, derivatives or mimetics of complement inhibitors, are detailed for use in limiting ischemia/ reperfusion injuries. Monosaccharides, both natural and synthetic, have been investigated for their in vivo anti-inflammatory and cardioprotective properties. Modification by glycosylation of natural products, or glycosylation-mimicking modification, has a significant effect on the parent molecule including increased plasma half-life and refining or increasing desired functions. It is hoped that this review will highlight the vast therapeutic potential of these natural bioactive molecules.

  2. Looking forward: novel therapeutic approaches in chronic and advanced phases of myelofibrosis.

    Science.gov (United States)

    Mascarenhas, John

    2015-01-01

    Myelofibrosis (MF) is complex at the pathobiologic level and heterogeneous at the clinical level. The advances in molecular characterization of MF provide important insight into the mechanisms driving this chronic myeloid malignancy, refine risk stratification, offer novel therapeutic targets, and serve to measure therapeutic response. Although JAK2 inhibition has been the focus of laboratory and clinical efforts over the last decade, current experimental therapeutic approaches have broadened to include inhibitors of key alternative signaling pathways, epigenetic modulators, anti-fibrotics, and immunotherapies. Based on compelling preclinical rationale, a number of JAK2 inhibitor based combination therapies are now actively being evaluated in the clinic with the goal of disease course modification. The role and timing of hematopoietic stem cell transplant (HSCT) for MF has been challenged with the availability of commercial ruxolitinib and the plethora of experimental treatment options that exist. Integration of preconditioning JAK2 inhibition, reduced intensity conditioning regimens, and alternative donor sources are all being explored in an attempt to optimize this potentially curative modality. This review will summarize modern MF risk stratification, current clinical research approaches to chronic and advance phase MF focusing on novel agents alone and in combination, and update the reader on new directions in HSCT.

  3. Characteristics of HIV antiretroviral regimen and treatment adherence

    Directory of Open Access Journals (Sweden)

    Vera Lúcia da Silveira

    2003-06-01

    Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.

  4. Characteristics of HIV antiretroviral regimen and treatment adherence

    Directory of Open Access Journals (Sweden)

    Vera Lúcia da Silveira

    Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.

  5. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Van Beneden, Katrien, E-mail: kvbenede@vub.ac.be [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Geers, Caroline [Department of Pathology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Pauwels, Marina [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Mannaerts, Inge [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Wissing, Karl M. [Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Van den Branden, Christiane [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Grunsven, Leo A. van, E-mail: lvgrunsv@vub.ac.be [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium)

    2013-09-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  6. TAC-TIC use of tacrolimus-based regimens in lupus nephritis.

    Science.gov (United States)

    Kraaij, Tineke; Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

    2016-01-01

    Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN.

  7. Clinical efficacy of Ayurveda treatment regimen on Subfertility with Poly Cystic Ovarian Syndrome (PCOS).

    Science.gov (United States)

    Dayani Siriwardene, S A; Karunathilaka, L P A; Kodituwakku, N D; Karunarathne, Y A U D

    2010-01-01

    Poly Cystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, resulting from insulin resistance and the compensatory hyperinsulinemia. This results in adverse effect on multiple organ systems and may result in alteration in serum lipids, anovulation, abnormal uterine bleeding and infertility. According to Ayurvedic view PCOS can be correlated with Aarthava Kshaya. It was revealed that most of subfertility patients who were presented Osuki Ayurveda Centre suffered from the PCOS. Therefore the present study was carried out for the clinical evaluation of the efficacy of Ayurveda treatment regimen on subfertility with PCOS. Total 40 patients were selected by using purposive sampling method. According to the Ayurveda theories of Shodhana, Shamana and Tarpana, the treatment was conducted in 3 stages for the duration of 6 months. The response to the treatment was recorded and therapeutic effects were evaluated by symptomatic relief and through Trans Vaginal Scan and LH, FSH hormone levels. The results revealed that, subfertility due to PCOS can be cured successfully by using this Ayurveda treatment regimen.

  8. Alternative temozolomide dosing regimens and novel combinations for the treatment of advanced metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Wen-Jen Hwu

    2011-12-01

    Full Text Available Over the past 30 years, there has been no significant improvement in treatment outcomes for patients with advanced stage IV metastatic melanoma, and prognosis remains poor. Melanoma is known to be responsive to immunomodulatory agents, to be a highly vascular tumor, and to be fairly resistant to standard cytotoxic chemotherapy. Ongoing research is attempting to find novel combinations that may have therapeutic synergy. Alternative dosedense schedules of temozolomide appear promising and are being actively investigated, based on their potential to overcome chemoresistance to alkylating agents and the proven activity of temozolomide in the brain. Outcomes of studies investigating single-agent temozolomide suggest that it has activity similar to single-agent dacarbazine. Other studies combining temozolomide with either interferon- alfa or thalidomide suggest that the addition of these immunomodulatory agents to temozolomide improves response rates and may improve overall survival. The best results have been achieved with the extended, daily, dosedense temozolomide regimen. Further research is needed to determine the optimal temozolomide regimen and best combination approach

  9. Evaluation of the benefit of addition of clidinium C to a Helicobacter pylori eradication regimen

    Science.gov (United States)

    Chorami, Maryam; Naderi, Nosratollah; Moghimi-Dehkordi, Bijan; Mirsattari, Dariush; Shalmani, Hamid Mohaghegh

    2013-01-01

    Aim This study aimed to evaluate the success of H.pylori eradication therapy in patients with dyspepsia by therapeutics regimes with and without clidinium C. Background Helicobacter pylori infections are reported in all parts of the world. Appropriate antibiotic therapy can treat infection. The ideal treatment regimen has not been specified. Patients and methods In a randomized, double blind clinical trials study, 250 patients with dyspepsia were enrolled. All patients were treated by Omeprazole, Metronidazole, Amoxicillin and Bismuth (OMAB) for two weeks. One tablet clidinium C before each meal was added to this regimen in the intervention group (A). Urea Breath Test (UBT) was carried out after 8-12 weeks after treatment for evaluation of H.pylori eradication. Results 132 patients in the intervention group (A) and 118 patients in the control group (B) were enrolled to the study. The rate of eradication in group A was significantly higher than group B (62.1% vs. 50%, p=0.04). Conclusion The results supported the effect of clidinium C for increasing of helicobacter pylori eradication, but further studies need to be performed. PMID:24834261

  10. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

    Directory of Open Access Journals (Sweden)

    Balk JM

    2015-08-01

    Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

  11. Persistence to single-tablet regimen versus less-drug regimen in treatment experienced HIV-infected patients on antiretroviral therapy

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    Rocio Jiménez-Galán

    2016-07-01

    Full Text Available Background: Decreased antiretroviral therapy persistence is associated with increased rates of virologic failure, development of antiretroviral resistance, and increased morbidity and mortality. Different therapeutic strategies, such as single-tablet regimens (STR and less-drug regimens (LDR, have been developed in order to simplify antiretroviral therapy (ART and increase persistence. Objectives: The primary objective was to compare antiretroviral persistence among patients receiving STRs and patients receiving LDRs. A secondary objective was to identify factors associated with non-persistence. Methods: This was a retrospective study that included treatment- experienced HIV-infected patients who received ART based on STR or LDR. Baseline patient characteristics collected included demographic information, HIV risk transmission, substance abuse during the therapy, presence of psychiatric disorder and hepatitis B or C virus infection. Kaplan-Meier analysis and Log rank was utilized to compare persistence to STR and LDR. To identify independent predictors of non-persistence we developed a multivariate Cox regression analysis. Results: A total of 244 patients were included, 176 with STR and 68 with LDR. 60 (34.1% patients discontinued in the STR group and 13 (19.1% in the LDR group. The Cox regression model showed that the only variable associated with higher risk of non-persistence was the substance abuse (HR = 2.59; p = 0.005. Adverse events were the main reason for ART discontinuation in the STR group and virologic failure in the LDR group. Conclusions: Persistence to STR and LDR seems to be similar in pretreated HIV-infected patients. Drug abuse was the only factor identified with a higher risk of non-persistence.

  12. The Impact and Cost-Effectiveness of a Four-Month Regimen for First-Line Treatment of Active Tuberculosis in South Africa.

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    Gwenan M Knight

    Full Text Available A 4-month first-line treatment regimen for tuberculosis disease (TB is expected to have a direct impact on patient outcomes and societal costs, as well as an indirect impact on Mycobacterium tuberculosis transmission. We aimed to estimate this combined impact in a high TB-burden country: South Africa.An individual based M. tb transmission model was fitted to the TB burden of South Africa using a standard TB natural history framework. We measured the impact on TB burden from 2015-2035 of introduction of a non-inferior 4-month regimen replacing the standard 6-month regimen as first-line therapy. Impact was measured with respect to three separate baselines (Guidelines, Policy and Current, reflecting differences in adherence to TB and HIV treatment guidelines. Further scenario analyses considered the variation in treatment-related parameters and resistance levels. Impact was measured in terms of differences in TB burden and Disability Adjusted Life Years (DALYs averted. We also examined the highest cost at which the new regimen would be cost-effective for several willingness-to-pay thresholds.It was estimated that a 4-month regimen would avert less than 1% of the predicted 6 million person years with TB disease in South Africa between 2015 and 2035. A similarly small impact was seen on deaths and DALYs averted. Despite this small impact, with the health systems and patient cost savings from regimen shortening, the 4-month regimen could be cost-effective at $436 [NA, 5983] (mean [range] per month at a willingness-to-pay threshold of one GDP per capita ($6,618.The introduction of a non-inferior 4-month first-line TB regimen into South Africa would have little impact on the TB burden. However, under several scenarios, it is likely that the averted societal costs would make such a regimen cost-effective in South Africa.

  13. Treatment of multidrug-resistant pseudomonas aeruginosa using extended-infusion antimicrobial regimens.

    Science.gov (United States)

    Heil, Emily L; Lowery, Ashleigh V; Thom, Kerri A; Nicolau, David P

    2015-01-01

    In the management of multidrug-resistant infections in critically ill patients with multiorgan dysfunction, consideration must be given to the pharmacokinetics and pharmacodynamics of an antimicrobial agent to optimize dosing. We describe a 25-year-old woman who was undergoing thrice-weekly hemodialysis and developed multidrug-resistant Pseudomonas aeruginosa bacteremia secondary to infected left and right ventricular assist devices. After multiple courses of antibiotics, her blood cultures revealed that the infecting organism was becoming progressively more resistant to antibiotic options. Cefepime 2 g administered over 3 hours/day (in combination with colistimethate) provided adequate drug levels for multidrug-resistant, cefepime-intermediate P. aeruginosa bacteremia in this patient. We present the clinical case of this patient, followed by a discussion of possible therapeutic approaches to be considered, including illustration of the principles of using extended-infusion antimicrobial regimens, and present the patient's resulting clinical course.

  14. Perceived efficacy of analgesic drug regimens used for koalas (Phascolarctos cinereus) in Australia.

    Science.gov (United States)

    de Kauwe, Tyron; Kimble, Benjamin; Govendir, Merran

    2014-06-01

    Recent publications report that some therapeutic drugs used in koalas (Phascolarctos cinereus) have poor oral absorption and are rapidly eliminated. Therefore, information on both the analgesic drug dosage regimens used to treat koalas in Australia and koala caretakers' perceptions of the efficacy of these drugs to control pain was collected for the purpose of identifying the most popular analgesics to prioritize future analgesic pharmacokinetic studies for this species. A one-page, double-sided questionnaire was distributed both electronically and by mail to Australian koala care facilities such as zoos and wildlife hospitals. Information was received from 13 respondents. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most frequently used analgesics, followed by full micro- and partial opioid receptor agonists and acetaminophen with or without codeine. The full micro-opioid receptor agonists and acetaminophen with or without codeine were most consistently considered efficacious, with wider variation in perceived efficacy of the NSAIDs. Analgesic drug combinations were generally thought efficacious.

  15. Comparison of different insulin regimens in elderly patients with NIDDM

    NARCIS (Netherlands)

    Wolffenbuttel, B H; Sels, J P; Rondas-Colbers, G J; Menheere, P P; Nieuwenhuijzen Kruseman, A C

    1996-01-01

    OBJECTIVE: To compare the metabolic effects of three different frequently used regimens of insulin administration on blood glucose control and serum lipids, and the costs associated with this treatment, in subjects with NIDDM, who were poorly controlled with oral antihyperglycemic agents. RESEARCH D

  16. Comparison of different insulin regimens in elderly patients with NIDDM

    NARCIS (Netherlands)

    Wolffenbuttel, B H; Sels, J P; Rondas-Colbers, G J; Menheere, P P; Nieuwenhuijzen Kruseman, A C

    1996-01-01

    OBJECTIVE: To compare the metabolic effects of three different frequently used regimens of insulin administration on blood glucose control and serum lipids, and the costs associated with this treatment, in subjects with NIDDM, who were poorly controlled with oral antihyperglycemic agents. RESEARCH D

  17. Outcomes of CAG Regimen for Refractory Biphenotypic Acute Leukemia Patients

    Institute of Scientific and Technical Information of China (English)

    Guang-sheng He; Xiang Zhang; De-pei Wu; Ai-ning Sun; Zheng-ming Jin; Hui-ying Qiu; Miao Miao; Xiao-wen Tang; Zheng-zheng Fu; Yue Han

    2009-01-01

    Objective To evaluated the efficiency of low-dose cytosine arabinoside plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor(CAG)regimen for refractory biphenotypic acute leukemia(BAL).Methods We treated 5 refractory BAL patients by CAG regimen(10 mg·m 2 cytosine arabinoside subcutaneously administrated every 12 hours,day 1-14;5-7 mg·m2 aclarubicin intravenously administrated daily,day 1-8;and concurrently used 200 μg.m-2·d-1 granulocyte colony-stimulating factor subcutaneously)from November 2002 to April 2007.The efficacy of the regimen was evaluated by response rate,and the side effects were also measured.Results The complete remission rate was 80% ,median duration of absolute neutrophil count<5.0×108/L and platelet count<2.0×1010/L was day 13 and day 1,respectively;and the infection rate was low(Ⅲ-Ⅳ infection rate,20.00% ).Conclusion CAG regimen as remission induction chemotherapy for BAL patients is effective with a high remission rate and low toxicity.

  18. Tuberculous meningitis: is a 6-month treatment regimen sufficient?

    NARCIS (Netherlands)

    Loenhout-Rooyackers, J.H. van; Keyser, A.J.M.; Laheij, R.J.F.; Verbeek, A.L.M.; Meer, J.W.M. van der

    2001-01-01

    SETTING: The British Thoracic Society and the American Thoracic Society advise 12 months treatment for tuberculous meningitis, with at least isoniazid (H), rifampicin (R) and pyrazinamide (Z). OBJECTIVE: To establish whether a 6-month treatment regimen for tuberculous meningitis is equally as effect

  19. Gonzalez Regimen (PDQ®)—Health Professional Version

    Science.gov (United States)

    The Gonzalez regimen is a specialized diet that uses enzymes, supplements, and other factors in cancer management based on a theory that involves the use of pancreatic enzymes to help the body get rid of toxins that lead to cancer. Read about existing clinical data in this expert-reviewed summary.

  20. Efficacy of Some Combination Regimens of Oral Hypoglycaemic ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights ... Hypoglycaemic Agents in Type 2 Diabetes Mellitus Patients ... levels induced by several OHA cobmination regimens were documented. ... highlighting the important benefits conferred by the use of multiple OHAs.

  1. Metronomic chemotherapy in anaplastic thyroid carcinoma: A potentially feasible alternative to therapeutic nihilism

    Directory of Open Access Journals (Sweden)

    Swaroop Revannasiddaiah

    2015-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most aggressive malignancies and prognostic outlook remains very dismal. Treatment most often is palliative in intent attempting to relieve the patients from local compressive symptoms in the neck. Radical surgery, radiotherapy (RT, and chemotherapy have not been tested in large prospective trials, and current evidence from retrospective series and small trials indicate only marginal survival benefits. Given the poor prognostic and therapeutic outlook, patients must be encouraged to be actively involved in the decision making process. We report the case of an elderly patient who had no response to palliative RT, and was treated with oral metronomic chemotherapy. The response to oral metronomic chemotherapy was dramatic, and the patient has enjoyed complete freedom from symptoms as well as radiologically exhibits a complete regression. Thus, we document the first ever use of a simple, cost-effective, and convenient oral metronomic chemotherapeutic regimen delivering a remarkable response in an elderly patient with ATC.

  2. Rethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study.

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    Nancy C Sambol

    Full Text Available The combination of short-acting dihydroartemisinin and long-acting piperaquine (DP is among the first-line therapies for the treatment of uncomplicated Plasmodium falciparum malaria. Population pharmacokinetic models of piperaquine (PQ based on data from acute treatment of young children can be used to predict exposure profiles of piperaquine under different DP chemoprevention regimens. The purpose of our study was to make such predictions in young children.Based on a prior population pharmacokinetic model of PQ in young Ugandan children, we simulated capillary plasma concentration-time profiles (including their variability of candidate chemoprevention regimens for a reference population of 1-2 year olds weighing at least 11 kg. Candidate regimens that were tested included monthly administration of standard therapeutic doses, bimonthly dosing, and weekly dosing (with and without a loading dose.Once daily doses of 320 mg for three days (960 mg total at the beginning of each month are predicted to achieve an average steady-state trough capillary piperaquine concentration of 35 ng/mL, with 60% achieving a level of 30 ng/mL or higher. In contrast, weekly dosing of 320 mg (i.e., 33% higher amount per month is predicted to approximately double the average steady-state trough concentration, increase the percent of children predicted to achieve 30 ng/mL or higher (94%, while at the same time lowering peak concentrations. Exposure at steady-state, reached at approximately 3 months of multiple dosing, is expected to be approximately 2-fold higher than exposure following initial dosing, due to accumulation. A loading dose improves early exposure, thereby reducing the risk of breakthrough infections at the initiation of chemoprevention.Once weekly chemoprevention of DP predicts favourable exposures with respect to both trough and peak concentrations. These predictions need to be verified, as well as safety evaluated, in field-based clinical studies of young

  3. Aggressive regimens for multidrug-resistant tuberculosis reduce recurrence.

    Science.gov (United States)

    Franke, Molly F; Appleton, Sasha C; Mitnick, Carole D; Furin, Jennifer J; Bayona, Jaime; Chalco, Katiuska; Shin, Sonya; Murray, Megan; Becerra, Mercedes C

    2013-03-01

    Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy. We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis. Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2-53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17-0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17-50.60]; P = .004). Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease.

