WorldWideScience

Sample records for pre-release therapeutic treatment

  1. Extended-release naltrexone for pre-release prisoners: A randomized trial of medical mobile treatment

    Science.gov (United States)

    Gordon, Michael S.; Vocci, Frank J.; Fitzgerald, Terrence T.; O'Grady, Kevin E.; O'Brien, Charles P.

    2017-01-01

    Background Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases have been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Methods Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. Results We describe the background and rationale for the study, its aims, hypotheses, and study design. Conclusions The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. PMID:28011389

  2. Extended-release naltrexone for pre-release prisoners: A randomized trial of medical mobile treatment.

    Science.gov (United States)

    Gordon, Michael S; Vocci, Frank J; Fitzgerald, Terrence T; O'Grady, Kevin E; O'Brien, Charles P

    2017-02-01

    Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases has been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. We describe the background and rationale for the study, its aims, hypotheses, and study design. The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. ClinicalTrials.gov: NCT02867124. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. A prison mental health in-reach model informed by assertive community treatment principles: evaluation of its impact on planning during the pre-release period, community mental health service engagement and reoffending.

    Science.gov (United States)

    McKenna, Brian; Skipworth, Jeremy; Tapsell, Rees; Madell, Dominic; Pillai, Krishna; Simpson, Alexander; Cavney, James; Rouse, Paul

    2015-12-01

    It is well recognised that prisoners with serious mental illness (SMI) are at high risk of poor outcomes on return to the community. Early engagement with mental health services and other community agencies could provide the substrate for reducing risk. To evaluate the impact of implementing an assertive community treatment informed prison in-reach model of care (PMOC) on post-release engagement with community mental health services and on reoffending rates. One hundred and eighty prisoners with SMI released from four prisons in the year before implementation of the PMOC were compared with 170 such prisoners released the year after its implementation. The assertive prison model of care was associated with more pre-release contacts with community mental health services and contacts with some social care agencies in some prisons. There were significantly more post-release community mental health service engagements after implementation of this model (Z = -2.388, p = 0.02). There was a trend towards reduction in reoffending rates after release from some of the prisons (Z =1.82, p = 0.07). Assertive community treatment applied to prisoners with mental health problems was superior to 'treatment as usual', but more work is needed to ensure that agencies will engage prisoners in pre-release care. The fact that the model showed some benefits in the absence of any increase in resources suggests that it may be the model per se that is effective. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Therapeutic Inertia and Treatment Intensification.

    Science.gov (United States)

    Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

    2018-01-29

    This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

  5. Buprenorphine dose induction in non-opioid-tolerant pre-release prisoners.

    Science.gov (United States)

    Vocci, Frank J; Schwartz, Robert P; Wilson, Monique E; Gordon, Michael S; Kinlock, Timothy W; Fitzgerald, Terrence T; O'Grady, Kevin E; Jaffe, Jerome H

    2015-11-01

    In a previously reported randomized controlled trial, formerly opioid-dependent prisoners were more likely to enter community drug abuse treatment when they were inducted in prison onto buprenorphine/naloxone (hereafter called buprenorphine) than when they received counseling without buprenorphine in prison (47.5% vs. 33.7%, p=0.012) (Gordon et al., 2014). In this communication we report on the results of the induction schedule and the adverse event profile seen in pre-release prisoners inducted onto buprenorphine. This paper examines the dose induction procedure, a comparison of the proposed versus actual doses given per week, and side effects reported for 104 adult participants who were randomized to buprenorphine treatment in prison. Self-reported side effects were analyzed using generalized estimated equations to determine changes over time in side effects. Study participants were inducted onto buprenorphine at a rate faster than the induction schedule. Of the 104 (72 males, 32 females) buprenorphine recipients, 64 (37 males, 27 females) remained on medication at release from prison. Nine participants (8.6%) discontinued buprenorphine because of unpleasant opioid side effects. There were no serious adverse events reported during the in-prison phase of the study. Constipation was the most frequent symptom reported (69 percent). Our findings suggest that buprenorphine administered to non-opioid-tolerant adults should be started at a lower, individualized dose than customarily used for adults actively using opioids, and that non-opioid-tolerant pre-release prisoners can be successfully inducted onto therapeutic doses prior to release. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. SHAKER Version 0.0/5 Pre-release Notes

    CERN Document Server

    CERN. Geneva

    1993-01-01

    SHAKER V0.0/5 is a pre-release of a simple cocktail central rapidity phase space event generator developed for the simulation of LHC Heavy Ion events. A modified version of JETSET 7.3 (the / LUJETS / common has been enlarged to 50000 particles and the LUEDIT routine has been modified to rearrange the particle weights vectors when called with MEDIT=1) is used to manage the events. All event information is included in / LUJETS / according to Lund conventions [1].

  7. Therapeutic strategies in the treatment of periodontitis

    Directory of Open Access Journals (Sweden)

    Liljana Bogdanovska

    2012-04-01

    Full Text Available Periodontitis is a chronic inflammatory process which affects the tooth - supporting structures of the teeth. The disease is initiated by subgingival periopathogenic bacteria in susceptible periodontal sites. The host immune response towards periodontal pathogens helps to sustain periodontal disease and eventual alveolar bone loss. Although scaling and root planing is the standard treatment modality for periodontitis, it suffers from several drawbacks such as the inability to reach the base of deep pockets and doesn’t arrest migration of periodontal pathogens from other sites in the oral cavity. In order to overcome the limitations of scaling and root planning, adjunctive chemotherapeutics and host modulatory agents to the treatment are used. These therapeutic agents show substantial beneficial effects when compared to scaling and root planning alone. This review will cover an update on chemotherapeutic and past and future host immune modulatory agents used adjunctively to treat and manage periodontal diseases.

  8. Therapeutic Engagement as a Predictor of Retention in Adolescent Therapeutic Community Treatment

    Science.gov (United States)

    Abdel-Salam, Sami; Gunter, Whitney D.

    2014-01-01

    The adolescent drug problem places a huge toll on society and a heavy burden on the criminal justice system. Research regarding the benefits of therapeutic community (TC) treatment for adolescents has shown it to be effective. Despite the ability of therapeutic communities to lower drug relapse and reduce criminality, a great deal remains unknown…

  9. Therapeutic Responses of Psychopathic Sexual Offenders: Treatment Attrition, Therapeutic Change, and Long-Term Recidivism

    Science.gov (United States)

    Olver, Mark E.; Wong, Stephen C. P.

    2009-01-01

    The authors examined the therapeutic responses of psychopathic sex offenders (greater than or equal to 25 Psychopathy Checklist-Revised; PCL-R) in terms of treatment dropout and therapeutic change, as well as sexual and violent recidivism over a 10-year follow-up among 156 federally incarcerated sex offenders treated in a high-intensity inpatient…

  10. Clinical Significance: a Therapeutic Approach Topsychological Assessment in Treatment Planning

    Directory of Open Access Journals (Sweden)

    Afolabi Olusegun Emmanuel

    2015-06-01

    Full Text Available Psychological assessment has long been reported as a key component of clinical psychology. This paper examines the complexities surrounding the clinical significance of therapeutic approach to treatment planning. To achieve this objective, the paper searched and used the PsycINFO and PubMed databases and the reference sections of chapters and journal articles to analysed, 1 a strong basis for the usage of therapeutic approach to psychological assessment in treatment plans, 2 explained the conceptual meaning of clinical significant change in therapeutic assessment, 3 answered some of the questions regarding practicability and the clinical significance of therapeutic approach to treatment plans, particularly during or before treatment, 4 linked therapeutic assessment to change in clients’ clinical impression, functioning and therapeutic needs 5 analysed the empirically documenting clinically significant change in therapeutic assessment. Finally, the study suggested that though therapeutic assessment is not sufficient for the systematic study of psychotherapy outcome and process, it is still consistent with both the layman and professional expectations regarding treatment outcome and also provides a precise method for classifying clients as ‘changed’ or ‘unchanged’ on the basis of clinical significance criteria.

  11. 76 FR 58197 - Pre-Release Community Confinement

    Science.gov (United States)

    2011-09-20

    ... advance notice and comment'' under the Administrative Procedure Act (5 U.S.C. 552, et seq.). Sacora v... as follows: ``Community confinement'' means residence in a community treatment center, halfway house... defendant to his or her place of residence continuously, except for authorized absences, enforced by...

  12. Water (electrolyte) balance after abdominal therapeutic treatment

    Energy Technology Data Exchange (ETDEWEB)

    Cionini, L; Becciolini, A; Giannardi, G [Florence Univ. (Italy). Istituto di Radiologia

    1976-07-01

    Total body water, plasma volume and Na space have been studied in 34 patients receiving external radiotherapy on the pelvic region. Determinations were made on the same patients before, and half-way treatment; in a few cases, some determinations were also repeated after the end of treatment. The results failed to show any appreciable modification of the different parameters studied.

  13. Novel Therapeutic Target for the Treatment of Lupus

    Science.gov (United States)

    2014-09-01

    AWARD NUMBER: W81XWH-12-1-0205 TITLE: Novel Therapeutic Target for the Treatment of Lupus PRINCIPAL INVESTIGATOR: Lisa Laury-Kleintop...SUBTITLE 5a. CONTRACT NUMBER Novel Therapeutic Target for the Treatment of Lupus 5b. GRANT NUMBER W81XWH-12-1-0205 5c. PROGRAM ELEMENT NUMBER 6...Systemic lupus erythematosus, autoantibodies. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 7 19a. NAME OF

  14. Neurodevelopmental Treatment (NDT): Therapeutic Intervention and Its Efficacy.

    Science.gov (United States)

    Stern, Francine Martin; Gorga, Delia

    1988-01-01

    Use of neurodevelopmental treatment, also known as the Bobath method, is discussed, including its history, philosophy, goals, and treatment emphasis with infants and children with movement disorders. Examples of children before and after therapeutic intervention illustrate use of the technique, and controversies in measuring therapy efficacy are…

  15. Dam pre-release as an important operation strategy in reducing flood impact in Malaysia

    Science.gov (United States)

    Hidayah Ishak, Nurul; Mustafa Hashim, Ahmad

    2018-03-01

    The 2014 flood was reported to be one of the worst natural disaster has ever affected several states in the northern part of Peninsular Malaysia. Overwhelming rainfall was noted as one of the main factors causing such impact, which was claimed to be unprecedented to some extent. The state of Perak, which is blessed with four cascading dams had also experienced flood damage at a scale that was considered the worst in history. The rainfall received had caused the dam to reach danger level that necessitated additional discharge to be released. Safety of the dams was of great importance and such unavoidable additional discharge was allowed to avoid catastrophic failure of the dam structures. This paper discusses the dam pre-release as a significant dam management strategy in reducing flood impact. An important balance between required dam storage to be maintained and the risk element that can be afforded is the crucial factor in such enhanced operation strategy. While further possibility in developing a carefully engineered dam pre-release strategy can be explored for dam operation in Malaysia, this has already been introduced in some developed countries. Australia and South Africa are examples where pre-release has been practiced and proven to reduce flood risk. The concept involves controlling the dam lake level throughout the year, in reference to the rainfall data and the hydrological properties for the catchment area of the dams. Plentiful data analysis need to be done in contemplation of producing the optimal pre-release model. The amount of heavy rainfalls received is beyond human control but the distribution of the discharge from the dams can be further managed with the appropriate pre-release strategy.

  16. Psychological treatment and therapeutic change in incarcerated rapists

    Directory of Open Access Journals (Sweden)

    Ana Martínez-Catena

    2017-01-01

    Full Text Available Abstract Most Spanish prisons provide specialised treatment for incarcerated sex offenders, both rapists and child molesters. This treatment is a cognitive-behavioural intervention that has shown relative effectiveness in previous research. With regard to offenders’ rehabilitation, recidivism assessments are necessary as a final measure of treatment effectiveness. However, the evaluation of recidivism by itself does not provide sufficient information on the treatment process and the specific effects that treated subjects could undergo. This paper aims to analyse the therapeutic effectiveness of psychological treatment provided to rapists (in general, males sentenced for committing a sexual offence against women. To this aim, a group of treated rapists (N=153 serving a sentence in prison was analysed. Using a specially designed scale (PASSO, the global therapeutic change and ten specific variables (including assertiveness, readiness to change, cognitive distortions, impulsivity, etc. were assessed. The within-subjects comparison showed that treated sex offenders improved, in therapeutic terms, globally as well as in most of the specific variables assessed (improvements not experimented by the control group. Also, different therapeutic subscales showed relevant associations between them. The findings regarding treatment effectiveness are discussed.

  17. Predicting Social Anxiety Treatment Outcome based on Therapeutic Email Conversations

    NARCIS (Netherlands)

    Hoogendoorn, M.; Berger, Thomas; Schulz, Ava; Stolz, Timo; Szolovits, Peter

    2016-01-01

    Predicting therapeutic outcome in the mental health domain is of utmost importance to enable therapists to provide the most effective treatment to a patient. Using information from the writings of a patient can potentially be a valuable source of information, especially now that more and more

  18. A Web Based Framework for Pre-release Testing of Mobile Applications

    Directory of Open Access Journals (Sweden)

    Hamdy Abeer

    2016-01-01

    Full Text Available Mobile applications are becoming an integral part of daily life and of business’s marketing plan. They are helpful in promoting for the business, attracting and retaining customers. Software testing is vital to ensure the delivery of high quality mobile applications that could be accessed across different platforms and meet business and technical requirements. This paper proposes a web based tool, namely Pons, for the distribution of pre-release mobile applications for the purpose of manual testing. Pons facilities building, running, and manually testing Android applications directly in the browser. It gets the developers and end users engaged in testing the applications in one place, alleviates the tester’s burden of installing and maintaining testing environments, and provides a platform for developers to rapidly iterate on the software and integrate changes over time. Thus, it speeds up the pre-release testing process, reduces its cost and increases customer satisfaction.

  19. Monitoring of pre-release cracks in prestressed concrete using fiber optic sensors

    Science.gov (United States)

    Abdel-Jaber, Hiba; Glisic, Branko

    2015-04-01

    Prestressed concrete experiences low to no tensile stresses, which results in limiting the occurrence of cracks in prestressed concrete structures. However, the nature of construction of these structures requires the concrete not to be subjected to the compressive force from the prestressing tendons until after it has gained sufficient compressive strength. Although the structure is not subjected to any dead or live load during this period, it is influenced by shrinkage and thermal variations. Thus, the concrete can experience tensile stresses before the required compressive strength has been attained, which can result in the occurrence of "pre-release" cracks. Such cracks are visually closed after the transfer of the prestressing force. However, structural capacity and behavior can be impacted if cracks are not sufficiently closed. This paper researches a method for the verification of the status of pre-release cracks after transfer of the prestressing force, and it is oriented towards achievement of Level IV Structural Health Monitoring (SHM). The method relies on measurements from parallel long-gauge fiber optic sensors embedded in the concrete prior to pouring. The same sensor network is used for the detection and characterization of cracks, as well as the monitoring of the prestressing force transfer and the determination of the extent of closure of pre-release cracks. This paper outlines the researched method and presents its application to a real-life structure, the southeast leg of Streicker Bridge on the Princeton University campus. The application structure is a curved continuous girder that was constructed in 2009. Its deck experienced four pre-release cracks that were closed beyond the critical limits based on the results of this study.

  20. MicroRNA-targeted therapeutics for lung cancer treatment.

    Science.gov (United States)

    Xue, Jing; Yang, Jiali; Luo, Meihui; Cho, William C; Liu, Xiaoming

    2017-02-01

    Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists. Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease. Expert opinion: The development of miRNA-targeted therapeutics has become an important anti-cancer strategy. Results from both preclinical and clinical trials of microRNA replacement therapy have shown some promise in cancer treatment. However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed. Several delivery strategies have been employed, including naked oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors. However, delivery remains a main challenge in miRNA-targeting therapeutics. Furthermore, immune-related serious adverse events are also a concern, which indicates the complexity of miRNA-based therapy in clinical settings.

  1. Therapeutic Vaccines and Antibodies for Treatment of Orthopoxvirus Infections

    Directory of Open Access Journals (Sweden)

    Stuart N. Isaacs

    2010-10-01

    Full Text Available Despite the eradication of smallpox several decades ago, variola and monkeypox viruses still have the potential to become significant threats to public health. The current licensed live vaccinia virus-based smallpox vaccine is extremely effective as a prophylactic vaccine to prevent orthopoxvirus infections, but because of safety issues, it is no longer given as a routine vaccine to the general population. In the event of serious human orthopoxvirus infections, it is important to have treatments available for individual patients as well as their close contacts. The smallpox vaccine and vaccinia immune globulin (VIG were used in the past as therapeutics for patients exposed to smallpox. VIG was also used in patients who were at high risk of developing complications from smallpox vaccination. Thus post-exposure vaccination and VIG treatments may again become important therapeutic modalities. This paper summarizes some of the historic use of the smallpox vaccine and immunoglobulins in the post-exposure setting in humans and reviews in detail the newer animal studies that address the use of therapeutic vaccines and immunoglobulins in orthopoxvirus infections as well as the development of new therapeutic monoclonal antibodies.

  2. Gynecologic cancer treatment: risk factors for therapeutically induced neoplasia

    International Nuclear Information System (INIS)

    Messerschmidt, G.L.; Hoover, R.; Young, R.C.

    1980-01-01

    Therapeutic intervention in a course of illness, while producing the desired result, also may have some adverse long-term effects on the patient. Second malignancies are one of the known complications of therapy. The treatments of gynecologic cancers by surgery, irradiation and chemotherapy have been associated with subsequent neoplasms. The use of normal skin from the thigh to fabricate an artificial vagina has resulted in more squamous cell carcinomas than expected. Alkylating agents used in the treatment of ovarian cancer and other diseases have been shown to lead to an increased risk of leukemia. The incidence of lymphoma and uterine, urinary bladder and colon carcinomas has been associated with prior irradiation for gynecologic disease. The literature regarding the therapeutically induced risk factors in gynecologic therapy is reviewed and areas of our knowledge that require more investigation are identified

  3. Structural health monitoring methods for the evaluation of prestressing forces and pre-release cracks

    Directory of Open Access Journals (Sweden)

    Hiba Abdel-Jaber

    2016-08-01

    Full Text Available Prestressed concrete bridges currently account for 45% of bridges built in the last five years in the United States. This has resulted in an increase in the number of deficient bridges composed of prestressed concrete, which requires a better understanding of the on-site performance of this building material. The use of new materials, such as high performance concrete, in conjunction with prestressing provides additional motivation for the creation of structural health monitoring (SHM methods for prestressed concrete. This paper identifies two parameters relevant to prestressed concrete, along with methods for their evaluation. The parameters evaluated are the prestressing force value at transfer and the width of pre-release cracks, both of which are indicators of structural performance. Improper transfer of the prestressing force can result in tensile stresses in the concrete that exceed capacity and result in cracks and/or excessive deflections. Pre-release cracks occur in the concrete prior to transfer of the prestressing force and are mainly caused by autogenous shrinkage and thermal gradients. Closure of the cracks is expected by virtue of prestressing force transfer. However, the extent of crack closure is important in order to guarantee durability and structural integrity. This paper presents an integral overview of two novel methods for the statistical evaluation of the two monitored parameters: prestressing forces and the width of pre-release cracks. Validation of the methods is performed through application to two structures, both of which are components of Streicker Bridge on the Princeton University campus. Uncertainties are evaluated and thresholds for unusual behavior are set through the application.

  4. New therapeutic approaches for treatment of tularaemia: a review

    Directory of Open Access Journals (Sweden)

    Sandrine eBOISSET

    2014-03-01

    Full Text Available Antibiotic treatment of tularaemia is based on a few drugs, including the fluoroquinolones, the tetracyclines and the aminoglycosides. Because no effective and safe vaccine is currently available, tularaemia prophylaxis following proven exposure to F. tularensis also relies on administration of antibiotics. A number of reasons make it necessary to search for new therapeutic alternatives: the potential toxicity of first-line drugs, especially in children and pregnant women; a high rate of treatment relapses and failures, especially for severe and/or suppurated forms of the disease; and the possible use of antibiotic-resistant strains in the context of a biological threat. This review presents novel therapeutic approaches that have been explored in recent years to improve tularaemia patients’ management and prognosis. First, the activities of newly available antibiotic compounds were evaluated against F. tularensis, including tigecycline (a glycylcycline, ketolides (telithromycin and cethromycin and fluoroquinolones (moxifloxacin, gatifloxacin, trovafloxacin and grepafloxacin. The liposome delivery of some antibiotics was evaluated. The effect of antimicrobial peptides against F. tularensis was also considered. Other drugs were evaluated for their ability to suppress the intracellular multiplication of F. tularensis. The effects of the modulation of the innate immune response (especially via TLR receptors on the course of F. tularensis infection were characterized. Another approach was the administration of specific antibodies to induce passive resistance to F. tularensis infection. All of these studies highlight the need to develop new therapeutic strategies to improve the management of patients with tularaemia. Many possibilities exist, some unexplored. Moreover, it is likely that new therapeutic alternatives that are effective against this intracellular pathogen could be, at least partially, extrapolated to other human pathogens.

  5. In Search of New Therapeutic Targets in Obesity Treatment: Sirtuins

    Directory of Open Access Journals (Sweden)

    Alina Kurylowicz

    2016-04-01

    Full Text Available Most of the available non-invasive medical therapies for obesity are non-efficient in a long-term evaluation; therefore there is a constant need for new methods of treatment. Research on calorie restriction has led to the discovery of sirtuins (silent information regulators, SIRTs, enzymes regulating different cellular pathways that may constitute potential targets in the treatment of obesity. This review paper presents the role of SIRTs in the regulation of glucose and lipid metabolism as well as in the differentiation of adipocytes. How disturbances of SIRTs’ expression and activity may lead to the development of obesity and related complications is discussed. A special emphasis is placed on polymorphisms in genes encoding SIRTs and their possible association with susceptibility to obesity and metabolic complications, as well as on data regarding altered expression of SIRTs in human obesity. Finally, the therapeutic potential of SIRTs-targeted strategies in the treatment of obesity and related disorders is discussed.

  6. Therapeutic Bronchoalveolar Lavage with Conventional Treatment in Allergic Bronchopulmonary Aspergillosis

    International Nuclear Information System (INIS)

    Khalil, K. F.

    2015-01-01

    Objective: To establish the role of therapeutic bronchoalveolar lavage in addition to conventional treatment among two groups, with allergic bronchopulmonary aspergillosis, in terms of regression in serum IgE levels and clinical recurrence at 3 and 6 months of follow-up. Study Design: Aquasi-experimental study. Place and Duration of Study: Department of Pulmonology, Fauji Foundation Hospital, Rawalpindi, from July 2010 to December 2013. Methodology: The study was carried out on 132 patients who fulfilled the Greenberger and Patterson criteria and underwent a chest X-ray, an HRCT chest and classified radiologically as with Central Bronchiectasis (CB), High Attenuation Mucus (HAM) or Other Radiological Features (ORF). Baseline serum IgE levels were noted. All patients were given treatment including prednisolone and antifungal agent itraconazole for 4 months. Patients with ORF on HRCT chest and just received the medical treatment were labeled as conventional group. Those patients who had CB or HAM radiological features also underwent bronchoscopy with therapeutic Bronchoalveolar Lavage (BAL), labeled as BAL group. Clinical recurrence and serum IgE levels were noted at 3 and 6 months. Values were compared using chi-square and Mann-Whitney tests respectively. Results: Around 78 (59.1 percentage) of patients underwent bronchoscopy with therapeutic bronchoalveolar lavage to remove the mucus plugs. The mean serum IgE levels at baseline were 3312.04 ± 2526.217 and 3486.15 ± 2528.324 IU/ml in the BAL and conventional groups respectively. There was a statistically significant reduction in the mean serum IgE levels at 3 (p < 0.00) and 6 months (p < 0.001) of follow-up in BALas compared to conventional group. There was no significant difference in the clinical recurrence rate in both the groups (p=0.078 at 3 and 0.343 at 6 months respectively). Conclusion: Therapeutic bronchoalveolar lavage may be a useful adjunct to treatment in patients with allergic bronchopulmonary

  7. Cisplatin encapsulated nanoparticle as a therapeutic agent for anticancer treatment

    Science.gov (United States)

    Eka Putra, Gusti Ngurah Putu; Huang, Leaf; Hsu, Yih-Chih

    2016-03-01

    The knowledge of manipulating size of biomaterials encapsulated drug into nano-scale particles has been researched and developed in treating cancer. Cancer is the second worldwide cause of death, therefore it is critical to treat cancers challenging with therapeutic modality of various mechanisms. Our preliminary investigation has studied cisplatin encapsulated into lipid-based nanoparticle and examined the therapeutic effect on xenografted animal model. We used mice with tumor volume ranging from 195 to 214 mm3 and then few mice were grouped into three groups including: control (PBS), lipid platinum chloride (LPC) nanoparticles and CDDP (cis-diamminedichloroplatinum(II) at dose of 3mg cisplatin /kg body weight. The effect of the treatment was observed for 12 days post-injection. It showed that LPC NPs demonstrated a better therapeutic effect compared to CDDP at same 3mg cisplatin/kg drug dose of tumor size reduction, 96.6% and 11.1% respectively. In addition, mouse body weight loss of LPC, CDDP and PBS treated group are 12.1%, 24.3% and 1.4%. It means that by compared to CDDP group, LPC group demonstrated less side effect as not much reduction of body weight have found. Our findings have shown to be a potential modality to further investigate as a feasible cancer therapy modality.

  8. Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

    Science.gov (United States)

    Balivada, Sivasai

    Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

  9. Gynecologic cancer treatment: risk factors for therapeutically induced neoplasia

    International Nuclear Information System (INIS)

    Messerschmidt, G.L.; Hoover, R.; Young, R.C.

    1981-01-01

    Therapeutic intervention in a course of illness, while producing the desired result, also may have some adverse long-term effects on the patient. Second malignancies are one of the known complications of therapy. The treatments of gynecologic cancers by surgery, irradiation and chemotherapy have been associated with subsequent neoplasms. Care must be exercised in associating previous therapy and a subsequent malignancy. Naturally occurring second cancers must be separated from those which are iatrogenic. Associations in the literature have been made involving malignancies as a sequelae of prior gynecologic therapy. The use of normal skin from the thigh to fabricate an artificial vagina has resulted in more squamous cell carcinomas than expected. Alkylating agents used in the treatment of ovarian cancer and other diseases have been shown to lead to an increased risk of leukemia. Irradiation therapy, however, has not yet been shown to be related to leukemia in cervical cancer patients. The incidence of lymphoma and uterine, urinary bladder and colon carcinomas has been associated with prior irradiation for gynecologic disease. The literature regarding the therapeutically induced risk factors in gynecologic therapy is reviewed and areas of our knowledge that require more investigation are identified

  10. Polymer Therapeutics: Biomarkers and New Approaches for Personalized Cancer Treatment.

    Science.gov (United States)

    Atkinson, Stuart P; Andreu, Zoraida; Vicent, María J

    2018-01-23

    Polymer therapeutics (PTs) provides a potentially exciting approach for the treatment of many diseases by enhancing aqueous solubility and altering drug pharmacokinetics at both the whole organism and subcellular level leading to improved therapeutic outcomes. However, the failure of many polymer-drug conjugates in clinical trials suggests that we may need to stratify patients in order to match each patient to the right PT. In this concise review, we hope to assess potential PT-specific biomarkers for cancer treatment, with a focus on new studies, detection methods, new models and the opportunities this knowledge will bring for the development of novel PT-based anti-cancer strategies. We discuss the various "hurdles" that a given PT faces on its passage from the syringe to the tumor (and beyond), including the passage through the bloodstream, tumor targeting, tumor uptake and the intracellular release of the active agent. However, we also discuss other relevant concepts and new considerations in the field, which we hope will provide new insight into the possible applications of PT-related biomarkers.

  11. Predicting Social Anxiety Treatment Outcome Based on Therapeutic Email Conversations.

    Science.gov (United States)

    Hoogendoorn, Mark; Berger, Thomas; Schulz, Ava; Stolz, Timo; Szolovits, Peter

    2017-09-01

    Predicting therapeutic outcome in the mental health domain is of utmost importance to enable therapists to provide the most effective treatment to a patient. Using information from the writings of a patient can potentially be a valuable source of information, especially now that more and more treatments involve computer-based exercises or electronic conversations between patient and therapist. In this paper, we study predictive modeling using writings of patients under treatment for a social anxiety disorder. We extract a wealth of information from the text written by patients including their usage of words, the topics they talk about, the sentiment of the messages, and the style of writing. In addition, we study trends over time with respect to those measures. We then apply machine learning algorithms to generate the predictive models. Based on a dataset of 69 patients, we are able to show that we can predict therapy outcome with an area under the curve of 0.83 halfway through the therapy and with a precision of 0.78 when using the full data (i.e., the entire treatment period). Due to the limited number of participants, it is hard to generalize the results, but they do show great potential in this type of information.

  12. Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

    Directory of Open Access Journals (Sweden)

    Sayeda Yasmin-Karim

    2018-04-01

    Full Text Available Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs, with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed.

  13. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

    Directory of Open Access Journals (Sweden)

    Neil V. Klinger

    2016-01-01

    Full Text Available Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin’s ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors.

  14. Long-term evaluation of treatment of chronic, therapeutically refractory tinnitus by neurostimulation

    NARCIS (Netherlands)

    Staal, M. J.; Holm, A. F.; Mooij, J. J. A.; Albers, F. W. J.; Bartels, H.

    2007-01-01

    Objective: Long-term evaluation of treatment of chronic, therapeutically refractory tinnitus by means of chronic electrical stimulation of the vestibulocochlear nerve. Patients: Inclusion criteria were severe, chronic, therapeutically refractory, unilateral tinnitus and severe hearing loss at the

  15. Therapeutic effect of beta radiation on onychomycosis: An innovative treatment

    International Nuclear Information System (INIS)

    Afroz, S.; Islam, N.; Rashid, H.; Shahidullah, M.; Ali, S.; Islam, S.K.M.; Hossain, S.; Ali, N.