  4. Oxytocin Regimen for Labor Augmentation, Labor Progression, Perinatal Outcomes

    Science.gov (United States)

    Zhang, Jun; Branch, D. Ware; Ramirez, Mildred M.; Laughon, S. Katherine; Reddy, Uma; Hoffman, Mathew; Bailit, Jennifer; Kominiarek, Michelle; Chen, Zhen; Hibbard, Judith U.

    2013-01-01

    Objective To examine the effects and safety of high-dose (compared with low-dose) oxytocin regimen for labor augmentation on perinatal outcomes. Methods Data from the Consortium on Safe Labor were used. A total of 15,054 women from six hospitals were eligible for the analysis. Women were grouped based on their oxytocin starting dose and incremental dosing: 1, 2, and 4 mU/min. Duration of labor and a number of maternal and neonatal outcomes were compared among these three groups stratified by parity. Multivariable logistic regression and generalized linear mixed model were used to adjust for potential confounders. Results Oxytocin regimen did not affect the rate of cesarean delivery or other perinatal outcomes. Compared to 1 mU/min, the regimens starting with 2 mU/min and 4 mU/min reduced the duration of 1st stage by 0.8 hours (95% confidence interval 0.5 – 1.1) and 1.3 hours (1.0 – 1.7), respectively, in nulliparas. No effect was observed on the second stage of labor. Similar patterns were observed in multiparas. High-dose regimen was associated with a reduced risk of meconium stain, chorioamnionitis, and newborn fever in multiparas. Conclusion High-dose oxytocin regimen (starting dose at 4 mU/min and increment of 4 mU/min) is associated with a shorter duration of first stage of labor in all parities without increasing the cesarean delivery rate or adversely affecting perinatal outcomes. PMID:21775839

  5. Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: analysis of the French administrative health databases 2009-2014.

    Science.gov (United States)

    Kirchgesner, J; Lemaitre, M; Rudnichi, A; Racine, A; Zureik, M; Carbonnel, F; Dray-Spira, R

    2017-01-01

    Management of inflammatory bowel disease (IBD) has evolved in the last decade. To assess IBD therapeutic management, including treatment withdrawal and early treatment use in the current era of anti-TNF agents (anti-TNFs). All patients affiliated to the French national health insurance diagnosed with IBD were included from 2009 to 2013 and followed up until 31 December 2014. Medication uses, treatment sequences after introduction of thiopurine or anti-TNF monotherapies or both (combination therapy), surgical procedures and hospitalisations were assessed. A total of 210 001 patients were diagnosed with IBD [Crohn's disease (CD), 100 112; ulcerative colitis (UC), 109 889]. Five years after diagnosis, cumulative probabilities of anti-TNF monotherapy and combination therapy exposures were 33.8% and 18.3% in CD patients and 12.9% and 7.4% in UC patients, respectively. Among incident patients who received thiopurines or anti-TNFs, the first treatment was thiopurine in 69.1% of CD and 78.2% of UC patients. Among patients treated with anti-TNFs, 45.2% and 54.5% of CD patients and 38.2% and 39.9% of UC patients started monotherapy and combination therapy within 3 months after diagnosis, respectively; 31.3% of CD and 27.1% of UC incident patients withdrew from thiopurine or anti-TNFs for more than 3 months after their first course of treatment. Five years after diagnosis, the cumulative risks of first intestinal resection in CD patients and colectomy in UC patients were 11.9% and 5.7%, respectively. Step-up approach remains the predominant strategy, while exposure to anti-TNFs is high. Surgery rates are low. Treatment withdrawal in IBD is more common than expected. © 2016 John Wiley & Sons Ltd.

  6. Evaluation of hippuric acid content in goat milk as a marker of feeding regimen.

    Science.gov (United States)

    Carpio, A; Bonilla-Valverde, D; Arce, C; Rodríguez-Estévez, V; Sánchez-Rodríguez, M; Arce, L; Valcárcel, M

    2013-09-01

    Organic producers, traders, and consumers must address 2 issues related to milk: authentication of the production system and nutritional differentiation. The presence of hippuric acid (HA) in goat milk samples has been proposed as a possible marker to differentiate the feeding regimen of goats. The objective of this work is to check the hypothesis that HA could be a marker for the type of feeding regimen of goats by studying the influence of production system (conventional or organic) and feeding regimen (with or without grazing fodder). With this purpose, commercial cow and goat milk samples (n=27) and raw goat milk samples (n=185; collected from different breeds, localizations, and dates) were analyzed. Samples were grouped according to breed, feeding regimen, production system, and origin to compare HA content by ANOVA and honestly significant difference Tukey test at a confidence level of ≥95%. Hippuric acid content was obtained by analyzing milk samples with capillary electrophoresis. This method was validated by analyzing part of the samples with HPLC as a reference technique. Sixty-nine raw goat milk samples (of the total 158 samples analyzed in this work) were quantified by capillary electrophoresis. In these samples, the lowest average content for HA was 7±3 mg/L. This value corresponds to a group of conventional raw milk samples from goats fed with compound feed. The highest value of this group was 28±10 mg/L, corresponding to goats fed compound feed plus grass. Conversely, for organic raw goat milk samples, the highest concentration was 67±14 mg/L, which corresponds to goats fed grass. By contrast, the lowest value of this organic group was 26±10 mg/L, which belongs to goats fed organic compounds. Notice that the highest HA average content was found in samples from grazing animals corresponding to the organic group. This result suggests that HA is a good marker to determine the type of goats feeding regimen; a high content of HA represents a diet

  7. Therapeutic options for peritoneal metastasis arising from colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Gabriel Glockzin; Hans J Schlitt; Pompiliu Piso

    2016-01-01

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

  8. Immunotherapy and lung cancer: current developments and novel targeted therapies.

    Science.gov (United States)

    Domingues, Duarte; Turner, Alice; Silva, Maria Dília; Marques, Dânia Sofia; Mellidez, Juan Carlos; Wannesson, Luciano; Mountzios, Giannis; de Mello, Ramon Andrade

    2014-01-01

    Non-small-cell lung cancer (NSCLC) is a highly prevalent and aggressive disease. In the metastatic setting, major advances include the incorporation of immunotherapy and targeted therapies into the clinician's therapeutic armamentarium. Standard chemotherapeutic regimens have long been reported to interfere with the immune response to the tumor; conversely, antitumor immunity may add to the effects of those therapies. The aim of immunotherapy is to specifically enhance the immune response directed to the tumor. Recently, many trials addressed the role of such therapies for metastatic NSCLC treatment: ipilimumab, tremelimumab, nivolumab and lambrolizumab are immunotherapeutic agents of main interest in this field. In addition, anti-tumor vaccines, such as MAGE-A3, Tecetomide, TG4010, CIMAvax, ganglioside vaccines, tumor cell vaccines and dendritic cell vaccines, emerged as potent inducers of immune response against the tumor. The current work aims to address the most recent developments regarding these innovative immunotherapies and their implementation in the treatment of metastatic NSCLC.

  9. Omega-3 Fatty Acids in Modern Parenteral Nutrition: A Review of the Current Evidence.

    Science.gov (United States)

    Klek, Stanislaw

    2016-03-07

    Intravenous lipid emulsions are an essential component of parenteral nutrition regimens. Originally employed as an efficient non-glucose energy source to reduce the adverse effects of high glucose intake and provide essential fatty acids, lipid emulsions have assumed a larger therapeutic role due to research demonstrating the effects of omega-3 and omega-6 polyunsaturated fatty acids (PUFA) on key metabolic functions, including inflammatory and immune response, coagulation, and cell signaling. Indeed, emerging evidence suggests that the effects of omega-3 PUFA on inflammation and immune response result in meaningful therapeutic benefits in surgical, cancer, and critically ill patients as well as patients requiring long-term parenteral nutrition. The present review provides an overview of the mechanisms of action through which omega-3 and omega-6 PUFA modulate the immune-inflammatory response and summarizes the current body of evidence regarding the clinical and pharmacoeconomic benefits of intravenous n-3 fatty acid-containing lipid emulsions in patients requiring parenteral nutrition.

  10. The evolution of the therapeutic strategy in hepatitis C: features of sofosbuvir and indications.

    Science.gov (United States)

    Alberti, Alfredo; Piovesan, Sara

    2014-12-15

    The treatment of chronic hepatitis C virus infection is rapidly evolving with the entry into the therapeutic armamentarium of a series of new and highly effective direct antiviral agents, targeted to the different virus structures involved in hepatitis C virus replication and assembly. Sofosbuvir is considered, without controversies, the most promising single direct antiviral agent in the current scenario. The pharmacological properties of sofosbuvir allow a single oral daily administration and ensure a favourable drug-drug interaction profile, compared to other direct antiviral agents. Clinical development of sofosbuvir has been conducted with the strategy of positioning it as the backbone drug of several combination regimes, including triple therapy with pegylated interferon and ribavirin, but also IFN-free regimen with ribavirin alone as well as with complementary direct antiviral agents directed against other virus targets. Based on available data and International guidelines sofosbuvir is indicated in combination with pegylated interferon and ribavirin in patients infected with hepatitis C virus 1 to 6 that can take interferon, and this regimen is particularly efficacious in those who have not received any previous antiviral treatment. The pangenotypic activity, excellent safety (even in advanced liver disease) make sofosbuvir the ideal backbone for combination therapy in all hepatitis C virus patients subgroups, the limiting factors being safety and tolerability of the combined direct antiviral agent rather than those of sofosbuvir itself.

  11. Therapeutic efficacy of artemether-lumefantrine for Plasmodium vivax infections in a prospective study in Guyana

    Directory of Open Access Journals (Sweden)

    Eibach Daniel

    2012-10-01

    Full Text Available Abstract Background In Guyana, chloroquine + primaquine is used for the treatment of vivax malaria. A worldwide increase of chloroquine resistance in Plasmodium vivax led to questioning of the current malaria treatment guidelines. A therapeutic efficacy study was conducted using artemether-lumefantrine + primaquine against P. vivax to evaluate a treatment alternative for chloroquine. Methods From 2009 to 2010, a non-controlled study in two hospitals in Guyana was conducted. A total 61 patients with P. vivax infection were treated with artemether-lumefantrine as a six-dose regimen twice a day for three days with additional 0.25 mg/kg/d primaquine at day 0 for 14 days. Clinical and parasitological parameters were followed on days 0,1,2,3,7,14 and 28 in agreement with WHO guidelines. Plasmodium vivax DNA from eight patients was analysed for pvmdr1, molecular marker of resistance. Results Artemether-lumefantrine cleared 100% of parasites on day 1, but two patients (3% had recurrence of parasites on day 28, suggesting relapse. No pvmdr1 Y976F polymorphism was detected. The treatment regimen was well tolerated. Conclusions In Guyana, artemether-lumefantrine represents an adequate treatment option against P. vivax when combined with primaquine. Availability of this alternative will be of great importance in case of emerging chloroquine resistance against P. vivax.

  12. To cardiovascular disease and beyond: new therapeutic perspectives of statins in autoimmune diseases and cancer.

    Science.gov (United States)

    Lopez-Pedrera, Chary; Ruiz-Limon, Patricia; Valverde-Estepa, Araceli; Barbarroja, Nuria; Rodriguez-Ariza, Antonio

    2012-06-01

    Statins have been successfully used in patients with hypercholesterolemia and cardiovascular diseases, but there is increasing evidence that they exert effects by much exceeding the lowering of cholesterol levels. Statins have antiatherosclerotic, antiinflammatory, antioxidant, immunomodulatory and antithrombotic effects. These "pleiotropic" effects stem from their inhibition of prenylation of the small GTP-binding proteins Ras and Rho, and to the disruption, or depletion, of cholesterol rich membrane micro-domains (membrane rafts). Through these pathways statins modulate immune responses by altering cytokine levels and by affecting the function of cells involved in both innate and adaptive responses. Anti-inflammatory and immunosuppressory properties of statins provide the rationale for their potential application in conditions in which the inflammation and immune response represent key pathogenic mechanisms, such as antiphospholipid syndrome, rheumatoid arthritis and systemic lupus erythematosus. Reduction of atherosclerosis progression in autoimmunity is also a very important effect. Statins pathways of action in systemic autoimmune diseases, and their potential therapeutic use are discussed in this review. The inhibition of mevalonate pathway by statins impairs modification of Ras and Rho GTPases, which play key roles in signaling pathways related to tumor formation, metastasis and cell death. There is experimental and clinical evidence that statins may improve the therapeutic outcome of anticancer drugs. Thus, this review will also discuss recent insights into the molecular mechanisms underlying the anticancer effects of statins and their assessment as promising candidates for inclusion into current therapeutic regimens for the treatment of malignant diseases.

  13. Resource Utilization for Chemotherapy-Induced Nausea and Vomiting Events in Patients with Solid Tumors Treated with Antiemetic Regimens

    Science.gov (United States)

    Schwartzberg, Lee; Harrow, Brooke; Lal, Lincy S.; Radtchenko, Janna; Lyman, Gary H.

    2015-01-01

    Background Chemotherapy-induced nausea and vomiting (CINV) can lead to increased emergency department visits and hospitalizations, which may contribute to increased cost of care. Antiemetic agents, such as neurokinin-1 (NK1) receptor antagonists and 5-hydroxytryptamine (5-HT3) receptor antagonists, are prescribed for patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). The current guidelines recommend a 3-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone with HEC regimens and certain MEC regimens. Objective To compare the incidence of CINV and CINV-related resource utilization among patients who receive guideline-adherent HEC and MEC regimens and patients who receive non–guideline-adherent regimens. Methods In this retrospective, claims-based study, Inovalon's Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) Research Edition database was used to identify 8089 patients with solid tumors receiving therapy with anthracycline plus cyclophosphamide (AC), cisplatin, or carboplatin from June 2013 to December 2013. The patients were stratified according to the use of an NK1 receptor antagonist regimen. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify CINV events associated with hospital, emergency department, and outpatient office visits among patients in the NK1 receptor antagonist group and the non-NK1 receptor antagonist group. Results A total of 1059 patients were included in the analysis, of whom 51% (N = 536) used an NK1 receptor antagonist–based regimen and 49% (N = 523) used non-NK1 receptor antagonist therapy. A higher percentage of patients receiving AC (73%) than cisplatin (56%) or carboplatin (23%) received an NK1 receptor antagonist. The incidence rates of total CINV events and CINV-related emergency department visits were lower in the group receiving an NK1 receptor

  14. [The fourth report from Sapporo Tsukisamu Hospital - chemotherapy and its regimen as second choice for patients with early gastric cancer].

    Science.gov (United States)

    Yamamitsu, Susumu; Kimura, Hiromichi; Yamada, Yoshiyuki; Inui, Noriaki; Hiyama, Shigemi; Hirata, Koichi; Kimura, Yasutoshi; Yamaguchi, Kouji; Shirasaka, Tetsuhiko

    2007-10-01

    Surgical treatments for early gastric cancer, such as endoscopic procedures, are currently performed as standard therapy. However, when surgery is not possible due to physical or mental conditions, effective chemotherapy with minimum side effects is a second choice, although a suitable regimen has yet to be recommended. We thus retrospectively evaluated the Int FP regimen for 10 early gastric cancer patients. The results show an efficacy ratio of 100% (CR 8 cases, PR 2 cases). The two PR cases subsequently underwent surgical treatment. The 1-, 3-, and 5-year survival rates of all cases were 100%, 90% and 60%, respectively. The 1-, 3-, and 5-year survival rates of patients with chemotherapy alone were 100%, 87.5% and 50%, respectively, although none of the patients died of cancer (5-year survival rate of 100%). One out of the 8 CR cases relapsed 7 months after achieving CR. This patient then received chemotherapy with the same regimen, achieving a second CR and survived for 66 months without disease. All cases developed hematological toxicities, although they were all under grade 2 except for 2 cases which were grade 3 (decrease of WBC or Hb). Non-hematological toxicities were seen in 7 cases, all under grade 2. These results, although from a limited number of subjects, indicated that the IntFP regimen is safe and may contribute to achieving pathological CR and long-term survival of patients with early gastric cancer.

  15. Basis for selecting optimum antibiotic regimens for secondary peritonitis.

    Science.gov (United States)

    Maseda, Emilio; Gimenez, Maria-Jose; Gilsanz, Fernando; Aguilar, Lorenzo

    2016-01-01

    Adequate management of severely ill patients with secondary peritonitis requires supportive therapy of organ dysfunction, source control of infection and antimicrobial therapy. Since secondary peritonitis is polymicrobial, appropriate empiric therapy requires combination therapy in order to achieve the needed coverage for both common and more unusual organisms. This article reviews etiological agents, resistance mechanisms and their prevalence, how and when to cover them and guidelines for treatment in the literature. Local surveillances are the basis for the selection of compounds in antibiotic regimens, which should be further adapted to the increasing number of patients with risk factors for resistance (clinical setting, comorbidities, previous antibiotic treatments, previous colonization, severity…). Inadequate antimicrobial regimens are strongly associated with unfavorable outcomes. Awareness of resistance epidemiology and of clinical consequences of inadequate therapy against resistant bacteria is crucial for clinicians treating secondary peritonitis, with delicate balance between optimization of empirical therapy (improving outcomes) and antimicrobial overuse (increasing resistance emergence).

  16. Noncompliance with Medical Regimen in Haemodialysis Treatment: A Case Study

    Directory of Open Access Journals (Sweden)

    Paraskevi Theofilou

    2011-01-01

    Full Text Available Patients undergoing haemodialysis treatment have a high burden of disease (particularly cardiovascular comorbidities affecting their quality of life and dramatically shortening life expectancy. Effective chronic kidney disease (CKD control requires regular preventive medication and a response to that medication. Poor receptiveness to CKD medication can be related to individual variability in the dose needed to achieve a response, as well as to low-adherent behaviour in relation to the CKD medication regimen. Some patients, though not many, according to studies' findings, abuse the medical regimen as a result of suicidal tendencies. The present case gave us the opportunity to consider the causes and clinical findings and review the specific psychological interventions for patients with CKD.

  17. Predictive tools for designing new insulins and treatment regimens

    DEFF Research Database (Denmark)

    Klim, Søren

    The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part that des......The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part...... on ordinary differential equations. The absence of such a program motivated the development of new a tool with PK/PD features, SDEs and mixed effects. Part II presents a software package which was developed in order to be able to handle SDEs with mixed effects. The package was implemented in R which allowed...