    2005-01-01

    Full text: Onychomycosis is the most frequent cause of nail disease and the most prevalent type of dermatophytosis in Bangladesh. The humid and warm climate of this tropical country is congenial for the growth of fungi. Therapeutic limitations of conventional antimycotic agents in respect of low cure rates, high relapse rate, inherent side effects, long duration of treatment and high cost in treating onychomycosis have provided clear incentives to explore alternative forms of treatment procedure. The objectives of the present thesis work were: (i) To use beta radiation as a curative therapy for Onychomycosis, optimisation of its dosages and to promote an innovative clinical development in the field of therapeutic application of nuclear medicine; (ii) To assess the efficacy of beta radiation either alone or in combination with conventional antifungal therapy; and (iii) To reduce the duration of drug exposure and cost of treatment for onychomycosis. This is a PhD research work under the University of Dhaka and was sponsored by the Ministry of Science and Information and Communication Technology, Government of the people's republic of Bangladesh. This study is an open, randomised and controlled trial to verify the efficacy of beta radiation in patients with onychomycosis. Using the appropriate statistical formula, sample size of the study population was determined and in each group 92 patients were assigned. With an assumption of patients drop out and for better statistical analysis, a total of 330 patients, who fulfilled the inclusion criterion having diagnosed to have onychomycosis clinically and mycological were randomly allocated to enter in therapeutic regimen. Study population was randomised in three groups. Group A (n =110) received griseofulvin orally 500 mg once daily for 12-16 weeks; Group B (n=110) received beta radiation, 500 rads bi-weekly for 3 weeks (total 2500 rads); and Group C (n=110) received combined beta radiation (total 2500 rads in 3 weeks) and

  16. Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma.

    Science.gov (United States)

    Pritchard, Eleanor M; Dyer, Michael A; Guy, R Kiplin

    2016-01-01

    While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors.

  17. Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes

    Science.gov (United States)

    Bai, Litao; Gao, Jialiang; Wei, Fan; Zhao, Jing; Wang, Danwei; Wei, Junping

    2018-01-01

    Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction. Many effects are attributed to ginsenosides, including gluconeogenesis reduction, improvement of insulin resistance, glucose transport, insulinotropic action, islet cell protection, hepatoprotective activity, anti-inflammatory effect, myocardial protection, lipid regulation, improvement of glucose tolerance, antioxidation, improvement of erectile dysfunction, regulation of gut flora metabolism, neuroprotection, anti-angiopathy, anti-neurotoxic effects, immunosuppression, and renoprotection effect. The molecular targets of these effects mainly contains GLUTs, SGLT1, GLP-1, FoxO1, TNF-α, IL-6, caspase-3, bcl-2, MDA, SOD, STAT5-PPAR gamma pathway, PI3K/Akt pathway, AMPK-JNK pathway, NF-κB pathway, and endoplasmic reticulum stress. Rg1, Rg3, Rb1, and compound K demonstrated the most promising therapeutic prospects as potential adjuvant medicines for the treatment of diabetes. This paper highlights the underlying pharmacological mechanisms of the

  18. Acupuncture as a therapeutic treatment option for threatened miscarriage

    Directory of Open Access Journals (Sweden)

    Betts Debra

    2012-03-01

    Full Text Available Abstract Background Threatened miscarriage involves vaginal bleeding in a pregnancy that remains viable. This is a common early pregnancy complication with increased risk factors for early pregnancy loss, preterm premature rupture of membranes (PPROM, preterm delivery, low birth weight babies and maternal antepartum haemorrhage. Currently there are no recommended medical treatment options, rather women receive advice that centres on a 'wait and see' approach. For women with a history of unexplained recurrent miscarriage providing supportive care in a subsequent pregnancy improves live birthing outcomes, but the provision of supportive care to women experiencing threatened miscarriage has to date not been examined. Discussion While it is known that 50-70% of miscarriages occur due to chromosomal abnormalities, the potential for therapeutic intervention amongst the remaining percentage of women remains unknown. Complementary and alternative medicine (CAM therapies have the potential to provide supportive care for women presenting with threatened miscarriage. Within fertility research, acupuncture demonstrates beneficial hormonal responses with decreased miscarriage rates, raising the possibility acupuncture may promote specific beneficial effects in early pregnancy. With the lack of current medical options for women presenting with threatened miscarriage it is timely to examine the possible treatment benefits of providing CAM therapies such as acupuncture. Summary Despite vaginal bleeding being a common complication of early pregnancy there is often reluctance from practitioners to discuss with women and medical personal how and why CAM may be beneficial. In this debate article, the physiological processes of early pregnancy together with the concept of providing supportive care and acupuncture are examined. The aim is to raise awareness and promote discussion as to the beneficial role CAM may have for women presenting with threatened miscarriage.

  19. Therapeutic antibodies as a treatment option for dengue fever.

    Science.gov (United States)

    Chan, Kuan Rong; Ong, Eugenia Z; Ooi, Eng Eong

    2013-11-01

    Dengue fever is the most prevalent mosquito-borne viral disease globally with about 100 million cases of acute dengue annually. Severe dengue infection can result in a life-threatening illness. In the absence of either a licensed vaccine or antiviral drug against dengue, therapeutic antibodies that neutralize dengue virus (DENV) may serve as an effective medical countermeasure against severe dengue. However, therapeutic antibodies would need to effectively neutralize all four DENV serotypes. It must not induce antibody-dependent enhancement of DENV infection in monocytes/macrophages through Fc gamma receptor (FcγR)-mediated phagocytosis, which is hypothesized to increase the risk of severe dengue. Here, we review the strategies and technologies that can be adopted to develop antibodies for therapeutic applications. We also discuss the mechanism of antibody neutralization in the cells targeted by DENV that express Fc gamma receptor. These studies have provided significant insight toward the use of therapeutic antibodies as a potentially promising bulwark against dengue.

  20. Analysis of the status of pre-release cracks in prestressed concrete structures using long-gauge sensors

    International Nuclear Information System (INIS)

    Abdel-Jaber, H; Glisic, B

    2015-01-01

    Prestressed structures experience limited tensile stresses in concrete, which limits or completely eliminates the occurrence of cracks. However, in some cases, large tensile stresses can develop during the early age of the concrete due to thermal gradients and shrinkage effects. Such stresses can cause early-age cracks, termed ‘pre-release cracks’, which occur prior to the transfer of the prestressing force. When the prestressing force is applied to the cross-section, it is assumed that partial or full closure of the cracks occurs by virtue of the force transfer through the cracked cross-section. Verification of the closure of the cracks after the application of the prestressing force is important as it can either confirm continued structural integrity or indicate and approximate reduced structural capacity. Structural health monitoring (SHM) can be used for this purpose. This paper researches an SHM method that can be applied to prestressed beam structures to assess the condition of pre-release cracks. The sensor network used in this method consists of parallel long-gauge fiber optic strain sensors embedded in the concrete cross-sections at various locations. The same network is used for damage detection, i.e. detection and characterization of the pre-release cracks, and for monitoring the prestress force transfer. The method is validated on a real structure, a curved continuous girder. Results from the analysis confirm the safety and integrity of the structure. The method and its application are presented in this paper. (paper)

  1. Analysis of the status of pre-release cracks in prestressed concrete structures using long-gauge sensors

    Science.gov (United States)

    Abdel-Jaber, H.; Glisic, B.

    2015-02-01

    Prestressed structures experience limited tensile stresses in concrete, which limits or completely eliminates the occurrence of cracks. However, in some cases, large tensile stresses can develop during the early age of the concrete due to thermal gradients and shrinkage effects. Such stresses can cause early-age cracks, termed ‘pre-release cracks’, which occur prior to the transfer of the prestressing force. When the prestressing force is applied to the cross-section, it is assumed that partial or full closure of the cracks occurs by virtue of the force transfer through the cracked cross-section. Verification of the closure of the cracks after the application of the prestressing force is important as it can either confirm continued structural integrity or indicate and approximate reduced structural capacity. Structural health monitoring (SHM) can be used for this purpose. This paper researches an SHM method that can be applied to prestressed beam structures to assess the condition of pre-release cracks. The sensor network used in this method consists of parallel long-gauge fiber optic strain sensors embedded in the concrete cross-sections at various locations. The same network is used for damage detection, i.e. detection and characterization of the pre-release cracks, and for monitoring the prestress force transfer. The method is validated on a real structure, a curved continuous girder. Results from the analysis confirm the safety and integrity of the structure. The method and its application are presented in this paper.

  2. Recombinant proteins in therapeutics: haemophilia treatment as an example

    Directory of Open Access Journals (Sweden)

    Liras Antonio

    2008-04-01

    Full Text Available Abstract One of the most spectacular advances in the history of scientific knowledge was the discovery of deoxyribonucleic acid (DNA by Watson and Crick in 1953. This enabled certain proteins to be prepared in this way for their therapeutic use in clinical practice. Today, in the first decade of the 21st century, hundreds of therapeutic proteins have been produced recombinantly and about 50 of them have been approved for clinical use. Because of the specific procedure used for obtaining these products, which is based on expressing a atherapeutica gene from a fragment of DNA in a cell to produce a functional protein that is free from any human or animal component, they are especially acleana and thus the therapy of choice for many current diseases. The immediate question is: why are recombinant products not used more extensively given their high efficacy and maximum safety? In short, we are faced with an interesting but also unfortunate paradox of pharmacology that greater progress in therapeutic procedures is not always associated with greater introduction of those resources that are safest, for the simple reason that they are more costly.

  3. Therapeutic Advances using Combinational Therapy in the Treatment of Glioblastoma

    DEFF Research Database (Denmark)

    Staberg, Mikkel

    2017-01-01

    Glioblastoma is the most malignant brain tumor in adults. Median survival is only about 15 months despite aggressive treatment, consisting of surgery followed by radio- and chemotherapy, stressing the need for new therapies. Development of glioblastoma is thought to be a result of both genetic...... and epigenetic alterations, ultimately leading to oncogenic transformation of normal glia cells. Several features are suggested to give rise to the poor prognosis of glioblastoma including treatment resistance, a high degree of abnormal blood vessels, and high heterogeneity, both within the single tumor and from...... patient to patient. Thus, investigations are needed to identify the genetic-molecular alterations that glioblastoma tumors depend on in order to overcome treatment and regrow after initial surgery. The findings presented in this thesis illustrate the promising potential of combinational treatments...

  4. Study and evaluation of radiometry in photo therapeutic treatment of the neonatal hyperbilirubinaemia

    International Nuclear Information System (INIS)

    Caly, Jose Pucci

    2009-01-01

    Phototherapy is a procedure established more than 50 years ago in the treatment of the newborn jaundice. However there is no a standard method to quantify the photo therapeutic dose in published clinical studies, hindering the comparison of previous studies on photo therapeutic effectiveness, as well as the establishment of safe and predictable doses. The photo therapeutic dose depends, among other factors, on the effective mean irradiance produced by the photo therapeutic unit. There are no standard procedures, however, neither to quantify the effective irradiance, nor to estimate the mean effective irradiance. As a consequence, large measurement variations in a same photo therapeutic unit are observed using different commercially available radiometers, as a consequence of the vast diversity of spectral responsivities of the instruments. An objective of this work was to adapt and to apply the bases of the wideband ultraviolet radiometry to quantify the available irradiance from photo therapeutic units, establishing procedures that allow us to compare measured irradiances from different sources, using radiometers presenting different spectral responsivities. Another objective was to characterize samples of photo therapeutic units commonly used, focusing the problem of the estimation of the effective mean irradiance from photo therapeutic units, proposing a method to estimate of the effective irradiance from focused sources. The experimental results allow us to conclude that it is not only necessary to standardize the photo therapeutic radiometry, but also the method of estimation of the effective mean irradiance. (author)

  5. Rapid arc in cancer treatment - a therapeutic perspective

    International Nuclear Information System (INIS)

    Rao, Suresh

    2013-01-01

    Recently, volumetric-modulated arc therapy (VMAT) has demonstrated the ability to deliver radiation dose precisely and accurately with a shorter delivery time compared to conventional intensity-modulated fixed-field treatment (IMRT). We applied the hypothesis of VMAT technique at our hospital to determine the superior dose coverage for planning target volume (PTV) with adequate sparing of organs-at-risk (OARs). The delivery time and monitor units (MUs) is reduced in comparison with conventional fixed-field IMRT. Rapid Arc (RA) plans had a pre-treatment quality assurance and results were summarised in terms of the Gamma Agreement Index (GAI) scoring criteria of 3% and 3 mm thresholds. A total of 771 patients were treated between July 2011 and August 2013 of which head and neck cancer were 385, prostate cancer 53, brain tumours 112, cervical and endometrial cancer 77, breast cancer 38, rectal and bladder cancer 56, special technique using SBRT 45 (Liver and Lung) and Cranio-spinal irradiation 5 patients using RA single (177 control points) and double arcs (354 control points). The Average treatment time was 4.8 ±0.2 minutes (220 seconds of beam-on). The number of MU per fraction of 2.0 Gy was 522.5 ± 133.62. VMAT can be a valuable clinical tool that can deliver the prescribed dose efficiently in 1.5-3 minutes (single or double arcs) with high target homogeneity and adequate sparing of organs at risk. It would allow to reduce patient lying time on couch and over all beam on time from 4 hours to one hour. The toxicity (Tracheal fistula) observed in two patients of Carcinoma Lung receiving SRT high lights the need for peer review. (author)

  6. 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.

  7. Therapeutic Erythrocytapheresis in the Initial Treatment of Hereditary Hemochromatosis

    Directory of Open Access Journals (Sweden)

    Vít Řeháček

    2012-01-01

    Full Text Available Background: The current treatment of hereditary hemochromatosis (HH consists of performing periodic whole blood phlebotomies. Erythrocytapheresis (EA can remove up to three times more red blood cells per single procedure and could thus have a clinical benefit. A prospective study of 30 consecutive cases of HH were included in a periodic EA program. Methods and patients: EA were performed using a discontinuous flow cell separators. The protocol consisted of a bimonthly EA until normalization of the serum ferritin was reached. The aim was to reduce the total erythrocyte volume by 25–35%, eventually, to adjust the amount so that hematocrit would not drop below 0.25. Results: 530 ± 101 ml of erythrocytes were removed (median 517, range 116–761 ml. Iron depletion (ferritin < 20 μg/l was achieved in all patients after a mean 6.9 ± 7.6 months, median 5 months, range 1–36 months and a mean 14 EA sessions. The procedures were well tolerated and there were no severe side-effects. Conclusions: We conclude that HH patients treated with EA achieved iron depletion quickly under good conditions of tolerance. The efficacy, speed, tolerability, and more favorable schedule of an EA program facilitate treatment of HH.

  8. Plant-derived therapeutics for the treatment of metabolic syndrome.

    Science.gov (United States)

    Graf, Brittany L; Raskin, Ilya; Cefalu, William T; Ribnicky, David M

    2010-10-01

    Metabolic syndrome is defined as a set of coexisting metabolic disorders that increase an individual's likelihood of developing type 2 diabetes, cardiovascular disease and stroke. Medicinal plants, some of which have been used for thousands of years, serve as an excellent source of bioactive compounds for the treatment of metabolic syndrome because they contain a wide range of phytochemicals with diverse metabolic effects. In order for botanicals to be effectively used against metabolic syndrome, however, botanical preparations must be characterized and standardized through the identification of their active compounds and respective modes of action, followed by validation in controlled clinical trials with clearly defined endpoints. This review assesses examples of commonly known and partially characterized botanicals to describe specific considerations for the phytochemical, preclinical and clinical characterization of botanicals associated with metabolic syndrome.

  9. 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.

  10. Changes in Personality Disorder Traits Following 2 Years of Treatment in a Secure Therapeutic Community Milieu

    Science.gov (United States)

    Morrissey, Catrin; Taylor, Jon

    2014-01-01

    Therapeutic community treatment models have not previously been applied to forensic patients with mild intellectual disabilities (IDs) with a comorbid diagnosis of personality disorder. Thirteen patients with mild IDs were allocated to a unit within a high secure psychiatric service operating a model of treatment based on the principles and…

  11. Experience in treatment of hyperthyroidism with I-131 diagnosis, patient preparation and therapeutic procedure

    International Nuclear Information System (INIS)

    Zhongyun, Pan

    2003-01-01

    Treatment of hyperthyroidism with I-131 diagnosis is being performed after clinical diagnosis of thyrotoxicosis based on clinical manifestations of hypermetabolic state, serumT3 and T4 determination; medical preparation of patients and therapeutic procedure is obtained for better efficacy, relieve symptoms and prevent aggravation of thyrotoxicosis after I-131 treatment

  12. Therapeutic inhibitors for the treatment of dry eye syndrome.

    Science.gov (United States)

    Rodríguez-Pomar, Candela; Pintor, Jesus; Colligris, Basilio; Carracedo, Gonzalo

    2017-12-01

    Dry eye disease (DED), defined as a multifactorial disease of tears and ocular surface, results in symptoms of discomfort, ocular irritation, visual disturbance and tear film instability. This syndrome is accompanied of ocular surface inflammation and it is produced by a deficient activity of the lacrimal functional unit. In addition, it is associated with systemic autoimmune diseases such as Sjögren´s Syndrome, rheumatoid arthritis, systemic lupus erythematosus and some drug administration. The treatment of dry eye disease is based on the typical signs and symptoms of dry eye, which are associated with hyperosmolarity, ocular surface inflammation, discomfort, visual disturbance, and tear film instability. Areas covered: This review is focused on synthetic drugs currently used in clinical practice, from phase III development onwards to treat the ocular surface signs and symptoms of dry eye disease. Expert opinion: The multifactorial disease and the lack of correlation between signs and symptoms imply that not all the pharmacological approaches will be successful for dry eye. The correct design of the clinical trials, with appropriate endpoints, and the type of dry eye under study are complicated but mandatory. The anti-inflammatory and secretagogues drugs are both the main compounds to currently treat the dry eye disease.

  13. Comparative analysis of success of psoriasis treatment with standard therapeutic modalities and balneotherapy.

    Science.gov (United States)

    Baros, Duka Ninković; Gajanin, Vesna S; Gajanin, Radoslav B; Zrnić, Bogdan

    2014-01-01

    Psoriasis is a chronic, inflammatory, immune-mediated skin disease. In addition to standard therapeutic modalities (antibiotics, cytostatics, phototherapy, photochemotherapy and retinoids), nonstandard methods can be used in the treatment of psoriasis. This includes balneotherapy which is most commonly used in combination with therapeutic resources. The aim of this research was to determine the length of remission of psoriasis in patients treated with standard therapeutic modalities, balneotherapy, and combined treatment (standard therapeutic modalities and balneotherapy). The study analyzed 60 adult patients, of both sexes, with different clinical forms of psoriasis, who were divided into three groups according to the applied therapeutic modalities: the first group (treated with standard therapeutic modalities), the second group (treated with balneotherapy) and the third group (treated with combined therapy-standard methods therapy and balneotherapy). The Psoriasis Area and Severity Index was determined in first, third and sixth week of treatment for all patients. The following laboratory analysis were performed and monitored: C reactive protein, iron with total iron binding capacity, unsaturated iron binding capacity and ferritin, uric acid, rheumatoid factors and antibodies to streptolysin O in the first and sixth week of treatment. The average length of remission in patients treated with standard therapeutic modalities and in those treated with balneotherapy was 1.77 +/- 0.951 months and 1.79 +/- 0.918 months, respectively. There was a statistically significant difference in the duration of remission between the patients treated with combination therapy and patients treated with standard therapeutic modalities (p = 0.019) and balneotherapy (p = 0.032). The best results have been achieved when the combination therapy was administered.

  14. Pharmacological treatment and therapeutic perspectives of metabolic syndrome.

    Science.gov (United States)

    Lim, Soo; Eckel, Robert H

    2014-12-01

    Metabolic syndrome is a disorder based on insulin resistance. Metabolic syndrome is diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal obesity, elevated blood pressures, elevated glucose, high triglycerides, and low high-density lipoprotein-cholesterol (HDL-C) levels. Clinical implication of metabolic syndrome is that it increases the risk of developing type 2 diabetes and cardiovascular diseases. Prevalence of the metabolic syndrome has increased globally, particularly in the last decade, to the point of being regarded as an epidemic. The prevalence of metabolic syndrome in the USA is estimated to be 34% of adult population. Moreover, increasing rate of metabolic syndrome in developing countries is dramatic. One can speculate that metabolic syndrome is going to induce huge impact on our lives. The metabolic syndrome cannot be treated with a single agent, since it is a multifaceted health problem. A healthy lifestyle including weight reduction is likely most effective in controlling metabolic syndrome. However, it is difficult to initiate and maintain healthy lifestyles, and in particular, with the recidivism of obesity in most patients who lose weight. Next, pharmacological agents that deal with obesity, diabetes, hypertension, and dyslipidemia can be used singly or in combination: anti-obesity drugs, thiazolidinediones, metformin, statins, fibrates, renin-angiotensin system blockers, glucagon like peptide-1 agonists, sodium glucose transporter-2 inhibitors, and some antiplatelet agents such as cilostazol. These drugs have not only their own pharmacologic targets on individual components of metabolic syndrome but some other properties may prove beneficial, i.e. anti-inflammatory and anti-oxidative. This review will describe pathophysiologic features of metabolic syndrome and pharmacologic agents for the treatment of metabolic syndrome, which are currently available.

  15. Therapeutical options for the treatment of Cheyne-Stokes respiration.

    Science.gov (United States)

    Randerath, Winfried J

    2009-03-07

    The awareness of Cheyne-Stokes respiration (CSR) and of the co-existence of the obstructive sleep apnoea syndrome and central breathing disturbances has rapidly grown in recent years. CSR is defined by a waxing and waning pattern of the breathing amplitude. Sleep related breathing disorders in patients with heart failure are associated with impaired clinical outcome and survival. While continuous positive airway pressure treatment (CPAP) is widely used to treat CSR, it has failed to improve overall survival of heart failure patients. Nevertheless, it has been shown that CPAP reduces mortality if breathing disturbances were sufficiently eliminated. Therefore, optimal suppression of CSR is critical. While CPAP reduces CSR by 50% on average, adaptive servoventilation (ASV) normalises CSR in most patients. ASV devices apply different levels of pressure support: during periods of hypoventilation the inspiratory pressure is increased while it is reduced to the lowest possible level during hyperventilation. The devices deliver an expiratory pressure to overcome upper airways obstruction. Pressure support is defined by the difference between expiratory and inspiratory pressure. Thus, while pressure support is fixed in bilevel devices, it varies under ASV. However, the hypothesis that ASV might improve survival in CSR patients has to be proved in prospective studies in CPAP nonresponders. There is a lack of evidence on the use of bilevel devices in CSR. However, ASV has proven both to effectively treat CSR and to be superior to CPAP in respiratory and sleep parameters in short term and medium term studies. Nevertheless, data on the long term use and the influence on cardiac parameters are necessary.

  16. Linezolid in the treatment of drug-resistant tuberculosis: the challenge of its narrow therapeutic index.

    Science.gov (United States)

    Wasserman, Sean; Meintjes, Graeme; Maartens, Gary

    2016-10-01

    Linezolid is an oxazolidinone with potent activity against M tuberculosis, and improves culture conversion and cure rates when added to treatment regimens for drug resistant tuberculosis. However, linezolid has a narrow therapeutic window, and the optimal dosing strategy that minimizes the substantial toxicity associated with linezolid's prolonged use in tuberculosis treatment has not been determined, limiting the potential impact of this anti-mycobacterial agent. This paper aims to review and summarize the current knowledge on linezolid for the treatment of drug-resistant tuberculosis. The focus is on the pharmacokinetic-pharmacodynamic determinants of linezolid's efficacy and toxicity in tuberculosis, and how this relates to defining an optimal dose. Mechanisms of linezolid toxicity and resistance, and the potential role of therapeutic drug monitoring are also covered. Expert commentary: Prospective pharmacokinetic-pharmacodynamic studies are required to define optimal therapeutic targets and to inform improved linezolid dosing strategies for drug-resistant tuberculosis.

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

    Science.gov (United States)

    2011-05-01

    cystoid macular oedema in uveitis . Clin. Exp. Ophthalmol. 29, 2–6 (2001). 36 Campochiaro PA, Lim JI. Aminoglycoside toxicity in the treatment of...TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Improved Therapeutic Regimens for Treatment of...injury and adequate treatment . This proposal was designed to analyze the effectiveness of antibiotics, anti-inflammatory drugs, and non-conventional

  18. The effects of feeding unpredictability and classical conditioning on pre-release training of white-lipped peccary (Mammalia, Tayassuidae.

    Directory of Open Access Journals (Sweden)

    Selene S C Nogueira

    Full Text Available Some authors have suggested that environmental unpredictability, accompanied by some sort of signal for behavioral conditioning, can boost activity or foster exploratory behavior, which may increase post-release success in re-introduction programs. Thus, using white-lipped peccary (Tayassu pecari, a vulnerable Neotropical species, as a model, we evaluated an unpredictable feeding schedule. Associating this with the effect of classical conditioning on behavioral activities, we assessed the inclusion of this approach in pre-release training protocols. The experimental design comprised predictable feeding phases (control phases: C1, C2 and C3 and unpredictable feeding phases (U1- signaled and U2- non-signaled. The animals explored more during the signaled and non-signaled unpredictable phases and during the second control phase (C2 than during the other two predictable phases (C1 and C3. The peccaries also spent less time feeding during the signaled unpredictable phase (U1 and the following control phase (C2 than during the other phases. Moreover, they spent more time in aggressive encounters during U1 than the other experimental phases. However, the animals did not show differences in the time they spent on affiliative interactions or in the body weight change during the different phases. The signaled unpredictability, besides improving foraging behavior, showing a prolonged effect on the next control phase (C2, also increased the competition for food. The signaled feeding unpredictability schedule, mimicking wild conditions by eliciting the expression of naturalistic behaviors in pre-release training, may be essential to fully prepare them for survival in the wild.

  19. The effects of feeding unpredictability and classical conditioning on pre-release training of white-lipped peccary (Mammalia, Tayassuidae).

    Science.gov (United States)

    Nogueira, Selene S C; Abreu, Shauana A; Peregrino, Helderes; Nogueira-Filho, Sérgio L G

    2014-01-01

    Some authors have suggested that environmental unpredictability, accompanied by some sort of signal for behavioral conditioning, can boost activity or foster exploratory behavior, which may increase post-release success in re-introduction programs. Thus, using white-lipped peccary (Tayassu pecari), a vulnerable Neotropical species, as a model, we evaluated an unpredictable feeding schedule. Associating this with the effect of classical conditioning on behavioral activities, we assessed the inclusion of this approach in pre-release training protocols. The experimental design comprised predictable feeding phases (control phases: C1, C2 and C3) and unpredictable feeding phases (U1- signaled and U2- non-signaled). The animals explored more during the signaled and non-signaled unpredictable phases and during the second control phase (C2) than during the other two predictable phases (C1 and C3). The peccaries also spent less time feeding during the signaled unpredictable phase (U1) and the following control phase (C2) than during the other phases. Moreover, they spent more time in aggressive encounters during U1 than the other experimental phases. However, the animals did not show differences in the time they spent on affiliative interactions or in the body weight change during the different phases. The signaled unpredictability, besides improving foraging behavior, showing a prolonged effect on the next control phase (C2), also increased the competition for food. The signaled feeding unpredictability schedule, mimicking wild conditions by eliciting the expression of naturalistic behaviors in pre-release training, may be essential to fully prepare them for survival in the wild.

  20. [The relationship of therapeutic alliance with a symptom reduction and treatment satisfaction in the therapeutic treatment of children and adolescents with ADHD and/or conduct disorder].

    Science.gov (United States)

    Kinnen, Claudia; Döpfner, Manfred

    2013-03-01

    The relationship of therapeutic alliance and outcome is investigated in outpatient behavior therapies of children and adolescents with externalizing problem behavior. Therapist-patient and therapist-parent relationships were evaluated twice during the therapies of N = 53 patients using German relationship questionnaires adapted for use in child and adolescent psychotherapy (BeKi). Pre-post symptom reduction in parent and patient rating, treatment satisfaction as rated by therapist, parent and patient as well as child's global functioning by therapist rating are examined as outcome parameters. The correlations between therapeutic alliance and symptom reduction vary depending on the rater between absence of correlation and high correlation (maximum: r = .53). Most correlations are low to moderate. These results are comparable to those reported in recently published meta-analyses and studies of adult psychotherapy. There are moderate correlations between therapist-patient and therapist-parent alliance and treatment satisfaction and low to moderate correlations with improvements in the children's global functioning. Only few studies have focused on treatment satisfaction and improvements in children's global functioning as outcome variables. Besides symptom reduction, these two variables also correlate significantly with the therapist-patient and therapist-parent alliance. Because correlations highly depend on the rater, future studies should consider the various perspectives.

  1. Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.

    Science.gov (United States)

    Kim, Ye-Ram; Yang, Chul-Su

    2017-09-28

    Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

  2. Modified Therapeutic Community Treatment for Offenders with Co-Occurring Disorders: Mental Health Outcomes

    Science.gov (United States)

    Sullivan, Christopher J.; Sacks, Stanley; McKendrick, Karen; Banks, Steven; Sacks, Joann Y.; Stommel, Joseph

    2007-01-01

    This paper examines outcomes 12 months post-prison release for offenders with co-occurring disorders (n = 185) randomly assigned to either a mental health control treatment (C) or a modified therapeutic community (E). Significant between-group differences were not found for mental health measures, although improvements were observed for each…

  3. Early Therapeutic Alliance and Treatment Outcome in Individual and Family Therapy for Adolescent Behavior Problems

    Science.gov (United States)

    Hogue, Aaron; Dauber, Sarah; Stambaugh, Leyla Faw; Cecero, John J.; Liddle, Howard A.

    2006-01-01

    The impact of early therapeutic alliance was examined in 100 clients receiving either individual cognitive-behavioral therapy (CBT) or family therapy for adolescent substance abuse. Observational ratings of adolescent alliance in CBT and adolescent and parent alliance in family therapy were used to predict treatment retention (in CBT only) and…

  4. 77 FR 62521 - Prospective Grant of Exclusive License: The Development of Therapeutic Agents for the Treatment...

    Science.gov (United States)

    2012-10-15

    ... interleukin-10 (IL-10) inhibitor as a dual-biologic therapy to treat metastatic breast cancer, or ii) incorporating a p53 isoform antisense oligonucleotide as a single biologic therapy to treat T- cell lymphoma... Exclusive License: The Development of Therapeutic Agents for the Treatment of Metastatic Breast Cancer and T...

  5. In-Session Exposure Tasks and Therapeutic Alliance across the Treatment of Childhood Anxiety Disorders

    Science.gov (United States)

    Kendall, Philip C.; Comer, Jonathan S.; Marker, Craig D.; Creed, Torrey A.; Puliafico, Anthony C.; Hughes, Alicia A.; Martin, Erin D.; Suveg, Cynthia; Hudson, Jennifer

    2009-01-01

    The study examined the shape of therapeutic alliance using latent growth curve modeling and data from multiple informants (therapist, child, mother, father). Children (n = 86) with anxiety disorders were randomized to family-based cognitive-behavioral treatment (FCBT; N = 47) with exposure tasks or to family education, support, and attention…

  6. Therapeutic efficacy of natural prostaglandin in the treatment of pyometra in bitches

    Directory of Open Access Journals (Sweden)

    Basanti Jena

    2013-12-01

    Full Text Available Aim: The current study was done to study the therapeutic effect of natural prostaglandin in treatment of canine pyometra. Materials and Methods: Seven bitches were treated with natural PGF2 á i.e. dinoprost tromethamine at the dose rate of 100 μg/kg body weight subcutaneously once daily for 7 days with supportive therapies. The physiological, haematological and biochemical parameters were studied before (0th day and after treatment (8th day. Therapeutic efficacy was assessed in terms of return of abnormal parameters to either normal or near normal value as compared to the untreated control group, intensity of side effects and post treatment reproductive status. Results: All physiological, haematological and biochemical parameters in the seven treated bitches returned to normal range at the end of treatment. The intensity of side effects was quite severe in the treatment group. Six bitches came to estrus within 2 months of treatment and out of them four conceived on subsequent mating. In rest three bitches there was recurrence of pyometra within 4 months of treatment. Conclusion: Though conception rate of recovered bitches is decreased when compared with that of normal healthy bitches still this treatment protocol can be used successfully in treatment of canine pyometra to conserve the breeding capability of bitches. [Vet World 2013; 6(6.000: 295-299

  7. Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics?

    Science.gov (United States)

    Brito, Ana Filipa; Ribeiro, Marina; Abrantes, Ana Margarida; Pires, Ana Salomé; Teixo, Ricardo Jorge; Tralhão, José Guilherme; Botelho, Maria Filomena

    2015-01-01

    Cancer is a problem of global importance, since the incidence is increasing worldwide and therapeutic options are generally limited. Thus, it becomes imperative to find new therapeutic targets as well as new molecules with therapeutic potential for tumors. Flavonoids are polyphenolic compounds that may be potential therapeutic agents. Several studies have shown that these compounds have a higher anticancer potential. Among the flavonoids in the human diet, quercetin is one of the most important. In the last decades, several anticancer properties of quercetin have been described, such as cell signaling, pro-apoptotic, anti-proliferative and anti-oxidant effects, growth suppression. In fact, it is now well known that quercetin has diverse biological effects, inhibiting multiple enzymes involved in cell proliferation, as well as, in signal transduction pathways. On the other hand, there are also studies reporting potential synergistic effects when combined quercetin with chemotherapeutic agents or radiotherapy. In fact, several studies which aim to explore the anticancer potential of these combined treatments have already been published, the majority with promising results. Actually it is well known that quercetin can act on the chemosensitization and radiosensitization but also as chemoprotective and radioprotective, protecting normal cells of the side effects that results from chemotherapy and radiotherapy, which obviously provides notable advantages in their use in anticancer treatment. Thus, all these data indicate that quercetin may have a key role in anticancer treatment. In this context, this review is focused on the relationship between flavonoids and cancer, with special emphasis on the role of quercetin.

  8. Mesenchymal Stem Cells as New Therapeutic Agents for the Treatment of Primary Biliary Cholangitis

    Directory of Open Access Journals (Sweden)

    Aleksandar Arsenijevic

    2017-01-01

    Full Text Available Primary biliary cholangitis (PBC is a chronic autoimmune cholestatic liver disease characterized by the progressive destruction of small- and medium-sized intrahepatic bile ducts with resultant cholestasis and progressive fibrosis. Ursodeoxycholic acid and obethicholic acid are the only agents approved by the US Food and Drug Administration (FDA for the treatment of PBC. However, for patients with advanced, end-stage PBC, liver transplantation is still the most effective treatment. Accordingly, the alternative approaches, such as mesenchymal stem cell (MSC transplantation, have been suggested as an effective alternative therapy for these patients. Due to their immunomodulatory characteristics, MSCs are considered as promising therapeutic agents for the therapy of autoimmune liver diseases, including PBC. In this review, we have summarized the therapeutic potential of MSCs for the treatment of these diseases, emphasizing molecular and cellular mechanisms responsible for MSC-based effects in an animal model of PBC and therapeutic potential observed in recently conducted clinical trials. We have also presented several outstanding problems including safety issues regarding unwanted differentiation of transplanted MSCs which limit their therapeutic use. Efficient and safe MSC-based therapy for PBC remains a challenging issue that requires continuous cooperation between clinicians, researchers, and patients.

  9. Uterine arterial embolization for the treatment of adenomyosis: an analysis of therapeutic results in 80 cases

    International Nuclear Information System (INIS)

    Ai Zigang; Yang Yanfen; Guan Jie

    2010-01-01

    Objective: To discuss the therapeutic effect of uterine arterial embolization in treating adenomyosis. Methods: Uterine arterial embolization was performed in 80 patients with adenomyosis. The patients were followed up for 3, 6, 12 and 24 months after the operation. After the treatment the degree of dysmenorrhea, the menstrual flow and the uterine volume were observed and were compared with those before the treatment. Results: After uterine arterial embolization the clinical symptoms were relieved in all 80 patients. The menstrual flow was markedly decreased, the anemia was obviously improved and the uterine volume was significantly reduced, while the ovary functioning was not apparently affected. The symptom of dysmenorrhea completely disappeared one month after the therapy in 76 cases and four months after the therapy in the remaining 4 cases. Conclusion: Uterine arterial embolization is a mini-invasive and safe therapy with remarkable therapeutic results and few side-effects. Therefore, this treatment can significantly improve the patient's living quality. (authors)

  10. Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases

    Directory of Open Access Journals (Sweden)

    Sathish Sundar Dhilip Kumar

    2018-04-01

    Full Text Available Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (Curcuma longa plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

  11. Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases.

    Science.gov (United States)

    Sundar Dhilip Kumar, Sathish; Houreld, Nicolette Nadene; Abrahamse, Heidi

    2018-04-05

    Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric ( Curcuma longa ) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

  12. Development of Potential Small Molecule Therapeutics for Treatment of Ebola Virus.

    Science.gov (United States)

    Schafer, Adam Michael; Cheng, Han; Lee, Charles; Du, Ruikun; Han, Julianna; Perez, Jasmine; Peet, Norton; Manicassamy, Balaji; Rong, Lijun

    2017-10-10

    Ebola virus has caused 26 outbreaks in 10 different countries since its identification in 1976, making it one of the deadliest emerging viral pathogens. The most recent outbreak in West Africa from 2014-16 was the deadliest yet and culminated in 11,310 deaths out of 28,616 confirmed cases. Currently there are no FDA-approved therapeutics or vaccines to treat Ebola virus infections. The slow development of effective vaccines combined with the severity of past outbreaks emphasizes the need to accelerate research into understanding the virus lifecycle and the development of therapeutics for post exposure treatment. Here we present a summary of the major findings on the Ebola virus replication cycle and the therapeutic approaches explored to treat this devastating disease. The major focus of this review is on small molecule inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. An exploration of therapeutic evaluation of traditional Chinese medicine in treatment of hepatic fibrosis

    Directory of Open Access Journals (Sweden)

    XU Lieming

    2017-05-01

    Full Text Available China has become one of the leading counties in the world to treat hepatic fibrosis with Chinese patent drugs. The therapeutic effect of traditional Chinese medicine (TCM should be evaluated from the aspects of short-term therapeutic effect, long-term therapeutic effect, and effect of relief of symptoms. This article introduces the results of our exploration of the application of liver stiffness measurement to evaluate therapeutic effect, five-year survival rate to assess long-term therapeutic effect, and a “TCM syndrome scale” to evaluate effect of relief of symptoms, suggesting that the Chinese patent drug Fuzheng Huayu capsules/tablets have a marked clinical effect in the treatment of hepatic fibrosis. It is recommended to use serological diagnostic models, conduct prospective studies with long-term follow-up, and analyze the samples and data accumulated over a long period of time, in order to perfect the methods for evaluating the outcome of hepatic fibrosis.

  14. Follow-up at a Dutch addiction hospital and effectiveness of therapeutic community treatment.

    Science.gov (United States)

    van de Velde, J C; Schaap, G E; Land, H

    1998-06-01

    This paper reports on inpatient treatment of addicts. Attention is paid to the Therapeutic Community (TC) model employed with alcoholics. A sample of 881 patients was assessed at intake and was followed up. The results demonstrate that the patients improved on a variety of outcome measures. Some associations were found between patient variables and improvement. Treatment variables predicting a positive outcome were sustained treatment in a TC and attending AA meetings. The relative efficacy of TCs, originally created by drug users, holds for alcoholics as well. It is concluded that an important precondition to a positive treatment outcome is the continuity of the treatment process. Pursuing that continuity seems to be an excellent mediate goal for both addicts and treatment personnel.

  15. Therapeutic impact of CT-guided percutaneous catheter drainage in treatment of deep tissue abscesses

    International Nuclear Information System (INIS)

    Asai, Nobuhiro; Ohkuni, Yoshihiro; Kaneko, Norihiro; Aoshima, Masahiro; Yamazaki, Ikuo; Kawamura, Yasutaka

    2013-01-01

    Combination therapy of CT-guided percutaneous drainage and antibiotics is the first-line treatment for abscesses. Its effectiveness has been demonstrated. However, the therapeutic impact of this procedure for infection treatment has never been reported. We retrospectively analyzed all 47 patients who received CT-guided percutaneous drainage for infection treatment. Patients' characteristics, pathogens isolated, antibiotics administered, technical and clinical outcomes, complications related to this procedure and therapeutic impacts were investigated. Patients were 26 males and 21 females. The mean age was 63.5 years (±18.7). The diseases targeted were 19 retroperitoneal abscesses, 18 intraabdominal abscesses, three pelvic abscesses, and seven others. As for technical outcomes, all of the 54 procedures (100%) were successful. As for clinical outcomes, 44 (93.6%) were cured and three patients (6.4%) died. No complications related to this procedure were found in this study. A total of 42 patients (88%) had a change in the management of their infection as a result of CT-guided percutaneous drainage, such as selection and discontinuation of antibiotics. In conclusion, CT-guided percutaneous drainage is a safe and favorable procedure in the treatment of deep tissue abscesses. Therapeutic impact of these procedures helped physicians make a rational decision for antibiotics selection. (author)

  16. Therapeutic Success of the Ketogenic Diet as a Treatment Option for Epilepsy: a Meta-analysis

    Science.gov (United States)

    Li, Hai-feng; Zou, Yan; Ding, Gangqiang

    2013-01-01

    Objective To systematically evaluate therapeutic success of the ketogenic diet (KD) as a treatment option for epilepsy. Methods Using MEDLINE and Google Scholar search, we searched for studies investigating the therapeutic success of ketogenic diet for epilepsy. We estimated therapeutic success rate for ketogenic diet as a treatment option for epilepsy and its 95% CIs using generic inverse variance method. Findings A total of 38 studies met the inclusion criteria. In retrospective studies, the weighted success rate of the patients who take the KD as a treatment option for epilepsy was 58.4% (95% confidence interval (95%CI)=48.7% – 69.9%) at 3 months (n=336); 42.8% (95%CI =36.3% – 50.3%) at 6 months (n=492), and 30.1% (95%CI =24.3% – 37.2%) at 12 months (n=387); in prospective studies, weighted success rate was 53.9% (95%CI 45.5% – 63.8%) at 3 months (n=474); 53.2% (95%CI =44.0% – 64.2%) at 6 months (n=321), and 55.0% (95%CI =45.9% – 65.9%) at 12 months (n=347). Conclusion This meta-analysis provides formal statistical support for the efficacy of the ketogenic diet in the treatment of epileptic patients. PMID:24910737

  17. Therapeutic impact of CT-guided percutaneous catheter drainage in treatment of deep tissue abscesses

    Energy Technology Data Exchange (ETDEWEB)

    Asai, Nobuhiro; Ohkuni, Yoshihiro; Kaneko, Norihiro; Aoshima, Masahiro; Yamazaki, Ikuo; Kawamura, Yasutaka, E-mail: nobuhiro0204@hotmail.com [Kameda Medical Center, Chiba (Japan)

    2013-03-15

    Combination therapy of CT-guided percutaneous drainage and antibiotics is the first-line treatment for abscesses. Its effectiveness has been demonstrated. However, the therapeutic impact of this procedure for infection treatment has never been reported. We retrospectively analyzed all 47 patients who received CT-guided percutaneous drainage for infection treatment. Patients' characteristics, pathogens isolated, antibiotics administered, technical and clinical outcomes, complications related to this procedure and therapeutic impacts were investigated. Patients were 26 males and 21 females. The mean age was 63.5 years ({+-}18.7). The diseases targeted were 19 retroperitoneal abscesses, 18 intraabdominal abscesses, three pelvic abscesses, and seven others. As for technical outcomes, all of the 54 procedures (100%) were successful. As for clinical outcomes, 44 (93.6%) were cured and three patients (6.4%) died. No complications related to this procedure were found in this study. A total of 42 patients (88%) had a change in the management of their infection as a result of CT-guided percutaneous drainage, such as selection and discontinuation of antibiotics. In conclusion, CT-guided percutaneous drainage is a safe and favorable procedure in the treatment of deep tissue abscesses. Therapeutic impact of these procedures helped physicians make a rational decision for antibiotics selection. (author)

  18. Therapeutic treatment with a novel hypoxia-inducible factor hydroxylase inhibitor (TRC160334 ameliorates murine colitis

    Directory of Open Access Journals (Sweden)

    Gupta R

    2014-01-01

    Full Text Available Ram Gupta,1 Anita R Chaudhary,2 Binita N Shah,1 Avinash V Jadhav,3 Shitalkumar P Zambad,1 Ramesh Chandra Gupta,4 Shailesh Deshpande,4 Vijay Chauthaiwale,4 Chaitanya Dutt4 1Department of Pharmacology, 2Cellular and Molecular Biology, 3Preclinical Safety Evaluation, 4Discovery, Torrent Research Centre, Torrent Pharmaceuticals Ltd, Gandhinagar, Gujarat, India Background and aim: Mucosal healing in inflammatory bowel disease (IBD can be achieved by improvement of intestinal barrier protection. Activation of hypoxia-inducible factor (HIF has been identified as a critical factor for barrier protection during mucosal insult and is linked with improvement in symptoms of colitis. Although prophylactic efficacy of HIF hydroxylase inhibitors in murine colitis have been established, its therapeutic efficacy in clinically relevant therapeutic settings have not been established. In the present study we aim to establish therapeutic efficacy of TRC160334, a novel HIF hydroxylase inhibitor, in animal models of colitis. Methods: The efficacy of TRC160334 was evaluated in two different mouse models of colitis by oral route. A prophylactic efficacy study was performed in a 2,4,6-trinitrobenzene sulfonic acid-induced mouse model of colitis representing human Crohn's disease pathology. Additionally, a therapeutic efficacy study was performed in a dextran sulfate sodium-induced mouse model of colitis, a model simulating human ulcerative colitis. Results: TRC160334 treatment resulted in significant improvement in disease end points in both models of colitis. TRC160334 treatment resulted into cytoprotective heatshock protein 70 induction in inflamed colon. TRC160334 successfully attenuated the rate of fall in body weight, disease activity index, and macroscopic and microscopic scores of colonic damage leading to overall improvement in study outcome. Conclusion: Our findings are the first to demonstrate that therapeutic intervention with a HIF hydroxylase inhibitor

  19. Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases.

    Science.gov (United States)

    Harrell, C Randall; Simovic Markovic, Bojana; Fellabaum, Crissy; Arsenijevic, Aleksandar; Djonov, Valentin; Arsenijevic, Nebojsa; Volarevic, Vladislav

    2018-05-18

    Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases.MSC-derived exosomes were as efficient as transplanted MSCs in limiting the extent of eye injury and inflammation. Immediately after intravitreal injection, MSC-derived exosomes, due to nano-dimension, diffused rapidly throughout the retina and significantly attenuated retinal damage and inflammation. MSC-derived exosomes successfully delivered trophic and immunomodulatory factors to the inner retina and efficiently promoted survival and neuritogenesis of injured retinal ganglion cells. MSC-derived exosomes efficiently suppressed migration of inflammatory cells, attenuated detrimental Th1 and Th17 cell-driven immune response and ameliorated experimental autoimmune uveitis. MSC-derived exosomes were able to fuse with the lysosomes within corneal cells, enabling delivering of MSC-derived active β-glucuronidase and consequent catabolism of accumulated glycosaminoglycans, indicating their therapeutic potential in the treatment of Mucopolysaccharidosis VII (Sly Syndrome). Importantly, beneficent effects were noticed only in animals that received MSC-derived exosomes and were not seen after therapy with fibroblasts-derived exosomes confirming specific therapeutic potential of MSCs and their products in the treatment of eye diseases.In conclusion, MSC-derived exosomes represent potentially new therapeutic agents in the therapy of degenerative and inflammatory ocular diseases.

  20. Combined Kinesiotaoe and Therapeutic Ultrasound in the Treatment of Carpal Tunnel Syndrome

    International Nuclear Information System (INIS)

    Mohamed, O.G.; Elhafez, H.M.; Alshatoury, H.A.; Refaat, R.

    2016-01-01

    Background : Carpal tunnel syndrome is the most common neuropathy of the upper limb and a significant contributor to hand functional impairment and disability. Hand is an Accepted November 2016 . important part of body to perform the complex daily living activities. Purpose: To find out effect of combined kinesiotape and therapeutic ultrasound in the treatment of carpal tunnel syndrome. Material and Methods :Thirty Carpal Tunnel Syndrome female patients with positive electro diagnostic findings (MMDL >4.2 ms) participated in this study, their ages ranged between 40 and 50 years. Design of study :They were divided randomly into two equal groups. Group (A) received kinesiotape applicatio n on the affected wrist for 3 days, then day off and then another three days each week for 4 weeks combined with a program of 12 sessions of continuous ultrasound, 3 sessions per week for 5 minute persession in addition nerve and tendon gliding exercise . While, Group (B) received a program of 12 sessions of continuous ultrasound, 3 sessions per week for 5 minute per session in addition tendon and nerve gliding exercise. The treatment program continued for 4 weeks. Boston carpal tunnel questionnaire and median motor distallatency, visual analogue scale and hand grip dynamometer were performed before and after the treatment program for all patients of the two groups. Results : The obtained results showed a highly statistically significant (P< 0.0001) improvement in both groups (A and B) concerning Boston carpal tunnel questionnaire , visual analogue scale and hand grip dynamometer but there was significant improvement in group (A) only concerning median motor distal latency. The improvement was highly significant (P< 0.0001) in group (A) when compared with group (B). Conclusion: It could be concluded that the use of combined kinesiotape and therapeutic ultrasound in the treatment of carpal tunnel syndrome appeared to be effective. Yet the combined effect of kinesiotape with

  1. THERAPEUTIC EYELIDS HYGIENE IN THE ALGORITHMS OF PREVENTION AND TREATMENT OF OCULAR SURFACE DISEASES. PART II

    Directory of Open Access Journals (Sweden)

    V. N. Trubilin

    2016-01-01

    Full Text Available The second part of the article is focused on the issue of prevention and treatment of the most common clinical situations in which applicable therapeutic hygiene: seborrheic blepharitis; Staphylococcal blepharitis; Allergic blepharitis; barley and chalazion; prevention keratoconjunctival xerosis (during the preoperative and postoperative period, while wearing contact lenses, in computer vision syndrome, in remission after acute inflammation of the conjunctiva and cornea. There is an algorithm for the therapeutic care of eyelids and the basic mechanisms of action of this procedure. Until recently, the treatment of dry eye syndrome involves the use tearsubstitude therapy. Ten or fifteen years ago, 2–3 tearsubstitudes were presented at the domestic market. Currently, there are doses of different forms of artificial tears, while there are hundreds of them on the western pharmaceutical market. The rapid development in the search for new forms tearsubstitudes is not accident. This is due to the increasing number of patients suffering from disorders of the tear membrane stability, which achieves, according to different sources, up to 40–60% of the adult population. It should be noted that the primary cause of dry eye syndrome in 85–95% of patients is meibomian gland’s dysfunction, thus applying tearsubstitudes symptomatic therapy is treatment that does not solve the problem on the pathogenic level. For this reason, conducting therapeutic hygiene century (warm compresses + self-massage is an important component of the treatment of this group of patients. Objective evidence of relevance and effectiveness of therapeutic care age, in our opinion, is the rapid development of the pharmaceutical market in this area. There is a large number of new gels, lotions, wipes and other products for hygiene century every year. Clear algorithms that include therapeutic hygiene century (dates, the indications for the use of certain hygiene products is an actual

  2. Standardised classification of pre-release development in male-brooding pipefish, seahorses, and seadragons (Family Syngnathidae)

    Science.gov (United States)

    2012-01-01

    Background Members of the family Syngnathidae share a unique reproductive mode termed male pregnancy. Males carry eggs in specialised brooding structures for several weeks and release free-swimming offspring. Here we describe a systematic investigation of pre-release development in syngnathid fishes, reviewing available data for 17 species distributed across the family. This work is complemented by in-depth examinations of the straight-nosed pipefish Nerophis ophidion, the black-striped pipefish Syngnathus abaster, and the potbellied seahorse Hippocampus abdominalis. Results We propose a standardised classification of early syngnathid development that extends from the activation of the egg to the release of newborn. The classification consists of four developmental periods – early embryogenesis, eye development, snout formation, and juvenile – which are further divided into 11 stages. Stages are characterised by morphological traits that are easily visible in live and preserved specimens using incident-light microscopy. Conclusions Our classification is derived from examinations of species representing the full range of brooding-structure complexity found in the Syngnathidae, including tail-brooding as well as trunk-brooding species, which represent independent evolutionary lineages. We chose conspicuous common traits as diagnostic features of stages to allow for rapid and consistent staging of embryos and larvae across the entire family. In view of the growing interest in the biology of the Syngnathidae, we believe that the classification proposed here will prove useful for a wide range of studies on the unique reproductive biology of these male-brooding fish. PMID:23273265

  3. Tiapride: Therapeutic possibilities of its use in narcology, gerontopsychiatry, and in the treatment of Tourette's syndrome

    Directory of Open Access Journals (Sweden)

    Aleksandr Nikolaevich Basov

    2013-01-01

    Full Text Available The literature review deals with the evaluation of the efficacy and safety of tiapride used in the treatment of addictions of alcohol and psychoactive substances, such as opiate and heroin, vascular dementia with the signs of acute psychic confusion and Tourette's syndrome. The spectrum of neurochemical activity and mechanism of action of tiapride and the possibility of its combination with other drugs to enhance the therapeutic efficacy in the above disorders are described.

  4. Reasons for the treatment of users of crack in a therapeutic community

    Directory of Open Access Journals (Sweden)

    Maycon Rogério Seleghim

    2015-07-01

    Full Text Available Objective: Knowing the motivation of crack users for treatment in hospital environments. Method: Descriptive and qualitative search, using the design of some cases. Twenty male crack users, aged over 18 years old, hospitalized in a Therapeutic Community in Southern Brazil, were interviewed. A semi-structured interview was used and the data were analyzed by their thematic content. Results: Were found three categories that reflect the treatment motivations: perception of the crack harmful consequences; the compulsive use of drugs as the treatment initiation; and, the family participation looking for a treatment. Conclusion: Significant events (turning points favored the interruption of the crack use and the family assumed a very important place to the users behavior in relation to the use of the drug, exclusively. Descriptors: Street drugs, Crack Cocaine, Substance Abuse Treatment Centers, Family.

  5. Therapeutic Efficacy of Meropenem for Treatment of Experimental Penicillin-Resistant Pneumococcal Meningitis

    Science.gov (United States)

    Kim, Shin-Woo; Jin, Joung Hwa; Kang, Soo Jung; Jung, Sook-In; Kim, Yeon-Sook; Kim, Choon-Kwan; Lee, Hyuck; Oh, Won Sup; Kim, Sungmin; Peck, Kyong Ran

    2004-01-01

    With the widespread emergence of antimicrobial resistance, combination regimens of ceftriaxone and vancomycin (C+V) or ceftriaxone and rifampin (C+R) are recommended for empirical treatment of pneumococcal meningitis. To evaluate the therapeutic efficacy of meropenem (M), we compared various treatment regimens in arabbit model of meningitis caused by penicillin-resistant Streptococcus pneumoniae (PRSP). Therapeutic efficacy was also evaluated by the final bacterial concentration in the cerebrospinal fluid (CSF) at 24 hr. Each group consisted of six rabbits. C+V cleared the CSF at 10 hr, but regrowth was noted in 3 rabbits at 24 hr. Meropenem monotherapy resulted in sterilization at 10 hr, but regrowth was observed in all 6 rabbits at 24 hr. M+V also resulted in sterilization at 10 hr, but regrowth was observed in 2 rabbits at 24 hr. M+V was superior to the meropenem monotherapy at 24 hr (reduction of 4.8 vs. 1.8 log10 cfu/mL, respectively; p=0.003). The therapeutic efficacy of M+V was comparable to that of C+V (reduction of 4.8 vs. 4.0 log10 cfu/mL, respectively; p=0.054). The meropenem monotherapy may not be a suitable choice for PRSP meningitis, while combination of meropenem and vancomycin could be a possible alternative in the treatment of PRSP meningitis. PMID:14966336

  6. Mesenchymal stem cells as therapeutic target of biophysical stimulation for the treatment of musculoskeletal disorders.

    Science.gov (United States)

    Viganò, Marco; Sansone, Valerio; d'Agostino, Maria Cristina; Romeo, Pietro; Perucca Orfei, Carlotta; de Girolamo, Laura

    2016-12-16

    Musculoskeletal disorders are regarded as a major cause of worldwide morbidity and disability, and they result in huge costs for national health care systems. Traditional therapies frequently turned out to be poorly effective in treating bone, cartilage, and tendon disorders or joint degeneration. As a consequence, the development of novel biological therapies that can treat more effectively these conditions should be the highest priority in regenerative medicine. Mesenchymal stem cells (MSCs) represent one of the most promising tools in musculoskeletal tissue regenerative medicine, thanks to their proliferation and differentiation potential and their immunomodulatory and trophic ability. Indeed, MSC-based approaches have been proposed for the treatment of almost all orthopedic conditions, starting from different cell sources, alone or in combination with scaffolds and growth factors, and in one-step or two-step procedures. While all these approaches would require cell harvesting and transplantation, the possibility to stimulate the endogenous MSCs to enhance their tissue homeostasis activity represents a less-invasive and cost-effective therapeutic strategy. Nowadays, the role of tissue-specific resident stem cells as possible therapeutic target in degenerative pathologies is underinvestigated. Biophysical stimulations, and in particular extracorporeal shock waves treatment and pulsed electromagnetic fields, are able to induce proliferation and support differentiation of MSCs from different origins and affect their paracrine production of growth factors and cytokines. The present review reports the attempts to exploit the resident stem cell potential in musculoskeletal pathologies, highlighting the role of MSCs as therapeutic target of currently applied biophysical treatments.

  7. Application of Mesenchymal Stem Cells for Therapeutic Agent Delivery in Anti-tumor Treatment

    Directory of Open Access Journals (Sweden)

    Daria S. Chulpanova

    2018-03-01

    Full Text Available Mesenchymal stem cells (MSCs are non-hematopoietic progenitor cells, which can be isolated from different types of tissues including bone marrow, adipose tissue, tooth pulp, and placenta/umbilical cord blood. There isolation from adult tissues circumvents the ethical concerns of working with embryonic or fetal stem cells, whilst still providing cells capable of differentiating into various cell lineages, such as adipocytes, osteocytes and chondrocytes. An important feature of MSCs is the low immunogenicity due to the lack of co-stimulatory molecules expression, meaning there is no need for immunosuppression during allogenic transplantation. The tropism of MSCs to damaged tissues and tumor sites makes them a promising vector for therapeutic agent delivery to tumors and metastatic niches. MSCs can be genetically modified by virus vectors to encode tumor suppressor genes, immunomodulating cytokines and their combinations, other therapeutic approaches include MSCs priming/loading with chemotherapeutic drugs or nanoparticles. MSCs derived membrane microvesicles (MVs, which play an important role in intercellular communication, are also considered as a new therapeutic agent and drug delivery vector. Recruited by the tumor, MSCs can exhibit both pro- and anti-oncogenic properties. In this regard, for the development of new methods for cancer therapy using MSCs, a deeper understanding of the molecular and cellular interactions between MSCs and the tumor microenvironment is necessary. In this review, we discuss MSC and tumor interaction mechanisms and review the new therapeutic strategies using MSCs and MSCs derived MVs for cancer treatment.

  8. Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Fabliha Ahmed Chowdhury

    2018-01-01

    Full Text Available Glioblastoma multiforme (GBM is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ, the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM.