  18. Efficacy of a Morinda citrifolia Based Skin Care Regimen

    Directory of Open Access Journals (Sweden)

    Brett J. West

    2012-04-01

    Full Text Available A six week clinical trial of a Morinda citrifolia (noni based skin care regimen was conducted with 49 women, ages 38 to 55 years. Daily application of three product formulations to the face and neck resulted in significant reductions in lateral canthal fine lines and wrinkles (crow’s feet, as measured by technician scoring and digital image analysis. Use of the regimen also improved skin elasticity and firmness Cutometer® measurements. No evidence of skin irritation was present in any participant at any time during the trial. A study questionnaire revealed that the measured improvements were visibly perceptible to more than 90% of the participants. The trial results substantiate traditional uses of the noni plant to improve skin health.

  19. Pro and con arguments in using alternative dialysis regimens in the frail and elderly patients.

    Science.gov (United States)

    Chazot, Charles; Farrington, Ken; Nistor, Ionut; Van Biesen, Wim; Joosten, Hanneke; Teta, Daniel; Siriopol, Dimitrie; Covic, Adrian

    2015-11-01

    In the last decade, an increasing number of patients over 75 years of age are starting renal replacement therapy. Frailty is highly prevalent in elderly patients with end-stage renal disease (ESRD) in the context of the increased prevalence of some ESRD-associated conditions: protein-energy wasting, inflammation, anaemia, acidosis or hormonal disturbances. There are currently no hard data to support guidance on the optimal duration of dialysis for frail/elderly ESRD patients. The current debate is not about starting dialysis or managing conservatory frail ESRD patients, but whether a more intensive regimen once dialysis is initiated (for whatever reasons and circumstances) would improve patients' outcome. The most important issue is that all studies performed with extended/alternative dialysis regimens do not specifically address this particular type of patients and therefore all the inferences are derived from the general ESRD population. Care planning should be responsive to end-of-life needs whatever the treatment modality. Care in this setting should focus on symptom control and quality of life rather than life extension. We conclude that, similar to the general dialysed population, extensive application of more intensive dialysis schedules is not based on solid evidence. However, after a thorough clinical evaluation, a limited period of a trial of intensive dialysis could be prescribed in more problematic patients.

  20. Antiepileptic drug regimens and major congenital abnormalities in the offspring.

    Science.gov (United States)

    Samrén, E B; van Duijn, C M; Christiaens, G C; Hofman, A; Lindhout, D

    1999-11-01

    To assess the risk of major congenital abnormalities associated with specific antiepileptic drug regimens, a large retrospective cohort study was performed. The study comprised 1,411 children born between 1972 and 1992 in four provinces in The Netherlands who were born to mothers with epilepsy and using antiepileptic drugs during the first trimester of pregnancy, and 2,000 nonepileptic matched controls. We found significantly increased risks of major congenital abnormalities for carbamazepine and valproate monotherapy, with evidence for a significant dose-response relationship for valproate. The risk of major congenital abnormalities was nonsignificantly increased for phenobarbital monotherapy when caffeine comedication was excluded, but a significant increase in risk was found when caffeine was included. Phenytoin monotherapy was not associated with an increased risk of major congenital abnormalities. Regarding polytherapy regimens, increased risks were found for several antiepileptic drug combinations. Clonazepam, in combination with other antiepileptic drugs, showed a significantly increased relative risk. Furthermore, there were significantly increased relative risks for the combination of carbamazepine and valproate and the combination of phenobarbital and caffeine with other antiepileptic drugs. This study shows that most antiepileptic drug regimens were associated with an increased risk of major congenital abnormalities in the offspring, in particular valproate (dose-response relationship) and carbamazepine monotherapy, benzodiazepines in polytherapy, and caffeine comedication in combinations with phenobarbital.

  1. Risk Factors and Therapeutic Targets in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sonja Maria Wörmann

    2013-11-01

    Full Text Available Pancreatic cancer (PC is one of the most challenging tumor entities worldwide, characterized as a highly aggressive disease with dismal overall prognosis and an incidence rate equalling mortality rate. Over the last decade, substantial progress has been made to define the morphological changes and key genetic events in pancreatic carcinogenesis. And yet, it is still unclear what factors trigger PC. Some risk factors appear to be associated with sex, age, race/ethnicity, or other rare genetic conditions. Additionally, modifying factors such as smoking, obesity, diabetes, occupational risk factors, etc. increase the potential for acquiring genetic mutations that may result in PC.Another hallmark of PC is its poor response to radio- and chemotherapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches to significantly improve the clinical outcome of PC have been described involving downstream signalling cascades desmoplasia and stromal response as well as tumor microenvironment, immune response, vasculature, and angiogenesis. This review summarizes major risk factors for PC and tries to illuminate relevant targets considerable for new therapeutic approaches.

  2. Specific tolerance induction across a xenogeneic barrier: production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimen

    OpenAIRE

    1990-01-01

    The development of safe methods for inducing donor-specific tolerance across xenogeneic barriers could potentially relieve the critical shortage of allograft donors that currently limits the applicability of organ transplantation. We report here that such tolerance can be induced in a xenogeneic combination (rat----mouse) using a nonmyeloablative and nonlethal preparative regimen. Successful induction of chimerism and donor-specific transplantation tolerance required pretreatment of recipient...

  3. Insulin therapy for diabetes mellitus: treatment regimens and associated costs.

    Science.gov (United States)

    Charbonnel, B; Penfornis, A; Varroud-Vial, M; Kusnik-Joinville, O; Detournay, B

    2012-04-01

    To describe insulin therapy in patients with diabetes, to determine treatment costs and to compare costs among treatment regimens. This observational study was performed by 734 French pharmacists. Adult patients filling an insulin prescription were invited to participate. Participants provided information on their diabetes history and management. Levels of intensification of insulin therapy were determined by the number of injections in type 1 diabetes mellitus (T1DM) patients, and by the different schemes used in type 2 (T2DM) patients, such as basal/intermediate-acting insulin only, and regimens using both basal and rapid-acting insulin. Costs were evaluated according to official medication costs, nurse visits and glucose monitoring kits. A total of 361 patients with T1DM and 1902 with T2DM were enrolled in the survey. Patients with T1DM more frequently took 1-2 injections per day (46.3% of patients) and used single-dose basal insulin together with ≥1 dose of rapid insulin (43.8%). Patients with T2DM used multiple treatment regimens, with 58 different combinations documented. Most took basal/intermediate insulin only (42.5%) or combinations of basal/intermediate and rapid insulins (52.7%). Mean cost of insulin therapy was €27.4/week for T1DM and €45.4/week for T2DM. In T1DM, insulin was the biggest cost component and increased with the number of injections/day. In T2DM, nurse visits were the most important cost contributors irrespective of treatment regimen. Overall, the cost of insulin therapy increased with the complexity of the insulin schemes. Considerable heterogeneity is found in insulin treatment regimens used in everyday diabetes care. Payers should consider the full costs associated with the use of insulin rather than the cost of insulin alone. Treatment algorithms to harmonize insulin therapy should help to improve care, while encouraging patients to self-inject insulin should help to reduce costs. Copyright © 2011 Elsevier Masson SAS. All rights

  4. Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection

    Science.gov (United States)

    Nielsen-Saines, Karin; Watts, D. Heather; Veloso, Valdilea G.; Bryson, Yvonne J.; Joao, Esau C.; Pilotto, Jose Henrique; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M.; Ceriotto, Mariana; Machado, Daisy; Bethel, James; Morgado, Marisa G.; Dickover, Ruth; Camarca, Margaret; Mirochnick, Mark; Siberry, George; Grinsztejn, Beatriz; Moreira, Ronaldo I.; Bastos, Francisco I.; Xu, Jiahong; Moye, Jack; Mofenson, Lynne M.

    2013-01-01

    Background The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants. Methods Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth. Results A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan–Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intra-partum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P = 0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P = 0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P = 0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups). Conclusions In neonates whose mothers did not receive ART

  5. Acid demineralization susceptibility of dental enamel submitted to different bleaching techniques and fluoridation regimens.

    Science.gov (United States)

    Salomão, Dlf; Santos, Dm; Nogueira, Rd; Palma-Dibb, Rg; Geraldo-Martins, Vr

    2014-01-01

    The aim of the current study was to assess the acid demineralization susceptibility of bleached dental enamel submitted to different fluoride regimens. One hundred bovine enamel blocks (6×6×3 mm) were randomly divided into 10 groups (n=10). Groups 1 and 2 received no bleaching. Groups 3 to 6 were submitted to an at-home bleaching technique using 6% hydrogen peroxide (HP; G3 and G4) or 10% carbamide peroxide (CP; G5 and G6). Groups 7 to 10 were submitted to an in-office bleaching technique using 35% HP (G7 and G8) or 35% CP (G9 and G10). During bleaching, a daily fluoridation regimen of 0.05% sodium fluoride (NaF) solution was performed on groups 3, 5, 7, and 9, while weekly fluoridation with a 2% NaF gel was performed on groups 4, 6, 8, and 10. The samples in groups 2 to 10 were pH cycled for 14 consecutive days. The samples from all groups were then assessed by cross-sectional Knoop microhardness at different depths from the outer enamel surface. The average Knoop hardness numbers (KHNs) were compared using one-way analysis of variance and Tukey tests (α=0.05). The comparison between groups 1 and 2 showed that the demineralization method was effective. The comparison among groups 2 to 6 showed the same susceptibility to acid demineralization, regardless of the fluoridation method used. However, the samples from groups 8 and 10 showed more susceptibility to acid demineralization when compared with group 2 (penamel to acid demineralization. However, the use of 35% HP and 35% CP must be associated with a daily fluoridation regimen, otherwise the in-office bleaching makes the bleached enamel more susceptible to acid demineralization.

  6. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    Science.gov (United States)

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  7. Outcomes of autologous transplantation for multiple myeloma according to different induction regimens

    Directory of Open Access Journals (Sweden)

    Edvan de Queiroz Crusoe

    2014-01-01

    Full Text Available Background: Induction therapy followed by high-dose chemotherapy and autologous transplantation is the standard treatment for suitable patients with multiple myeloma. Objective: The aim of this study was to assess whether induction therapy with thalidomidecontaining regimens was associated with improved results compared to vincristine, doxorubicin, and dexamethasone, and whether cyclophosphamide, thalidomide, and dexamethasone were associated with better results than thalidomide and dexamethasone. Methods: The records of 152 patients who underwent autologous transplantation at this institution from August of 2004 to January of 2012 were reviewed, selecting those with at least partial response to a maximum of eight cycles of induction therapy and sufficient follow-up information for analysis. Results: This study included 89 patients; 44 were female, with a mean age of 55 years (there was a significant trend for increasing age over the years of the study.The median number of induction therapy cycles was four, again with a trend of increase over the years.At least a very good partial response to induction therapy was achieved more often in the cyclophosphamide, thalidomide, and dexamethasone group (61.1% and in the thalidomide and dexamethasone group (59.2% than in the vincristine, doxorubicin, and dexamethasone group (16.2%. The overall median progression-free survival was 34 months, with no statistically significant difference between the three groups. The overall median survival was not reached, and there was no significant difference between the three groups; the estimated five-year overall survival was 55%. Conclusion: Although the quality of responses appeared to be better with thalidomidecontaining regimens, these improvements did not translate into improved long-term outcomes. Given its track record, cyclophosphamide, thalidomide, and dexamethasone is currently considered the preferred regimen for first-line induction therapy in the

  8. Toxicities of different first-line chemotherapy regimens in the treatment of advanced ovarian cancer

    Science.gov (United States)

    Qu, Chang-Ping; Sun, Gui-Xia; Yang, Shao-Qin; Tian, Jun; Si, Jin-Ge; Wang, Yi-Feng

    2017-01-01

    Abstract Background: Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths around the world, and several chemotherapy regimens have been applied in the treatment of OC. We aim to compare toxicities of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) using network meta-analysis. Methods: Literature research in Cochrane Library, PubMed, and EMBASE was performed up to November 2015. Eligible randomized controlled trials (RCTs) of different chemotherapy regimens were included. Network meta-analysis combined direct and indirect evidence to assess pooled odds ratios (ORs) and draw the surface under the cumulative ranking (SUCRA) curves. Results: Thirteen eligible RCTs were included in this network meta-analysis, including 8 chemotherapy regimens (paclitaxel + carboplatin [PC], pegylated liposomal doxorubicin [PLD] + carboplatin, carboplatin, gemcitabine + carboplatin, paclitaxel, PC + epirubicin, PC + topotecan, docetaxel + carboplatin). Gemcitabine + carboplatin regimen exerted higher incidence of anemia when compared with carboplatin and paclitaxel regimens. The incidence of febrile neutropenia of gemcitabine + carboplatin regimen was higher than that of PC, PLD + carboplatin, carboplatin, and PC + topotecan regimens. Topotecan PC + epirubicin regimen had a higher toxicity, comparing with PC, PLD + carboplatin, and PC + topotecan regimens. As for thrombocytopenia, gemcitabine + carboplatin chemotherapy regimen produced an obviously higher toxicity than PC and carboplatin. As for nausea, PLD + carboplatin chemotherapy regimen had a significantly higher toxicity than that of carboplatin chemotherapy regimen. Moreover, when compared with PC and carboplatin chemotherapy regimens, the toxicity of PC + epirubicin was greatly higher to patients with AOC. Conclusion: The nonhematologic toxicity of PLD + carboplatin regimen was higher than other regimens, which

  9. The Relationship between Cognitive Appraisal and Adherence to Medical Regimens in Type 2 Diabetic Patients

    OpenAIRE

    Shahnaz Ahrari; Ali Mohammadpour; Zahra Amouzeshi; Alireza Agha-Yousefi

    2014-01-01

    Introduction: Non-adherence to medical regimen has remained a challenge to the medical profession as well as to social sciences. To achieve positive results, the factors negatively impacting patient adherence to medical regimens (i.e., diet, drug and exercise regimen) must be scrutinized in detail. The objective of this research was to explore the relationship between cognitive appraisal and adherence to medical regimens in type 2 diabetic patients. Methods: In this correla...

  10. Placebo-controlled comparison of three dose-regimens of 5-hydroxytryptophan challenge test in healthy volunteers.

    Science.gov (United States)

    Gijsman, Harm J; van Gerven, Joop M A; de Kam, Marieke L; Schoemaker, Rik C; Pieters, Monique S M; Weemaes, Margo; de Rijk, Roel; van der Post, Jeroen; Cohen, Adam F

    2002-04-01

    Single-dose administration of 5-hydroxytryptophan (5-HTP) is regularly used as a challenge test of the serotonergic system. The use of 5-HTP has been limited by an apparent small window between the occurrence of neuroendocrine endpoints and the occurrence of side effects. Therefore, many dosing strategies have been tried with and without concurrent administration of carbidopa, a peripheral inhibitor of the decarboxylation from 5-HTP to serotonin. The aim of the current study was to assess the relation between pharmacokinetics and pharmacodynamics of 5-HTP. Twelve healthy male volunteers were included in a placebo-controlled, randomized, four-way crossover, double-blind, single-dose investigation of oral 5-HTP with or without coadministration of carbidopa. The four dose regimens were placebo, 5-HTP 100 mg, 5-HTP 200 mg, and 5-HTP 100 mg with coadministration of carbidopa 100 mg and 50 mg at 3 hours before and 3 hours after the administration of 5-HTP, respectively. The last regimen resulted in a doubling of the elimination half-life, an apparent clearance at least 14 times smaller, and a 15.4 times greater area under the curve compared with 5-HTP 100 mg without carbidopa. Furthermore, it was the only regimen to induce a significant change in cortisol and prolactin. It did not induce any change in subjective psychologic symptoms or cardiovascular parameters, but it was the only regimen to induce some nausea in three participants. The authors conclude that this regimen of 5-HTP 100 mg plus carbidopa is a relatively simple, effective, and tolerable challenge of the presynaptic serotonergic system. Further increase of the dose of 5-HTP might improve the size of the effect on endpoints as long as the tolerability remains good.

  11. Association between Regimen Composition and Treatment Response in Patients with Multidrug-Resistant Tuberculosis: A Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Courtney M Yuen

    2015-12-01

    average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09-1.69. Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65-2.41 or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48-1.84, per drug in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18-1.51, per drug. Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09-1.76, per drug when three effective drugs present in regimen. The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse.MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens.

  12. Eradication of Helicobacter pylori in Children by Triple Therapy Regimens of Amoxicillin, Omeprazole, and Clarithromycin or Azithromycin

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Esmaeili-Dooki

    2015-12-01

    Full Text Available Background and Objectives: The present study aimed to evaluate the effect of classical and azithromycin-containing triple therapy eradication regimen against H. Pylori in children, and to determine the level of patients’ tolerance. Patients and Methods: This single clinical trial was performed in 2014 on 2 to 15 years old children. All children, in whom H. Pylori infection was confirmed through multiple biopsies of the stomach and required treatment, were enrolled in the study. H. Pylori-positive patients were treated alternately with two different drug regimens; Group OCA received clarithromycin 7.5 mg/kg/day every 12 hours for 10 days, amoxicillin 50 mg/kg/day every 12 hours for 10 days, and omeprazole 1 mg/kg/day every 12 hours for two weeks, and Group OAA received azithromycin 10 mg/kg/day once a day (before meal for 6 days along with amoxicillin and omeprazole. Four to six weeks after completion of treatment, patients’ stool was tested for H. Pylori through the monoclonal method using the Helicobacter antigen quick kit. Results: There were no significant differences between the two groups regarding gender and age of patients. Based on ITT analysis, the therapeutic response in the OAA and OCA groups were 56.2% and 62.5%, respectively (P = 0.40. Drug adverse effects were 15.6% in the OCA and 3.1% in the OAA group (P = 0.19. Conclusions: The therapeutic response was seen in more than half of the patients treated with triple therapy of H. Pylori eradication regimen including azithromycin or clarithromycin, and there was no significant difference between the two treatment groups.