  9. Therapeutic fasting as a potential effective treatment for type 2 diabetes: A 4-month case study

    Directory of Open Access Journals (Sweden)

    Michael Ku

    2017-12-01

    Full Text Available Lifestyle therapy is an integral part of type 2 diabetes (T2D management, but there remains no consensus on an optimal diet. The objective of this study is to evaluate the efficacy of therapeutic fasting as a treatment for T2D. This case follows a male T2D patient treated at the Intensive Dietary Management Clinic in Scarborough, Ontario, over a 4-month period. The patient’s initial fasting regimen consisted of a 24-h fast, three times a week. Over the course of treatment, the patient gradually extended his fasting period, eventually fasting for 42 h, two to three times a week. By the end of treatment, the patient’s weight was reduced by 17.8% and his waist circumference was reduced by 11.0%. In addition, the patient’s glycated haemoglobin levels decreased from 7.7% to 7.2%, and he was able to completely discontinue his insulin treatment, despite over a decade of insulin usage. The patient did not find it difficult to adhere to the fasting schedule and did not experience any hypoglycaemic episodes or other significant adverse effects. These observations suggest that therapeutic fasting may be a viable treatment option for T2D patients.

  10. Novel Therapeutic Approaches to the Treatment of Chronic Abdominal Visceral Pain

    Directory of Open Access Journals (Sweden)

    Franca Patrizi

    2006-01-01

    Full Text Available Chronic abdominal visceral pain (CAVP has a significant clinical impact and represents one of the most frequent and debilitating disorders in the general population. It also leads to a significant economic burden due to workdays lost, reduced productivity, and long-term use of medications with their associated side effects. Despite the availability of several therapeutic options, the management of patients with CAVP is often inadequate, resulting in frustration for both patients and physicians. This may in part be explained by the lack of understanding of the mechanisms underlying chronic pain; in contrast with acute pain in which the pathophysiology is relatively well known and has several satisfactory therapeutic options. Recently, the development of tools for brain investigation, such as functional magnetic resonance imaging, has provided new insights on the pathophysiology of chronic pain. These new data have shown that plastic changes in the central and peripheral nervous system might play an important role in the maintenance of chronic pain. Therefore, approaches aimed at the modulation of the nervous system, rather than the ones interfering with the inflammatory pathways, may be more effective for chronic pain treatment. We propose that noninvasive central nervous system stimulation, with transcranial magnetic stimulation (TMS, might be a novel therapeutic option for CAVP. This paper will present an overview of the pathophysiology and the available therapies for CAVP, focusing on the recent advances in the treatment of this pathology.

  11. Standardised classification of pre-release development in male-brooding pipefish, seahorses, and seadragons (Family Syngnathidae

    Directory of Open Access Journals (Sweden)

    Sommer Stefan

    2012-12-01

    Full Text Available Abstract Background Members of the family Syngnathidae share a unique reproductive mode termed male pregnancy. Males carry eggs in specialised brooding structures for several weeks and release free-swimming offspring. Here we describe a systematic investigation of pre-release development in syngnathid fishes, reviewing available data for 17 species distributed across the family. This work is complemented by in-depth examinations of the straight-nosed pipefish Nerophis ophidion, the black-striped pipefish Syngnathus abaster, and the potbellied seahorse Hippocampus abdominalis. Results We propose a standardised classification of early syngnathid development that extends from the activation of the egg to the release of newborn. The classification consists of four developmental periods – early embryogenesis, eye development, snout formation, and juvenile – which are further divided into 11 stages. Stages are characterised by morphological traits that are easily visible in live and preserved specimens using incident-light microscopy. Conclusions Our classification is derived from examinations of species representing the full range of brooding-structure complexity found in the Syngnathidae, including tail-brooding as well as trunk-brooding species, which represent independent evolutionary lineages. We chose conspicuous common traits as diagnostic features of stages to allow for rapid and consistent staging of embryos and larvae across the entire family. In view of the growing interest in the biology of the Syngnathidae, we believe that the classification proposed here will prove useful for a wide range of studies on the unique reproductive biology of these male-brooding fish.

  12. Therapeutic inertia in the treatment of hyperglycaemia in patients with type 2 diabetes: A systematic review.

    Science.gov (United States)

    Khunti, Kamlesh; Gomes, Marilia B; Pocock, Stuart; Shestakova, Marina V; Pintat, Stéphane; Fenici, Peter; Hammar, Niklas; Medina, Jesús

    2018-02-01

    Therapeutic inertia, defined as the failure to initiate or intensify therapy in a timely manner according to evidence-based clinical guidelines, is a key reason for uncontrolled hyperglycaemia in patients with type 2 diabetes. The aims of this systematic review were to identify how therapeutic inertia in the management of hyperglycaemia was measured and to assess its extent over the past decade. Systematic searches for articles published from January 1, 2004 to August 1, 2016 were conducted in MEDLINE and Embase. Two researchers independently screened all of the titles and abstracts, and the full texts of publications deemed relevant. Data were extracted by a single researcher using a standardized data extraction form. The final selection for the review included 53 articles. Measurements used to assess therapeutic inertia varied across studies, making comparisons difficult. Data from low- to middle-income countries were scarce. In most studies, the median time to treatment intensification after a glycated haemoglobin (HbA1c) measurement above target was more than 1 year (range 0.3 to >7.2 years). Therapeutic inertia increased as the number of antidiabetic drugs rose and decreased with increasing HbA1c levels. Data were mainly available from Western countries. Diversity of inertia measures precluded meta-analysis. Therapeutic inertia in the management of hyperglycaemia in patients with type 2 diabetes is a major concern. This is well documented in Western countries, but corresponding data are urgently needed in low- and middle-income countries, in view of their high prevalence of type 2 diabetes. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  13. A reinforcement-based therapeutic workplace for the treatment of drug abuse: three-year abstinence outcomes.

    Science.gov (United States)

    Silverman, Kenneth; Svikis, Dace; Wong, Conrad J; Hampton, Jacqueline; Stitzer, Maxine L; Bigelow, George E

    2002-08-01

    Long-term Therapeutic Workplace effects were evaluated in heroin- and cocaine-dependent, unemployed, treatment-resistant young mothers. Participants were paid to work or to train in the Therapeutic Workplace but had to provide drug-free urine samples to gain daily access. Participants (N = 40) were randomly assigned to a Therapeutic Workplace or usual care control group. Therapeutic Workplace participants could work for 3 years. Relative to controls, Therapeutic Workplace participants increased cocaine (28% vs. 54% negative; p = .04) and opiate (37% vs. 60% negative; p = .05) abstinence on the basis of monthly urine samples collected until 3 years after intake. The Therapeutic Workplace can be an effective long-term treatment of cocaine and heroin addiction in poor and chronically unemployed young mothers.

  14. [Therapeutic patient education--method of optimizing treatment in chronic diseases].

    Science.gov (United States)

    Vulpoi, Carmen; Ungureanu, Gabriel; Stoica, Ortansa

    2007-01-01

    The technological revolution of the 20th century has changed not only the life style but also the human interrelations, including the physician-patient relationship. The old, primarily patriarchal, system (in which the patient trusted completely the physician and followed religiously his commandments) evolved into the current system in which the patient is an active partner in medical care. Patient education is increasingly recognized as an integral part of the therapy. The objectives of therapeutical education rely essentially in the improvement of the patient knowledge and skills concerning the disease and its treatment in order to harmonize his life style with the restrains of the illness. Therapeutical education must be complex, individualized, repeated, motivating, and controlled. In chronic diseases, both the health provider and the patient are in front of a permanent challenge. The educational process is in continuous movement, liable to permanent improvement.

  15. Treatment Model in Children with Speech Disorders and Its Therapeutic Efficiency

    Directory of Open Access Journals (Sweden)

    Barberena, Luciana

    2014-05-01

    Full Text Available Introduction Speech articulation disorders affect the intelligibility of speech. Studies on therapeutic models show the effectiveness of the communication treatment. Objective To analyze the progress achieved by treatment with the ABAB—Withdrawal and Multiple Probes Model in children with different degrees of phonological disorders. Methods The diagnosis of speech articulation disorder was determined by speech and hearing evaluation and complementary tests. The subjects of this research were eight children, with the average age of 5:5. The children were distributed into four groups according to the degrees of the phonological disorders, based on the percentage of correct consonants, as follows: severe, moderate to severe, mild to moderate, and mild. The phonological treatment applied was the ABAB—Withdrawal and Multiple Probes Model. The development of the therapy by generalization was observed through the comparison between the two analyses: contrastive and distinctive features at the moment of evaluation and reevaluation. Results The following types of generalization were found: to the items not used in the treatment (other words, to another position in the word, within a sound class, to other classes of sounds, and to another syllable structure. Conclusion The different types of generalization studied showed the expansion of production and proper use of therapy-trained targets in other contexts or untrained environments. Therefore, the analysis of the generalizations proved to be an important criterion to measure the therapeutic efficacy.

  16. Novel compounds for the treatment of Duchenne muscular dystrophy: emerging therapeutic agents

    Directory of Open Access Journals (Sweden)

    Steve D Wilton

    2011-03-01

    Full Text Available Steve D Wilton, Sue FletcherCentre for Neuromuscular and Neurological Disorders, University of Western Australia, Crawley, Perth, WA, AustraliaAbstract: The identification of dystrophin and the causative role of mutations in this gene in Duchenne and Becker muscular dystrophies (D/BMD was expected to lead to timely development of effective therapies. Despite over 20 years of research, corticosteroids remain the only available pharmacological treatment for DMD, although significant benefits and extended life have resulted from advances in the clinical care and management of DMD individuals. Effective treatment of DMD will require dystrophin restitution in skeletal, cardiac, and smooth muscles and nonmuscle tissues; however, modulation of muscle loss and regeneration has the potential to play an important role in altering the natural history of DMD, particularly in combination with other treatments. Emerging biological, molecular, and small molecule therapeutics are showing promise in ameliorating this devastating disease, and it is anticipated that regulatory environments will need to display some flexibility in order to accommodate the new treatment paradigms.Keywords: Duchenne muscular dystrophy, molecular therapeutics, small molecules

  17. Caries preventive efficiency of therapeutic complex accomponying orthodontic treatment of children with initial dental caries

    Directory of Open Access Journals (Sweden)

    Denga A.E.

    2013-12-01

    Full Text Available The use of orthodontic non-removable appliance in orthodontic treatment inter¬feres with the process of teeth mineralization, worsens level of oral cavity hygiene, stimulates development of caries process. The situation is complicated when a patient has an initial tooth decay. The aim of this study was to determine genetic characteristics of children with initial caries and clinical evaluation of effectiveness of the developed caries preventive therapeutic complex accompanying treatment of jaw facial anomalies (JFA. 47 children aged 12-14 with initial tooth decay participated in the examination. Complex diagnostics, including molecular genetic studies was carried out. Therapeutic complex for children, of the main group included remineralizing, adaptogenic, biogenic agents, which increase non-specific resistance, as well as infiltration ICON therapy before fixing braces. Caries preventive complex accompanying JFA treatment in children with primary tooth decay developed with regard to revealed genetic disorders of amelogenesis, 2-nd of phase detoxification, collagen formation, functional responses in the oral cavity, state of hard tissues of teeth and periodontal tissues enabled to preserve existing carious process, normalize periodontal and hygienic indices at all stages of treatment.

  18. Coolmine Therapeutic Community, Dublin: a 40-year history of Ireland's first voluntary drug treatment service.

    Science.gov (United States)

    Butler, Shane

    2016-02-01

    To document the evolution over 40 years (from 1973 to 2013) of Coolmine Therapeutic Community (Ireland's first voluntary drug treatment service) against a background of broader drug policy developments in the Republic of Ireland and elsewhere during this period. Data were gathered by means of archival research within Coolmine, complemented by semi-structured interviews with former clients, current and former Coolmine management and staff, and representatives of outsider stakeholder interests. Coolmines's history has three phases: (1) an early and uncontentious phase, in which external authorities provided financial support for Coolmine without questioning its work practices or outcomes; (2) a middle, controversial phase, in which Coolmine struggled for survival in an external policy environment now dominated by harm reduction strategies; and (3) a final phase in which, through the use of conventional corporate governance, Coolmine management sought to repair its damaged reputation by introducing evidence-based clinical practices. Coolmine Therapeutic Community was established when drug treatment services in Ireland were in their infancy, and its changing fortunes over subsequent decades reflected changing perceptions of what constitutes appropriate addiction treatment-and in particular the role to be played by former addicts within addiction treatment systems-as well as changing perceptions of funding relationships between statutory authorities and voluntary providers of health and social services. © 2015 Society for the Study of Addiction.

  19. Therapeutic effects of ritual ayahuasca use in the treatment of substance dependence--qualitative results.

    Science.gov (United States)

    Loizaga-Velder, Anja; Verres, Rolf

    2014-01-01

    This qualitative empirical study explores the ritual use of ayahuasca in the treatment of addictions. Ayahuasca is an Amazonian psychedelic plant compound created from an admixture of the vine Banisteriopsis caapi and the bush Psychotria viridis. The study included interviews with 13 therapists who apply ayahuasca professionally in the treatment of addictions (four indigenous healers and nine Western mental health professionals with university degrees), two expert researchers, and 14 individuals who had undergone ayahuasca-assisted therapy for addictions in diverse contexts in South America. The study provides empirically based hypotheses on therapeutic mechanisms of ayahuasca in substance dependence treatment. Findings indicate that ayahuasca can serve as a valuable therapeutic tool that, in carefully structured settings, can catalyze neurobiological and psychological processes that support recovery from substance dependencies and the prevention of relapse. Treatment outcomes, however, can be influenced by a number of variables that are explained in this study. In addition, issues related to ritual transfer and strategies for minimizing undesired side-effects are discussed.

  20. Understanding Factors Associated with Early Therapeutic Alliance in PTSD Treatment: Adherence, Childhood Sexual Abuse History, and Social Support

    Science.gov (United States)

    Keller, Stephanie M.; Zoellner, Lori A.; Feeny, Norah C.

    2010-01-01

    Objective: Therapeutic alliance has been associated with better treatment engagement, better adherence, and less dropout across various treatments and disorders. In treatment of posttraumatic stress disorder (PTSD), it may be particularly important to establish a strong early alliance to facilitate treatment adherence. However, factors such as…

  1. Influence of comorbidities on therapeutic progression of diabetes treatment in Australian veterans: a cohort study.

    Directory of Open Access Journals (Sweden)

    Agnes I Vitry

    Full Text Available BACKGROUND: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20,134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84-0.91], P<0.001. Depression, cancer, chronic obstructive pulmonary disease, dementia, and Parkinson's disease were individually associated with a decreased likelihood of therapeutic progression. Age, residential status, number of hospitalisations and adherence to anti-diabetic medicines delayed therapeutic progression. CONCLUSIONS/SIGNIFICANCE: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities.

  2. Improving Therapeutic Ratio in Head and Neck Cancer with Adjuvant and Cisplatin-Based Treatments

    Directory of Open Access Journals (Sweden)

    Loredana G. Marcu

    2013-01-01

    Full Text Available Advanced head and neck cancers are difficult to manage despite the large treatment arsenal currently available. The multidisciplinary effort to increase disease-free survival and diminish normal tissue toxicity was rewarded with better locoregional control and sometimes fewer side effects. Nevertheless, locoregional recurrence is still one of the main reasons for treatment failure. Today, the standard of care in head and neck cancer management is represented by altered fractionation radiotherapy combined with platinum-based chemotherapy. Targeted therapies as well as chronotherapy were trialled with more or less success. The aim of the current work is to review the available techniques, which could contribute towards a higher therapeutic ratio in the treatment of advanced head and neck cancer patients.

  3. Fixed and dynamic predictors of treatment process in therapeutic communities for substance abusers in Belgium.

    Science.gov (United States)

    Goethals, Ilse; Vanderplasschen, Wouter; Vandevelde, Stijn; Broekaert, Eric

    2012-10-11

    Research on substance abuse treatment services in general reflects substantial attention to the notion of treatment process. Despite the growing popularity of process studies, only a few researchers have used instruments specifically tailored to measure the therapeutic community (TC) treatment process, and even fewer have investigated client attributes in relation to early TC treatment process experiences. The aim of the current study is to address this gap by exploring clients' early in-treatment experiences and to determine the predictors that are related to the treatment process, using a TC-specific multidimensional instrument. Data was gathered among 157 adults in five TCs in Flanders (Belgium). Descriptive statistics were used to explore clients' early in-treatment experiences and multiple linear regressions were conducted to determine the fixed and dynamic predictors of Community Environment and Personal Development and Change (two indicators of TC treatment process). Clients reveal a more positive first-month response to TC social processes than to personal-development processes that require self-reflection and insight. The variance in clients' ratings of Community Environment was primarily due to dynamic client factors, while the variance in clients' ratings of Personal Development and Change was only related to fixed client factors. Suitability for treatment was the strongest predictor of Community Environment ratings, whereas a judicial referral more strongly predicted Personal Development and Change scores. Special attention should be devoted to suitability for treatment as part of motivational assessment as this seems to be a very strong predictor of how clients react to the initiation stage of TC treatment. To help improve clients' (meta-)cognitive skills needed to achieve insight and self-reflection and perhaps speed up the process of recovery, the authors suggest the introduction of (meta-)cognitive training strategies in the pre-program and/or the

  4. [Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions].

    Science.gov (United States)

    Allouche, G

    2016-02-01

    Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses

  5. Treatment for Sulfur Mustard Lung Injuries; New Therapeutic Approaches from Acute to Chronic Phase

    Directory of Open Access Journals (Sweden)

    Zohreh Poursaleh

    2012-09-01

    Full Text Available Objective: Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980-1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries.Method:This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment.Results:Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion:Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  6. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    Directory of Open Access Journals (Sweden)

    Poursaleh Zohreh

    2012-09-01

    Full Text Available Abstract Objective Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  7. Network Meta-Analysis Comparing the Efficacy of Therapeutic Treatments for Bronchiolitis in Children.

    Science.gov (United States)

    Guo, Caili; Sun, Xiaomin; Wang, Xiaowen; Guo, Qing; Chen, Dan

    2018-01-01

    This study aims to compare placebo (PBO) and 7 therapeutic regimens-namely, bronchodilator agents (BAs), hypertonic saline (HS), BA ± HS, corticosteroids (CS), epinephrine (EP), EP ± CS, and EP ± HS-to determine the optimal bronchiolitis treatment. We plotted networks using the curative outcome of several studies and specified the relations among the experiments by using mean difference, standardized mean difference, and corresponding 95% credible interval. The surface under the cumulative ranking curve (SUCRA) was used to separately rank each therapy on clinical severity score (CSS) and length of hospital stay (LHS). This network meta-analysis included 40 articles from 1995 to 2016 concerning the treatment of bronchiolitis in children. All 7 therapeutic regimens displayed no significant difference to PBO with regard to CSS in our study. Among the 7 therapies, BA performed better than CS. As for LHS, EP and EP ± HS had an advantage over PBO. Moreover, EP and EP ± HS were also more efficient than BA. The SUCRA results showed that EP ± CS is most effective, and EP ± HS is second most effective with regard to CSS. With regard to LHS, EP ± HS ranked first, EP ± CS ranked second, and EP ranked third. We recommend EP ± CS and EP ± HS as the first choice for bronchiolitis treatment in children because of their outstanding performance with regard to CSS and LHS. © 2017 American Society for Parenteral and Enteral Nutrition.

  8. Modified Therapeutic Community Treatment for Offenders with MICA Disorders: Antisocial Personality Disorder and Treatment Outcomes

    Science.gov (United States)

    McKendrick, Karen; Sullivan, Christopher; Banks, Steven; Sacks, Stanley

    2006-01-01

    Treatment outcomes 1 year after release from prison were compared for two subgroups of male inmates with co-occurring serious mental illness and chemical abuse (MICA) disorders, those with a diagnosis for Antisocial Personality Disorder (APD), and those without a diagnosis of APD. The foundation study had randomly assigned inmates to either…

  9. RNAi therapeutics and applications of microRNAs in cancer treatment.

    Science.gov (United States)

    Uchino, Keita; Ochiya, Takahiro; Takeshita, Fumitaka

    2013-06-01

    RNA interference-based therapies are proving to be powerful tools for combating various diseases, including cancer. Scientists are researching the development of safe and efficient systems for the delivery of small RNA molecules, which are extremely fragile in serum, to target organs and cells in the human body. A dozen pre-clinical and clinical trials have been under way over the past few years involving biodegradable nanoparticles, lipids, chemical modification and conjugation. On the other hand, microRNAs, which control the balance of cellular biological processes, have been studied as attractive therapeutic targets in cancer treatment. In this review, we provide an overview of RNA interference-based therapeutics in clinical trials and discuss the latest technology for the systemic delivery of nucleic acid drugs. Furthermore, we focus on dysregulated microRNAs in human cancer, which have progressed in pre-clinical trials as therapeutic targets, and describe a wide range of strategies to control the expression levels of endogenous microRNAs. Further development of RNA interference technologies and progression of clinical trials will contribute to the achievement of practical applications of nucleic acid drugs.

  10. Therapeutic drug monitoring of isoniazid and rifampicin during anti-tuberculosis treatment in Auckland, New Zealand.

    Science.gov (United States)

    Maze, M J; Paynter, J; Chiu, W; Hu, R; Nisbet, M; Lewis, C

    2016-07-01

    There is uncertainty as to the optimal therapeutic concentrations of anti-tuberculosis drugs to achieve cure. To characterise the use of therapeutic drug monitoring (TDM), and identify risk factors and outcomes for those with concentrations below the drug interval. Patients treated for tuberculosis (TB) who had rifampicin (RMP) or isoniazid (INH) concentrations measured between 1 January 2005 and 31 December 2012 were studied retrospectively. Matched concentrations and drug dosing time were assessed according to contemporary regional drug intervals (RMP > 6 μmol/l, INH > 7.5 μmol/l) and current international recommendations (RMP > 10 μmol/l, INH > 22 μmol/l). Outcomes were assessed using World Health Organization criteria. Of 865 patients, 121 had concentrations of either or both medications. RMP concentrations were within the regional drug intervals in 106/114 (93%) and INH in 91/100 (91%). Concentrations were within international drug intervals for RMP in 76/114 (67%) and INH in 53/100 (53%). Low weight-based dose was the only statistically significant risk factor for concentrations below the drug interval. Of the 35 patients with low concentrations, 21 were cured, 9 completed treatment and 5 transferred out. There were no relapses during follow-up (mean 66.5 months). There were no clinically useful characteristics to guide use of TDM. Many patients had concentrations below international therapeutic intervals, but were successfully treated.

  11. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury.

    Science.gov (United States)

    Pachori, Alok S; Melo, Luis G; Hart, Melanie L; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D; Stahl, Gregory L; Pratt, Richard E; Dzau, Victor J

    2004-08-17

    Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

  12. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

    Science.gov (United States)

    Pachori, Alok S.; Melo, Luis G.; Hart, Melanie L.; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D.; Stahl, Gregory L.; Pratt, Richard E.; Dzau, Victor J.

    2004-08-01

    Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

  13. "We are people too": consumer participation and the potential transformation of therapeutic relations within drug treatment.

    Science.gov (United States)

    Rance, Jake; Treloar, Carla

    2015-01-01

    While there is growing recognition of the benefits of user involvement within drug treatment there is scant literature documenting the actual implementation of such initiatives. Nonetheless, the extant research is remarkably consistent in identifying poor relationships between service users and staff as a principal barrier to the successful implementation of consumer participation. Focussing on participants' accounts of change within the 'therapeutic alliance', this paper investigates a consumer participation initiative introduced within three Australian drug treatment services. In 2012, the New South Wales Users and AIDS Association (NUAA), a state-based drug user organisation, introduced a consumer participation initiative within three treatment facilities across the state. This paper draws on 57 semi-structured interviews with staff and service-user project participants. Approximately ten participants from each site were recruited and interviewed at baseline and six months later at evaluation. The enhanced opportunities for interaction enabled by the consumer participation initiative fostered a sense of service users and staff coming to know one another beyond the usual constraints and limitations of their relationship. Both sets of participants described a diminution of adversarial relations: an unsettling of the 'them and us' treatment divide. The routine separation of users and staff was challenged by the emergence of a more collaborative ethos of 'working together'. Participants noted 'seeing' one another--the other--differently; as people rather than simply an identity category. For service users, the opportunity to have 'a voice' began to disrupt the routine objectification or dehumanisation that consistently, if unintentionally, characterises the treatment experience. Having a voice, it seemed, was synonymous with being human, with having ones' 'humanness' recognised. We contend that not only did the introduction of consumer participation appear to

  14. Written case formulations in the treatment of anorexia nervosa: Evidence for therapeutic benefits.

    Science.gov (United States)

    Allen, Karina L; O'Hara, Caitlin B; Bartholdy, Savani; Renwick, Beth; Keyes, Alexandra; Lose, Anna; Kenyon, Martha; DeJong, Hannah; Broadbent, Hannah; Loomes, Rachel; McClelland, Jessica; Serpell, Lucy; Richards, Lorna; Johnson-Sabine, Eric; Boughton, Nicky; Whitehead, Linette; Treasure, Janet; Wade, Tracey; Schmidt, Ulrike

    2016-09-01

    Case formulation is a core component of many psychotherapies and formulation letters may provide an opportunity to enhance the therapeutic alliance and improve treatment outcomes. This study aimed to determine if formulation letters predict treatment satisfaction, session attendance, and symptom reductions in anorexia nervosa (AN). It was hypothesized that higher quality formulation letters would predict greater treatment satisfaction, a greater number of attended sessions, and greater improvement in eating disorder symptoms. Patients were adult outpatients with AN (n = 46) who received Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) in the context of a clinical trial. A Case Formulation Rating Scheme was used to rate letters for adherence to the MANTRA model and use of a collaborative, reflective, affirming stance. Analyses included linear regression and mixed models. Formulation letters that paid attention to the development of the AN predicted greater treatment acceptability ratings (p = 0.002). More reflective and respectful letters predicted greater reductions in Eating Disorder Examination scores (p = 0.003). Results highlight the potential significance of a particular style of written formulation as part of treatment for AN. Future research should examine applicability to other psychiatric disorders. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:874-882). © 2016 Wiley Periodicals, Inc.

  15. Endocrine Society of Australia position statement on male hypogonadism (part 2): treatment and therapeutic considerations.

    Science.gov (United States)

    Yeap, Bu B; Grossmann, Mathis; McLachlan, Robert I; Handelsman, David J; Wittert, Gary A; Conway, Ann J; Stuckey, Bronwyn Ga; Lording, Douglas W; Allan, Carolyn A; Zajac, Jeffrey D; Burger, Henry G

    2016-09-05

    Part 1 of this position statement dealt with the assessment of male hypogonadism, including the indications for testosterone therapy. This article, Part 2, focuses on treatment and therapeutic considerations for male hypogonadism and identifies key questions for future research. Key points and recommendations are:Excess cardiovascular events have been reported in some but not all studies of older men without pathological hypogonadism who were given testosterone treatment. Additional studies are needed to clarify whether testosterone therapy influences cardiovascular risk.Testosterone is the native hormone that should be replaced in men being treated for pathological hypogonadism. Convenient and cost-effective treatment modalities include depot intramuscular injection and transdermal administration (gel, cream or liquid formulations).Monitoring of testosterone therapy is recommended for efficacy and safety, focusing on ameliorating symptoms, restoring virilisation, avoiding polycythaemia and maintaining or improving bone mineral density.Treatment aims to relieve an individual's symptoms and signs of androgen deficiency by administering standard doses and maintaining circulating testosterone levels within the reference interval for eugonadal men.Evaluation for cardiovascular disease and prostate cancer risks should be undertaken as appropriate for eugonadal men of similar age. Nevertheless, when there is a reasonable possibility of substantive pre-existing prostate disease, digital rectal examination and prostate-specific antigen testing should be performed before commencing testosterone treatment.Changes in management as result of the position statement: Treatment aims to relieve symptoms and signs of androgen deficiency, using convenient and effective formulations of testosterone. Therapy should be monitored for efficacy and safety.

  16. Therapeutic strategy for the treatment of isolated spontaneous dissection of superior mesenteric arteries

    International Nuclear Information System (INIS)

    Xu Yongle; Xiong Jiang; Guo Wei; Liu Xiaoping; Liu Meng

    2010-01-01

    Objective: To summarize the treatment strategies of isolated superior mesenteric artery (SMA) dissection and to discuss the selection of therapeutic methods. Methods: The clinical data of ten patients, who were encountered during the period from Jan. 2007 to Feb. 2010 in General Hospital of Chinese PLA and diagnosed as isolated SMA dissection,were retrospectively analyzed. According to the presence or absence of intestinal ischemic necrosis and SMA rupture, the patients were divided into simple group (n = 9) and complicated group(n = 1). The treatments for different type of SMA dissection were discussed and the results and prognosis were analyzed. Results: Nine patients were divided into simple group and received conservative treatment, of which anticoagulation was not employed in 5. One patient was divided into complicated group and had to receive an iliomesenteric bypass surgery after the patient had failed to respond to conservative treatment. After the treatment the abdominal pain was relieved in all ten patients. Conclusion: With the wide use of computer tomography angiography and digital subtraction angiography, more and more isolated SMA dissections have been confirmed. For most patients with SMA dissection, especially for simple ones (i.e. without bowel ischemia or SMA rupture), excellent short-term results can be achieved by pure conservative treatment, even no anticoagulation needed. However, for the complicated isolated SMA dissections, vascular reconstruction procedure with various techniques, including open surgery, is necessary in order to obtain satisfactory short-term results. (authors)

  17. The therapeutic eyelids hygiene for prophylaxis and treatment complications caused by change of microflora and tear production after refractive surgery

    Directory of Open Access Journals (Sweden)

    A. V. Zhemchugova

    2012-01-01

    Full Text Available The review presents possibilities of dry eye prophylaxis and treatment caused blepharitis and blepharoconjunctivitis after refrac- tive surgery. Among modern prophylactic approaches therapeutic eyelids hygiene is most promising for the everyday clinical practice. 

  18. 166 Ho-HA Evaluation as therapeutic agent for rheumatoid arthritis treatment

    International Nuclear Information System (INIS)

    Chandia, M; Errazu, X; Mendoza, P; Troncoso, F; Jofre, J; Sierralta, P

    2003-01-01

    Aim: Rheumatoid arthritis is a limiting disease having, among its pathological features, the inflammation of synovial tissue with progressive and later destruction of the articulation. This lead to joint deformation and loss of its function, generating pain and reducing the mobility of the affected articulation. The aim was to evaluate 166 Ho-Hydroxyapatite ( 166 Ho-HA) as potential radiopharmaceutical for the syntomatic treatment of chronic and acute arthritis Materials and Methods: 166 Holmiun was produced by irradiation of Ho 2 O 3 at La Reina Research Reactor, Nuclear Chilean Energy Commission. Hydroxyapatite was in-house synthetized. Its labelling and quality controls follows the internationally accepted procedures. An antigen arthritis was induced to eight New Zealand rabbits with the 166 Ho-HA radiochemical being administred thereafter in two dosage modalities (single and double). The compound therapeutic efficiency was evaluated based upon clinical improvement and images from the inflamated articulation using 67 Ga citrate before and after 166 Ho-HA injection. Results: The radiochemical purity of the innoculated compound was greater than 98% as measured under sterility conditions. Clinically, an inflamation reduction (2 cm), appetite improvement and general well being was observed. The 166 Ho-HA distribution and localization was monitored using gamma camera images taken at 4 and 24 h. There was no evidence of extraarticular leakage. From the 67 Ga citrate imaging, the acute group shows an overall improvement of well being corresponding to a lesser uptake at the inflamated articulation, regarding to the chronic group. The 166 Ho-HA double dosis, compared to the single dosis, suggest a reduced uptake of 67 Ga citrate at the inflamated tissue, meaning an increased therapeutic effect. Conclusions: 166 Ho-HA is usefull as therapeutic agent for the syntomatic treatment of rheumatoideal arthritis as shown by imaging and clinical examination (author)

  19. 166Ho-HA evaluation as therapeutic agent for rheumatoid arthritis treatment

    International Nuclear Information System (INIS)

    Chandia, M.C.; Errazu, X.C.; Pinto, L.N.; Godoy, N.O.; Avila, M.J.; Mendoza, P.; Mendoza, J.; Jofre, J.; Sirraalta, P.

    2002-01-01

    Aim: Rheumatoid arthritis is a limiting disease having, among its pathological features, the inflammation of synovial tissue with progressive and later destruction of the articulation. This leads to joint deformation and loss of its function, generating pain and reducing the mobility of the affected articulation. The aim was to evaluate 166 Ho-Hydroxyapatite ( 166 Ho-HA) as potential radiopharmaceutical for the symptomatic treatment of chronic and acute arthritis. Materials and Methods: Holmiun-166 was produced by irradiation of Ho 2 O 3 at La Reina Research Reactor, Nuclear Chilean Energy Commission. Hydroxyapatite was in-house synthesized. Its labelling and quality controls follows the internationally accepted procedures. An antigen's arthritis was induced to eight New Zealand rabbits with the 166 Ho-HA radiochemical being administered thereafter in two dosage modalities (single and double). The compound therapeutic efficiency was evaluated based upon clinical improvement and images from the inflamated articulation using 67 Ga citrate before and after 166 Ho-HA injection. Results: The radiochemical purity of the inoculated compound was greater than 98% as measured under sterility conditions. Clinically, an inflammation reduction (2 cm), appetite improvement and general well being was observed. The 166 Ho-HA distribution and localization was monitored using gamma camera images taken at 4 and 24 h. There was no evidence of extra articular leakage. From the 67 Ga citrate imaging, the acute group shows an overall improvement of well being corresponding to a lesser uptake at the inflamated articulation, regarding to the chronic group. The 166 Ho-HA double doses, compared to the single doses, suggest a reduced uptake of 67 Ga citrate at the inflamated tissue, meaning an increased therapeutic effect. Conclusions: 166 Ho-HA is useful as therapeutic agent for the symptomatic treatment of rheumatoid arthritis as shown by imaging and clinical examination

  20. ECONOMIC ASPECTS OF THERAPEUTIC EYELID HYGIENE IN MEIBOMIAN GLAND DYSFUNCTION TREATMENT

    Directory of Open Access Journals (Sweden)

    V. N. Trubilin

    2015-01-01

    Full Text Available The value of dry eye for general public health increases due to its high occurence in elderly persons and aging population. Non-specific questionnaires are adopted for dry eye. Additionally, 36‑item Medical Outcomes Study-Short Form (MOS-SF-36 and benefit evaluation method were developed. Methods. Information analysis and mathematical methods and public health technology evaluation methods (i.e., modelling, analysis of disease burden, and budget impact analysis were applied to economic aspect study. Decision tree model based on these finding was developed and applied to cost estimating of blepharoconjunctival and exogenous dry eye treatment in computer vision syndrome. Two scenarios of patient management were considered, i.e., typical management and management using therapeutic eyelid hygiene. Similar model was developed for early postoperative period after LASIK. Short-run analysis (1 year was performed, direct medical costs were considered. This analysis implies the calculation of overall cost (economic burden of the disease. Official data on adult population size in 2014 and the occurrence of the disease were used to assess prevalence. Budget impact analysis evaluates the difference in total economic effects due to comparison technology use in money terms. Sensitivity analysis assesses the stability of simulation results. Medical treatment cost was considered the most valuable parameter. Results and conclusions. Direct medical costs of typical management and management using therapeutic eyelid hygiene in demodicosis, computer vision syndrome, and after LASIK were 14,623 RUB and 9,200 RUB (savings of 37 %, 17,630 RUB and 9,200 RUB (savings of 47 %, 4,425.5 RUB and 3,004 RUB (savings of 32 %, respectively. Analysis of economic burden with respect to disease occurrence and typical management costs demonstrated that in 2015 this parameter was estimated as 576,198,416,556 RUB. In terms of direct medical costs, therapeutic eyelid hygiene saves 44

  1. The Therapeutic Alliance and Family Psychoeducation in the Treatment of Schizophrenia: An Exploratory Prospective Change Process Study

    Science.gov (United States)

    Smerud, Phyllis E.; Rosenfarb, Irwin S.

    2008-01-01

    Although family psychoeducation has been shown to be highly efficacious in the treatment of schizophrenia, the mechanisms underlying the treatment's success are poorly understood. The therapeutic alliance in behavioral family management (BFM) was examined to determine whether the alliance plays a role in the efficacy of this treatment. One early…

  2. Therapeutic effect of 99Tc - MDP observed in the treatment of rheumatoid arthritis

    International Nuclear Information System (INIS)

    Sang Shibiao; Wu Yiwei; Su Chenghai; Zhang Wei; Dong Shenan

    2003-01-01

    Objective: To evaluate the therapeutic effect and safety of 99 Tc - MDP in the treatment of rheumatoid arthritis (RA). Methods: Two hundred and eight patients with active RA have been treated using 99 Tc - MDP. The clinical manifestation and laboratory examination before and after treatment were observed. Results: The total effective rate of the 99 Tc - MDP was 86.1%. The effectiveness of relieving pain, diminishing swelling, increasing immune function etc was significant. It was most effective in improving morning stiffness, limitation of articulation function and decreasing ESR. Conclusion: The clinical effect of the 99 Tc - MDP is obvious. Application of the 99 Tc - MDP is safety, no significant adverse action and worth clinical using

  3. A gamma-ray therapeutic system applied to treatment of body

    International Nuclear Information System (INIS)

    Huang Yu; Duan Zhengcheng; Zhu Guoli; Gong Shihua; Li Xiaoping

    2004-01-01

    In order to treat malignant tumors in human body, a stereotactic gamma-ray whole-body therapeutic system has been developed. This system is a typical large mechatronics treatment machine. In this paper, its main working principles and characteristics are introduced. This system comprises a special gallows frame with an open vertical structure, a changeable collimator device by which the size of convergence center can be chosen, and a 3D treatment couch. A computer brings the couch to target position automatically. Therefore precise and dynamic rotary converging therapy for tumors located anywhere in the body has been realized. The system's performance has been proved in practice, which includes good curative effect, reliable automation, and safe and secure operation. (authors)

  4. Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.

    Science.gov (United States)

    Rahman, Wahida; Dickenson, Anthony H

    2015-06-01

    Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics. Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy. Somatosensory phenotyping of chronic pain patients, as a surrogate of putative pain generating mechanisms, may predict patient response to treatment. Identification of new targets will inform and guide future research, aiding the development of more effective analgesics. Future clinical trial designs should implement sensory phenotyping of patients, as an inclusion or stratification criterion, in order to establish an individualized, mechanism-based treatment of osteoarthritis pain.

  5. Therapeutic antibodies: A new era in the treatment of respiratory diseases?

    Science.gov (United States)

    Sécher, T; Guilleminault, L; Reckamp, K; Amanam, I; Plantier, L; Heuzé-Vourc'h, N

    2018-05-04

    Respiratory diseases affect millions of people worldwide, and account for significant levels of disability and mortality. The treatment of lung cancer and asthma with therapeutic antibodies (Abs) is a breakthrough that opens up new paradigms for the management of respiratory diseases. Antibodies are becoming increasingly important in respiratory medicine; dozens of Abs have received marketing approval, and many more are currently in clinical development. Most of these Abs target asthma, lung cancer and respiratory infections, while very few target chronic obstructive pulmonary disease - one of the most common non-communicable causes of death - and idiopathic pulmonary fibrosis. Here, we review Abs approved for or in clinical development for the treatment of respiratory diseases. We notably highlight their molecular mechanisms, strengths, and likely future trends. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. SGLT2 inhibitors: a promising new therapeutic option for treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Misra, Monika

    2013-03-01

    Hyperglycemia is an important pathogenic component in the development of microvascular and macrovascular complications in type 2 diabetes mellitus. Inhibition of renal tubular glucose reabsorption that leads to glycosuria has been proposed as a new mechanism to attain normoglycemia and thus prevent and diminish these complications. Sodium glucose cotransporter 2 (SGLT2) has a key role in reabsorption of glucose in kidney. Competitive inhibitors of SGLT2 have been discovered and a few of them have also been advanced in clinical trials for the treatment of diabetes. To discuss the therapeutic potential of SGLT2 inhibitors currently in clinical development. A number of preclinical and clinical studies of SGLT2 inhibitors have demonstrated a good safety profile and beneficial effects in lowering plasma glucose levels, diminishing glucotoxicity, improving glycemic control and reducing weight in diabetes. Of all the SGLT2 inhibitors, dapagliflozin is a relatively advanced compound with regards to clinical development. SGLT2 inhibitors are emerging as a promising therapeutic option for the treatment of diabetes. Their unique mechanism of action offers them the potential to be used in combination with other oral anti-diabetic drugs as well as with insulin. © 2012 The Author. JPP © 2012 Royal Pharmaceutical Society.

  7. [Therapeutic Concepts for Treatment of Patients with Non-infectious Uveitis Biologic Disease Modifying Antirheumatic Drugs].

    Science.gov (United States)

    Walscheid, Karoline; Pleyer, Uwe; Heiligenhaus, Arnd

    2018-04-12

    Biologic disease modifying antirheumatic drugs (bDMARDs) can be highly efficient in the treatment of various non-infectious uveitis entities. Currently, the TNF-α-inhibitor Adalimumab is the only in-label therapeutic option, whereas, all other bDMARDs need to be given as an off-label therapy. bDMARDs are indicated in diseases refractory to conventional synthetic DMARD therapy and/or systemic steroids, or in patients in whom treatment with those is not possible due to side effects. Therapeutic mechanisms currently employed are cytokine-specific (interferons, inhibition of TNF-α or of interleukin [IL]-1-, IL-6- or IL-17-signalling), inhibit T cell costimulation (CTLA-4 fusion protein), or act via depletion of B cells (anti-CD20). All bDMARDs need to be administered parenterally, and therapy is initiated by the treating internal specialist only after interdisciplinary coordination of all treating subspecialties and after exclusion of contraindications. Regular clinical and laboratory monitoring is mandatory for all patients while under bDMARD therapy. Georg Thieme Verlag KG Stuttgart · New York.

  8. Epigenetics: A novel therapeutic approach for the treatment of Alzheimer’s disease

    Science.gov (United States)

    Adwan, Lina; Zawia, Nasser H.

    2013-01-01

    Alzheimer’s disease (AD) is the most common type of dementia in the elderly. It is characterized by the deposition of two forms of aggregates within the brain, the amyloid β plaques and tau neurofibrillary tangles. Currently, no disease-modifying agent is approved for the treatment of AD. Approved pharmacotherapies target the peripheral symptoms but they do not prevent or slow down the progression of the disease. Although several disease-modifying immunotherapeutic agents are in clinical development, many have failed due to lack of efficacy or serious adverse events. Epigenetic changes including DNA methylation and histone modifications are involved in learning and memory and have been recently highlighted for holding promise as potential targets for AD therapeutics. Dynamic and latent epigenetic alterations are incorporated in AD pathological pathways and present valuable reversible targets for AD and other neurological disorders. The approval of epigenetic drugs for cancer treatment has opened the door for the development of epigenetic drugs for other disorders including neurodegenerative diseases. In particular, methyl donors and histone deacetylase inhibitors are being investigated for possible therapeutic effects to rescue memory and cognitive decline found in such disorders. This review explores the area of epigenetics for potential AD interventions and presents the most recent findings in this field. PMID:23562602

  9. Relating Therapist Characteristics to Client Engagement and the Therapeutic Alliance in an Adolescent Custodial Group Substance Misuse Treatment Program.

    Science.gov (United States)

    Daniels, Rachael Anne; Holdsworth, Emma; Tramontano, Carlo

    2017-07-29

    Client engagement in substance misuse treatment programs is directly associated with positive treatment outcomes. The nature of these programs means there are often difficulties engaging and retaining clients, but authors have consistently found a strong therapeutic alliance is associated with client engagement. While research has focused on the association between the alliance and engagement, the factors that influence the therapeutic alliance have received less attention. To examine therapists' characteristics, namely therapists' stress and empathy levels, as potential predictors of client engagement and the therapeutic alliance, within an adolescent substance misuse group treatment program. The sample included 84 adolescent clients and 14 therapists from a Secure Training Centre in England. Client engagement in the treatment program was observed, while self-reporting measures assessed the therapeutic alliance (client and therapist-rated), and therapists' stress and empathy levels. Multiple regression analysis revealed that therapists' stress levels negatively influenced the therapeutic alliance and had a curvilinear relationship with client engagement, indicating that stress is not exclusively negatively related to engagement. Although stress was found to negatively impact both cognitive and affective empathy, neither cognitive nor affective empathy were significantly related to client engagement or the therapeutic alliance. This study demonstrates the importance of therapist characteristics on client engagement and the therapeutic alliance. Within practice stress can have a positive impact on clients' engagement. Nevertheless, therapists may need additional support to deal with stress effectively. Therapists' empathy may too be fundamental to client engagement, but only it if is perceived by clients.

  10. The impact of early symptom change and therapeutic alliance on treatment outcome in cognitive-behavioural therapy for eating disorders.

    Science.gov (United States)

    Turner, Hannah; Bryant-Waugh, Rachel; Marshall, Emily

    2015-10-01

    The present study explored the impact of early symptom change (cognitive and behavioural) and the early therapeutic alliance on treatment outcome in cognitive-behavioural therapy (CBT) for the eating disorders. Participants were 94 adults with diagnosed eating disorders who completed a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment, following the 6th session and at the end of treatment. They also completed a measure of therapeutic alliance following the 6th session. Greater early reduction in dietary restraint and eating concerns, and smaller levels of change in shape concern, significantly predicted later reduction in global eating pathology. The early therapeutic alliance was strong across the three domains of tasks, goals and bond. Early symptom reduction was a stronger predictor of later reduction in eating pathology than early therapeutic alliance. The early therapeutic alliance did not mediate the relationship between early symptom reduction and later reduction in global eating pathology. Instead, greater early symptom reduction predicted a strong early therapeutic alliance. Early clinical change was the strongest predictor of treatment outcome and this also facilitated the development of a strong early alliance. Clinicians should be encouraged to deliver all aspects of evidence-based CBT, including behavioural change. The findings suggest that this will have a positive impact on both the early therapeutic alliance and later change in eating pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Mind the gap: In-session silences are associated with client attachment insecurity, therapeutic alliance, and treatment outcome

    DEFF Research Database (Denmark)

    Daniel, Sarah Ingrid Franksdatter; Folke, Sofie; Lunn, Susanne

    2018-01-01

    Objective: The association between in-session silences and client attachment, therapeutic alliance, and treatment outcome was investigated in two treatments for bulimia nervosa. Method: 69 women and one man were randomized to two years of psychoanalytic psychotherapy (PPT) or 20 sessions of cogni......Objective: The association between in-session silences and client attachment, therapeutic alliance, and treatment outcome was investigated in two treatments for bulimia nervosa. Method: 69 women and one man were randomized to two years of psychoanalytic psychotherapy (PPT) or 20 sessions...

  12. Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Shailendra Giri

    Full Text Available This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO, a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5, OVCAR7, OVCAR8, OVCAR10, PE01 and PE04 in a dose dependent manner. GSNO treatment abrogated growth factor (HB-EGF induced signal transduction including phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles in ovarian cancer growth and progression. To examine the therapeutic potential of GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780 ovarian carcinoma cell line (2 × 10(6 were orally administered GSNO at the dose of 1 mg/kg body weight. Daily oral administration of GSNO significantly attenuated tumor mass (p<0.001 in the peritoneal cavity compared to vehicle (phosphate buffered saline treated group at 4 weeks. GSNO also potentiated cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model. GSNO's nitrosylating ability was reflected in the induced nitrosylation of various known proteins including NFκB p65, Akt and EGFR. As a novel finding, we observed that GSNO also induced nitrosylation with inverse relationship at tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance and cell proliferation in ovarian cancer and in cancer in general. Overall, our study underlines the significance of S-nitrosylation of key cancer promoting proteins in modulating ovarian cancer and proposes the therapeutic potential of nitrosylating agents (like GSNO for the treatment of ovarian cancer alone or in combination with chemotherapeutic drugs.

  13. Therapeutic Mechanisms of Vernonia amygdalina Delile in the Treatment of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    William Johnson

    2017-09-01

    Full Text Available Prostate cancer patients have been suffering from limited treatment options due to late diagnosis, poor drug tolerance, and multi-drug resistance to almost all the current drug treatments. Therefore, it is important to seek a new alternative therapeutic medicine that can effectively prevent the disease and even eradicate the progression and metastasis of prostate cancer. Vernonia amygdalina Delile (VAD is a common edible vegetable in Cameroon that has been used as a traditional medicine for some human diseases. However, to the best of our knowledge, no previous reports have explored its therapeutic efficacy against human prostate cancer. The objective of the present study was to assess the anticancer activities of VAD methanolic extracts in the prevention and treatment of prostate cancer using human androgen-independent prostate cancer (PC-3 cells as a test model. To achieve our objective, PC-3 cells were treated with various doses of VAD for 48 h. Data generated from the trypan blue test and MTT assay demonstrated that VAD extracts exhibited significant growth-inhibitory effects on PC-3 cells. Collectively, we established for the first time the antiproliferative effects of VAD on PC-3 cells, with an IC50 value of about 196.6 µg/mL. Further experiments, including cell morphology, lipid peroxidation and comet assays, and apoptosis analysis showed that VAD caused growth-inhibitory effects on PC-3 cells through the induction of cell growth arrest, DNA damage, apoptosis, and necrosis in vitro and may provide protection from oxidative stress diseases as a result of its high antioxidant content. These results provide useful data on the anticancer activities of VAD for prostate cancer and demonstrate the novel possibilities of this medicinal plant for developing prostate cancer therapies.

  14. Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets

    Science.gov (United States)

    Siles-Lucas, Mar; Casulli, Adriano; Cirilli, Roberto

    2018-01-01

    Human cystic and alveolar echinococcosis are helmintic zoonotic diseases caused by infections with the larval stages of the cestode parasites Echinococcus granulosus and E. multilocularis, respectively. Both diseases are progressive and chronic, and often fatal if left unattended for E. multilocularis. As a treatment approach, chemotherapy against these orphan and neglected diseases has been available for more than 40 years. However, drug options were limited to the benzimidazoles albendazole and mebendazole, the only chemical compounds currently licensed for treatment in humans. To compensate this therapeutic shortfall, new treatment alternatives are urgently needed, including the identification, development, and assessment of novel compound classes and drug targets. Here is presented a thorough overview of the range of compounds that have been tested against E. granulosus and E. multilocularis in recent years, including in vitro and in vivo data on their mode of action, dosage, administration regimen, therapeutic outcomes, and associated clinical symptoms. Drugs covered included albendazole, mebendazole, and other members of the benzimidazole family and their derivatives, including improved formulations and combined therapies with other biocidal agents. Chemically synthetized molecules previously known to be effective against other infectious and non-infectious conditions such as anti-virals, antibiotics, anti-parasites, anti-mycotics, and anti-neoplastics are addressed. In view of their increasing relevance, natural occurring compounds derived from plant and fungal extracts are also discussed. Special attention has been paid to the recent application of genomic science on drug discovery and clinical medicine, particularly through the identification of small inhibitor molecules tackling key metabolic enzymes or signalling pathways. PMID:29677189

  15. Contributing factors for therapeutic diet adherence in patients receiving haemodialysis treatment: an integrative review.

    Science.gov (United States)

    Oquendo, Lissete González; Asencio, José Miguel Morales; de Las Nieves, Candela Bonill

    2017-12-01

    The objective of this integrative review is to identify the factors that contribute to diet adherence in people suffering from kidney disease who are receiving haemodialysis treatment. Adherence to the therapeutic regimen determines therapeutic success, quality of life and survival in patients on haemodialysis. Lack of diet adherence ranges from 25%-86% in patients receiving haemodialysis treatment and affects patient morbidity and mortality. An integrative literature review was conducted based on the criteria of Whittemore & Knafl. A literature review was performed by two members of the team using twelve databases including PubMed, CUIDEN, CINAHL, The Cochrane Library and ScienceDirect. The main issues identified after analysing the results were as follows: the intrinsic barriers (age, dialysis time, motivation, perceived benefit, distorted perception of adherence) and facilitators (self-efficacy, perception of disease, perception of control), extrinsic barriers (family dysfunction, lack of social support, cultural patterns of consumption of food) and facilitators (social support, relationship with healthcare providers), and interventions to encourage diet adherence, such as the use of motivational interviewing in educational interventions, and the training and education of relevant professionals in communication skills. Diet nonadherence remains a serious health problem and suffers from a lack of solid criteria to identify this condition. The onset of depression signs and the level of social support available to the patient should be assessed, because these are important factors that determine adherence to treatment. Professionals should be trained in health education and communication techniques to contribute to the patient's self-management and motivation for diet adherence. Controlled and randomised clinical studies involving predialysis stages should be performed to investigate the impact of the assessment and control of barriers to diet adherence. © 2017

  16. Therapeutic Effects of Topical Tranexamic Acid in Comparison with Hydroquinone in Treatment of Women with Melasma.

    Science.gov (United States)

    Atefi, Najmolsadat; Dalvand, Behzad; Ghassemi, Mahammadreza; Mehran, Golnaz; Heydarian, Amir

    2017-09-01

    Few studies have focused on therapeutic as well as side effects of tranexamic acid (TXA) as a topical drug compared to other topical drugs in treating melasma. The present study aimed to assess and compare the beneficial therapeutic effects and also side effects of local TXA in comparison with hydroquinone in treating women with melasma. This randomized double-blinded clinical trial was performed on 60 women who suffered from melasma and were referred to the skin disorders clinic at the Rasoul-e-Akram hospital in Tehran in 2015. The patients were then randomly assigned via computerized randomization to two groups: group A received TXA%5 (topically twice a day for 12 weeks in the location of the melasma) and group B (received hydroquinone 2% with the same treatment order). Prior to intervention and at 12 weeks after intervention, the intensity and extension of melasma were assessed based on the Melasma Area and Severity Index (MASI) scoring method. The mean MASI score in both treatment groups decreased considerably after completion of treatment and was not significant between the two groups. No side effects were detected in group A, but 10% of those in group B complained of drug-related side effects including erythema and skin irritation (p = 0.131). Regarding the level of patient satisfaction, the patients in group A had a significantly higher level of satisfaction level of 33.3% compared with 6.7% in group B (p = 0.015) (Fig. 9). Multivariate linear regression modeling with the presence of age, history of systemic disorder, drug history, and family history of melasma demonstrated no difference in the mean MASI between the two groups. Topical use of TXA significantly reduced both melanin level and MASI score. Given its high efficiency and low drug side effects, this regimen results in high patient satisfaction compared with topical hydroquinone. IRCT code: IRCT2016040627220N2.

  17. Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets.

    Directory of Open Access Journals (Sweden)

    Mar Siles-Lucas

    2018-04-01

    Full Text Available Human cystic and alveolar echinococcosis are helmintic zoonotic diseases caused by infections with the larval stages of the cestode parasites Echinococcus granulosus and E. multilocularis, respectively. Both diseases are progressive and chronic, and often fatal if left unattended for E. multilocularis. As a treatment approach, chemotherapy against these orphan and neglected diseases has been available for more than 40 years. However, drug options were limited to the benzimidazoles albendazole and mebendazole, the only chemical compounds currently licensed for treatment in humans. To compensate this therapeutic shortfall, new treatment alternatives are urgently needed, including the identification, development, and assessment of novel compound classes and drug targets. Here is presented a thorough overview of the range of compounds that have been tested against E. granulosus and E. multilocularis in recent years, including in vitro and in vivo data on their mode of action, dosage, administration regimen, therapeutic outcomes, and associated clinical symptoms. Drugs covered included albendazole, mebendazole, and other members of the benzimidazole family and their derivatives, including improved formulations and combined therapies with other biocidal agents. Chemically synthetized molecules previously known to be effective against other infectious and non-infectious conditions such as anti-virals, antibiotics, anti-parasites, anti-mycotics, and anti-neoplastics are addressed. In view of their increasing relevance, natural occurring compounds derived from plant and fungal extracts are also discussed. Special attention has been paid to the recent application of genomic science on drug discovery and clinical medicine, particularly through the identification of small inhibitor molecules tackling key metabolic enzymes or signalling pathways.

  18. MUCOLYTIC AGENTS IN PEDIATRICS: RATIONAL SELECTION, THERAPEUTIC EFFECTS AND SPECIFIC ASPECTS OF TREATMENT

    Directory of Open Access Journals (Sweden)

    O. I. Simonova

    2013-01-01

    Full Text Available The article deals with the cough treatment options with mucolytic agents administration at the first several days of acute respiratory tract infections in children. Efficacy of treatment with secretolytic and secretomotoric drugs significantly depends on certain factors. The article contains the criteria of therapeutic efficacy of expectorants. A special attention is given to N-acetylcysteine — a direct acting mucolytic agent, which effect is caused by presence of free sulfhydryl groups, disrupting disulfide bonds between molecules of acid mucopolysaccharides and glycoproteins therefore changing the structure of sputum. Acetylcysteine is active against every type of sputum (mucous, muco-purulent, purulent, that is especially important in treatment of bacterial infections, when it is necessary to quickly decrease sputum thickness, eliminate it from the respiratory tract and prevent dissemination of the infection. High efficacy of acetylcysteine is caused by its unique triple action: mucolytic, antioxidant and antitoxic. Mechanism of action of acetylcysteine is discussed in detail. Timely administered treatment will improve sputum discharge and therefore eliminate one of the main factors of bronchial obstruction and decrease the risk of microbial colonization of the respiratory tract. The article also includes indications, contraindications and dosage regimens of acetylcysteine in children. The most common mistakes and specific aspects of mucolytic drugs in pediatrics are listed in the conclusion. 

  19. THERAPEUTIC EFFECTS OF A COGNITIVE-BEHAVIOURAL TREATMENT WITH JUVENILE OFFENDERS

    Directory of Open Access Journals (Sweden)

    Antonio Andrés-Pueyo

    2012-07-01

    Full Text Available Several treatment evaluations have highlighted the effectiveness of cognitive-behavioural programmes with both youth and adult offenders. This paper describes the application and assessment of a cognitive-behavioural treatment (adapted to Spanish from Ross and Fabiano’s Reasoning & Rehabilitation Programme with juvenile offenders serving community orders in an educational measure called in Spanish ‘libertad vigilada’ (similar to parole. The intervention comprised six different therapeutic components: self-control, cognitive restructuring, problem solving, social skills/assertiveness, values/empathy, and relapse prevention. Treatment effectiveness was tested using a quasi-experimental design involving two groups and pre/post evaluation. The results show that the programme was effective (with low to moderate effect sizes in improving participants’ social skills and self-esteem, as well as in reducing their aggressiveness. However, the intervention had no positive influence on empathy, cognitive distortions or impulsiveness. These results are in line with those of many other correctional studies, in which the treatment applied had a significant but partial effect on participants.

  20. Efficiency of modified therapeutic protocol in the treatment of some varieties of canine cardiovascular dirofilariasis

    Directory of Open Access Journals (Sweden)

    Stepanović

    2015-12-01

    Full Text Available The paper presents clinical diagnostic approaches and therapeutic effects of a specific protocol for the treatment of dogs with cardiovascular dirofilariasis in the Belgrade City (Serbia territory. The study involved 50 privately owned dogs of different breeds, gender, and age, all showing signs of cardio - respiratory disorders. In addition to a general physical examination, blood tests were done to detect microfilaria and adult forms, and X-ray, ECG, and echocardiography were performed as well. At the first examination, 34 out of 50 examined dogs were positive for microfilaria and adult forms. Because of a lack of drug used as „the golden standard“ in dirofilariasis treatment, it involved a combination of doxycycline (10 mg/kg and ivermectin (6 μg/kg supported with Advocate - Bayer spot-on. After six months, the first control was performed while continuing treatment with the aforesaid protocol, and the second control was performed after 12 months. Of the 34 treated dogs, all were negative for microfilaria, as early as after the first six months of the treatment (100%. One dog was positive for adult forms of the parasite after six and 12 months. In echocardiography and X-ray examination after 12 months, six dogs showed evident chronic changes. At controls conducted at sixth month and at one year, the implemented therapy was successful in 97.05% (33/34 of primarily infected dogs.