  13. Postmenopausal hormone use and incident ovarian cancer: Associations differ by regimen.

    Science.gov (United States)

    Hildebrand, Janet S; Gapstur, Susan M; Feigelson, Heather Spencer; Teras, Lauren R; Thun, Michael J; Patel, Alpa V

    2010-12-15

    Ovarian cancer has been associated in epidemiologic studies with postmenopausal hormone use. Whether associations differ by hormone regimen, current status or duration of use is unclear. We examined epithelial ovarian cancer incidence in relation to unopposed estrogen (E-only) and estrogen plus progestin (E + P) among 54,436 postmenopausal women of the Cancer Prevention Study II Nutrition Cohort, a US cohort prospectively followed for cancer incidence since 1992. Demographic, medical, reproductive and lifestyle information was collected at enrollment and updated throughout follow-up via self-administered questionnaire. Extended Cox models were used to estimate age- and multivariate-adjusted relative risk (RR) of ovarian cancer according to hormone regimen, current status and duration of use. During 15 years of follow-up, 297 incident cases were identified. Relative to "never" use of hormones, current E-only use was associated with a twofold higher risk [RR 2.07, 95% confidence interval (CI) 1.50-2.85]; each 5-year increment of use was associated with a 25% higher risk (RR 1.25, 95% CI 1.15-1.36); ≥ 20 years of use was associated with a near threefold higher risk (RR 2.89; 95% CI 1.71-4.87; trend p = 0.01). Past E-only use was not significantly associated with ovarian cancer, although a modest increase in risk per each 5-year increment of use was suggested (RR 1.14, 95% CI 0.92-1.41). Neither current nor former E + P use was associated with ovarian cancer risk (RR 1.08, 95% CI 0.86-1.35; RR 1.08, 95% CI 0.68-1.71, respectively, per 5-year increment). These findings suggest that progestins may mitigate some of the detrimental effects of estrogen on the ovarian epithelium.

  14. [Therapeutic education didactic techniques].

    Science.gov (United States)

    Valverde, Maite; Vidal, Mercè; Jansa, Margarida

    2012-10-01

    This article includes an introduction to the role of Therapeutic Education for Diabetes treatment according to the recommendations of the American Diabetes Association (ADA), the Diabetes Education Study Group (DESG) of the "European Association for Study of Diabetes (EASD) and the clinical Practice Guidelines (CPG) of the Spanish Ministry of Health. We analyze theoretical models and the differences between teaching vs. learning as well as current trends (including Internet), that can facilitate meaningful learning of people with diabetes and their families and relatives. We analyze the differences, similarities, advantages and disadvantages of individual and group education. Finally, we describe different educational techniques (metaplan, case method, brainstorming, role playing, games, seminars, autobiography, forums, chats,..) applicable to individual, group or virtual education and its application depending on the learning objective.

  15. Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults : 48-week results from the antiretroviral regimen evaluation study (ARES)

    NARCIS (Netherlands)

    Lowe, SH; Wensing, AMJ; Hassink, EAM; ten Kate, RW; Richter, C; Schreij, G; Koopmans, PP; Juttmann, J.; van der Tweel, I.; Lange, JMA; Borleffs, JCC

    2005-01-01

    Background: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. Method: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida

  16. Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults: 48-week results from the Antiretroviral Regimen Evaluation Study (ARES).

    NARCIS (Netherlands)

    Lowe, S.H.; Wensing, B.M.; Hassink, E.A.M.; Kate, R.W. ten; Richter, C.; Schreij, G.; Koopmans, P.P.; Juttmann, J.R.; Tweel, I. van de; Lange, J.M.A.; Borleffs, J.C.

    2005-01-01

    BACKGROUND: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. METHOD: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida

  17. Labour induction with an intermediate-dose oxytocin regimen has advantages over a high-dose regimen.

    Science.gov (United States)

    Manjula, B G; Bagga, R; Kalra, J; Dutta, S

    2015-05-01

    A total of 200 women planned for labour induction were randomised to receive high-dose oxytocin (6 mU/min with similar increments every 45 min) or intermediate-dose oxytocin (3 mU/min with similar increments every 45 min). Oxytocin solution was prepared with 30 units in 500 ml saline with which the infusion rate in ml/h is numerically equal to oxytocin in mU/min. We observed that the caesarean rate (18% vs 6%, p = 0.009), contraction abnormalities (35% vs 14%, p = 0.0005) and neonatal bilirubin levels (7.99 ± 2.70 vs 6.80 ± 2.65, p = 0.002) were higher with high-dose than with intermediate-dose. The induction-delivery interval (IDI) was similar (10 h 13 min with high-dose and 11 h 5 min with intermediate-dose; p = 0.237, NS). Nulliparous women benefited more with intermediate-dose as the caesarean rate was higher with high-dose (24.6% vs 7.9%, p = 0.011). Although the caesarean rate was higher in multiparous women with high-dose oxytocin, it was statistically not significant (5.7% vs 2.7%; p = 0.609). Oxytocin regimens for labour induction are usually high-dose (4-6 mU/min) or low-dose (1-1.5 mU/min). The former is associated with more contraction abnormalities and the latter with prolonged IDI; both result in an increased caesarean rate. In order to offset these disadvantages, an intermediate- dose regimen was selected. The increment interval of 45 min was selected in accordance with the pharmacokinetics of oxytocin. We observed a lower caesarean rate when compared with the high-dose regimen, without any increase in the IDI. Hence, we propose that the intermediate-dose oxytocin regimen should be preferred to the high-dose regimen for labour induction.

  18. [Clinical efficacy of decitabine combined with modified CAG regimen for relapsed-refractory acute myeloid leukemia with AML1-ETO⁺].

    Science.gov (United States)

    Jing, Yu; Zhu, Cheng-Ying; Zhang, Qi; Niu, Jian-Hua; Yang, Hua; Liu, Shi-Yan; Zhu, Hai-Yan; Yu, Li

    2014-10-01

    This study was aimed to investigate the clinical characteristics of relapsed-refractory acute myeloid leukemia (AML) with AML1-ETO⁺, and its therapeutic efficacy and side effects when decitabine combined with modified CAG regimen was used. Clinical data of 5 cases of AML with AML1-ETO⁺ from January 2013 to Agust 2013 were analyzed retrospectively. The analyzed data included age, sex, initial symptoms, peripheral blood and bone marrow characteristics. Meanwhile, the therapeutic effecacy and side effects of decitabine combined with modified CAG regimen were evaluated. The 5 patients were with median age of 35 (17-43) years. Among these 5 patients, 2 patients were relapsed and other 3 patients were relapsed-refractory patients, their median white blood cell count was 12.55 (7.8-66.55) × 10⁹/L, median platelets count was 44 (20-72) × 10⁹/L, median hemoglobin level was 110 (77-128) g/L, median lactate dehydrogenase level was 312.9 U/L (123.6-877.8) at the initial diagnosis. The results showed that after decitabine combined with modified CAG regimen was administered, 4 patients achieved complete remission, 1 patient did not achieve remission, the overall remission rate was 80% (4/5). The main side effects of this regimen was myelosuppression, these were no new lung infection and other serious complications, one case without complete remission treated with FLAG once again died of heart failure when being mobilized for transplantation. It is concluded that according to preliminary results of decitabine combined with modified CAG regimen for relapsed and refractory AML patients with AML1-ETO⁺ displays higher remission rate and lower side effects, which worthy to further explore for clinal application.

  19. Practical strategies for enhancing adherence to treatment regimen in inflammatory bowel disease.

    Science.gov (United States)

    Greenley, Rachel N; Kunz, Jennifer H; Walter, Jennifer; Hommel, Kevin A

    2013-06-01

    Promoting adherence to treatment among pediatric and adult patients with inflammatory bowel disease (IBD) is a critical yet challenging task for health care providers. Several existing interventions to enhance adherence among individuals with IBD offer useful information about practical strategies to enhance adherence. The current review article has 3 goals. First, the review provides a context for understanding treatment regimen adherence in IBD by reviewing key definitional, measurement, and conceptual challenges in this area. Next, published studies focused on interventions to enhance adherence in IBD are briefly summarized, followed by a synthesis of practical adherence promotion strategies for use in IBD by health care providers. Strategies are distinguished by the level of evidence supporting their utility as well as by age group. Finally, recommendations for future research to facilitate the development and implementation of practical, evidence-based strategies for adherence promotion in IBD are provided. Findings from the literature review suggest that strategies including education, regimen simplification, and use of reminder systems and organizational strategies (e.g., pill boxes) are likely to be best suited for addressing accidental nonadherence. In contrast, addressing motivational issues, teaching problem-solving skills, and addressing problematic patterns of family functioning are more likely to benefit individuals displaying intentional nonadherence.

  20. Advances in conditioning regimens for older adults undergoing allogeneic stem cell transplantation to treat hematologic malignancies.

    Science.gov (United States)

    William, Basem M; de Lima, Marcos

    2013-06-01

    Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematological malignancies. These diseases, however, have their peak incidence in the sixth to eighth decades of life. Historically, elderly patients have been considered unsuitable candidates for SCT because of high treatment-related mortality (TRM). Over the past 15 years, the use of reduced-intensity conditioning (RIC) regimens before SCT has allowed patients in the sixth and seventh decades of life to be routinely transplanted. Despite major differences among transplant centers in the intensity and composition of the conditioning regimen and immunosuppression, choice of graft source, postgraft immunomodulation, and supportive care, there has been a dramatic decrease in TRM, allowing safer delivery of SCT. Major obstacles to SCT in elderly patients include donor availability, graft-versus-host disease, delayed immune recovery, multiple comorbidities, and chemo refractoriness. Here we review the current results of SCT in elderly patients, focusing on the role of RIC, and using myeloid diseases as the model for discussion.

  1. Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

    Directory of Open Access Journals (Sweden)

    Julia L. Hurwitz

    2010-02-01

    Full Text Available Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans.

  2. Molecular therapeutics in pancreas cancer

    Institute of Scientific and Technical Information of China (English)

    Vignesh Narayanan; Colin D Weekes

    2016-01-01

    The emergence of the "precision-medicine" paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma(PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease.

  3. Predictors of nonadherence with blood pressure regimens in hemodialysis

    Directory of Open Access Journals (Sweden)

    Kauric-Klein Z

    2013-09-01

    Full Text Available Zorica Kauric-KleinCollege of Nursing, Wayne State University, Detroit, MI, USABackground: Hypertension is very poorly controlled in patients on hemodialysis (HD. Demographic and psychosocial predictors of nonadherence with blood pressure (BP regimens in HD have not been investigated. A study of 118 HD patients from six outpatient HD units was conducted to determine the relationship between demographic/psychosocial factors and adherence with BP-related regimens, ie, fluid restriction, BP medication adherence, and HD treatment adherence.Methods: Descriptive statistics, Pearson correlations, and multiple regressions were conducted to analyze and determine the relationships between variables.Results: Younger age was related to increased fluid gains (r = -0.37, P < 0.01, decreased medication adherence (r = -0.19, P = 0.04, increased missed HD treatments (r = -0.37, P < 0.01, and diastolic BP (r = -0.60, P < 0.01. Female sex was significantly related to decreased fluid gains (r = -0.28, P < 0.01. Race was related to increased missed HD treatments (r = 0.22, P = 0.02. Increased social support was related to decreased missed HD treatments (r = -0.22, P = 0.02. Depression scores were inversely related to decreased medication adherence scores (r = 0.24, P = 0.01.Conclusion: By identifying risk factors for nonadherence with BP-related regimens (young age, male sex, decreased social support, and depression, health care providers can plan early clinical intervention to minimize the risk of nonadherence.Keywords: nonadherence, hemodialysis, blood pressure, demographic predictors, psychosocial predictors

  4. Esquemas alternativos de hemodiálise Alternative hemodialysis regimens

    Directory of Open Access Journals (Sweden)

    Jorge Paulo Strogoff de Matos

    2010-03-01

    Full Text Available A taxa de mortalidade entre os pacientes em hemodiálise (HD é extremamente elevada. A expectativa de vida restante de um paciente ao iniciar HD é apenas cerca de um quarto daquela da população geral com a mesma idade. O esquema convencional de HD, com três sessões semanais de cerca de quatro horas, foi estabelecido de maneira empírica há cerca de quatro décadas e merece ser reavaliado criticamente. Desde a falha do Estudo HEMO em demonstrar benefícios clínicos com o aumento do Kt/V de ureia nos pacientes em esquema convencional de HD, tem havido um crescente interesse pelos esquemas alternativos de HD com o intuito de prover um tratamento associado com uma melhor sobrevida. Dentre os esquemas mais promissores, destacam-se a HD diária de curta duração e a HD noturna prolongada. As limitações econômicas que inibem a aplicação dos conhecimentos emergentes nesta área devem ser vencidas.The mortality rate among patients on hemodialysis (HD is extremely high. Remaining life expectancy for a patient initiating HD is only approximately one quarter of that of the general population at the same age bracket. The conventional HD regimen based on four-hour sessions three times a week was empirically established nearly four decades ago and needs to be revisited. Since the failure of the HEMO Study to demonstrate the clinical benefits of higher urea Kt/V for patients on conventional HD, an increasing interest for alternative HD regimens has emerged aiming at providing a treatment for improving survival rates. Short daily HD and long nocturnal HD stand out as the most promising alternative regimens. Economical obstacles which could hinder the clinical application of emerging knowledge in the field should be overcome.

  5. Management of patients using unproven regimens for arthritis.

    Science.gov (United States)

    Wolman, P G

    1987-09-01

    Such treatments as vegetarian diets, fresh or raw diets, allergy diets, no-dairy-products diets, fasting, vitamin and mineral supplementation, apple cider vinegar, and honey drinks are touted in the popular press as effective for the treatment of arthritis. In contrast to conventional therapies, the unproven treatments promise not only relief from symptoms but freedom from the disease as long as the diet regimen is followed. Several of the remedies appear to be harmless, but others are dangerous, especially if followed for prolonged periods. Nutrition professionals should be aware of the nature of these treatments and be prepared to offer sound, scientifically based but nonjudgmental care and information.

  6. Adherence to diabetes regimens: empirical status and clinical applications.

    Science.gov (United States)

    Kurtz, S M

    1990-01-01

    Adherence to diabetes treatment regimens has proved to be a conceptual and empirical enigma. Consequently, reliable and valid applications to the clinical practice of diabetes care and education have been wanting. Rates of nonadherence are staggeringly high, regardless of the methodology employed, and verification of self-reports is complicated by social desirability to appear compliant. Low intertask correlations further complicate our understanding of adherence-metabolic control relationships. Studies relating to the Health Belief Model, social learning theory, and the psychology of interpersonal relationships that have sought to identify determinants of adherence behaviors have specific relevance to the clinical practice of diabetes education.

  7. Potential therapeutic applications of biosurfactants.

    Science.gov (United States)

    Gudiña, Eduardo J; Rangarajan, Vivek; Sen, Ramkrishna; Rodrigues, Lígia R

    2013-12-01

    Biosurfactants have recently emerged as promising molecules for their structural novelty, versatility, and diverse properties that are potentially useful for many therapeutic applications. Mainly due to their surface activity, these molecules interact with cell membranes of several organisms and/or with the surrounding environments, and thus can be viewed as potential cancer therapeutics or as constituents of drug delivery systems. Some types of microbial surfactants, such as lipopeptides and glycolipids, have been shown to selectively inhibit the proliferation of cancer cells and to disrupt cell membranes causing their lysis through apoptosis pathways. Moreover, biosurfactants as drug delivery vehicles offer commercially attractive and scientifically novel applications. This review covers the current state-of-the-art in biosurfactant research for therapeutic purposes, providing new directions towards the discovery and development of molecules with novel structures and diverse functions for advanced applications.

  8. Economic Outcomes of First-Line Regimen Switching Among Stable Patients with HIV.

    Science.gov (United States)

    Rosenblatt, Lisa; Buikema, Ami R; Seare, Jerry; Bengtson, Lindsay G S; Johnson, Jonathan; Cao, Feng; Villasis-Keever, Angelina

    2017-07-01

    Although switching of antiretroviral therapy (ART) is a valid approach for addressing treatment failure in patients with human immunodeficiency virus (HIV), ART changes among those who are well maintained on their current regimens may lead to the development of new side effects or resistance. To examine the effect of first-line regimen switching on subsequent health care utilization and cost among stable HIV patients. This was a retrospective claims data study of adult patients with HIV who initiated ART between 2007 and 2013 and had been treated with their initial regimens for at least 6 continuous months. Those with evidence of pregnancy or HIV-2 were excluded. Patients who underwent an ART change were assigned to a switcher cohort; a nonswitcher cohort was then generated by matching up to 20 nonswitchers for each switcher, with replacement. The index date was the date of the first ART change for switchers and was the claim date closest to the corresponding switcher's switch date for nonswitchers. Patient characteristics at baseline and post-index annualized health care utilization and costs were analyzed descriptively and with multivariable models. Analyses were performed in the full population and among patients designated as virologically stable (had undetectable viral ribonucleic acid [RNA] for 90 days pre-index) and virologically and clinically stable (had undetectable viral RNA and no apparent clinical reason for switching ART). The study population consisted of 6,983 individuals, which included 927 switchers (168 virologically stable; 55 virologically+clinically stable), who were matched with replacement with 18,511 nonswitcher comparators. The switcher cohort was 88.8% male (mean age 43.8 years). Mean preindex and follow-up treatment durations for switchers and nonswitchers were 1.8 years and 1.5 years, respectively; demographic characteristics, pre-index treatment duration, and follow-up duration were similar between cohorts. Significantly more

  9. Postcesarean Thromboprophylaxis with Two Different Regimens of Bemiparin

    Directory of Open Access Journals (Sweden)

    Milagros Cruz

    2011-01-01

    Full Text Available Objectives. To compare the effectiveness of postcesarean thromboprophylaxis with two different regimens of bemiparin. Material and Methods. The study included 646 women with cesarean delivery in our hospital within a 1-year period, randomly assigned to one of two groups for prophylaxis with 3500 IU bemiparin once daily for 5 days or 3500 IU bemiparin once daily for 10 days. Results. There was one case of pulmonary embolism (first day following cesarean. An additional risk factor was present in 98.52% of the women, most frequently emergency cesarean, anemia, or obesity. The only risk factors for thromboembolic disease significantly related to pulmonary thromboembolism were placental abruption and prematurity. There were no differences in thromboembolic events among the two thromboprophylaxis regimens. Conclusions. Cesarean-related thromboembolic events were reduced in our study population due to the thromboprophylactic measures taken. Thromboprophylaxis with 3500 IU bemiparin once daily for 5 days following cesarean was sufficient to avoid thromboembolic events.

  10. Low Dose Mesalazine Plus Bismuth Regimen and Symptoms of Irritable Bowel Syndrome in Patients with Bloating: A Quasi-Experimental Study

    Directory of Open Access Journals (Sweden)

    Alavinejad

    2016-08-01

    randomized clinical trials evaluate this therapeutic regimen.

  11. Docetaxel plus cetuximab biweekly is an active regimen for the first-line treatment of patients with recurrent/metastatic head and neck cancer

    Science.gov (United States)

    Posch, Doris; Fuchs, Hannah; Kornek, Gabriela; Grah, Anja; Pammer, Johannes; Aretin, Marie-Bernadette; Fuereder, Thorsten

    2016-09-01

    For patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCCHN) limited therapeutic options exist. Only a subset of patients is suitable for combination chemotherapy regimens. Biweekly docetaxel plus cetuximab might be an alternative option. Thus, we performed this retrospective analysis in unselected patients in order to investigate the efficacy and safety of this regimen. Thirty-one patients receiving off protocol docetaxel (50 mg/m2) plus cetuximab (500 mg/m2) biweekly were included. Data collection included baseline demographic, response rate (ORR), disease control rate (DCR), overall survival (OS), progression free survival (PFS) as well as toxicity. OS and PFS were 8.3 months (95% CI 4.8-11.8) and 4.0 months (95% CI 1.0-7.0), respectively. Three (9.7%) patients achieved a complete response and one patient (3.2%) a partial response. The DCR was 41.9% and we observed an ORR of 12.9%. The one-year survival rate was 25.8%. The therapy was well tolerated and the most common grade 3/4 adverse events were neutropenia (19.4%), hypomagnesaemia (12.9%) and acne-like rash (9.7%). Biweekly cetuximab/docetaxel is an effective regimen and well tolerated in R/M SCCHN patients not suitable for platinum doublet treatment. Further evaluation of this regimen in prospective clinical trials is warranted.

  12. Rapid evaluation in whole blood culture of regimens for XDR-TB containing PNU-100480 (sutezolid), TMC207, PA-824, SQ109, and pyrazinamide.

    Science.gov (United States)

    Wallis, Robert S; Jakubiec, Wesley; Mitton-Fry, Mark; Ladutko, Lynn; Campbell, Sheldon; Paige, Darcy; Silvia, Annette; Miller, Paul F

    2012-01-01

    There presently is no rapid method to assess the bactericidal activity of new regimens for tuberculosis. This study examined PNU-100480, TMC207, PA-824, SQ109, and pyrazinamide, singly and in various combinations, against intracellular M. tuberculosis, using whole blood culture (WBA). The addition of 1,25-dihydroxy vitamin D facilitated detection of the activity of TMC207 in the 3-day cultures. Pyrazinamide failed to show significant activity against a PZA-resistant strain (M. bovis BCG), and was not further considered. Low, mid, and high therapeutic concentrations of each remaining drug were tested individually and in a paired checkerboard fashion. Observed bactericidal activity was compared to that predicted by the sum of the effects of individual drugs. Combinations of PNU-100480, TMC207, and SQ109 were fully additive, whereas those including PA-824 were less than additive or antagonistic. The cumulative activities of 2, 3, and 4 drug combinations were predicted based on the observed concentration-activity relationship, published pharmacokinetic data, and, for PNU-100480, published WBA data after oral dosing. The most active regimens, including PNU-100480, TMC207, and SQ109, were predicted to have cumulative activity comparable to standard TB therapy. Further testing of regimens including these compounds is warranted. Measurement of whole blood bactericidal activity can accelerate the development of novel TB regimens.

  13. Rapid evaluation in whole blood culture of regimens for XDR-TB containing PNU-100480 (sutezolid, TMC207, PA-824, SQ109, and pyrazinamide.

    Directory of Open Access Journals (Sweden)

    Robert S Wallis

    Full Text Available There presently is no rapid method to assess the bactericidal activity of new regimens for tuberculosis. This study examined PNU-100480, TMC207, PA-824, SQ109, and pyrazinamide, singly and in various combinations, against intracellular M. tuberculosis, using whole blood culture (WBA. The addition of 1,25-dihydroxy vitamin D facilitated detection of the activity of TMC207 in the 3-day cultures. Pyrazinamide failed to show significant activity against a PZA-resistant strain (M. bovis BCG, and was not further considered. Low, mid, and high therapeutic concentrations of each remaining drug were tested individually and in a paired checkerboard fashion. Observed bactericidal activity was compared to that predicted by the sum of the effects of individual drugs. Combinations of PNU-100480, TMC207, and SQ109 were fully additive, whereas those including PA-824 were less than additive or antagonistic. The cumulative activities of 2, 3, and 4 drug combinations were predicted based on the observed concentration-activity relationship, published pharmacokinetic data, and, for PNU-100480, published WBA data after oral dosing. The most active regimens, including PNU-100480, TMC207, and SQ109, were predicted to have cumulative activity comparable to standard TB therapy. Further testing of regimens including these compounds is warranted. Measurement of whole blood bactericidal activity can accelerate the development of novel TB regimens.

  14. Comparison of effectiveness and safety of imipenem/clavulanate- versus meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB.

    Science.gov (United States)

    Tiberi, Simon; Sotgiu, Giovanni; D'Ambrosio, Lia; Centis, Rosella; Abdo Arbex, Marcos; Alarcon Arrascue, Edith; Alffenaar, Jan Willem; Caminero, Jose A; Gaga, Mina; Gualano, Gina; Skrahina, Alena; Solovic, Ivan; Sulis, Giorgia; Tadolini, Marina; Alarcon Guizado, Valentina; De Lorenzo, Saverio; Roby Arias, Aurora Jazmín; Scardigli, Anna; Akkerman, Onno W; Aleksa, Alena; Artsukevich, Janina; Auchynka, Vera; Bonini, Eduardo Henrique; Chong Marín, Félix Antonio; Collahuazo López, Lorena; de Vries, Gerard; Dore, Simone; Kunst, Heinke; Matteelli, Alberto; Moschos, Charalampos; Palmieri, Fabrizio; Papavasileiou, Apostolos; Payen, Marie-Christine; Piana, Andrea; Spanevello, Antonio; Vargas Vasquez, Dante; Viggiani, Pietro; White, Veronica; Zumla, Alimuddin; Migliori, Giovanni Battista

    2016-06-01

    No large study to date has ever evaluated the effectiveness, safety and tolerability of imipenem/clavulanate versus meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to compare the therapeutic contribution of imipenem/clavulanate versus meropenem/clavulanate added to background regimens to treat MDR- and XDR-TB cases.84 patients treated with imipenem/clavulanate-containing regimens showed a similar median number of antibiotic resistances (8 versus 8) but more fluoroquinolone resistance (79.0% versus 48.9%, pTB prevalence (67.9% versus 49.0%, p=0.01) in comparison with 96 patients exposed to meropenem/clavulanate-containing regimens. Patients were treated with imipenem/clavulanate- and meropenem/clavulanate-containing regimens for a median (interquartile range) of 187 (60-428) versus 85 (49-156) days, respectively.Statistically significant differences were observed on sputum smear and culture conversion rates (79.7% versus 94.8%, p=0.02 and 71.9% versus 94.8%, pMDR/XDR-TB patients.

  15. Epstein-Barr infection: Current treatment options

    Directory of Open Access Journals (Sweden)

    Abubakar Yaro

    2013-01-01

    Full Text Available Epstein-Barr virus is one of the causes of known human cancers such as PLTD, BL and XLP. It is persistent in about 90% of the global population. Prevalent antiviral agents are not effective. A systematic review was undertaken to discuss current treatment options available for EBV infection. A search was made of PubMed to identify relevant papers published from 2000 to 2010 using various search indexes. The review is based on 11 articles included in the study. The result showed that there is no studies which analyzed antiviral agents in EBV infection. Combinational therapy using antiviral agents, immunotherapy and anticancer agents should be considered while antibiotic regimen should be considered to take care of any sepsis. Resistance to antiviral agents especially cross-resistance is burden in EBV infection Studies should be undertaken to evaluate resistance pattern in EBV infection. To assess the efficacy of EBV therapeutics. Viral load using molecular techniques should be used as biomarker of efficacy.

  16. The pathophysiology of heterotopic ossification: Current treatment considerations in dentistry

    Directory of Open Access Journals (Sweden)

    Kengo Shimono

    2014-02-01

    Full Text Available Heterotopic ossification (HO consists of the formation of ectopic cartilage followed by endochondral bone, and is triggered by major surgeries, large wounds, and other conditions. Daily functions of HO patients can be hampered by the loss of normal posture, pain, inflammation, reduced mobility, formation of pressure ulcers, deep venous thrombosis, and other complications. Research so far revealed the molecular and cellular pathways leading HO formation, and proposed several possible mechanisms behind such pathways. Nonsteroidal anti-inflammatory drug (NSAID regimens and localized low-dose irradiation are currently available as prophylaxis of HO formation. However, they are not always effective and do not target skeletogenic processes directly. New therapeutic modalities targeting pathological process of HO formation, such as bone morphogenetic proteins (BMP inhibitors like Noggin, BMP type 1 receptor inhibitor, and nuclear retinoic acid receptor-gamma (RARγ agonists are currently under investigation. In this review, we will summarize our current understanding of the pathology and molecular and cellular mechanisms of HO, especially endochondral heterotopic ossification, and then discuss its current and future therapies. We will also discuss the potential application of heterotopic ossification in the dental field.

  17. Development of therapeutic HPV vaccines

    OpenAIRE

    Trimble, Cornelia L.; Frazer, Ian H

    2009-01-01

    At least 15% of human malignant diseases are attributable to the consequences of persistent viral or bacterial infection. Chronic infection with oncogenic human papillomavirus (HPV) types is a necessary, but insufficient, cause in the development of more cancers than any other virus. Currently available prophylactic vaccines have no therapeutic effect for established infection or for disease. Early disease is characterised by tissue sequestration. However, because a proportion of intraepithel...

  18. Randomised controlled trial of two sequential artemisinin-based combination therapy regimens to treat uncomplicated falciparum malaria in African children: a protocol to investigate safety, efficacy and adherence

    DEFF Research Database (Denmark)

    Schallig, Henk D. F. H.; Tinto, Halidou; Sawa, Patrick

    2017-01-01

    Background Management of uncomplicated Plasmodium falciparum malaria relies on artemisinin-based combination therapies (ACTs). These highly effective regimens have contributed to reductions in malaria morbidity and mortality. However, artemisinin resistance in Asia and changing parasite...... whether prolonged ACT-based regimens using currently available formulations can eliminate potentially resistant parasites. The protocol investigates whether a sequential course of two licensed ACT in 1080 children aged 6–120 months exhibits superior efficacy against acute P. falciparum malaria and non...... gametocytaemia, occurrence of treatment-related adverse events in the double-ACT versus single-ACT arms, carriage of molecular markers of drug resistance, drug kinetics and patient adherence to treatment. Discussion This protocol addresses efficacy and safety of sequential ACT regimens in P. falciparum malaria...

  19. Variability in the pharmacokinetics of mycophenolic acid: Implications for therapeutic drug monitoring

    NARCIS (Netherlands)

    B.C.M. de Winter (Brenda)

    2010-01-01

    textabstractMycophenolate mofetil (MMF) is an immunosuppressive drug used to prevent rejection following solid organ transplantation. MMF was introduced in 1995 with a recommended fixed-dose regimen of 1 g twice daily. Nowadays, dose individualization using therapeutic drug monitoring (TDM) of the a

  20. Efficacy, nephrotoxicity and ototoxicity of aminoglycosides, mathematically modelled for modelling-supported therapeutic drug monitoring

    NARCIS (Netherlands)

    Croes, Sander; Koop, Arjen H.; van Gils, Stephanus A.; Neef, Cees

    Therapeutic drug monitoring (TDM) of aminoglycosides has been a topic during the last thirty years. There is a tendency that – because of the once-daily regimen – TDM is considered not necessary anymore. Although once daily dosing has the potential for decreased toxicity, long-term usage can cause

  1. Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy.

    Science.gov (United States)

    Guinto, Valerie T; De Guia, Blanca; Festin, Mario R; Dowswell, Therese

    2010-09-08

    Asymptomatic bacteriuria occurs in 5% to 10% of pregnancies and, if left untreated, can lead to serious complications. To assess which antibiotic is most effective and least harmful as initial treatment for asymptomatic bacteriuria in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2010) and reference lists of retrieved studies. Randomized controlled trials comparing two antibiotic regimens for treating asymptomatic bacteriuria. Review authors independently screened the studies for inclusion and extracted data. We included five studies involving 1140 women with asymptomatic bacteriuria. We did not perform meta-analysis; each trial examined different antibiotic regimens and so we were not able to pool results. In a study comparing a single dose of fosfomycin trometamol 3 g with a five-day course of cefuroxime, there was no significant difference in persistent infection (risk ratio (RR) 1.36, 95% confidence interval (CI) 0.24 to 7.75), shift to other antibiotics (RR 0.08, 95% CI 0.00 to 1.45), or in allergy or pruritus (RR 2.73, 95% CI 0.11 to 65.24). A comparison of seven-day courses of 400 mg pivmecillinam versus 500 mg ampicillin, both given four times daily, showed no significant difference in persistent infection at two weeks or recurrent infection, but there was an increase in vomiting (RR 4.57, 95% CI 1.40 to 14.90) and women were more likely to stop treatment early with pivmecillinam (RR 8.82, 95% CI 1.16 to 66.95). When cephalexin 1 g versus Miraxid(R) (pivmecillinam 200 mg and pivampicillin 250 mg) were given twice-daily for three days, there was no significant difference in persistent or recurrent infection. A one- versus seven-day course of nitrofurantoin resulted in more persistent infection with the shorter course (RR 1.76, 95% CI 1.29 to 2.40), but no significant difference in symptomatic infection at two weeks, nausea, or preterm birth. Comparing cycloserine with sulphadimidine, no significant differences in

  2. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial

    DEFF Research Database (Denmark)

    Brandstrup, Birgitte; Tønnesen, Hanne; Beier-Holgersen, Randi;

    2003-01-01

    To investigate the effect of a restricted intravenous fluid regimen versus a standard regimen on complications after colorectal resection.......To investigate the effect of a restricted intravenous fluid regimen versus a standard regimen on complications after colorectal resection....

  3. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth.

    Science.gov (United States)

    Brownfoot, Fiona C; Gagliardi, Daniela I; Bain, Emily; Middleton, Philippa; Crowther, Caroline A

    2013-08-29

    Despite the widespread use of antenatal corticosteroids to prevent respiratory distress syndrome in preterm infants, there is currently no consensus as to the type of corticosteroid to use; nor the dose, frequency, timing of use or the route of administration. To assess the effects of different corticosteroid regimens for women at risk of preterm birth. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (13 February 2013). All identified published and unpublished randomised controlled trials or quasi-randomised control trials comparing any two corticosteroids (dexamethasone or betamethasone or any other corticosteroid that can cross the placenta), comparing different dose regimens (including frequency and timing of administration) in women at risk of preterm birth were included. We planned to exclude cross-over trials and cluster-randomised trials. We included studies published as abstracts only along with studies published as full-text manuscripts Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. For this update, 12 trials (1557 women and 1661 infants) were included. Dexamethasone was associated with a reduced risk of intraventricular haemorrhage (IVH) compared with betamethasone (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.21 to 0.92; four trials, 549 infants). No statistically significant differences were seen for other primary outcomes: respiratory distress syndrome (RDS) (RR 1.06, 95% CI 0.88 to 1.27; five trials, 753 infants) and perinatal death (neonatal death RR 1.41, 95% CI 0.54 to 3.67; four trials, 596 infants). Similarly, very few differences were seen for secondary outcomes such as rate of admission to the neonatal intensive care unit (NICU) although in one trial, those infants exposed to dexamethasone, compared with betamethasone, had a significantly shorter length of NICU admission (mean difference (MD) -0

  4. Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

    Science.gov (United States)

    Cunha-Júnior, Edézio Ferreira; Martins, Thiago Martino; Canto-Cavalheiro, Marilene Marcuzzo; Marques, Paulo Roberto; Portari, Elyzabeth Avvad; Coelho, Marsen Garcia Pinto; Netto, Chaquip Daher; Costa, Paulo Roberto Ribeiro; Sabino, Katia Costa de Carvalho

    2016-01-01

    Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis. PMID:27067332

  5. Potential and development of inhaled RNAi therapeutics for the treatment of pulmonary tuberculosis.

    Science.gov (United States)

    Man, Dede K W; Chow, Michael Y T; Casettari, Luca; Gonzalez-Juarrero, Mercedes; Lam, Jenny K W

    2016-07-01

    Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (Mtb), continues to pose a serious threat to public health, and the situation is worsening with the rapid emergence of multidrug resistant (MDR) TB. Current TB regimens require long duration of treatment, and their toxic side effects often lead to poor adherence and low success rates. There is an urgent need for shorter and more effective treatment for TB. In recent years, RNA interference (RNAi) has become a powerful tool for studying gene function by silencing the target genes. The survival of Mtb in host macrophages involves the attenuation of the antimicrobial responses mounted by the host cells. RNAi technology has helped to improve our understanding of how these bacilli interferes with the bactericidal effect and host immunity during TB infection. It has been suggested that the host-directed intervention by modulation of host pathways can be employed as a novel and effective therapy against TB. This therapeutic approach could be achieved by RNAi, which holds enormous potential beyond a laboratory to the clinic. RNAi therapy targeting TB is being investigated for enhancing host antibacterial capacity or improving drug efficacy on drug resistance strains while minimizing the associated adverse effects. One of the key challenges of RNAi therapeutics arises from the delivery of the RNAi molecules into the target cells, and inhalation could serve as a direct administration route for the treatment of pulmonary TB in a non-invasive manner. However, there are still major obstacles that need to be overcome. This review focuses on the RNAi candidates that are currently explored for the treatment of TB and discusses the major barriers of pulmonary RNAi delivery. From this, we hope to stimulate further studies of local RNAi therapeutics for pulmonary TB treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Plant-derived flavone Apigenin: The small-molecule with promising activity against therapeutically resistant prostate cancer.