  1. Therapeutic drug monitoring: how to improve drug dosage and patient safety in tuberculosis treatment

    Directory of Open Access Journals (Sweden)

    Giovanni Sotgiu

    2015-03-01

    Full Text Available In this article we describe the key role of tuberculosis (TB treatment, the challenges (mainly the emergence of drug resistance, and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM is discussed in detail. Treatment success in multidrug-resistant (MDR TB cases is low (62%, with 7% failing or relapsing and 9% dying and in extensively drug-resistant (XDR TB cases is even lower (40%, with 22% failing or relapsing and 15% dying. The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world.

  2. Self care programs and multiple sclerosis: physical therapeutics treatment - literature review.

    Science.gov (United States)

    Demaille-Wlodyka, S; Donze, C; Givron, P; Gallien, P

    2011-03-01

    To clarify the therapeutic education program impact with multiple sclerosis patients, literature review. Highlight contents and efficacy. A non-systematic review on Medline, PubMed and Cochrane library databases from 1966 to 2010 using the following keywords: "multiple sclerosis", "self-care", "self-management" and specific symptoms keywords. Clinical trials and randomized clinical trials, as well as literature reviews published in English, French and German will be analyzed. Counseling is a part of the non-pharmacological management of chronic illnesses such as multiple sclerosis. Symptoms' diversity and the different clinical forms limit standardized programs of self-care management, applicable to patients. In the literature review, counseling programs have often low metrology. A behavior change with patients and medical staff could exist. To empower the patient, to reduce symptoms' impact and to improve treatment access are the aims of educational therapy. Therapeutic education program for multiple sclerosis patients could progress with their standardization and assessment, for each sign. To promote the educational therapy of multiple sclerosis patients, a specific training for medical staff, as specific financing are necessary. 2011 Elsevier Masson SAS. All rights reserved.

  3. Glucocorticoids for the treatment of post-traumatic stress disorder and phobias: a novel therapeutic approach.

    Science.gov (United States)

    de Quervain, Dominique J-F; Margraf, Jürgen

    2008-04-07

    Post-traumatic stress disorder (PTSD) and phobias belong to the most common anxiety disorders and to the most common psychiatric illnesses in general. In both disorders, aversive memories are thought to play an important role in the pathogenesis and symptomatology. Previously, we have reported that elevated glucocorticoid levels inhibit memory retrieval in animals and healthy humans. We therefore hypothesized that the administration of glucocorticoids might also inhibit the retrieval of aversive memory, thereby reducing symptoms in patients with PTSD and phobias. In recent clinical studies, we found first evidence to support this hypothesis. In patients with PTSD, low-dose cortisol treatment for one month reduced symptoms of traumatic memories without causing adverse side effects. Furthermore, we found evidence for a prolonged effect of the cortisol treatment. Persistent retrieval and reconsolidation of traumatic memories is a process that keeps these memories vivid and thereby the disorder alive. By inhibiting memory retrieval, cortisol may weaken the traumatic memory trace, and thus reduce symptoms even beyond the treatment period. In patients with social phobia, we found that a single oral administration of cortisone 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation-, exposure-, and recovery phase of the stressor. In subjects with spider phobia, repeated oral administration of cortisol 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again two days after the last cortisol administration, indicating that cortisol facilitated the extinction of phobic fear. In conclusion, by a common mechanism of reducing the retrieval of aversive memories, glucocorticoids may be suited for the treatment of PTSD as well as phobias. More studies are needed to further evaluate the therapeutic efficacy of

  4. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy

    Science.gov (United States)

    Marshall, Jamie L.; Kwok, Yukwah; McMorran, Brian; Baum, Linda G.; Crosbie-Watson, Rachelle H.

    2013-01-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important therapeutic target. Here, we review current protein replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. PMID:23601082

  5. Emerging Strategies for Developing Next-Generation Protein Therapeutics for Cancer Treatment.

    Science.gov (United States)

    Kintzing, James R; Filsinger Interrante, Maria V; Cochran, Jennifer R

    2016-12-01

    Protein-based therapeutics have been revolutionizing the oncology space since they first appeared in the clinic two decades ago. Unlike traditional small-molecule chemotherapeutics, protein biologics promote active targeting of cancer cells by binding to cell-surface receptors and other markers specifically associated with or overexpressed on tumors versus healthy tissue. While the first approved cancer biologics were monoclonal antibodies, the burgeoning field of protein engineering is spawning research on an expanded range of protein formats and modifications that allow tuning of properties such as target-binding affinity, serum half-life, stability, and immunogenicity. In this review we highlight some of these strategies and provide examples of modified and engineered proteins under development as preclinical and clinical-stage drug candidates for the treatment of cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Therapeutic Plasmapheresis. A Gate to an Effective Treatment of Severe Pathological Conditions

    Directory of Open Access Journals (Sweden)

    Claudia Stefanutti

    2014-07-01

        Table 1. Different clinical use of conventional and selective apheresis techniques in relation to the pathology to be treated in emergency or on long (chronic-term.  Throughout the acute phase of hyperlipidemic pancreatitis (HLP, PEX (Lipid-apheresis could be of considerable assistance not only in lowering TG levels but also in the prevention of recurrent HLP (3. Furthermore, patients with homo-, double- compound-, and heterozygous Familial Hypercholesterolemia and HyperLp(a lipoproteinemia would benefit lipoprotein-apheresis (LA as an extracorporeal procedure providing selective removal of lipids and lipoproteins including Low Density Lipoproteins (LDL and other apolipoprotein B100-containing lipoproteins (4, 5. Having numerous metabolic and clinical superiorities, LA characterizes an upgraded selective form of conventional extracorporeal therapies, e.g. plasma-exchange (PEX- Lipid-apheresis, which were broadly-used for managing severe hypercholesterolemia in the seventies. However, LA is primarily used in the treatment of previously-mentioned severe forms of dyslipidemia. FH patients are particularly prone to coronary ischemic events necessitating a tailored, intensive, efficient, continuous, and unceasing form of treatment. Obviously, a therapeutic approach exclusively relying on existing accessible medications would not lead to preferred clinical outcomes. The above reported clinical examples clearly suggest what differences exist between the non-selective and selective apheresis techniques as far as different pathologies exhibiting affinity are concerned. In particular, the clinical presentation, emergency or not, greatly affects the use of a given extracorporeal technique. However, depending upon the indication, a selective technique not usually utilized in emergency, such as selective dextran sulfate cellulose LA was recently suggested to treat acutely preeclampsia, where targeted therapies to stabilize the clinical manifestations and prolong

  7. Interventional and surgical therapeutic strategies for pulmonary arterial hypertension: Beyond palliative treatments.

    Science.gov (United States)

    Sandoval, Julio; Gomez-Arroyo, Jose; Gaspar, Jorge; Pulido-Zamudio, Tomas

    2015-10-01

    Despite significant advances in pharmacological treatments, pulmonary arterial hypertension remains an incurable disease with an unreasonably high morbidity and mortality. Although specific pharmacotherapies have shifted the survival curves of patients and improved exercise endurance as well as quality of life, it is also true that these pharmacological interventions are not always accessible (particularly in developing countries) and, perhaps most importantly, not all patients respond similarly to these drugs. Furthermore, many patients will continue to deteriorate and will eventually require an additional, non-pharmacological, intervention. In this review we analyze the role of atrial septostomy and Potts anastomosis in the management of patients with pulmonary arterial hypertension, we summarize the current worldwide clinical experience (case reports and case series), and discuss why these interventional/surgical strategies might have a therapeutic role beyond that of a "bridge" to transplantation. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  8. Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders

    Directory of Open Access Journals (Sweden)

    Bernard Vanhove

    2017-11-01

    Full Text Available The effector functions of T lymphocytes are responsible for most autoimmune disorders and act by directly damaging tissues or by indirectly promoting inflammation and antibody responses. Co-stimulatory and co-inhibitory T cell receptor molecules are the primary pharmacological targets that enable interference with immune-mediated diseases. Among these, selective CD28 antagonists have drawn special interest, since they tip the co-stimulation/co-inhibition balance towards efficiently inhibiting effector T cells while promoting suppression by pre-existing regulatory T-cells. After having demonstrated outstanding therapeutic efficacy in multiple models of autoimmunity, inflammation and transplantation, and safety in phase-I studies in humans, selective CD28 antagonists are currently in early clinical development for the treatment of systemic lupus erythematous and rheumatoid arthritis. Here, we review the available proof of concept studies for CD28 antagonists in autoimmunity, with a special focus on the mechanisms of action.

  9. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy.

    Science.gov (United States)

    Marshall, Jamie L; Kwok, Yukwah; McMorran, Brian J; Baum, Linda G; Crosbie-Watson, Rachelle H

    2013-09-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. © 2013 FEBS.

  10. Manual therapy and therapeutic exercise in the treatment of osteoarthritis of the hip: a systematic review

    Directory of Open Access Journals (Sweden)

    A. Romeo

    2013-05-01

    Full Text Available This systematic review aimed at investigating the role of therapeutic exercise and/or manual therapy in the treatment of hip osteoarthritis (OA. Two independent reviewers (AR, CV searched PubMed, Cinahl, Cochrane Library, PEDro and Scopus databases and a third one (SP was consulted in case of disagreement. The research criteria were publication period (from May 2007 to April 2012 and publication language (English or Italian. Ten randomized controlled trials matched inclusion criteria, eight of which concerning therapeutic exercise and two manual therapy. Few good quality studies were found. At mid- and long-term follow-up land-based exercises showed insufficient evidence of effectiveness with respect to pain and quality of life, but positive results were found for physical function. Water exercises significantly reduced fall risk when combined with functional exercises. Programs containing progressive and gradual exposure of difficult activities, education and exercises promoted better outcomes, higher adherence to home program and increased amount of physical activity, especially walking. Manual therapy seemed to reduce pain and decrease disability at short-term. Less use of nonsteroidal anti-inflammatory drugs was statistically significant at long-term follow-up in patients treated with manual therapy. The relationship between clinical results and radiological grade of OA was not investigated. Encouraging results were found in recent literature for manual therapy and functional training. Further research is needed to elucidate this issue through high-quality trials, especially addressing the aspects that have not been thoroughly explored yet, for instance type, amount and scheduling of conservative treatment.

  11. Treatment of carprofen overdose with therapeutic plasma exchange in a dog.

    Science.gov (United States)

    Kjaergaard, Astrid B; Davis, Jennifer L; Acierno, Mark J

    2018-06-13

    To report the use of therapeutic plasma exchange (TPE) in a dog with carprofen toxicosis. A 6-year-old female neutered Bichon Frise weighing 6.9 kg was examined after it had ingested 72 mg/kg carprofen. Mild dehydration without azotemia and with a urine specific gravity of 1.050 was noted at presentation. Treatment consisted of induction of emesis, symptomatic medical therapy, and TPE. The TPE achieved 1.5 plasma volume exchanges over 3 hours. Blood samples and effluent samples were collected every 30 minutes during TPE and additional blood samples were collected 11 and 35 hours after treatment. Carprofen concentrations in these samples were determined by high-pressure liquid chromatography. A 51% reduction in serum carprofen concentration was achieved following TPE. This report describes the successful reduction of plasma carprofen concentration in a dog using TPE. Although recent studies suggest that this particular dog may not have received a toxic dose, a 51% reduction of plasma carprofen concentration was achieved over 180 minutes, and TPE may be beneficial for treatment of dogs that have ingested higher doses. © Veterinary Emergency and Critical Care Society 2018.

  12. MDMA and PTSD treatment: "PTSD: From novel pathophysiology to innovative therapeutics".

    Science.gov (United States)

    Sessa, Ben

    2017-05-10

    There is a range of therapies to treat Post Traumatic Stress Disorder (PTSD) but treatment resistance remains high, with many sufferers experiencing the chronic condition. Engagement in trauma-focused psychotherapy is difficult for some patients with PTSD, especially those with extreme affect dysregulation associated with recall of traumatic memories. In recent years there have been a number of neuroscientific and clinical studies examining the potential role for adjunctive drug-assisted psychotherapy using 3,4,-methylenedioxmethamphetamine (MDMA) as a treatment for PTSD. re-visiting of a novel approach to trauma-focused psychotherapy with Used just two or three times, under careful medical supervision and specialised psychotherapy support MDMA appears to facilitate the recall of traumatic memories without the user feeling overwhelmed by the negative affect that usually accompanies such memories. This therapeutic approach began in the 1980s and was subsequently shelved in the midst of public health concerns surrounding the recreational use of the drug ecstasy. When pharmaceutical grade MDMA is used in a clinical setting it does not share the same risk profiles as ecstasy. Recent phase one neurophysiological studies and phase two clinical studies are showing promise as a potential new approach to managing treatment-resistant PTSD. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  13. Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients

    Directory of Open Access Journals (Sweden)

    Joanna Huszno

    2016-03-01

    Full Text Available The HER2/neu ( ERBB2 oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody – trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed.

  14. Postoperative Treatment in a Patient After Hemithyroidectomy: the Therapeutic Challenges of a Hidden Thyrotropinoma

    Directory of Open Access Journals (Sweden)

    Sabine Vermeersch

    2015-07-01

    Full Text Available Objectives: We report the unusual case of a patient with a thyrotropinoma, discovered after a hemithyroidectomy for a suspicious thyroid nodule, and its therapeutic challenges. Materials and methods: In a patient who underwent hemithyroidectomy for cold thyroid nodule, hyperthyroid symptoms persisted, despite stopping levothyroxine treatment. Further investigation was carried out through the following laboratory tests: thyroid-stimulating hormone (TSH test; free thyroxine (fT4 test; and the thyrotropin releasing hormone (TRH test. A pituitary magnetic resonance imaging (MRI scan and genetic analysis was also carried out. The test results confirmed the diagnosis of a thyrotropinoma. Results: Treatment with long-acting somatostatin analogues normalised thyroid hormones and symptoms of hyperthyroidism. Conclusion: The diagnostic approach to the thyroid nodule should include a detailed clinical and biochemical examination. Initial biochemical evaluation by TSH alone does not allow detecting inappropriate TSH secretion that may increase the risk of thyroid malignancy. In case of a thyrotropinoma, the ideal treatment consists of combined care of central and peripheral thyroid disease.

  15. [Xenogeneic cell therapeutics: Treatment of type 1 diabetes using porcine pancreatic islets and islet cells].

    Science.gov (United States)

    Godehardt, Antonia W; Schilling-Leiß, Dagmar; Sanzenbacher, Ralf; Tönjes, Ralf R

    2015-11-01

    In view of the existing shortage of human donor organs and tissues, xenogeneic cell therapeutics (xCT) offer an alternative for adequate treatment. In particular, porcine pancreatic islets and islet cells have already entered the field of experimental therapy for type-1 diabetes mellitus (T1DM) patients. Thereby, xCT depict challenging products with a glance on medical, ethical, and regulatory questions. With cross-species transplantation (xenotransplantation), the risk of immunological graft rejection as well as the risk of infectious transmission of microbial and viral pathogens must be considered. This includes the bidirectional transmission of microorganisms from graft to host as well as from host to graft. Crossing the border of species requires a critical risk-benefit evaluation as well as a thorough longtime surveillance of transplant recipients after treatment. The international legal and regulatory requirements for xCT are inter alia based on the World Health Organization criteria summarized in the Changsha Communiqué (2008). In the European Union, they were reflected by the European Medicines Agency (EMA) Guideline on Xenogeneic Cell-based Medicinal Products following the implementation of the Regulation on Advanced Therapies (ATMP). On the basis of this regulation, the first non-clinical and clinical experiences were obtained for porcine islets. The results suggest that supportive treatment of T1DM risk patients with xCT may be an alternative to established allogeneic organ transplantation in the future.

  16. Cellulose degradation: a therapeutic strategy in the improved treatment of Acanthamoeba infections.

    Science.gov (United States)

    Lakhundi, Sahreena; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2015-01-14

    Acanthamoeba is an opportunistic free-living amoeba that can cause blinding keratitis and fatal brain infection. Early diagnosis, followed by aggressive treatment is a pre-requisite in the successful treatment but even then the prognosis remains poor. A major drawback during the course of treatment is the ability of the amoeba to enclose itself within a shell (a process known as encystment), making it resistant to chemotherapeutic agents. As the cyst wall is partly made of cellulose, thus cellulose degradation offers a potential therapeutic strategy in the effective targeting of trophozoite encased within the cyst walls. Here, we present a comprehensive report on the structure of cellulose and cellulases, as well as known cellulose degradation mechanisms with an eye to target the Acanthamoeba cyst wall. The disruption of the cyst wall will make amoeba (concealed within) susceptible to chemotherapeutic agents, and at the very least inhibition of the excystment process will impede infection recurrence, as we bring these promising drug targets into focus so that they can be explored to their fullest.

  17. A reinforcement-based therapeutic workplace for the treatment of drug abuse: six-month abstinence outcomes.

    Science.gov (United States)

    Silverman, K; Svikis, D; Robles, E; Stitzer, M L; Bigelow, G E

    2001-02-01

    This study evaluated a novel drug abuse treatment, the Therapeutic Workplace. In this treatment, patients are paid to perform jobs or to participate in job training. Salary is linked to abstinence by requiring patients to provide drug-free urine samples to gain access to the workplace. Pregnant and postpartum drug abuse patients (N = 40) were randomly assigned to a Therapeutic Workplace or usual care control group. Therapeutic Workplace participants were invited to work 3 hr every weekday for 6 months and could earn up to $4,030 in vouchers for abstinence, workplace attendance, and performance. On average, 45% of participants attended the workplace per day. Relative to controls, the Therapeutic Workplace nearly doubled patients' abstinence from opiates and cocaine (33% vs. 59% of thrice-weekly urine samples drug negative, respectively, p Workplace can effectively treat heroin and cocaine abuse in pregnant and postpartum women.

  18. Therapeutic outcome of various treatment modalities for the management of 34 cases of mandibular unicystic ameloblastoma

    Directory of Open Access Journals (Sweden)

    Rajib Khadka

    2018-03-01

    Full Text Available Background & Objectives: Unicystic ameloblastoma is a challenge, as conservative modalities have high recurrence chances whereas radical modalities have high morbidity for defects and deformity. Enucleation with peripheral ostectomy and Carnoy’s solution is an intermediate treatment with less risk of recurrence and good outcome. The objectives of the study was to determine the therapeutic outcome for various treatment modalities for the management of mandibular unicystic ameloblastoma.Materials & Methods:Retrospective analysis of 34 cases from 2005 to 2014 was done and were analysed in terms of demographic profiles, treatment modalities and its efficacy (recurrence in 6 years’ follow up time.Results: The total number of patients was 34. The age ranged from 12 years to 28 years with a mean age of 18.82 years. Gender distribution was 21 males (61.8% and 13 females (38.2%. The location found was 26 (76.5% cases in posterior mandibular region and 8 (23.5% cases in the anterior mandibular region. Size of the lesions was small in 10 (29.4% cases, medium in 18 (52.9% cases and large in 6 (17.6% cases. Perforation of buccal or lingual cortex was present in 6 (17.6% and no preforation in 28 (82.4%. Treatment modalities done was marsupilisation in 6 (17.6% cases, enucleation with peripheral ostectomy with caroney solution in 22 (64.7% cases and resection with safe margin in 6 (17.6% cases. Recurrence occurred in 8 (23.5% cases and no recurrence in 26 (76.5% cases.Conclusion:Enucleation with peripheral ostectomy and Carnoy’s solution is one of the good treatment modality for unicystic ameloblastoma of the mandible whereas complete resection of the mandible with safe margin has low risk of recurrence in long term follow up.

  19. Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Schulz, Kurt P; Fan, Jin; Bédard, Anne-Claude V; Clerkin, Suzanne M; Ivanov, Iliyan; Tang, Cheuk Y; Halperin, Jeffrey M; Newcorn, Jeffrey H

    2012-09-01

    CONTEXT Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing psychiatric disorder that affects both children and adults. There are Food and Drug Administration-approved stimulant and nonstimulant medications for treating ADHD; however, little is known about the mechanisms by which these different treatments exert their therapeutic effects. OBJECTIVE To contrast changes in brain activation related to symptomatic improvement with use of the stimulant methylphenidate hydrochloride vs the nonstimulant atomoxetine hydrochloride. DESIGN Functional magnetic resonance imaging before and after 6 to 8 weeks of treatment with methylphenidate (n = 18) or atomoxetine (n = 18) using a parallel-groups design. SETTING Specialized ADHD clinical research program at Mount Sinai School of Medicine, New York, New York. PARTICIPANTS Thirty-six youth with ADHD (mean [SD] age, 11.2 [2.7] years; 27 boys) recruited from randomized clinical trials. MAIN OUTCOME MEASURES Changes in brain activation during a go/no-go test of response inhibition and investigator-completed ratings on the ADHD Rating Scale-IV-Parent Version. RESULTS Treatment with methylphenidate vs atomoxetine was associated with comparable improvements in both response inhibition on the go/no-go test and mean (SD) improvements in ratings of ADHD symptoms (55% [30%] vs 57% [25%]). Improvement in ADHD symptoms was associated with common reductions in bilateral motor cortex activation for both treatments. Symptomatic improvement was also differentially related to gains in task-related activation for atomoxetine and reductions in activation for methylphenidate in the right inferior frontal gyrus, left anterior cingulate/supplementary motor area, and bilateral posterior cingulate cortex. These findings were not attributable to baseline differences in activation. CONCLUSIONS Treatment with methylphenidate and atomoxetine produces symptomatic improvement via both common and divergent neurophysiologic

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

    Directory of Open Access Journals (Sweden)

    Couldwell DL

    2015-05-01

    failure, due to bacteria with coexistent macrolide-associated and fluoroquinolone-associated resistance mutations, were recently published by Australian investigators. Pristinamycin and solithromycin may be of clinical benefit for such multidrug-resistant infections. Further clinical studies are required to determine the optimal therapeutic dosing schedules for both agents to effect clinical cure and minimize the risk of emergent antimicrobial resistance. Continual inappropriate M. genitalium treatments will likely lead to untreatable infections in the future. Keywords: Mycoplasma genitalium, non-gonococcal urethritis, macrolide, fluoroquinolone, resistance, treatment failure

  1. Cost-effective therapeutic hypothermia treatment device for hypoxic ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Allen RH

    2013-01-01

    Full Text Available John J Kim,1,2 Nathan Buchbinder,1,† Simon Ammanuel,1,4,5,† Robert Kim,1,† Erika Moore,1 Neil O'Donnell,1 Jennifer K Lee,3 Ewa Kulikowicz,3 Soumyadipta Acharya,1 Robert H Allen,1,9 Ryan W Lee,6,7 Michael V Johnston4–81Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, 2The James Buchanan Brady Urological Institute, Department of Urology, The Johns Hopkins University School of Medicine, 3Department of Anesthesia and Critical Care Medicine, Johns Hopkins University, 4Kennedy Krieger Institute, 5Hugo W Moser Research Institute, 6Department of Neurology, 7Department of Pediatrics, 8Department of Physical Medicine and Rehabilitation Johns Hopkins University School of Medicine, Baltimore, MD; 9Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA†These authors contributed equally to this workAbstract: Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE. Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%–50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors

  2. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Paola Savoia

    2015-09-01

    Full Text Available Basal cell carcinoma (BCC is the most common cancer in individuals with fair skin type (I–II and steadily increasing in incidence (70% of skin malignancy. It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC.

  3. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    Science.gov (United States)

    Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

    2015-01-01

    Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I–II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

  4. Effectiveness of urgent DTPA therapeutic treatment following penetration of 239Pu via skin

    International Nuclear Information System (INIS)

    Khokhryakov, V.F.; Belyaev, A.P.; Kudryavtseva, T.I.; Moroz, G.S.; Shalaginov, V.A.

    2001-01-01

    Results of radiological examination and to evaluate therapeutic treatment with DTPA in a worker of the Mayak radiochemical plant, affected by a chemical burn of the skin caused by concentrated plutonium nitrate solutions are assessed. The plutonium content was specified by radiochemical techniques in samples of urine, blood, iliac bone biopsy, skin and bandage. The content in the skin lesion was determined by means of scintillation gamma-spectrometry. The treatment was performed through intravenous DTPA injection without surgical intervention. The urinary excretion dynamics correlated with changes of the nuclide content in blood plasma and in the injured area of the skin. The value of the kidney clearance of plutonium was falling from 110-190 ml/min in the first week down to 3-4 ml/min in the latest periods due to decontamination of the wound. Plutonium resorption into the blood from the injured skin area was 4.1%. As a result of the intensive chelatotherapy 98% of plutonium resorbed was intercepted and excreted [ru

  5. Reflections on Dry Eye Syndrome Treatment: Therapeutic Role of Blood Products

    Directory of Open Access Journals (Sweden)

    Victor J. Drew

    2018-02-01

    Full Text Available Dry eye syndrome (DES is a multifactorial, frequent, pathology characterized by deficient tear production or increased evaporation of tears and associated with ocular surface alteration and inflammation. It mostly affects, but not exclusively, older individuals and leads to varying degrees of discomfort and decreased quality of life. Although the typical treatments of DES rely on using artificial tears, polyunsaturated fatty acids, integrin antagonists, anti-inflammatory agents, or on performing punctal occlusion, recently, standardized blood-derived serum eye drops (SED are generating much interest as a new physiological treatment option. The scientific rationale in using SED for treating or releasing the symptoms of DES is thought to lie in its composition in multiple factors that resembles that of tears and contributes to the healing and protection of the ocular surface. This manuscript seeks to provide relevant background information on the management of DES, and on the increasing role that various types of SED or platelet lysates, from autologous or allogeneic origins, are playing in the improved therapeutic management of this pathology. The increasing role played by blood establishments in producing better-standardized SED is also addressed.

  6. Interventional treatment of severe portal hypertension due to hepatolenticular degeneration: therapeutic evaluation of 8 cases

    International Nuclear Information System (INIS)

    Zhao Hongwei; Liu Fuquan; Yue Zhendong; Wang Lei

    2011-01-01

    Objective: To evaluate the therapeutic efficacy of sclerotic embolization of esophagogastric varices (SEEV) and partial splenic embolization (PSE) in treating esophagogastric varices and portal hypertension, respectively, in patients with hepatolenticular degeneration. Methods: Eight patients with severe portal hypertension complicated with upper gastrointestinal bleeding and hypersplenism were involved in this study. White blood cell (WBC) counts, platelet counts, and portal vein pressure were determined before and after operation, the results were compared with each other. Results: No recurrence or complication occurred after operation in all patients. After the treatment (SEEV and PSE) the hepatic function showed no obvious changes. The WBC counts increased obviously in the first week after operation, and returned to normal range in 2 weeks. The platelet counts gradually returned to normal level from the second week. The portal vein pressure after operation went up a little, from (45.13±8.69) cm H 2 O to (48.63±10.48) cm H 2 O in SEEV group and to (47.88±11.43) cm H 2 O in PSE group, but the difference was of no statistic significance (P>0.05). Conclusion: Interventional therapy can reduce the portal hypertension caused by hepatolenticular degeneration. The technique is safe and effective, and is very helpful for returning to anti-copper treatment. (authors)

  7. Treatment of ibuprofen intoxication in a dog via therapeutic plasma exchange.

    Science.gov (United States)

    Walton, Stuart; Ryan, Kirk A; Davis, Jennifer L; Acierno, Mark

    2017-07-01

    To describe the treatment of ibuprofen intoxication with therapeutic plasma exchange in a dog (TPE). A 13-year-old male neutered mixed breed dog presented after ingesting approximately 200 mg/kg of ibuprofen. Treatment consisted of supportive medical therapy with IV fluids, gastrointestinal protectants, antiemetics and prostaglandin analogs, and TPE. A cycle of TPE was performed over 180 minutes, achieving 1.5 plasma volume exchanges. During therapy, heparinized blood and effluent samples were collected. Ibuprofen concentrations were determined in the samples by high-pressure liquid chromatography. Post TPE, the dog was continued on supportive medical therapy and was discharged 96 hours after the overdose. This report describes the use of TPE as an adjunct for ibuprofen intoxication. An 85% reduction in plasma ibuprofen concentration occurred and recovery from a potentially lethal ingestion of ibuprofen was achieved with TPE and supportive care. TPE should be considered when presented with acute ibuprofen intoxication due to the rapid and efficacious nature of therapy. © Veterinary Emergency and Critical Care Society 2017.

  8. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression.

    Science.gov (United States)

    Roseman, Leor; Nutt, David J; Carhart-Harris, Robin L

    2017-01-01

    < 0.05). Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety. Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797.

  9. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression

    Directory of Open Access Journals (Sweden)

    Leor Roseman

    2018-01-01

    ASC (p < 0.05.Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety.Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797

  10. Comparing the therapeutic effects of finasteride gel and tablet in treatment of the androgenetic alopecia

    Directory of Open Access Journals (Sweden)

    Hajheydari Zohreh

    2009-01-01

    Full Text Available Background: Finasteride, a type P-selective 5a-reductase inhibitor, as a causative agent of decreasing dihydroxy testestrone (DHT level, is effective in the treatment of male androgenic alopecia. Aim: We compared the local and oral finasteride in the treatment of androgenic alopecia. Method: This is a double blind, randomized clinical trial study of 45 male patients, who were referred with alopecia to the private clinics and departments in Boo-Ali Sina Hospital, in Sari. Patients with male androgenic alopecia were selected according to the history and physical examinations. The patients were randomly divided into two: topical finasteride (A and oral finasteride (B groups. Topical finasteride group (A received a topical gel of 1% finasteride and placebo tablets, while the oral finasteride group (B received finasteride tablets (1 mg and gel base (without drug as placebo for 6 months. The patients were followed by clinical observation and recording of side effects prior to the treatment and at the end of first week, and then by a monthly follow-up. The size of bald area, total hair count, and terminal hair were studied. Data were analyzed by descriptive and Chi-square statistical test. Results: The mean duration of hair loss was 18.8±23.10 months. Each month the terminal hair, size of bald area and hair count between the two groups were compared. There were no significant differences between the two groups as a viewpoint of hair thickness, hair counts and the size of bald area. Serial measurements indicated a significant increase in hair counts and terminal hair counts between the two groups. Conclusions: The results of this study showed that the therapeutic effects of both finasteride gel and finasteride tablet were relatively similar to each other.