    Science.gov (United States)

    Ganai, Shabir Ahmad

    2017-01-01

    Prostate cancer is the second leading cause of cancer related deaths in men in the United States. Mounting evidences suggest that in the pathophysiology of prostate cancer epigenetic modifications play a considerable role. Histone deacetylases (HDACs) have strong crosstalk with prostate cancer progression as they regulate various genes meant for tumour suppression. HDACs are emerging as striking molecular targets for anticancer drugs and therapy as their aberrant expression has been implicated in several cancers. Histone deacetylase inhibitors (HDACi), the small molecules interfering HDACs are the propitious chemotherapeutic agents as they tune the altered acetylation homeostasis for attenuating disease signalling. More than 20 HDACi have entered into the clinical trials and 4 have crossed the journey by gaining FDA approval for treating distinct haematological malignancies including multiple myeloma. Despite the therapeutic benefits, the synthetic HDACi cause detrimental side effects like atrial fibrillation, raising concerns regarding their applicability. Taking these facts into consideration the current article focused on plant-derived HDAC inhibitor Apigenin and its marvelous role in prostate cancer therapy. Moreover, the article sheds light on Apigenin induced apoptosis in various prostate cancer models. The defined inhibitor provokes apoptotic signaling in these models by multiple mechanisms like restraining HDACs, declining the levels of antiapoptotic proteins. Importantly, Apigenin hampers NF-κB signalling and down-modulates its regulated gene products for bringing therapeutic effect. Furthermore, Apigenin shows synergistic effect in combinatorial therapy and induces apoptosis even in prostate cancer models resistant to conventional therapeutic regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Exploring breast with therapeutic ductoscopy.

    Science.gov (United States)

    Balci, Fatih Levent; Feldman, Sheldon Marc

    2014-05-01

    Breast lesions are thought to arise mostly from the epithelium of ductal lining. Conventional imaging could only show indirect images of suspected lesions which are confirmed by percutaneous biopsies. However, ductoscopy provides direct images of the ductal epithelium which is the source of most malignant and papillary lesions. As an advance of current ductoscopy systems, pathologic nipple discharge (PND) could be treated ductoscopically by miniaturized endo-baskets or wires. Our goal is to discuss current intraductal technology which enables diagnostic and therapeutic advance for breast lesions that cause nipple discharge.

  8. Toward the definition of immunosuppressive regimens with antitumor activity.

    Science.gov (United States)

    Casadio, F; Croci, S; D'Errico Grigioni, A; Corti, B; Grigioni, W F; Landuzzi, L; Lollini, P-L

    2005-06-01

    Immunosuppressive therapies associated with organ transplantation produce an increased risk of cancer development. Malignancies are increased in transplant recipients because of the impaired immune system. Moreover, experimental data point to a tumor-promoting activity of various immunosuppressive agents. In this study, we compared the effects of 4 immunosuppressive agents with different mechanisms of action (cyclosporine, rapamycin, mycophenolic acid, and leflunomide) on the in vitro growth of various tumor cell lines and umbilical vein endothelial cells. To varying degrees rapamycin (10 ng/mL), mycophenolic acid (300 nmol/L), and leflunomide (30 micromol/L) highly inhibited the growth of human rhabdomyosarcoma, hepatocellular carcinoma, colorectal carcinoma, and endothelial cells. In contrast, cyclosporine (100 ng/mL) did not affect their growth. Our data suggest that regimens containing rapamycin, mycophenolic acid, or leflunomide, which have both immunosuppressive and antitumor activities, should be preferred in transplant recipients to minimize the risk of tumors.

  9. Medication regimen complexity in ambulatory older adults with heart failure

    Directory of Open Access Journals (Sweden)

    Cobretti MR

    2017-04-01

    Full Text Available Michael R Cobretti,1 Robert L Page II,2 Sunny A Linnebur,2 Kimberly M Deininger,1 Amrut V Ambardekar,3 JoAnn Lindenfeld,4 Christina L Aquilante1 1Department of Pharmaceutical Sciences, 2Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 3Division of Cardiology, School of Medicine, University of Colorado, Aurora, CO, 4Advanced Heart Failure and Cardiac Transplant Program, Vanderbilt Heart and Vascular Institute, Nashville, TN, USA Purpose: Heart failure prevalence is increasing in older adults, and polypharmacy is a major problem in this population. We compared medication regimen complexity using the validated patient-level Medication Regimen Complexity Index (pMRCI tool in “young-old” (60–74 years versus “old-old” (75–89 years patients with heart failure. We also compared pMRCI between patients with ischemic cardiomyopathy (ISCM versus nonischemic cardiomyopathy (NISCM.Patients and methods: Medication lists were retrospectively abstracted from the electronic medical records of ambulatory patients aged 60–89 years with heart failure. Medications were categorized into three types – heart failure prescription medications, other prescription medications, and over-the-counter (OTC medications – and scored using the pMRCI tool.Results: The study evaluated 145 patients (n=80 young-old, n=65 old-old, n=85 ISCM, n=60 NISCM, mean age 73±7 years, 64% men, 81% Caucasian. Mean total pMRCI scores (32.1±14.4, range 3–84 and total medication counts (13.3±4.8, range 2–30 were high for the entire cohort, of which 72% of patients were taking eleven or more total medications. Total and subtype pMRCI scores and medication counts did not differ significantly between the young-old and old-old groups, with the exception of OTC medication pMRCI score (6.2±4 young-old versus 7.8±5.8 old-old, P=0.04. With regard to heart failure etiology, total pMRCI scores and medication

  10. Comparison of antiplatelet regimens in secondary stroke prevention

    DEFF Research Database (Denmark)

    Christiansen, Christine Benn; Pallisgaard, Jannik; Gerds, Thomas Alexander

    2015-01-01

    BACKGROUND: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent...... were calculated for each antiplatelet regimen. RESULTS: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus...... the combination of acetylsalicylic acid and dipyridamole were 1.02 (95% confidence interval [CI]: 0.89-1.17) for ischemic stroke and 1.06 (95% CI: 0.83-1.35) for bleeding. Adjusted HRs for acetylsalicylic acid versus the combination of acetylsalicylic acid and dipyridamole were 1.48 (95% CI: 1.31-1.67) for stroke...

  11. Newer therapeutic molecules for multiple myeloma

    Directory of Open Access Journals (Sweden)

    Jain P

    2008-01-01

    Full Text Available Therapeutic management of multiple myeloma (MM for the last several decades has mainly involved regimens based on use of glucocorticoids and cytotoxic chemotherapeutics. Despite progress in delineating the activity of such regimens, at either conventional or high doses, MM has remained an incurable disease. This has sparked major interest in the development of novel therapies that in part capitalize on recent advances in our understanding of the biology of MM, including the molecular mechanisms by which MM cell-host bone marrow (BM interactions regulate tumor-cell growth, survival, and drug resistance in the BM milieu. Herein, we review the latest progress in the development of these novel anti-MM therapies, with major focus on therapies which have translated from preclinical evaluation to clinical application, including thalidomide and its more potent immunomodulatory derivatives (IMiD, the first-in-class proteasome inhibitor bortezomib (formerly known as PS-341. Search strategy included Medline using the terms ′Myeloma and Newer Drugs′ citations relevant to treatment guidelines issued in 1999 and 2008 were screened.

  12. A modified regimen of extracorporeal cardiac shock wave therapy for treatment of coronary artery disease

    Directory of Open Access Journals (Sweden)

    Wang Yu

    2012-08-01

    Full Text Available Abstract Background Cardiac shock wave therapy (CSWT improves cardiac function in patients with severe coronary artery disease (CAD. We aimed to evaluate the clinical outcomes of a new CSWT treatment regimen. Methods The 55 patients with severe CAD were randomly divided into 3 treatment groups. The control group (n = 14 received only medical therapy. In group A ( n = 20, CSWT was performed 3 times within 3 months. In group B ( n = 21, patients underwent 3 CSWT sessions/week, and 9 treatment sessions were completed within 1 month. Primary outcome measurement was 6-minute walk test (6MWT. Other measurements were also evaluated. Results The 6MWT, CCS grading of angina, dosage of nitroglycerin, NYHA classification, and SAQ scores were improved in group A and B compared to control group. Conclusions A CSWT protocol with 1 month treatment duration showed similar therapeutic efficacy compared to a protocol of 3 months duration. Clinical trial registry We have registered on ClinicalTrials.gov, the protocol ID is CSWT IN CHINA.

  13. Breast Cancer Screening in an Era of Personalized Regimens

    Science.gov (United States)

    Onega, Tracy; Beaber, Elisabeth F.; Sprague, Brian L.; Barlow, William E.; Haas, Jennifer S.; Tosteson, Anna N.A.; Schnall, Mitchell D.; Armstrong, Katrina; Schapira, Marilyn M.; Geller, Berta; Weaver, Donald L.; Conant, Emily F.

    2014-01-01

    Breast cancer screening holds a prominent place in public health, health care delivery, policy, and women’s health care decisions. Several factors are driving shifts in how population-based breast cancer screening is approached, including advanced imaging technologies, health system performance measures, health care reform, concern for “overdiagnosis,” and improved understanding of risk. Maximizing benefits while minimizing the harms of screening requires moving from a “1-size-fits-all” guideline paradigm to more personalized strategies. A refined conceptual model for breast cancer screening is needed to align women’s risks and preferences with screening regimens. A conceptual model of personalized breast cancer screening is presented herein that emphasizes key domains and transitions throughout the screening process, as well as multilevel perspectives. The key domains of screening awareness, detection, diagnosis, and treatment and survivorship are conceptualized to function at the level of the patient, provider, facility, health care system, and population/policy arena. Personalized breast cancer screening can be assessed across these domains with both process and outcome measures. Identifying, evaluating, and monitoring process measures in screening is a focus of a National Cancer Institute initiative entitled PROSPR (Population-based Research Optimizing Screening through Personalized Regimens), which will provide generalizable evidence for a risk-based model of breast cancer screening, The model presented builds on prior breast cancer screening models and may serve to identify new measures to optimize benefits-to-harms tradeoffs in population-based screening, which is a timely goal in the era of health care reform. PMID:24830599

  14. Brown adipose tissue and its therapeutic potential.

    Science.gov (United States)

    Lidell, M E; Betz, M J; Enerbäck, S

    2014-10-01

    Obesity and related diseases are a major cause of human morbidity and mortality and constitute a substantial economic burden for society. Effective treatment regimens are scarce, and new therapeutic targets are needed. Brown adipose tissue, an energy-expending tissue that produces heat, represents a potential therapeutic target. Its presence is associated with low body mass index, low total adipose tissue content and a lower risk of type 2 diabetes mellitus. Knowledge about the development and function of thermogenic adipocytes in brown adipose tissue has increased substantially in the last decade. Important transcriptional regulators have been identified, and hormones able to modulate the thermogenic capacity of the tissue have been recognized. Intriguingly, it is now clear that humans, like rodents, possess two types of thermogenic adipocytes: the classical brown adipocytes found in the interscapular brown adipose organ and the so-called beige adipocytes primarily found in subcutaneous white adipose tissue after adrenergic stimulation. The presence of two distinct types of energy-expending adipocytes in humans is conceptually important because these cells might be stimulated and recruited by different signals, raising the possibility that they might be separate potential targets for therapeutic intervention. In this review, we will discuss important features of the energy-expending brown adipose tissue and highlight those that may serve as potential targets for pharmacological intervention aimed at expanding the tissue and/or enhancing its function to counteract obesity.

  15. Lithium in Paediatric Patients with Bipolar Disorder: Implications for Selection of Dosage Regimens via Population Pharmacokinetics/Pharmacodynamics.

    Science.gov (United States)

    Landersdorfer, Cornelia B; Findling, Robert L; Frazier, Jean A; Kafantaris, Vivian; Kirkpatrick, Carl M J

    2017-01-01

    Lithium is a well-established treatment for bipolar I disorder in adults. However, there is a paucity of information on its pharmacokinetics/pharmacodynamics in children and adolescents. We aimed to develop the first lithium dosage regimens based on population pharmacokinetics/pharmacodynamics for paediatric patients. Lithium concentrations, Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Improvement (CGI-I) scores over 24 weeks were available from 61 paediatric patients with bipolar I disorder. The population pharmacokinetics/pharmacodynamics were co-modelled. Concentrations and clinical effects following several dosage regimens were predicted by Monte Carlo simulations. The pharmacokinetics were well characterised by a two compartment model with linear elimination. Including the effect of total body weight (TBW) or lean body weight (LBW) on clearance and volume of distribution decreased the unexplained inter-individual variability by up to 12 %. The population mean (inter-individual variability) clearance was 1.64 L/h/53 kg LBW(0.75) (19 %) and central volume of distribution 23.6 L/53 kg LBW (6.8 %). The average lithium concentration over a dosing interval required for a 50 % reduction in YMRS was 0.711 mEq/L (59 %). A maintenance dose of 25 mg/kg TBW/day lithium carbonate in two daily doses was predicted to achieve a ≥50 % reduction in YMRS in 74 % of patients, while ~8 % of patients would be expected to have trough concentrations above the nominal safety threshold of 1.4 mEq/L. Therefore, therapeutic drug monitoring will still be required even with these dosing strategies. When accounting for body size, the pharmacokinetic parameters in paediatric patients were within the range of estimates from adults. Pharmacokinetic/pharmacodynamic modelling supported development of practical scientifically-based dosage regimens for paediatric patients.

  16. Phase 3 trial of three thalidomide-containing regimens in patients with newly diagnosed multiple myeloma not transplant-eligible.

    Science.gov (United States)

    Hungria, V T M; Crusoé, E Q; Maiolino, A; Bittencourt, R; Fantl, D; Maciel, J F R; Pessoa de Magalhaes, R J; Almeida, M S S; Cury, P; Hisgashi, F; Peres, A L; Chiattone, C S

    2016-01-01

    The introduction of agents such as thalidomide, lenalidomide, and bortezomib has changed the management of patients with multiple myeloma who are not eligible for autologous transplantation, many of whom are elderly. We sought to compare three thalidomide-based oral regimens among such patients in Latin America. We randomized patients with newly diagnosed multiple myeloma with measurable disease to one of the following regimens: melphalan, prednisone, and thalidomide (MPT); cyclophosphamide, thalidomide, and dexamethasone (CTD); and thalidomide and dexamethasone (TD). The TD arm was closed prematurely and was analyzed only descriptively. The primary endpoint was the overall response rate (ORR), whereas progression-free survival (PFS) and overall survival (OS) were secondary endpoints. The accrual rate was slower than expected, and the study was terminated after 82 patients had been randomized. The ORRs were 67.9 % with MPT, 89.7 % with CTD, and 68.7 % with TD (p = 0.056 for the comparison between MPT and CTD). The median PFS was 24.1 months for MPT, 25.9 months for CTD, and 21.5 months for TD. There were no statistically significant differences in PFS or OS between MPT and CTD. In an unplanned logistic regression analysis, ORR was significantly associated with treatment with CTD (p = 0.046) and with performance status of 0 or 1 (p = 0.035). Based on the current results, no definitive recommendations can be made regarding the comparative merit of the regimens tested. Nevertheless and until the results of further studies become available, we recommend either CTD or MPT as suitable frontline regimens for patients with multiple myeloma who are not candidates to transplantation in settings where lenalidomide and bortezomib are not available.

  17. Novel therapeutic agents for HbF induction: a new era for treatment of β thalassemia?

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    S.P. Perrine

    2011-12-01

    Full Text Available Fetal globin is endogenous, normally integrated in hematopoietic stem cells in all humans, and available for reactivation. Inducing expression of fetal globin (g-globin gene expression to 60-70% of a globin synthesis produces β-thalassemia trait globin synthetic ratios, and has been shown to reduce anemia to mild levels which do not require regular blood transfusion. Several classes of therapeutics have induced g-globin expression in β thalassemia patients, raised total hemoglobin levels, and even eliminated transfusion requirements in formerly transfusion-dependent patients, demonstrating proof-of-concept of the approach. However, prior generations of therapeutics were not readily feasible for widespread use. Currently, several recently discovered oral therapeutic candidates are more potent and/ or patientfriendly, requiring low oral doses, have distinct molecular mechanisms of action, and can be used in combination regimens. Tailoring therapeutic regimens to patient subsets stratified for solely β+ or a β0 globin mutation, and for quantitative trait loci (QTL which modulate HbF and clinical severity, can guide more effective and informative clinical trials. These advancements provide methods for a rational approach to applying fetal globin gene induction in therapeutic regimens suitable for use in diverse thalassemia patient populations world-wide. 胎儿珠蛋白是内生的,通常结合在所有人类的造血干细胞中,并可进行再激活。 包括胎儿珠蛋白的表达(g-珠蛋白),60%-70% 珠蛋白合成基因表达产生 β地中海贫血特征珠蛋白合成比率,并且已经显示将贫血降低至轻度水平,这不需要常规输血 几类疗法诱导β地中海贫血患者中的g-珠蛋白的表达,升高了血红蛋白的总体水平,甚至让以前依靠输血的患者不再需要输血,这演示了此方法的概念验证。 不过,先前几代疗法未能进行广泛使用。 目前,最近发

  18. Current approaches for the treatment of autoimmune hemolytic anemia.

    Science.gov (United States)

    Jaime-Pérez, José Carlos; Rodríguez-Martínez, Marisol; Gómez-de-León, Andrés; Tarín-Arzaga, Luz; Gómez-Almaguer, David

    2013-10-01

    Autoimmune hemolytic anemia (AIHA) is an infrequent group of diseases defined by autoantibody mediated red blood cell destruction. Correct diagnosis and classification of this condition are essential to provide appropriate treatment. AIHA is divided into warm and cold types according to the characteristics of the autoantibody involved and by the presence of an underlying or associated disorder into primary and secondary AIHA. Due to its low frequency, treatment for AIHA is largely based on small prospective trials, case series, and empirical observations. This review describes in detail the different treatment approaches for autoimmune hemolytic anemia. Warm antibody type AIHA should be treated with steroids, to which most patients respond, although relapse can occur and maintenance doses are frequently required. Splenectomy is an effective second line treatment and can provide long-term remission without medication. Rituximab is a useful alternative for steroid refractory patients, those requiring high maintenance doses and unfavorable candidates for surgery. Promising therapeutic modifications with this monoclonal antibody are emerging including drug combinations, lower doses, and long-term use. Primary cold agglutinin disease has been recognized as having a lymphoproliferative monoclonal origin. It is unresponsive to both steroids and splenectomy. Rituximab is currently the best therapeutic alternative for this condition, and several treatment regimens are available with variable responses.

  19. The Relationship between Cognitive Appraisal and Adherence to Medical Regimens in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Shahnaz Ahrari

    2014-12-01

    Full Text Available Introduction: Non-adherence to medical regimen has remained a challenge to the medical profession as well as to social sciences. To achieve positive results, the factors negatively impacting patient adherence to medical regimens (i.e., diet, drug and exercise regimen must be scrutinized in detail. The objective of this research was to explore the relationship between cognitive appraisal and adherence to medical regimens in type 2 diabetic patients. Methods: In this correlational study, 218 type 2 diabetes patients receiving treatment at the Diabetes Clinic affiliated with Gonabad University of Medical Sciences were selected through non-probability (convenience sampling from April 2012 to May 2013. Two valid and reliable questionnaires of cognitive appraisal and adherence to medical regimens were completed by each patient. The data were analyzed using SPSS ver 13. Results: A relationship was observed between perceived cognitive and adherence to some aspects of medical regimen. Also direct relationship was observedbetween perceived cognitive in form challenge and adherence of diet in patients with diabetes. There was no statistically significant relationship between aspects of cognitive appraisal and adherence to the drug regimen. Conclusion: The results suggest that interventions undertaken to improve adherence to medical regimen, particularly to drug regimen in patients with type 2 diabetes, should be focused on enriching cognitive appraisal. Nurses need to help patients perceive diabetes as less of a threat and in fact should empower them, so as to look upon it as more of a challenge.

  20. New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.

    Science.gov (United States)

    Mezzaroba, Nelly; Zorzet, Sonia; Secco, Erika; Biffi, Stefania; Tripodo, Claudio; Calvaruso, Marco; Mendoza-Maldonado, Ramiro; Capolla, Sara; Granzotto, Marilena; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Lucafò, Marianna; Mansilla, Eduardo; Garrovo, Chiara; Marín, Gustavo H; Baj, Gabriele; Gattei, Valter; Pozzato, Gabriele; Núñez, Luis; Macor, Paolo

    2013-01-01

    Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

  1. New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.

    Directory of Open Access Journals (Sweden)

    Nelly Mezzaroba

    Full Text Available Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

  2. [Clinical observation on LOP regimen combined with IMRT treatment for early nasal NK/T cell lymphoma].

    Science.gov (United States)

    Hu, Y F; Huang, Y H; Wu, T; Zhang, Y; Liu, X M; Song, Y; Gan, J Y

    2017-02-14

    Objective: To observe the clinical efficacy and safety of the LOP regimen (L-asparaginase, vincristine, dexamethasone) combined with intensity modulated radiation therapy(IMRT)in the treatment of early nasal NK/T cell lymphoma. Method: Clinical data of 65 patients with nasal NK/T cell lymphoma treated with LOP chemotherapy combined with IMRT at the Guizhou Province Tumor Hospital between March 2010 and January 2015 were retrospectively analyzed. Results: Among the 65 patients, 39 cases obtained complete remission (CR), 18 cases obtained partial remission(PR), 1 case obtained stable disease (SD), 7 cases had progressive disease(PD). The objective response rate (ORR) was 87.7%, the disease control rates (DCR) was 89.2%. The DCR was lower in the patients with B symptoms or over age of 60. Patients with super cavity obtained a worse progression-free survival(PFS). The 1-, 2-, 3-year PFS were 91.7%, 74.8% and 61.3%, the overall survival(OS) were 91.8%, 81.3% and 78.9%, respectively. Main adverse reactions were myelosuppression, gastrointestinal reaction, hepatic lesion, hypoproteinemia, percutaneous reaction and oral mucosa reaction. No severe pancreatitis, severe anaphylaxis and toxic related death were observed. Conclusion: The LOP regimen combined with IMRT treatment for nasal NK/T cell lymphoma may have a good therapeutic effect, low toxicity, and good tolerance.

  3. Therapeutic targeting of replicative immortality.

    Science.gov (United States)

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. Copyright © 2015 The Authors

  4. Student Wellbeing and the Therapeutic Turn in Education

    Science.gov (United States)

    Wright, Katie

    2014-01-01

    This article considers current concerns with promoting student mental health and wellbeing against the backdrop of critiques of the "therapeutic turn" in education. It begins by situating accounts of "therapeutic education" within broader theorisation of therapeutic culture. In doing so, the importance of this work is…

  5. Antitrypanosomal Treatment with Benznidazole Is Superior to Posaconazole Regimens in Mouse Models of Chagas Disease.

    Science.gov (United States)

    Khare, Shilpi; Liu, Xianzhong; Stinson, Monique; Rivera, Ianne; Groessl, Todd; Tuntland, Tove; Yeh, Vince; Wen, Ben; Molteni, Valentina; Glynne, Richard; Supek, Frantisek

    2015-10-01

    Two CYP51 inhibitors, posaconazole and the ravuconazole prodrug E1224, were recently tested in clinical trials for efficacy in indeterminate Chagas disease. The results from these studies show that both drugs cleared parasites from the blood of infected patients at the end of the treatment but that parasitemia rebounded over the following months. In the current study, we sought to identify a dosing regimen of posaconazole that could permanently clear Trypanosoma cruzi from mice with experimental Chagas disease. Infected mice were treated with posaconazole or benznidazole, an established Chagas disease drug, and parasitological cure was defined as an absence of parasitemia recrudescence after immunosuppression. Twenty-day therapy with benznidazole (10 to 100 mg/kg of body weight/day) resulted in a dose-dependent increase in antiparasitic activity, and the 100-mg/kg regimen effected parasitological cure in all treated mice. In contrast, all mice remained infected after a 25-day treatment with posaconazole at all tested doses (10 to 100 mg/kg/day). Further extension of posaconazole therapy to 40 days resulted in only a marginal improvement of treatment outcome. We also observed similar differences in antiparasitic activity between benznidazole and posaconazole in acute T. cruzi heart infections. While benznidazole induced rapid, dose-dependent reductions in heart parasite burdens, the antiparasitic activity of posaconazole plateaued at low doses (3 to 10 mg/kg/day) despite increasing drug exposure in plasma. These observations are in good agreement with the outcomes of recent phase 2 trials with posaconazole and suggest that the efficacy models combined with the pharmacokinetic analysis employed here will be useful in predicting clinical outcomes of new drug candidates.

  6. A successful case of anti-NMDAR encephalitis without tumor treated with a prolonged regimen of plasmapheresis

    Directory of Open Access Journals (Sweden)

    Mateus Mistieri Simabukuro

    Full Text Available ABSTRACT Anti-NMDA receptor encephalitis is a severe but treatable autoimmune disease of the CNS. However, the use of immunotherapy and long-term outcomes have yet to be defined for this disease. We describe a case of an 18-year-old male diagnosed with anti-NMDAR encephalitis not associated with tumor, which did not respond to initial treatment with immunoglobulin, followed by corticosteroids, cyclophosphamide and evolved with significant clinical improvement after a prolonged course of plasmapheresis. Although it is not possible to affirm the good outcome was due solely to the prolonged plasmapheresis regimen, recently published data shows that improvement may take weeks or months to occur. This case discloses another therapeutic possibility for patients with refractory disease who fail to respond to recommended first-line and second-line therapy.

  7. Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy

    Science.gov (United States)

    Guinto, Valerie T; De Guia, Blanca; Festin, Mario R; Dowswell, Therese

    2014-01-01

    Background Asymptomatic bacteriuria occurs in 5% to 10% of pregnancies and, if left untreated, can lead to serious complications. Objectives To assess which antibiotic is most effective and least harmful as initial treatment for asymptomatic bacteriuria in pregnancy. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (March 2010) and reference lists of retrieved studies. Selection criteria Randomized controlled trials comparing two antibiotic regimens for treating asymptomatic bacteriuria. Data collection and analysis Review authors independently screened the studies for inclusion and extracted data. Main results We included five studies involving 1140 women with asymptomatic bacteriuria. We did not perform meta-analysis; each trial examined different antibiotic regimens and so we were not able to pool results. In a study comparing a single dose of fosfomycin trometamol 3 g with a five-day course of cefuroxime, there was no significant difference in persistent infection (risk ratio (RR) 1.36, 95% confidence interval (CI) 0.24 to 7.75), shift to other antibiotics (RR 0.08, 95% CI 0.00 to 1.45), or in allergy or pruritus (RR 2.73, 95% CI 0.11 to 65.24). A comparison of seven-day courses of 400 mg pivmecillinam versus 500 mg ampicillin, both given four times daily, showed no significant difference in persistent infection at two weeks or recurrent infection, but there was an increase in vomiting (RR 4.57, 95% CI 1.40 to 14.90) and women were more likely to stop treatment early with pivmecillinam (RR 8.82, 95% CI 1.16 to 66.95). When cephalexin 1 g versus Miraxid® (pivmecillinam 200 mg and pivampicillin 250 mg) were given twice-daily for three days, there was no significant difference in persistent or recurrent infection. A one- versus seven-day course of nitrofurantoin resulted in more persistent infection with the shorter course (RR 1.76, 95% CI 1.29 to 2.40), but no significant difference in symptomatic infection at two weeks

  8. Cost-effectiveness of tipranavir versus comparator protease inhibitor regimens in HIV infected patients previously exposed to antiretroviral therapy in the Netherlands

    Directory of Open Access Journals (Sweden)

    Kappelhoff Bregt S

    2007-11-01

    Full Text Available Abstract Background This study compares the costs and effects of a regimen with ritonavir-boosted tipranavir (TPV/r to a physician-selected genotypically-defined standard-of-care comparator protease inhibitor regimen boosted with ritonavir (CPI/r in HIV infected patients that were previously exposed to antiretroviral therapy in the Netherlands. Methods We compared the projected lifetime costs and effects of two theoretical groups of 1000 patients, one receiving a standard of care regimen with TPV/r as a component and the other receiving a standard of care regimen with CPI/r. A 3-stage Markov model was formulated to represent three different consecutive HAART regimens. The model uses 12 health states based on viral load and CD4+ count to simulate disease progression. The transition probabilities for the Markov model were derived from a United States cohort of treatment experienced HIV patients. Furthermore, the study design was based on 48-week data from the RESIST-2 clinical trial and local Dutch costing data. Cost and health effects were discounted at 4% and 1.5% respectively according to the Dutch guideline. The analysis was conducted from the Dutch healthcare perspective using 2006 unit cost prices. Results Our model projects an accumulated discounted cost to the Dutch healthcare system per patient receiving the TPV/r regimen of €167,200 compared to €145,400 for the CPI/r regimen. This results in an incremental cost of €21,800 per patient. The accumulated discounted effect is 7.43 life years or 6.31 quality adjusted life years (QALYs per patient receiving TPV/r, compared to 6.91 life years or 5.80 QALYs per patient receiving CPI/r. This translates into an incremental effect of TPV/r over CPI/r of 0.52 life years gained (LYG or 0.51 QALYs gained. The corresponding incremental cost effectiveness ratios (iCERs are €41,600 per LYG and €42,500 per QALY. Conclusion We estimated the iCER for TPV/r compared to CPI/r at approximately €40

  9. Addressing the questions of tomorrow: melphalan and new combinations as conditioning regimens before autologous hematopoietic progenitor cell transplantation in multiple myeloma.

    Science.gov (United States)

    Martino, Massimo; Olivieri, Attilio; Offidani, Massimo; Vigna, Ernesto; Moscato, Tiziana; Fedele, Roberta; Montanari, Mauro; Console, Giuseppe; Gentile, Massimo; Messina, Giuseppe; Irrera, Giuseppe; Morabito, Fortunato

    2013-05-01

    The role of high-dose chemotherapy (HDC) followed by autologous-progenitor cell transplantation (auto-HPCT) in the treatment of multiple myeloma (MM) continues to evolve in the novel agent era. Administration of high-dose melphalan (HDM) is considered the standard conditioning regimen. Nevertheless, several attempts have recently been made to improve the conditioning phase of the HDC procedure. We reviewed all the reported experiences and illustrated current knowledge in the field of conditioning regimens. For fit MM patients, HDC followed by auto-HPCT remains the standard of care. The available data confirm that melphalan (MEL) 200 mg/m(2) should continue to be considered the gold standard conditioning regimen, with dose reduction based on age and renal function. Targeting exposure to MEL by using area under the curve is a particularly appealing approach that could be explored to maximize efficacy and minimize toxicity of this drug. Other strategies are currently being evaluated in different trials, and the most interesting areas of research involve the incorporation of newer agents like bortezomib (BOR) into conditioning regimens. Moreover, intravenous busulfan has become available and this formulation may reduce toxicity and result in greater efficacy in association with MEL-based conditioning.

  10. Chicanoizing the Therapeutic Community

    Science.gov (United States)

    Aron, William S.; And Others

    1974-01-01

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

  11. Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 2: Role of Growth Factors in Normal and Pathological Wound Healing: Therapeutic Potential and Methods of Delivery

    Science.gov (United States)

    Demidova-Rice, Tatiana N.; Hamblin, Michael R.; Herman, Ira M.

    2012-01-01

    This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed. PMID:22820962

  12. Keloids and Hypertrophic Scars Can Now Be Cured Completely: Recent Progress in Our Understanding of the Pathogenesis of Keloids and Hypertrophic Scars and the Most Promising Current Therapeutic Strategy.

    Science.gov (United States)

    Ogawa, Rei; Akaishi, Satoshi; Kuribayashi, Shigehiko; Miyashita, Tsuguhiro

    2016-01-01

    Keloids and hypertrophic scars are fibroproliferative disorders of the skin that are caused by abnormal healing of injured or irritated skin. It is possible that they are both manifestations of the same fibroproliferative skin disorder and just differ in terms of the intensity and duration of inflammation. These features may in turn be influenced by genetic, systemic, and local risk factors. Genetic factors may include single nucleotide polymorphisms, while systemic factors may include hypertension, pregnancy, hormones, and cytokines. The most important local factor is tension on the scar. Over the past 10 years, our understanding of the pathogenesis of keloids and hypertrophic scars has improved markedly. As a result, these previously intractable scars are now regarded as being treatable. There are many therapeutic options, including surgery, radiation, corticosteroids, 5-fluorouracil, cryotherapy, laser therapy, anti-allergy agents, anti-inflammatory agents, bleaching creams and make-up therapies. However, at present, we believe that the following combination of three therapies most reliably achieves a complete cure: surgery, followed by radiation and the use of steroid tape/plaster.

  13. [Therapeutic drug monitoring of stiripentol].

    Science.gov (United States)

    Verdier, Marie-Clémence; Tribut, Olivier; Bentué-Ferrer, Danièle

    2012-01-01

    Stiripentol is a third generation antiepileptic, marketed since 2007 under the name of Diacomit(®). It is indicated, always in combination, in the treatment of severe myoclonic epilepsy in infancy or Dravet syndrome. Its pharmacokinetics is not linear. It is a potent inhibitor of CYP3A4, 1A2 and 2C19 and increases the plasma concentrations of many other antiepileptic drugs. Without this being considered as a validated therapeutic range, the trough plasma concentrations at steady-state, corresponding to the usual doses are between 10 and 15 mg/L. The concentration-efficacy relationship is not established, but there is some evidence for a concentration-related toxicity. However, because of its non-linear kinetics, stiripentol should be a good candidate for therapeutic drug monitoring (TDM). Nonetheless, the current level of evidence for the advantage of TDM is "remains to be estimated".

  14. Therapeutic approaches for celiac disease

    Science.gov (United States)

    Plugis, Nicholas M.; Khosla, Chaitan

    2015-01-01

    Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

  15. Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality.

    Directory of Open Access Journals (Sweden)

    Carole D Mitnick

    Full Text Available RATIONALE: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. OBJECTIVES: This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort. METHODS: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. MEASUREMENTS AND MAIN RESULTS: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7 drugs. Cure or completion was achieved in 66.1% (442 of patients; death occurred in 20.8% (139. Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89, compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93. CONCLUSIONS: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

  16. Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality.

    Science.gov (United States)

    Mitnick, Carole D; Franke, Molly F; Rich, Michael L; Alcantara Viru, Felix A; Appleton, Sasha C; Atwood, Sidney S; Bayona, Jaime N; Bonilla, Cesar A; Chalco, Katiuska; Fraser, Hamish S F; Furin, Jennifer J; Guerra, Dalia; Hurtado, Rocio M; Joseph, Keith; Llaro, Karim; Mestanza, Lorena; Mukherjee, Joia S; Muñoz, Maribel; Palacios, Eda; Sanchez, Epifanio; Seung, Kwonjune J; Shin, Sonya S; Sloutsky, Alexander; Tolman, Arielle W; Becerra, Mercedes C

    2013-01-01

    A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort. This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

  17. Assessment of starch dietary regimen regarding pre-menstrual syndrome among high school students in Sari during 2007

    Directory of Open Access Journals (Sweden)

    K. Abedian Kasgari

    2008-01-01

    Full Text Available AbstractBackground and Purpose: Pre-menstrual syndrome (PMS is one of the abnormalities associated with pre-menstrual cycles. Approximately 85% to 97% of women are suffering from psycho-somatic of physiological and behavioral symptoms from PMS, prior to menstruation. The most common PMS symptoms include: flatulence, stress anxiety, breast tenderness, depression, fatigue, unknown irritability, anger, poor concentration, and some degree in extremities edema. There are several therapeutic methods for PMS such as: oral contraceptive pills, GnRH antagonisms, diazole, use of Calcium and vitamin supplements, and dietary modification in which there is a controversy regarding type of diet. We assessed the effect of third- hour starch dietary regimen on pre-menstrual syndrome among high school students.Materials and Methods: This randomized quasi- experimental study was performed on students in grade 2 and 3 in Private and Governmental high schools in Sari. The sample size was calculated using randomize numbers table (478 participants. A questionnaire composed of two parts was prepared. The first part included demographic characteristics, while the second part consisted of data related to history of menstrual cycle, pervious diseases and use of drugs. The symptoms of PMS were assessed at the beginning of the study and also at the end of the first, second and third month after beginning of the third-hours starch regimen. Data was gathered by self-reporting technique, analyzed by descriptive and comprehensive statistical techniques.Results: The age range of participants was 14 to 19 years of age (16.891.12. The mean of menstrual cycle was 28.872.1 days, and the mean of menstrual duration was 6.321.8. PMS symptoms score was 12.858.01 prior to dietary regimen, and at the end of one, two and three months, following dietary regimen in-take were 11.037.59, 12.477.79 and 11.136.71 respectively. This study indicated that there was significant

  18. Erlotinib: a new therapeutic approach for non-small cell lung cancer.

    Science.gov (United States)

    Bonomi, Philip

    2003-08-01

    Although treatment with cytotoxic agents has produced modest survival improvement in patients with stage III and IV non-small cell lung cancer (NSCLC), it appears that a plateau has been reached with currently available chemotherapeutic regimens. Increasing knowledge regarding the properties of malignant neoplasms has identified a number of potential therapeutic targets. The epidermal growth factor receptor (EGFR) is one of these targets. Preclinical models have revealed that tumour growth can be inhibited by monoclonal antibodies directed against EGFR and EGFR-specific tyrosine kinase inhibitors. Erlotinib (Tarceva trade mark; OSI Pharmaceuticals, Genentech and Roche), a quinazoline derivative with good oral absorption, is one of several EGFR tyrosine kinases that has been studied in clinical trials. In a Phase I study, mild diarrhoea and mild rash were the most common toxicities. At a dose of 200 mg/day, diarrhoea was the dose-limiting toxicity. The observation that EGFR overexpression is relatively common in NSCLC led to a Phase II trial of erlotinib at the maximum-tolerated dose (150 mg/day) in previously treated NSCLC patients. Erlotinib produced a 12% response rate and there was no apparent relationship between response and tumour EGFR levels. More recent reports suggest that patients who develop a rash have higher responses. Based on its single agent activity, erlotinib has been evaluated in two Phase III trials which compared erlotinib plus chemotherapy to chemotherapy alone in previously untreated NSCLC patients. Erlotinib has also been compared to placebo in a Phase III trial which was limited to advanced stage NSCLC patients whose disease had progressed after two previous chemotherapy regimens. The optimum use of erlotinib in NSCLC will be determined by the results of the completed and future Phase III trials.