  11. Photodynamic therapy as a local therapeutic adjunct for the treatment of vertebral metastases

    Science.gov (United States)

    Yee, Albert; Burch, Shane; Akens, Margarete; Won, Emily; Lo, Victor; Wise-Milestone, Lisa; Bisland, Stuart; Theriault, Aimee; Niu, Carolyn; Wilson, Brian C.; Whyne, Cari

    2013-03-01

    Metastatic cancer causes the majority of tumors in bone, most frequently detected in the spinal column. Skeletal complications cause pain and neurologic impairment. Photodynamic therapy (PDT) has been used to treat a variety of cancers. Minimally invasive surgical (MIS) strategies may allow targeted light application essential for PDT within bone structures. The purpose of this manuscript is to provide an update on pre-clinical status as well as early clinical experience of a Phase I clinical trial on vertebral PDT. A pre-clinical (rnu/rnu rat) vertebral metastasis model of osteolytic (MT-1 breast cancer) was optimized and used to evaluate the effect of vertebral PDT. PDT alone and in combination with other standard local (radiation therapy, RT) and systemic (bisphosphonates, BP) therapies was evaluated through bioluminescence imaging, micro-CT based stereology, histology, and biomechanical testing. Single PDT treatment (photosensitizer BPD-MA, 690nm light) ablated tumor tissue in targeted vertebrae. PDT led to significant increases in bone structural properties, with greatest benefits observed from combined BP+PDT therapy: 76% and 19% increases in bone volume fraction in treated tumor-bearing and healthy untreated controls, respectively. Similar synergistic improvements (but of lesser magnitude) were found in combined PDT+RT treatments. The safety and feasibility of MIS+PDT were evaluated in scale-up animal studies, refining surgical technique for clinical translation. Following appropriate institutional review board as well as Health Canada approval, 5 patients (light only control group) have undergone protocoled treatment to date. These patients have guided further refinement of human therapeutic application from a laser delivery and vertebral bone access perspective.

  12. Disposition kinetics of selenium in healthy volunteers following therapeutic shampoo treatment.

    Science.gov (United States)

    Noisel, Nolwenn; Bouchard, Michèle; Carrier, Gaétan

    2010-05-01

    This study was aimed at documenting the kinetic time courses of selenium (Se) in accessible biological matrices of volunteers following controlled applications of therapeutic shampoo containing Se, to better elucidate the mechanisms by which shampoo-Se accumulates in hair and hence estimate the contribution of this source to total Se body burden. Ten healthy volunteers were exposed to Se-shampoo three times a week over a month. Blood, hair and toenail concentrations along with daily urinary excretions were repeatedly measured over an 18-month period following the onset of application. Over the entire study period, blood concentrations of Se (range: 127-233μg/l) and daily urinary excretions (range: 11.9-150μg/d) remained within baseline range of the general population. Conversely, during shampoo application, mean Se concentrations in hair reached transitional levels of 89μg/g while, following cessation of treatment, a mono-exponential decrease was observed with a mean half-life of 4.5 weeks. Two of the volunteers also exhibited an increase in toenail concentrations of Se during the study period. Results show that Se-shampoo does not contribute significantly to total Se body burden, as assessed from blood and urine levels. Differences observed between blood and urine time courses as compared to hair profiles and the presence of Se on hair grown before treatment indicates an adsorption on hair; however, the gradual decrease in Se concentrations in successive centimeters of hair grown following the application period suggests a concomitant absorption from the scalp during treatment with subsequent excretion in hair. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease

    Science.gov (United States)

    Gentile, Christopher L.; Nivala, Angela M.; Gonzales, Jon C.; Pfaffenbach, Kyle T.; Wang, Dong; Wei, Yuren; Jiang, Hua; Orlicky, David J.; Petersen, Dennis R.; Maclean, Kenneth N.

    2011-01-01

    The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD. PMID:21957160

  14. [Chronic complex tinnitus: therapeutic results of inpatient treatment in a tinnitus clinic].

    Science.gov (United States)

    Hesse, G; Rienhoff, N K; Nelting, M; Laubert, A

    2001-09-01

    In-patient treatment of patients with chronic tinnitus is necessary only when these patients have a severe psychosomatic co-morbidity and suffer severely. However this therapeutic approach has to be supervised and evaluated properly. We present data and results of 1841 patients suffering from chronic tinnitus. Due to the severity of the symptom and psycho-neurotic side effects in-patient treatment was necessary. Therapy lasted 5 - 6 weeks, the main aspect was an intensive psychotherapeutic evaluation and stabilisation next to retraining and habituation programmes. Relaxation techniques were taught. Patients suffered from their tinnitus more than six month; 95 % further suffered from hearing-loss, mainly in high frequencies. The study evaluates results of patients from October 1994 until June 2000. Basis of the study was the evaluation of a specific tinnitus-questionnaire (TQ), published by Hallam in the UK and translated by Goebel and Hiller in Germany. Data was recorded at registration in our clinic, 4 - 6 months later during admission and at the end of the therapy. Final data was gained during a special meeting or questioning 6 months after dismissal from the clinic. Patients that suffered most showed the greatest improvement; directly after therapy there was a highly significant improvement in the TQ for an average of 13.01 points. Highly significant improvements were found in all the TQ-subscales respectively. Only 10 % of the patients did not show any improvement at all. Therapy of most severe cases of chronic tinnitus is possible, using an integrated concept of otologic and psychosomatic treatments. With large numbers of patients and sufficient data a thorough and necessary evaluation of this therapy can be achieved.

  15. Manual Therapy, Therapeutic Patient Education, and Therapeutic Exercise, an Effective Multimodal Treatment of Nonspecific Chronic Neck Pain: A Randomized Controlled Trial.

    Science.gov (United States)

    Beltran-Alacreu, Hector; López-de-Uralde-Villanueva, Ibai; Fernández-Carnero, Josué; La Touche, Roy

    2015-10-01

    The aim of this study was to determine the effectiveness of a multimodal treatment in the short and medium term for disability in nonspecific chronic neck pain. The design of this study is a single-blinded randomized controlled trial carried out in a university research laboratory. Forty-five patients between 18 and 65 yrs with nonspecific chronic neck pain were included in this study. Each patient was treated eight times over a 4-wk period. The sample was divided into three groups: control group, subjected to a protocol of manual therapy; experimental group 1, subjected to a protocol of manual therapy and therapeutic patient education; and experimental group 2, subjected to manual therapy, therapeutic patient education, and a therapeutic exercise protocol. Assessments were performed at baseline and at 4, 8, and 16 wks using the following measurements: the Neck Disability Index, the 11-item Tampa Scale of Kinesiophobia, the Fear Avoidance Beliefs Questionnaire, the Neck Flexor Muscle Endurance Test, and the Visual Analog Fatigue Scale. The nonparametric Kruskal-Wallis test for the Neck Disability Index showed statistically significant differences between baseline outcomes and all follow-up periods (P Kruskal-Wallis test, differences were found for the Visual Analog Fatigue Scale and the Neck Flexor Muscle Endurance Test in the follow-ups at 8 and 16 wks (P < 0.05). Analysis of variance for group × time interaction showed statistically significant changes (Tampa Scale of Kinesiophobia, F = 3.613, P = 0.005; Fear Avoidance Beliefs Questionnaire, F = 2.803, P = 0.022). Minimal detectable changes were obtained in both experimental groups for the 11-item Tampa Scale of Kinesiophobia but not in the control group. Differences between experimental groups and the control group were found in the short and medium term. A multimodal treatment is a good method for reducing disability in patients with nonspecific chronic neck pain in the short and medium term.

  16. CLINICAL FEATURES, DIAGNOSIS, THE RESULTS OF THERAPEUTIC AND SURGICAL TREATMENT OF ACANTHAMOEBIC KERATITIS

    Directory of Open Access Journals (Sweden)

    Evg. A. Kasparova

    2017-01-01

    years.Conclusion. AK is an extremely dangerous cornea disease , in most cases developing with contact lenses. Effective instrumental diagnostics methods of AK are confocal microscopy and morphological examination of distant corneal discs. Often, AK combined with a herpetic and bacterial infection (mixed keratitis. AK treatment requires the active use of several antiseptic agents with amoebicidal action, mycostatic drugs, antibiotics and other drugs. Therapeutic keratoplasty, often necessary in AK, accompanied by a high risk of complications and relapses of the disease, but in 50% cases, good results were achieved.

  17. Understanding factors associated with early therapeutic alliance in PTSD treatment: adherence, childhood sexual abuse history, and social support.

    Science.gov (United States)

    Keller, Stephanie M; Zoellner, Lori A; Feeny, Norah C

    2010-12-01

    Therapeutic alliance has been associated with better treatment engagement, better adherence, and less dropout across various treatments and disorders. In treatment of posttraumatic stress disorder (PTSD), it may be particularly important to establish a strong early alliance to facilitate treatment adherence. However, factors such as childhood sexual abuse (CSA) history and poor social support may impede the development of early alliance in those receiving PTSD treatment. We sought to examine treatment adherence, CSA history, and social support as factors associated with early alliance in individuals with chronic PTSD who were receiving either prolonged exposure therapy (PE) or sertraline. At pretreatment, participants (76.6% female; 64.9% Caucasian; mean age = 37.1 years, SD = 11.3) completed measures of trauma history, general support (Inventory of Socially Supportive Behaviors), and trauma-related social support (Social Reactions Questionnaire). Over the course of 10 weeks of PE or sertraline, they completed early therapeutic alliance (Working Alliance Inventory) and treatment adherence measures. Early alliance was associated with PE adherence (r = .32, p history was not predictive of a lower early alliance. Given the associations with adherence, clinicians may find it useful to routinely assess alliance early in treatment. Positive trauma support, not CSA history, may be particularly important in the development of a strong early therapeutic alliance. (c) 2010 APA, all rights reserved.

  18. Alkaloids as important scaffolds in therapeutic drugs for the treatments of cancer, tuberculosis, and smoking cessation.

    Science.gov (United States)

    Kittakoop, Prasat; Mahidol, Chulabhorn; Ruchirawat, Somsak

    2014-01-01

    Alkaloid molecules can act, depending on a type of amine functionality present in alkalods, as either hydrogenacceptor or hydrogen-donor for hydrogen bonding that is critically important for the interaction (binding) between targets (enzymes, proteins and receptors) and drugs (ligands). Because of this unique property, alkaloid scaffolds are therefore present in several drugs and lead compounds. This review highlights alkaloid scaffolds in drugs, particularly those recently approved in 2012; it also covers the scaffolds in leads and drug candidates which are in clinical trials and preclinical pipeline. The review focuses on three therapeutic areas including treatments of cancer, tuberculosis, and tobacco cessation. Alkaloid scaffolds in drugs and leads are inspired by those of naturally occurring alkaloids, and these scaffolds include pyridine, piperidine, quinoline, quinolinone, quinazoline, isoquinoline, indole, indolinone, isoindole, isoxazole, imidazole, indazole, thiazole, pyrazole, oxazolidinone, oxadiazole, and benzazepine. In addition to medicinal chemistry aspects, natural products possessing an individual alkaloid scaffold, as well as the mechanism of action of drugs and leads, are also discussed in this review.

  19. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    Science.gov (United States)

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

  20. Microbiological study of therapeutic soft contact lenses used in the treatment of recurrent corneal erosion syndrome.

    Science.gov (United States)

    Park, Young Min; Kwon, Han Jo; Lee, Jong Soo

    2015-03-01

    To determine the bacteriological spectrum of the removed therapeutic soft contact lenses (TSCLs) and to establish efficacy of prophylactic antibiotics on TSCLs used for 2 weeks for treatment of patients with recurrent corneal erosion syndrome (RCES). This study included idiopathic RCES treated using highly oxygen-permeable silicone hydrogel contact lenses (CLs), and treated 4 times per day with topical tobramycin 3% for 2 weeks. After TSCLs were applied for 2 weeks, the lenses were removed with sterile forceps under which a speculum was inserted, and placed on blood agar with the inner face down. The TSCLs were analyzed for bacterial colonization, and antibiotic susceptibility tests were performed for the isolates, using disk diffusion. Of the 40 lenses analyzed, 9 (22.5%) yielded positive cultures. Staphylococcus epidermidis was the most commonly isolated microorganism; there were five methicillin-sensitive coagulase-negative staphylococci and two methicillin-resistant coagulase-negative staphylococci. Furthermore, we found two lenses that were colonized by Enterobacter gergoviae and Citrobacter freundii. All cultured bacteria showed intermediate or complete sensitivity to ciprofloxacin, tigecycline, and tobramycin. Despite bacterial colonization in 9 CLs, no clinical signs of infectious keratitis were found in any of the patients with prophylactic topical tobramycin 3%. In case of using TSCLs for 2 weeks, tobramycin or ciprofloxacin may be useful as prophylactic topical antibiotics for preventing secondary corneal infections. Considering currently growing incidence of ciprofloxacin-resistant ocular isolates, tobramycin seems to be a reasonable prophylactic topical antibiotic susceptible broad spectrum of bacteria in clinics.

  1. Oral zinc sulphate in treatment of patients with thallium poisoning: A clinical therapeutic trial

    Directory of Open Access Journals (Sweden)

    Ahmed A. Al-Mohammadi

    2011-06-01

    Full Text Available Thallium poisoning is usually associated with typical dermatological features simulating that of zinc deficiency. The aim of this study was to evaluate the role of oral zinc sulphate in the treatment of patients with thallium poisoning.Materials and methods: This clinical therapeutic trial study was conducted in Departments of Dermatology of Baghdad and Basrah Teaching Hospitals from February 2008 - February 2010, where a total of 37 patients with thallium poisoning were enrolled.A detailed history was taken from all patients and complete clinical examination was performed. All patients received zinc sulphate in a dose of 5 mg/kg three times a day few days before confirming the diagnosis of thallium poisoning. Thallium in urine had been measured using the colorimetric method and was positive in all patients. After confirming the diagnosis of thallium poisoning, thallium antidotes Prussian blue was given to 32 patients.Results: Age range of 37 patients was 5-33 (24±5.3 years. The dermatological findings were mainly: anagen hair loss affected the scalp and limbs. Also, dusky ecchymotic red dermatitis like rash was observed on the face and dorsum of hands and legs, while neurological manifestations were mainly of peripheral neuropathy, were reported in 21 (55% patients. All patients but two responded promptly to a trial of zinc sulphate within few days.Conclusion: Oral Zinc sulphate appears to be an effective and safe treatment for thallium poisoning particularly for skin and hair features and in reducing its lethal progression and complications. J Clin Exp Invest 2011;2(2:133-7

  2. A Web-Based Therapeutic Workplace for the Treatment of Drug Addiction and Chronic Unemployment

    Science.gov (United States)

    Silverman, Kenneth; Wong, Conrad J.; Grabinski, Michael J.; Hampton, Jacqueline; Sylvest, Christine E.; Dillon, Erin M.; Wentland, R. Daniel

    2005-01-01

    This article describes a Web-based therapeutic workplace intervention designed to promote heroin and cocaine abstinence and train and employ participants as data entry operators. Patients are paid to participate in training and then to perform data entry jobs in a therapeutic workplace business. Salary is linked to abstinence by requiring patients…

  3. Therapeutic Community in a California Prison: Treatment Outcomes after 5 Years

    Science.gov (United States)

    Zhang, Sheldon X.; Roberts, Robert E. L.; McCollister, Kathryn E.

    2011-01-01

    Therapeutic communities have become increasingly popular among correctional agencies with drug-involved offenders. This quasi-experimental study followed a group of inmates who participated in a prison-based therapeutic community in a California state prison, with a comparison group of matched offenders, for more than 5 years after their initial…

  4. Therapeutic Alliance and Treatment Adherence in Two Interventions for Bulimia Nervosa: A Study of Process and Outcome

    Science.gov (United States)

    Loeb, Katharine L.; Wilson, G. Terence; Labouvie, Erich; Pratt, Elizabeth M.; Hayaki, Jumi; Walsh, B. Timothy; Agras, W. Stewart; Fairburn, Christopher G.

    2005-01-01

    The relationship between therapeutic alliance, therapist adherence to treatment protocol, and outcome was analyzed in a randomized trial of cognitive-behavioral therapy (CBT) and interpersonal psychotherapy for bulimia nervosa. Independent observers rated audiotapes of full-length therapy sessions. Purging frequency was the primary outcome…

  5. Feasibility of adjunct therapeutic hypothermia treatment for hyperammonemia and encephalopathy due to urea cycle disorders and organic acidemias.

    Science.gov (United States)

    Lichter-Konecki, Uta; Nadkarni, Vinay; Moudgil, Asha; Cook, Noah; Poeschl, Johannes; Meyer, Michael T; Dimmock, David; Baumgart, Stephen

    2013-08-01

    Children with urea cycle disorders (UCDs) or organic acidemias (OAs) and acute hyperammonemia and encephalopathy are at great risk for neurological injury, developmental delay, intellectual disability, and death. Nutritional support, intravenous alternative pathway therapy, and dialysis are used to treat severe hyperammonemia associated with UCDs and nutritional support and dialysis are used to treat severe hyperammonemia in OAs. Brain protective treatment while therapy is initiated may improve neurological and cognitive function for the lifetime of the child. Animal experiments and small clinical trials in hepatic encephalopathy caused by acute liver failure suggest that therapeutic hypothermia provides neuroprotection in hyperammonemia associated encephalopathy. We report results of an ongoing pilot study that assesses if whole body cooling during rescue treatment of neonates with acute hyperammonemia and encephalopathy is feasible and can be conducted safely. Adjunct whole body therapeutic hypothermia was conducted in addition to standard treatment in acutely encephalopathic, hyperammonemic neonates with UCDs and OAs requiring dialysis. Therapeutic hypothermia was initiated using cooling blankets as preparations for dialysis were underway. Similar to standard therapeutic hypothermia treatment for neonatal hypoxic ischemic encephalopathy, patients were maintained at 33.5°C±1°C for 72h, they were then slowly rewarmed by 0.5°C every 3h over 18h. In addition data of age-matched historic controls were collected for comparison. Seven patients were cooled using the pilot study protocol and data of seven historic controls were reviewed. All seven patients survived the initial rescue and cooling treatment, 6 patients were discharged home 2-4weeks after hospitalization, five of them feeding orally. The main complication observed in a majority of patients was hypotension. Adjunct therapeutic hypothermia for neonates with UCDs and OAs receiving standard treatment was

  6. Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use.

    Science.gov (United States)

    Fischer, Benedikt; Kuganesan, Sharan; Gallassi, Andrea; Malcher-Lopes, Renato; van den Brink, Wim; Wood, Evan

    2015-12-01

    Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily - largely within urban contexts - in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results. An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases. Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) - one of the numerous cannabinoid components found in cannabis - with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems. The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users' 'self-medication' efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia. Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for - predominantly marginalized - crack-cocaine user populations. Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use. Given the high prevalence of this grave substance use problem in the Americas, opportunities for

  7. Formulation and PEGylation optimization of the therapeutic PEGylated phenylalanine ammonia lyase for the treatment of phenylketonuria.

    Science.gov (United States)

    Bell, Sean M; Wendt, Dan J; Zhang, Yanhong; Taylor, Timothy W; Long, Shinong; Tsuruda, Laurie; Zhao, Bin; Laipis, Phillip; Fitzpatrick, Paul A

    2017-01-01

    Phenylketonuria (PKU) is a genetic metabolic disease in which the decrease or loss of phenylalanine hydroxylase (PAH) activity results in elevated, neurotoxic levels of phenylalanine (Phe). Due to many obstacles, PAH enzyme replacement therapy is not currently an option. Treatment of PKU with an alternative enzyme, phenylalanine ammonia lyase (PAL), was first proposed in the 1970s. However, issues regarding immunogenicity, enzyme production and mode of delivery needed to be overcome. Through the evaluation of PAL enzymes from multiple species, three potential PAL enzymes from yeast and cyanobacteria were chosen for evaluation of their therapeutic potential. The addition of polyethylene glycol (PEG, MW = 20,000), at a particular ratio to modify the protein surface, attenuated immunogenicity in an animal model of PKU. All three PEGylated PAL candidates showed efficacy in a mouse model of PKU (BTBR Pahenu2) upon subcutaneous injection. However, only PEGylated Anabaena variabilis (Av) PAL-treated mice demonstrated sustained low Phe levels with weekly injection and was the only PAL evaluated that maintained full enzymatic activity upon PEGylation. A PEGylated recombinant double mutant version of AvPAL (Cys503Ser/Cys565Ser), rAvPAL-PEG, was selected for drug development based on its positive pharmacodynamic profile and favorable expression titers. PEGylation was shown to be critical for rAvPAL-PEG efficacy as under PEGylated rAvPAL had a lower pharmacodynamic effect. rAvPAL and rAvPAL-PEG had poor stability at 4°C. L-Phe and trans-cinnamate were identified as activity stabilizing excipients. rAvPAL-PEG is currently in Phase 3 clinical trials to assess efficacy in PKU patients.

  8. Formulation and PEGylation optimization of the therapeutic PEGylated phenylalanine ammonia lyase for the treatment of phenylketonuria.

    Directory of Open Access Journals (Sweden)

    Sean M Bell

    Full Text Available Phenylketonuria (PKU is a genetic metabolic disease in which the decrease or loss of phenylalanine hydroxylase (PAH activity results in elevated, neurotoxic levels of phenylalanine (Phe. Due to many obstacles, PAH enzyme replacement therapy is not currently an option. Treatment of PKU with an alternative enzyme, phenylalanine ammonia lyase (PAL, was first proposed in the 1970s. However, issues regarding immunogenicity, enzyme production and mode of delivery needed to be overcome. Through the evaluation of PAL enzymes from multiple species, three potential PAL enzymes from yeast and cyanobacteria were chosen for evaluation of their therapeutic potential. The addition of polyethylene glycol (PEG, MW = 20,000, at a particular ratio to modify the protein surface, attenuated immunogenicity in an animal model of PKU. All three PEGylated PAL candidates showed efficacy in a mouse model of PKU (BTBR Pahenu2 upon subcutaneous injection. However, only PEGylated Anabaena variabilis (Av PAL-treated mice demonstrated sustained low Phe levels with weekly injection and was the only PAL evaluated that maintained full enzymatic activity upon PEGylation. A PEGylated recombinant double mutant version of AvPAL (Cys503Ser/Cys565Ser, rAvPAL-PEG, was selected for drug development based on its positive pharmacodynamic profile and favorable expression titers. PEGylation was shown to be critical for rAvPAL-PEG efficacy as under PEGylated rAvPAL had a lower pharmacodynamic effect. rAvPAL and rAvPAL-PEG had poor stability at 4°C. L-Phe and trans-cinnamate were identified as activity stabilizing excipients. rAvPAL-PEG is currently in Phase 3 clinical trials to assess efficacy in PKU patients.

  9. Therapeutic effects of antimicrobial treatment during lactation of recently acquired bovine subclinical mastitis: two linked randomized field trials.

    Science.gov (United States)

    van den Borne, B H P; van Schaik, G; Lam, T J G M; Nielen, M

    2010-01-01

    Two linked randomized field trials were performed on 39 herds in the Netherlands to 1) determine therapeutic effects of antimicrobial treatment of recently acquired subclinical mastitis (RASCM) during lactation, 2) evaluate the effect of duration of subclinical mastitis on therapeutic outcome, and 3) identify factors related to the therapeutic success of RASCM. Cows with a first elevated composite somatic cell count (CSCC) after 2 consecutive low CSCC measurements were eligible for enrollment in trial 1 (treatment at the first elevated CSCC). Quarter milk samples were collected to determine bacteriological status for major pathogens and coagulase-negative staphylococci. Cows with one or more culture-positive quarters with a quarter somatic cell count (QSCC) >or=100,000 cells/mL were defined to have RASCM and were randomly assigned treatment or control (no treatment). Untreated cows from trial 1 that had a second elevated CSCC at the next milk recording were eligible for enrollment in trial 2 (treatment at the second elevated CSCC). In trial 2, staphylococci-positive cows (Staphylococcus aureus and coagulase-negative staphylococci) were randomly assigned to treatment or control. Farmers used their own treatment protocols to treat quarters in both trials. Bacteriological cure was defined as absence of the pathogen identified pre-intervention in 2 samples post-intervention; QSCC, CSCC, and milk yield were also analyzed. Hierarchical logistic and linear models were used to determine therapeutic effects and to identify factors related to therapy outcome. Treated quarters had a higher bacteriological cure rate than control quarters for all pathogens in both trials. Treatment resulted in lower QSCC and CSCC, whereas milk yield was not affected by treatment. Bacteriological cure of RASCM was better in quarters with a low QSCC pre-intervention and in coagulase-negative staphylococci-positive quarters. Control quarters with a single culture-positive sample pre

  10. Therapist self-disclosure and the therapeutic alliance in the treatment of eating problems.

    Science.gov (United States)

    Simonds, Laura M; Spokes, Naomi

    2017-01-01

    Evidence is mixed regarding the potential utility of therapist self-disclosure. The current study modelled relationships between perceived helpfulness of therapist self-disclosures, therapeutic alliance, patient non-disclosure, and shame in participants (n = 120; 95% women) with a history of eating problems. Serial multiple mediator analyses provided support for a putative model connecting the perceived helpfulness of therapist self-disclosures with current eating disorder symptom severity through therapeutic alliance, patient self-disclosure, and shame. The analyses presented provide support for the contention that therapist self-disclosure, if perceived as helpful, might strengthen the therapeutic alliance. A strong therapeutic alliance, in turn, has the potential to promote patient disclosure and reduce shame and eating problems.

  11. Urine colorimetry for therapeutic drug monitoring of pyrazinamide during tuberculosis treatment.

    Science.gov (United States)

    Zentner, Isaac; Modongo, Chawangwa; Zetola, Nicola M; Pasipanodya, Jotam G; Srivastava, Shashikant; Heysell, Scott K; Mpagama, Stellah; Schlect, Hans P; Gumbo, Tawanda; Bisson, Gregory P; Vinnard, Christopher

    2018-03-01

    Pyrazinamide is a key drug in the first-line treatment regimen for tuberculosis, with a potent sterilizing effect. Although low pyrazinamide peak serum concentrations (C max ) are associated with poor treatment outcomes, many resource-constrained settings do not have sufficient laboratory capacity to support therapeutic drug monitoring (TDM). The objective of this study was to determine whether a colorimetric test of urine can identify tuberculosis patients with adequate pyrazinamide exposures, as defined by serum C max above a target threshold. In the derivation study of healthy volunteers, three dose sizes of pyrazinamide were evaluated, and intensive pharmacokinetic blood sampling was performed over an 8-h period, with a timed urine void at 4h post-dosing. Pyrazinamide in urine was isolated by spin column centrifugation with an exchange resin, followed by colorimetric analysis; the absorbance peak at 495nm was measured. The urine assay was then evaluated in a study of 39 HIV/tuberculosis patients in Botswana enrolled in an intensive pharmacokinetic study. Receiver operating characteristics (ROC) curves were used to measure diagnostic accuracy. The guideline-recommended pyrazinamide serum C max target of 35mg/l was evaluated in the primary analysis; this target was found to be predictive of favorable outcomes in a clinical study. Following this, a higher serum C max target of 58mg/l was evaluated in the secondary analysis. At the optimal cut-off identified in the derivation sample, the urine colorimetric assay was 97% sensitive and 50% specific to identify 35 of 39 HIV/tuberculosis patients with pharmacokinetic target attainment, with an area under the ROC curve of 0.81 (95% confidence interval 0.60-0.97). Diagnostic accuracy was lower at the 58mg/l serum C max target, with an area under the ROC curve of 0.68 (95% confidence interval 0.48-0.84). Men were less likely than women to attain either serum pharmacokinetic target. The urine colorimetric assay was

  12. Evidence of novel miR-34a-based therapeutic approaches for multiple myeloma treatment

    Czech Academy of Sciences Publication Activity Database

    Zarone, M.R.; Misso, G.; Grimaldi, A.; Zappavigna, S.; Russo, M.; Amler, Evžen; Di Martino, M.T.; Amodio, N.; Tagliaferri, P.; Tassone, P.; Caraglia, M.

    2017-01-01

    Roč. 7, dec (2017), s. 17949 ISSN 2045-2322 Institutional support: RVO:68378041 Keywords : gamma-secretase inhibitors * tumor-suppressor network * breast - cancer Subject RIV: FP - Other Medical Disciplines OBOR OECD: Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions (pharmacogenomics, gene-based therapeutics) Impact factor: 4.259, year: 2016

  13. Therapeutic inertia and intensified treatment in diabetes mellitus prescription patterns: A nationwide population-based study in Taiwan.