  19. Pharmacist-patient communication about medication regimen adjustment during Ramadan.

    Science.gov (United States)

    Amin, Mohamed E K; Chewning, Betty

    2016-12-01

    During Ramadan, Muslims fast from dawn to sunset while abstaining from food and drink. Although Muslim patients may be aware of their religious exemption from fasting, many patients still choose not to take that exemption and fast. This study examines pharmacists' initiation and timing of communication about medication regimen adjustment (MRA) with patients related to Ramadan. Predictors for initiating this communication with patients were also explored. A probability sample of community pharmacists in Alexandria, Egypt was surveyed. The self-administered instrument covered timing and likelihood of initiating discussion about MRA. Using ordered logistic regression, a model was estimated to predict pharmacists' initiation of the conversation on MRA during Ramadan. Ninety-three percent of the 298 approached pharmacists completed surveys. Only 16% of the pharmacists reported that they themselves usually initiated the conversation on MRA. Pharmacists' initiation of these conversations was associated with pharmacists' perceived importance of MRA on pharmacy revenue odds ratio ((OR) = 1.24, CI = 1.03-1.48). Eighty percent of the responding pharmacists reported the MRA conversation for chronic conditions started either 1-3 days before, or during the first week of Ramadan. These results suggest considerable pharmacist patient communication gaps regarding medication use during Ramadan. It is especially important for pharmacists and other health professionals to initiate communication with Muslim patients early enough to identify how best to help patients transition safely into and out of Ramadan as they fast. © 2016 Royal Pharmaceutical Society.

  20. TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA WITH AIDA BASED REGIMEN

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    Ramzi Jeddi

    2011-09-01

    Full Text Available In Tunisia, the ATRA era began in 1998 with the use, consecutively, of two regimens combining ATRA and an anthracycline with cytarabine (APL93, and without cytarabine (LPA99. From 2004, 51 patients with confirmed APL either by t(15;17 or PML/RARA were treated according to the PETHEMA LPA 99 trial. Forty three patients achieved CR (86%. The remaining seven patients had early death (one died before treatment onset: four caused by differentiation syndrome (DS and three died from central nervous system hemorrhage. Multivariate analysis revealed that female gender (P=0.045, baseline WBC> 10 G/L ( P=0.041 and serum creatinine > 1.4mg/dl ( P=0.021 were predictive of mortality during induction. DS was observed in 16 patients (32% after a median onset time of 15 days from treatment onset (range, 2–29. Body mass index ≥ 30 (P=0.01 was the only independent predictor of DS. Occurrence of hypertensive peaks significantly predicted occurrence of DS (P=0.011 and was significantly associated with high BMI (p=0.003. With a median follow-up of 50 months, 5 year cumulative incidence of relapse, event free and overall survival were 4.7%, 74% and 78%, respectively.

  1. A comparison of different antibiotic regimens for the treatment of infective endocarditis.

    Science.gov (United States)

    Martí-Carvajal, Arturo J; Dayer, Mark; Conterno, Lucieni O; Gonzalez Garay, Alejandro G; Martí-Amarista, Cristina Elena; Simancas-Racines, Daniel

    2016-04-19

    alone reporting uncertain effects on all-cause mortality (8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; RR 1.12, 95% CI 0.49 to 2.56, very low quality evidence). The second trial compared daptomycin versus low-dose gentamicin plus an anti-staphylococcal penicillin (nafcillin, oxacillin or flucloxacillin) or vancomycin. This showed uncertain effects in terms of cure rates (9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus anti-staphylococcal penicillin or vancomycin, RR 0.89 95% CI 0.42 to 1.89; very low quality evidence). The third trial compared cloxacillin plus gentamicin with a glycopeptide (vancomycin or teicoplanin) plus gentamicin. In participants receiving gentamycin plus glycopeptide only 13/23 (56%) were cured versus 11/11 (100%) receiving cloxacillin plus gentamicin (RR 0.59, 95% CI 0.40 to 0.85; very low quality evidence). The fourth trial compared ceftriaxone plus gentamicin versus ceftriaxone alone and found no conclusive differences in terms of cure (15/34 (44%) with ceftriaxone plus gentamicin versus 21/33 (64%) with ceftriaxone alone, RR 0.69, 95% CI 0.44 to 1.10; very low quality evidence).The trials reported adverse events, need for cardiac surgical interventions, uncontrolled infection and relapse of endocarditis and found no conclusive differences between comparison groups (very low quality evidence). No trials assessed septic emboli or quality of life. Limited and very low quality evidence suggested that there were no conclusive differences between antibiotic regimens in terms of cure rates or other relevant clinical outcomes. However, because of the very low quality evidence, this needs confirmation. The conclusion of this Cochrane review was based on randomised controlled trials with high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for treatment of infective endocarditis.

  2. PEG-aspargase and DEP regimen combination therapy for refractory Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis

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    Jingshi Wang

    2016-09-01

    Full Text Available Abstract Background Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH is the most frequent subtype of secondary HLH triggered by infections. Previous studies have shown that ~30 % or more of patients with EBV-HLH do not respond to standard therapy. This study investigated the efficacy and safety profile of a modified DEP regimen in combination with PEG-aspargase (L-DEP as a salvage therapy for refractory EBV-HLH. Methods In this study from October 2014 to October 2015, 28 patients with refractory EBV-HLH received a L-DEP regimen at the Beijing Friendship Hospital, Capital Medical University. Treatment efficacy and adverse events were evaluated at 2 and 4 weeks after L-DEP treatment. Results Median EBV-DNA concentrations before and 2 weeks after receiving the L-DEP regimen were 9.6 × 105 (1.5 × 104 − 1 × 109 copies/mL and 2.2 × 105 (3.8 × 102 − 1.2 × 107 copies/mL, respectively; the post-treatment values were significantly lower than that of the pretreatment (P = 0.048. Nine of the 28 study patients achieved complete response (CR and 15 partial response (PR, resulting in an overall response rate of 85.7 % (CR+PR. Four patients who did not achieve response died within 4 weeks of receiving L-DEP. Thirteen of the 24 patients who achieved partial or complete response received subsequent allogenic hematopoietic stem cell transplantation (allo-HSCT. Ten of these 13 patients survived until 1 March 2016. The major adverse effects of the L-DEP regimen were high serum amylase concentrations, abnormal liver function, and coagulation disorders. Conclusions This study suggests that L-DEP is a safe and effective salvage therapy prior to allo-HSCT for refractory EBV-HLH and increases the possibility of such patients receiving allo-HSCT. A prospective multicenter large-scale clinical trial that aims to validate the L-DEP regimen for refractory EBV-HLH is currently underway (Clinical

  3. Current and emerging therapies in premature ejaculation: Where we are coming from, where we are going.

    Science.gov (United States)

    Martin, Christopher; Nolen, Hunter; Podolnick, Jason; Wang, Run

    2017-01-01

    Premature ejaculation is the most common form of sexual dysfunction among men. The pathophysiology of premature ejaculation appears to be multifactorial, implicating the need for multimodal therapeutic regimens to successfully treat premature ejaculation. Multiple treatment regimens have been shown to be effective in extending the time between penetration and ejaculation. These treatment modalities include everything from behavioral modifications and medications to diet alterations and major surgery. The goal of the present article was to review the commonly used treatment regimens used in the treatment of premature ejaculation, as well as to introduce and discuss the newest treatment routines under study for the treatment of premature ejaculation.

  4. Pharmacokinetic enhancers in HIV therapeutics.

    Science.gov (United States)

    Larson, Kajal B; Wang, Kun; Delille, Cecile; Otofokun, Igho; Acosta, Edward P

    2014-10-01

    Maximal and durable viral load suppression is one of the most important goals of HIV therapy and is directly related to adequate drug exposure. Protease inhibitors (PIs), an important component of the antiretroviral armada, were historically associated with poor oral bioavailability and high pill burden. However, because the PIs are metabolized by cytochrome P450 (CYP) 3A enzymes, intentional inhibition of these enzymes leads to higher drug exposure, lower pill burden, and therefore simplified dosing schedules with this class of drug. This is the basis of pharmacokinetic enhancement. In HIV therapy, two pharmacokinetic enhancers or boosting agents are used: ritonavir and cobicistat. Both agents inhibit CYP3A4, with cobicistat being a more specific CYP inhibitor than ritonavir. Unlike ritonavir, cobicistat does not have antiretroviral activity. Cobicistat has been evaluated in clinical trials and was recently approved in the USA as a fixed-dose combination with the integrase inhibitor, elvitegravir and two nucleos(t)ide analogs. Additional studies are examining cobicistat in fixed-dose combinations with various PIs. In this review, we summarize current knowledge of these agents and clinically relevant drug regimens and ongoing trials. Studies with elvitegravir and the novel PI TMC319011 are also discussed.

  5. Cycle regimens for frozen-thawed embryo transfer.

    Science.gov (United States)

    Ghobara, Tarek; Gelbaya, Tarek A; Ayeleke, Reuben Olugbenga

    2017-07-05

    Among subfertile couples undergoing assisted reproductive technology (ART), pregnancy rates following frozen-thawed embryo transfer (FET) treatment cycles have historically been found to be lower than following embryo transfer undertaken two to five days following oocyte retrieval. Nevertheless, FET increases the cumulative pregnancy rate, reduces cost, is relatively simple to undertake and can be accomplished in a shorter time period than repeated in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles with fresh embryo transfer. FET is performed using different cycle regimens: spontaneous ovulatory (natural) cycles; cycles in which the endometrium is artificially prepared by oestrogen and progesterone hormones, commonly known as hormone therapy (HT) FET cycles; and cycles in which ovulation is induced by drugs (ovulation induction FET cycles). HT can be used with or without a gonadotrophin releasing hormone agonist (GnRHa). This is an update of a Cochrane review; the first version was published in 2008. To compare the effectiveness and safety of natural cycle FET, HT cycle FET and ovulation induction cycle FET, and compare subtypes of these regimens. On 13 December 2016 we searched databases including Cochrane Gynaecology and Fertility's Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. Other search sources were trials registers and reference lists of included studies. We included randomized controlled trials (RCTs) comparing the various cycle regimens and different methods used to prepare the endometrium during FET. We used standard methodological procedures recommended by Cochrane. Our primary outcomes were live birth rates and miscarriage. We included 18 RCTs comparing different cycle regimens for FET in 3815 women. The quality of the evidence was low or very low. The main limitations were failure to report important clinical outcomes, poor reporting of study methods and imprecision due to low event rates. We found no

  6. Purinergic Signalling: Therapeutic Developments

    Directory of Open Access Journals (Sweden)

    Geoffrey Burnstock

    2017-09-01

    Full Text Available Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

  7. STUDY OF WHO SAFE ABORTION REGIMEN IN MEDICAL ABORTIONS IN A TERTIARY CENTRE

    OpenAIRE

    Joylene Diana; Sujaya V.

    2015-01-01

    Medical abortion is the use of drugs to induce abortion of a fetus. Due to the advances in the field of research , numerous regimens have been formulated to ensure a fast and complete expulsion of the fetus. These regimens also aim to towards reduced post abortal side effects and to decrease the need for surgical evacuation ...

  8. Following an HIV Regimen: Steps to Take Before and After Starting HIV Medicines

    Science.gov (United States)

    HIV Treatment Following an HIV Regimen: Steps to Take Before and After Starting HIV Medicines (Last updated 3/2/2017; last reviewed 3/2/2017) ... maintain long-term medication adherence. Before starting an HIV regimen, talk to your health care provider about ...

  9. A Modified Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers

    Science.gov (United States)

    2013-10-01

    Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers Authors: DISTRIBUTION STATEMENT A. Paul C. Algra, LT, MC...May 2012 – May 2013 4. TITLE AND SUBTITLE A Modified Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers...SUPPLEMENTARY NOTES 14. ABSTRACT To prevent acute otitis externa (AOE) in the saturation setting and to decrease the side effects

  10. Current and future antimicrobial treatment of gonorrhoea - the rapidly evolving Neisseria gonorrhoeae continues to challenge.

    Science.gov (United States)

    Unemo, Magnus

    2015-08-21

    Neisseria gonorrhoeae has developed antimicrobial resistance (AMR) to all drugs previously and currently recommended for empirical monotherapy of gonorrhoea. In vitro resistance, including high-level, to the last option ceftriaxone and sporadic failures to treat pharyngeal gonorrhoea with ceftriaxone have emerged. In response, empirical dual antimicrobial therapy (ceftriaxone 250-1000 mg plus azithromycin 1-2 g) has been introduced in several particularly high-income regions or countries. These treatment regimens appear currently effective and should be considered in all settings where local quality assured AMR data do not support other therapeutic options. However, the dual antimicrobial regimens, implemented in limited geographic regions, will not entirely prevent resistance emergence and, unfortunately, most likely it is only a matter of when, and not if, treatment failures with also these dual antimicrobial regimens will emerge. Accordingly, novel affordable antimicrobials for monotherapy or at least inclusion in new dual treatment regimens, which might need to be considered for all newly developed antimicrobials, are essential. Several of the recently developed antimicrobials deserve increased attention for potential future treatment of gonorrhoea. In vitro activity studies examining collections of geographically, temporally and genetically diverse gonococcal isolates, including multidrug-resistant strains particularly with resistance to ceftriaxone and azithromycin, are important. Furthermore, understanding of effects and biological fitness of current and emerging (in vitro induced/selected and in vivo emerged) genetic resistance mechanisms for these antimicrobials, prediction of resistance emergence, time-kill curve analysis to evaluate antibacterial activity, appropriate mice experiments, and correlates between genetic and phenotypic laboratory parameters, and clinical treatment outcomes, would also be valuable. Subsequently, appropriately designed

  11. [Comparison of clinical efficacy between decitabine combined with CAG regimen and CAG regimen alone in patients with intermediate to high-risk myelodysplastic syndromes].

    Science.gov (United States)

    Zhang, Yun-Ping; Wu, Wen-Zhong; Cui, Guo-Xing

    2014-10-01

    This study was purposed to compare the clinical efficacy and adverse reactions of low-dose decitabine combined with CAG regimen (aclarubicin, Ara-C, and G-CSF) and CAG regimen alone in intermediate to high-risk myelodysplastic syndromes (MDS), and evaluate the validity and efficacy of the former regimen as new treatment method of intermediate to high-risk myelodysplastic syndromes. A total of 12 patients with intermediate (IR) to high-risk (HR) MDS treated by low-dose decitabine combined with CAG regimen and 10 patients with IR to HR MDS treated by CAG regimen alone were evaluated after treatment of 1 cycle and at least after 2 cycles. The complete remission (CR) after 1 cycle, overall remission rate (ORR), progression free survival (PFS) and overall survival (OS) between them were analyzed. The results showed that 9 patients treated by low-dose decitabine combined with CAG regimen achieved complete remission after 1 cycle, 2 patients achieved partial remission, 1 patient did not show reaction. The complete remission rate was 75.0% and overall response rate was 91.7%. The median time of disease free survival was 9 months (0-27 months). The median overall survival time was 16 months (3-28 months). 4 patients suffered from pulmonary infection after treatment and then were all cured after treatment with anti-infective therapy. The 5 patients treated by CAG regimen alone achieved complete remission,3 patients achieved partial remission, 2 patients showed non-reaction. The complete remission rate was 50.0% and overall response rate was 80.0%. The median time of disease free survival was 6 months(0-18 months). The median overall survival time was 13 months(3-31 months), 4 patients suffered from pulmonary infection, 1 patient suffered from enteric infection and 1 patient suffered from Escherichia coli septicemia after treatment, all of them becomed better after active treatment. Two groups of patients all had no serious adverse reactions, All patients could tolerate, no

  12. Therapeutics in duchenne muscular dystrophy.

    Science.gov (United States)

    Strober, Jonathan B

    2006-04-01

    Duchenne muscular dystrophy (DMD) is a fatal disorder affecting approximately 1 in 3,500 live born males, characterized by progressive muscle weakness. Several different strategies are being investigated in developing a cure for this disorder. Until a cure is found, therapeutic and supportive care is essential in preventing complications and improving the afflicted child's quality of life. Currently, corticosteroids are the only class of drug that has been extensively studied in this condition, with controversy existing over the use of these drugs, especially in light of the multiple side effects that may occur. The use of nutritional supplements has expanded in recent years as researchers improve our abilities to use gene and stem cell therapies, which will hopefully lead to a cure soon. This article discusses the importance of therapeutic interventions in children with DMD, the current debate over the use of corticosteroids to treat this disease, the growing use of natural supplements as a new means of treating these boys and provides an update on the current state of gene and stem cell therapies.

  13. Therapeutic radionuclides in nuclear medicine:current and future prospects%核医学放射性核素治疗的研究现状及前景

    Institute of Scientific and Technical Information of China (English)

    Chai-Hong YEONG; Mu-hua CHENG; Kwan-Hoong NG

    2014-01-01

    本文目的:本文综述了临床常用的放射性治疗方式和应用现状以及新的放射性核素从科研至临床应用所存在的问题。  本文概放射性核素的临床应用及研究已历数十载,已有碘-131、磷-32、锶-90及钇-90等众多放射性核素被成功用于治疗良恶性疾病。随着新的放射性核素及药物不断应用于骨转移瘤疼痛治疗、神经内分泌肿瘤及其他良恶性肿瘤治疗,放射性核素治疗得到了快速发展。目前,放射性核素治疗已进入