    Science.gov (United States)

    Huang, Li-Ying; Yeh, Hseng-Long; Yang, Ming-Chin; Shau, Wen-Yi; Su, Syi; Lai, Mei-Shu

    2016-12-01

    Objective To measure therapeutic inertia by characterizing prescription patterns using secondary data obtained from the nationwide diabetes mellitus pay-for-performance (DM-P4P) programme in Taiwan. Methods Using reimbursement claims from Taiwan's National Health Insurance Research Database, a nationwide retrospective cohort study was undertaken of patients with diabetes mellitus who participated in the DM-P4P programme from 2006-2008. Glycosylated haemoglobin results were used to evaluate modifications in therapy in response to poor diabetes control. Prescription patterns were used to assign patients to either a therapeutic inertia group or an intensified treatment group. Therapeutic inertia was defined as the failure to act on a known problem. Results The research sample comprised of 168 876 patients with diabetes mellitus who had undergone 899 135 tests. Of these, 37.4% (336 615 visits) of prescriptions were for a combination of two types of drug and 27.7% (248 788 visits) were for a combination of three types of drug. The proportion of patients in the intensified therapy group who were prescribed more than two types of drug was considerably higher than that in the therapeutic inertia group. Conclusion In many cases in the therapeutic inertia group only a single type of hypoglycaemic drug was prescribed or the dosage remained unchanged.

  14. Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases.

    Science.gov (United States)

    Oh, Doo-Byoung

    2015-08-01

    Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy.

  15. Stem Cell Therapy and Breast Cancer Treatment: Review of Stem Cell Research and Potential Therapeutic Impact Against Cardiotoxicities Due to Breast Cancer Treatment

    OpenAIRE

    Sharp, Thomas E.; George, Jon C.

    2014-01-01

    A new problem has emerged with the ever-increasing number of breast cancer survivors. While early screening and advances in treatment have allowed these patients to overcome their cancer, these treatments often have adverse cardiovascular side effects that can produce abnormal cardiovascular function. Chemotherapeutic and radiation therapy have both been linked to cardiotoxicity; these therapeutics can cause a loss of cardiac muscle and deterioration of vascular structure that can eventually ...

  16. Establishing a compulsory drug treatment prison: Therapeutic policy, principles, and practices in addressing offender rights and rehabilitation.

    Science.gov (United States)

    Birgden, Astrid; Grant, Luke

    2010-01-01

    A Compulsory Drug Treatment Correctional Center (CDTCC) was established in Australia in 2006 for repeat drug-related male offenders. Compulsory treatment law is inconsistent with a therapeutic jurisprudence approach. Despite the compulsory law, a normative offender rehabilitation framework has been established based on offender moral rights. Within moral rights, the offender rehabilitation framework addresses the core values of freedom (supporting autonomous decision-making) and well-being (supporting support physical, social, and psychological needs). Moral rights are underpinned by a theory or principle which, in this instance, is a humane approach to offender rehabilitation. While a law that permits offenders to choose drug treatment and rehabilitation is preferable, the article discusses the establishment of a prison based on therapeutic policy, principles, and practices that respond to participants as both rights-violators and rights-holders. The opportunity for accelerated community access and a therapeutic alliance with staff has resulted in offenders actively seeking to be ordered into compulsory drug treatment and rehabilitation. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

  17. Stem Cell Therapy and Breast Cancer Treatment: review of stem cell research and potential therapeutic impact against cardiotoxicities due to breast cancer treatment

    Directory of Open Access Journals (Sweden)

    Thomas E. Sharp

    2014-11-01

    Full Text Available A new problem has emerged with the ever-increasing number of breast cancer survivors. While early screening and advances in treatment have allowed these patients to overcome their cancer, these treatments often have adverse cardiovascular side effects that can produce abnormal cardiovascular function. Chemotherapeutic and radiation therapy have both been linked to cardiotoxicity; these therapeutics can cause a loss of cardiac muscle and deterioration of vascular structure that can eventually lead to heart failure (HF. This cardiomyocyte toxicity can leave the breast cancer survivor with a probable diagnosis of dilated or restrictive cardiomyopathy (DCM or RCM. While current HF standard of care can alleviate symptoms, other than heart transplantation, there is no therapy that replaces cardiac myocytes that are killed during cancer therapies. There is a need to develop novel therapeutics that can either prevent or reverse the cardiac injury caused by cancer therapeutics. These new therapeutics should promote the regeneration of lost or deteriorating myocardium. Over the last several decades the therapeutic potential of cell-based therapy has been investigated for HF patients. In this review we discuss the progress of preclinical and clinical stem cell research for the diseased heart and discuss the possibility of utilizing these novel therapies to combat cardiotoxicity observed in breast cancer survivors.

  18. From non-pharmacological treatments for post-traumatic stress disorder to novel therapeutic targets

    NARCIS (Netherlands)

    Hendriksen, Erik; Olivier, Berend; Oosting, Ronald S

    2014-01-01

    The development of new pharmacological therapies starts with target discovery. Finding new therapeutic targets for anxiety disorders is a difficult process. Most of the currently described drugs for post-traumatic stress disorder (PTSD) are based on the inhibition of serotonin reuptake. The

  19. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment.

    Science.gov (United States)

    Kojima, Ryosuke; Bojar, Daniel; Rizzi, Giorgio; Hamri, Ghislaine Charpin-El; El-Baba, Marie Daoud; Saxena, Pratik; Ausländer, Simon; Tan, Kelly R; Fussenegger, Martin

    2018-04-03

    Exosomes are cell-derived nanovesicles (50-150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded devices in exosome producer cells enhance exosome production, specific mRNA packaging, and delivery of the mRNA into the cytosol of target cells, enabling efficient cell-to-cell communication without the need to concentrate exosomes. Further, engineered producer cells implanted in living mice could consistently deliver cargo mRNA to the brain. Therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in in vitro and in vivo models of Parkinson's disease, indicating the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications.

  20. Evolving paradigms in clinical pharmacology and therapeutics for the treatment of Duchenne muscular dystrophy.

    Science.gov (United States)

    Huard, J; Mu, X; Lu, A

    2016-08-01

    Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  1. The Complex Relationship between Antipsychotic-Induced Weight Gain and Therapeutic Benefits: A Systematic Review and Implications for Treatment

    Directory of Open Access Journals (Sweden)

    Alex T. Raben

    2018-01-01

    Full Text Available Background: Antipsychotic-induced weight gain (AIWG and other adverse metabolic effects represent serious side effects faced by many patients with psychosis that can lead to numerous comorbidities and which reduce the lifespan. While the pathophysiology of AIWG remains poorly understood, numerous studies have reported a positive association between AIWG and the therapeutic benefit of antipsychotic medications.Objectives: To review the literature to (1 determine if AIWG is consistently associated with therapeutic benefit and (2 investigate which variables may mediate such an association.Data Sources: MEDLINE, Google Scholar, Cochrane Database and PsycINFO databases were searched for articles containing all the following exploded MESH terms: schizophrenia [AND] antipsychotic agents/neuroleptics [AND] (weight gain [OR] lipids [OR] insulin [OR] leptin [AND] treatment outcome. Results were limited to full-text, English journal articles.Results: Our literature search uncovered 31 independent studies which investigated an AIWG-therapeutic benefit association with a total of 6063 enrolled individuals diagnosed with schizophrenia or another serious mental illness receiving antipsychotic medications. Twenty-two studies found a positive association while, 10 studies found no association and one study reported a negative association. Study variables including medication compliance, sex, ethnicity, or prior antipsychotic exposure did not appear to consistently affect the AIWG-therapeutic benefit relationship. In contrast, there was some evidence that controlling for baseline BMI/psychopathology, duration of treatment and specific agent studied [i.e., olanzapine (OLZ or clozapine (CLZ] strengthened the relationship between AIWG and therapeutic benefit.Limitations: There were limitations of the reviewed studies in that many had small sample sizes, and/or were retrospective. The heterogeneity of the studies also made comparisons difficult and publication bias

  2. Economic evaluation of therapeutic sequences in the treatment of patients with chronic lymphocytic leukemia and coexisting conditions

    Directory of Open Access Journals (Sweden)

    Antonio Cuneo

    2017-10-01

    Full Text Available Economic evaluation of therapeutic sequences in the treatment of patients with chronic lymphocytic leukemia and coexisting conditionsIntroductionChronic lymphocytic leukemia (CLL is a chronic lymphoproliferative syndrome and it is the most common hematological malignancy in Western countries. It has a tendency to develop subsequent relapses, so affected patients are likely to undergo more than one line of treatment.MethodsRather than evaluating the cost-effectiveness of individual therapeutic agents, it becomes therefore recommendable for decision-makers to identify an optimal sequencing of such agents. A four-year cost-consequence analysis was conducted, comparing three alternative strategies for the first-line treatment of patients with previously untreated CLL and coexisting conditions: i obinutuzumab with chlorambucil (Obi-Clb, ii rituximab with chlorambucil (Rtx-Clb, and iii ofatumumab with chlorambucil (Ofa-Clb. Only drug costs were considered in the analysis.ResultsIn two trials, median time to next treatment (TTNT was longer in Obi-Clb (51.1 months as compared to Rtx-Clb (38.2 months or to Ofa-Clb (39.8 months. Therefore, during a 48-month time horizon, patients treated with Obi-Clb would maintain on average the first line treatment; on the contrary, patients treated with Rtx-Clb or with Ofa-Clb would receive on average a second line treatment consisting in the majority of cases of ibrutinib monotherapy, or rituximab with idelalisib or rituximab with bendamustine. The sequence using Obi-Clb regimen in first line showed the lower mean cost of treatment: €22,958 over the 48-month time horizon. Sensitivity analyses on a couple of scenarios provided similar conclusions in terms of overall costs.ConclusionObi-Clb as first-line treatment appears a recommendable strategy in terms of drug costs in the treatment of patients with previously untreated CLL and coexisting conditions.

  3. INTRALESIONAL MEASLES, MUMPS AND RUBELLA (MMR VACCINE-AN EFFECTIVE THERAPEUTIC TOOL IN THE TREATMENT OF WART

    Directory of Open Access Journals (Sweden)

    Raju

    2015-11-01

    Full Text Available BACKGROUND: Warts are common cutaneous viral infection. Various therapeutic modalities have been using in treatment of wart, but none of them are standardised. Immunotherapy is new current approach in the treatment of wart. AIMS: To know the efficacy and safety profile of Measles Mumps Rubella (MMR Vaccine in the treatment of wart. METHODS: MMR vaccine was injected into a largest single wart intralesionally and subsequent injections given every 2 weeks apart for about 3 to 5 times. Every month followup of patients was done to know the clearance of wart. RESULTS: Complete remission of warts seen in 70.4% of patients, partial remission seen in 22.2% and no response was seen in 7.4% of patients. No serious adverse side effects were seen in the current study. CONCLUSION: MMR vaccine can be considered as a safe, effective, inexpensive intralesional immunotherapeutic modality in the treatment of wart.

  4. Therapeutic modulation of miRNA for the treatment of proinflammatory lung diseases.

    LENUS (Irish Health Repository)

    Hassan, Tidi

    2012-03-01

    miRNAs are short, nonprotein coding RNAs that regulate target gene expression principally by causing translational repression and\\/or mRNA degradation. miRNAs are involved in most mammalian biological processes and have pivotal roles in controlling the expression of factors involved in basal and stimulus-induced signaling pathways. Considering their central role in the regulation of gene expression, miRNAs represent therapeutic drug targets. Here we describe how miRNAs are involved in the regulation of aspects of innate immunity and inflammation, what happens when this goes awry, such as in the chronic inflammatory lung diseases cystic fibrosis and asthma, and discuss the current state-of-the-art miRNA-targeted therapeutics.

  5. The relationship between clinical findings and therapeutic approach in the treatment of fractured frontal sinus walls

    Directory of Open Access Journals (Sweden)

    Pešić Zoran

    2007-01-01

    Full Text Available Introduction The incidence of fractured frontal sinus walls vary from 6% to 12% of all craniofacial injuries. Objective Estimated relation between clinical findings and performed therapeutic procedures in treating fractured frontal sinus walls. To estimate success in performed therapeutic procedures, according to the incidence of postoperative complications and the integrity of injured regions from the functional and esthetical aspect. Method We analyzed, by retrospective clinical investigation, 19 patients with fractured frontal sinus walls and dislocated fragments, treated at the Department for Maxillofacial Surgery, Clinic of Dentistry in Niš, in the period March 1995 - March 2006. The success of therapy was estimated based on the incidence and type of complications and esthetical results in relation to preoperative findings. Results Predominant etiological factor in fractures of frontal sinus walls is trauma sustained in traffic accidents, which occurred in 52.6% of patients in our investigation. In clinical findings, the impression was the predominant sign, present in 16 patients. In 6 cases soft tissue access through already present lacerations or their extensions was employed, in 4 cases it was done by supraciliary access and in 9 by bicoronal access. As a therapeutic measure, drainage was performed in 5 cases, cranialisation in one, ostheoneogenetic access in 11 cases and a simple reposition of fragments in 2 patients with fractured frontal sinus walls. Infection as a complication was absent. All patients were satisfied with postoperative esthetical appearance of the injured region. Conclusion The infection, the lacerations and the direction of fractured lines are dominant factors in the determination of therapeutic procedures used to treat fractured frontal sinus walls. This will result in the low incidence of infection as a postoperative complication and in patient’s satisfaction with postoperative esthetical result of the injured

  6. Pre-Release Consumption of Methyl Eugenol Increases the Mating Competitiveness of Sterile Males of the Oriental Fruit Fly, Bactrocera dorsalis, in Large Field Enclosures

    Science.gov (United States)

    Shelly, Todd E.; Edu, James; McInnis, Donald

    2010-01-01

    The sterile insect technique may be implemented to control populations of the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), when environmental concerns preclude widespread use of chemical attractants or toxicants. The goal of the present study was to evaluate whether the mating competitiveness of sterile B. dorsalis males could be increased via pre-release feeding on methyl eugenol. Males of the oriental fruit fly are strongly attracted to this plant-borne compound, which they ingest and use in the synthesis of the sex pheromone. Previous studies conducted in the laboratory and small field-cages have shown that males given methyl eugenol produce a more attractive pheromone for females and have a higher mating success rate than males denied methyl eugenol. Here, levels of egg sterility were compared following the release of wild-like flies and either methyl eugenol-fed (treated) or methyl eugenol-deprived (control) sterile males in large field enclosures at four over flooding ratios ranging from 5:1 to 60:1 (sterile: wild-like males). Treated sterile males were fed methyl eugenol for 1–4 h (depending on the over flooding ratio tested) 3 d prior to release. Eggs were dissected from introduced fruits (apples), incubated in the laboratory, and scored for hatch rate. The effect of methyl eugenol was most pronounced at lower over flooding ratios. At the 5:1 and 10:1 over flooding ratios, the level of egg sterility observed for treated, sterile males was significantly greater than that observed for control, sterile males. In addition, the incidence of egg sterility reported for treated sterile males at these lower over flooding ratios was similar to that noted for treated or control sterile males at the 30:1 or 60:1 over flooding ratios. This latter result, in particular, suggests that pre-release feeding on methyl eugenol allows for a reduction in the number of sterile flies that are produced and released, thus increasing the cost

  7. The Multidimensional Therapeutic Potential of Targeting the Brain Oxytocin System for the Treatment of Substance Use Disorders.

    Science.gov (United States)

    Bowen, Michael T; Neumann, Inga D

    2017-09-24

    The neuropeptide oxytocin is released both into the blood and within the brain in response to reproductive stimuli, such as birth, suckling and sex, but also in response to social interaction and stressors. Substance use disorders, or addictions, are chronic, relapsing brain disorders and are one of the major causes of global burden of disease. Unfortunately, current treatment options for substance use disorders are extremely limited and a treatment breakthrough is sorely needed. There is mounting preclinical evidence that targeting the brain oxytocin system may provide that breakthrough. Substance use disorders are characterised by a viscous cycle of bingeing and intoxication, followed by withdrawal and negative affect, and finally preoccupation and anticipation that triggers relapse and further consumption. Administration of oxytocin has been shown to have a potential therapeutic benefit at each stage of this addiction cycle for numerous drugs of abuse. This multidimensional therapeutic utility is likely due to oxytocin's interactions with key biological systems that underlie the development and maintenance of addiction. Only a few human trials of oxytocin in addicted populations have been completed with the results thus far being mixed. There are numerous other trials underway, and the results are eagerly awaited. However, the ability to fully harness the potential therapeutic benefit of targeting the brain oxytocin system may depend on the development of molecules that selectively stimulate the oxytocin system, but that have superior pharmacokinetic properties to oxytocin itself.

  8. Observation on the therapeutic effect of aspirin in combined with acupuncture in the treatment of TIA

    Directory of Open Access Journals (Sweden)

    Jing Gao

    2017-02-01

    Full Text Available Objective: To observe the effect of aspirin in combined with acupuncture in the treatment of transient ischemic attack (TIA. Methods: A total of 90 patients with TIA who were admitted in our hospital were included in the study and randomized into the observation group and the control group with 45 cases in each group. The patients in the two groups were given aspirin and routine symptomatic treatments. On this basis, the patients in the observation group were given acupuncture. Two-week treatment was regarded as one course. The fasting venous blood before treatment and one course after treatment was collected to detect the serum lipid level. TCD was used to detect the average peak flow velocity of MCA, VA, and BA. A follow-up visit was paid to TIA attack times within 3 months. Results: TC, TG, and LDL levels after treatment in the two groups were significantly reduced when compared with before treatment, while HDL was significantly elevated when compared with before treatment. The comparison of TC, TG, LDL, and HDL after treatment between the two groups was not statistically significant. The comparison of the average peak flow velocity of MCA, VA, and BA before treatment between the two groups was not statistically significant. The average peak flow velocity of MCA and BA after treatment were significantly slowing down when compared with before treatment, while the average peak flow velocity of VA was not significantly different from that before treatment. The average peak flow velocity of MCA and BA after treatment in the treatment group was significantly lower than that in the control group. The average attack time of TIA every week after treatment in the observation group was significantly lower than that in the control group. Conclusions: Aspirin in combined with acupuncture in the treatment of TIA can effectively improve the cerebral hemodynamic indicators, and reduce TIA attack time; therefore, it deserves to be widely recommended in the

  9. A Comparative Study between Oxcarbazepine and Gabapentin Regarding Therapeutic Efficiency and Tolerability in the Treatment of Trigeminal Neuralgia

    Directory of Open Access Journals (Sweden)

    Fakir Mohan Debta

    2010-01-01

    Recently two newer anticonvulsant oxcarbazepine (OXC a ketoderivative of carbamazepine and gabapentin (GBP has been trailed in trigeminal neuralgia in different open clinical trial as monotherapy with encouraging results. These drugs have convenient dosage and surprisingly fewer side effects. These facts that trigeminal neuralgia responds to newer anticonvulsant (oxcarbazepine, gabapentin in a better perspective, enabled me to conduct the present clinical trial on 54 patients (both in newly diagnosed TN patient and refractive patient of trigeminal neuralgia who were made two randomized group for separate monotherapy study for a period of six months. The therapeutic effect of OXC and gabapentin (GBP in relation to reduction in number of attacks of pain and severity of pain were evaluated. All the scoring data showed OXC is more therapeutic efficacious cost-effective and well-tolerated profile than gabapentin and an emerging as a drug for treatment of TN in both new and refractive patients.

  10. OBSERVATION ON THE THERAPEUTIC EFFECT OF TREATMENT OF 150CASES OF INSOMNIA BY PUNCTURING BODY ACUPOINTS AND OTOPOINTS

    Institute of Scientific and Technical Information of China (English)

    李宗莲

    2000-01-01

    In the present paper,the therapeutic effect of needling Baihui(GV20)and Sishen-chong(EX-HN1)combined with otopoint Xin(MA-IC),Shenmen,Naodian and pizhixia(MA-AT1)for treatment of insomnia was observed in 150patients.Results showed that the cure rate,effective rate and ineffective rate were84%,13.33%and2.67%respectively.Comparison between Western medicine group and acupuncture group showed a significant difference in the therapeutic effect(P<0.01).It displays that acupuncture can correct the imbalance between excitement and suppression of the cerebral cortex and had effects of tranquilizing and allaying excitement.

  11. Therapeutic Effect of Caffeine Treatment Immediately Following Neonatal Hypoxic-Ischemic Injury on Spatial Memory in Male Rats

    Directory of Open Access Journals (Sweden)

    R. Holly Fitch

    2013-03-01

    Full Text Available Hypoxia Ischemia (HI refers to the disruption of blood and/or oxygen delivery to the brain. Term infants suffering perinatal complications that result in decreased blood flow and/or oxygen delivery to the brain are at risk for HI. Among a variety of developmental delays in this population, HI injured infants demonstrate subsequent memory deficits. The Rice-Vannucci rodent HI model can be used to explore behavioral deficits following early HI events, as well as possible therapeutic agents to help reduce deleterious outcomes. Caffeine is an adenosine receptor antagonist that has recently shown promising results as a therapeutic agent following HI injury. The current study sought to investigate the therapeutic benefit of caffeine following early HI injury in male rats. On post-natal day (P 7, HI injury was induced (cauterization of the right common carotid artery, followed by two hours of 8% oxygen. Male sham animals received only a midline incision with no manipulation of the artery followed by room air exposure for two hours. Subsets of HI and sham animals then received either an intraperitoneal (i.p. injection of caffeine (10 mg/kg, or vehicle (sterile saline immediately following hypoxia. All animals later underwent testing on the Morris Water Maze (MWM from P90 to P95. Results show that HI injured animals (with no caffeine treatment displayed significant deficits on the MWM task relative to shams. These deficits were attenuated by caffeine treatment when given immediately following the induction of HI. We also found a reduction in right cortical volume (ipsilateral to injury in HI saline animals as compared to shams, while right cortical volume in the HI caffeine treated animals was intermediate. These findings suggest that caffeine is a potential therapeutic agent that could be used in HI injured infants to reduce brain injury and preserve subsequent cognitive function.

  12. A Therapeutic Workplace for the Long-Term Treatment of Drug Addiction and Unemployment: Eight-Year Outcomes of a Social Business Intervention

    OpenAIRE

    Aklin, Will M.; Wong, Conrad J.; Hampton, Jacqueline; Svikis, Dace S.; Stitzer, Maxine L.; Bigelow, George E.; Silverman, Kenneth

    2014-01-01

    This study evaluated the long-term effects of a Therapeutic Workplace social business on drug abstinence and employment. Pregnant and postpartum women (N=40) enrolled in methadone treatment were randomly assigned to a Therapeutic Workplace or Usual Care Control group. Therapeutic Workplace participants could work weekdays in training and then as employees of a social business, but were required to provide drug-free urine samples to work and maintain maximum pay. Three-year outcomes were repor...

  13. Interventional treatment of diabetic ischemic diseases of lower limb:a therapeutic observation

    International Nuclear Information System (INIS)

    Wang Zhaoyang; Liu Xiang

    2010-01-01

    Objective: To assess the clinical effects of endovascular interventional treatment for diabetic ischemic diseases of lower limb. Methods: Endovascular interventional management was performed in 47 patients with diabetic ischemic diseases of lower limb. The ankle-to-brachial index and the diameter of lower limb vessel were estimated both before the treatment and 3, 30 days after the treatment. The results were compared and analyzed. Results: Obvious improvement in ankle-to-brachial index and the diameter of lower limb vessel were observed after the treatment. Conclusion: Endovascular interventional treatment is very effective and reliable for diabetic ischemic diseases of lower limb. (authors)

  14. Targeting Specific HATs for Neurodegenerative Disease Treatment: Translating Basic Biology to Therapeutic Possibilities

    Directory of Open Access Journals (Sweden)

    Sheila K. Pirooznia

    2013-03-01

    Full Text Available Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism by which neurons adapt their transcriptional responses to specific developmental and environmental cues. While defects within the neural epigenome have traditionally been studied in the context of early developmental and heritable cognitive disorders, recent studies point to aberrant histone acetylation status as a key mechanism underlying acquired inappropriate alterations of genome structure and function in post-mitotic neurons during the aging process. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the lifetime of neurons through mechanisms related to loss of function of histone acetyltransferase (HATs activity. Several HATs have been shown to participate in vital neuronal functions such as regulation of neuronal plasticity and memory formation. As such, dysregulation of such HATs has been implicated in the pathogenesis associated with age-associated neurodegenerative diseases and cognitive decline. In order to counteract the loss of HAT function in neurodegenerative diseases, the current therapeutic strategies involve the use of small molecules called histone deacetylase (HDAC inhibitors that antagonize HDAC activity and thus enhance acetylation levels. Although this strategy has displayed promising therapeutic effects, currently used HDAC inhibitors lack target specificity, raising concerns about their applicability. With rapidly evolving literature on HATs and their respective functions in mediating neuronal survival and higher order brain function such as learning and memory, modulating the function of specific HATs holds new promises as a therapeutic tool in neurodegenerative diseases. In this review, we focus on the recent progress in research regarding epigenetic histone acetylation mechanisms underlying neuronal activity and cognitive function. We discuss the current understanding of specific HDACs and

  15. Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases.

    Science.gov (United States)

    Cameron, Robert B; Beeson, Craig C; Schnellmann, Rick G

    2016-12-08

    Mitochondria have various roles in cellular metabolism and homeostasis. Because mitochondrial dysfunction is associated with many acute and chronic degenerative diseases, mitochondrial biogenesis (MB) is a therapeutic target for treating such diseases. Here, we review the role of mitochondrial dysfunction in acute and chronic degenerative diseases and the cellular signaling pathways by which MB is induced. We then review existing work describing the development and application of drugs that induce MB in vitro and in vivo. In particular, we discuss natural products and modulators of transcription factors, kinases, cyclic nucleotides, and G protein-coupled receptors.

  16. An integrative view of mechanisms underlying generalized spike-and-wave epileptic seizures and its implication on optimal therapeutic treatments.

    Directory of Open Access Journals (Sweden)

    Boyuan Yan

    Full Text Available Many types of epileptic seizures are characterized by generalized spike-and-wave discharges. In the past, notable effort has been devoted to understanding seizure dynamics and various hypotheses have been proposed to explain the underlying mechanisms. In this paper, by taking an integrative view of the underlying mechanisms, we demonstrate that epileptic seizures can be generated by many different combinations of synaptic strengths and intrinsic membrane properties. This integrative view has important medical implications: the specific state of a patient characterized by a set of biophysical characteristics ultimately determines the optimal therapeutic treatment. Through the same view, we further demonstrate the potentiation effect of rational polypharmacy in the treatment of epilepsy and provide a new angle to resolve the debate on polypharmacy. Our results underscore the need for personalized medicine and demonstrate that computer modeling and simulation may play an important role in assisting the clinicians in selecting the optimal treatment on an individual basis.

  17. Therapeutic touch for nausea in breast cancer patients receiving chemotherapy: Composing a treatment.

    Science.gov (United States)

    Vanaki, Zohreh; Matourypour, Pegah; Gholami, Roya; Zare, Zahra; Mehrzad, Valiolah; Dehghan, Mojtaba

    2016-02-01

    Therapeutic touch (TT) is independent nursing intervention which is effective on nausea induced by chemotherapy but technique, steps and variables affected by this therapy are not yet well known. The aim of this study was to elicit descriptions of how TT is used with cancer patients, providing a basis for the systematic use and evaluation of TT with patients. In this research, 108 patients were examined with intentional sampling and random allocation in 3 groups (control, placebo and intervention) in 2013 (each group 36). Intervention received therapeutic touch (touching of first energy layer) and demographic form, visual analog scale (VAS) for intensity of nausea, check list for duration and times of nausea in the morning, noon, afternoon and night at acute phase were used. Data were analyzed by Kruskal Wallis, χ(2) and analysis of variance (ANOVA). Duration, frequency and intensity of nausea were significantly lower in the test group (P < 0.001, P < 0.001 and P < 0.001). The mean duration of intervention (whole process) was 21.38 min [SD 6.04]. In 69.4% of women there was a need for re-intervention after reassessment phase. Results of this randomized control trial showed that TT is effective on duration, times and intensity of nausea; therefore, TT can be used as an alternative method for patients who are willing to use this technique. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Therapeutic potential and challenges of Natural killer cells in treatment of solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea eGras Navarro

    2015-04-01

    Full Text Available Natural killer (NK cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

  19. Overlapping activities of TGF-β and Hedgehog signaling in cancer: therapeutic targets for cancer treatment.

    Science.gov (United States)

    Perrot, Carole Y; Javelaud, Delphine; Mauviel, Alain

    2013-02-01

    Recent advances in the field of cancer therapeutics come from the development of drugs that specifically recognize validated oncogenic or pro-metastatic targets. The latter may be mutated proteins with altered function, such as kinases that become constitutively active, or critical components of growth factor signaling pathways, whose deregulation leads to aberrant malignant cell proliferation and dissemination to metastatic sites. We herein focus on the description of the overlapping activities of two important developmental pathways often exacerbated in cancer, namely Transforming Growth Factor-β (TGF-β) and Hedgehog (HH) signaling, with a special emphasis on the unifying oncogenic role played by GLI1/2 transcription factors. The latter are the main effectors of the canonical HH pathway, yet are direct target genes of TGF-β/SMAD signal transduction. While tumor-suppressor in healthy and pre-malignant tissues, TGF-β is often expressed at high levels in tumors and contributes to tumor growth, escape from immune surveillance, invasion and metastasis. HH signaling regulates cell proliferation, differentiation and apoptosis, and aberrant HH signaling is found in a variety of cancers. We discuss the current knowledge on HH and TGF-β implication in cancer including cancer stem cell biology, as well as the current state, both successes and failures, of targeted therapeutics aimed at blocking either of these pathways in the pre-clinical and clinical settings. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Specific RSK kinase inhibition by dibenzyl trisulfide and implication for therapeutic treatment of cancer.

    Science.gov (United States)

    Lowe, Henry I C; Facey, Caroline O B; Toyang, Ngeh J; Bryant, Joseph L

    2014-04-01

    The Jamaican "Guinea Hen Weed" (Petiveria alliacea L.) plant has been traditionally used in folklore medicine to treat a variety of diseases including cancer. In the present study we investigated on the therapeutic feasibility of dibenzyl trisulfide (DTS) (isolated from the Jamaican Guinea Hen Weed) as a potent small-molecule kinase inhibitor to treat cancer. We investigated the inhibitory effects of DTS against a large panel of kinases using a well-established competitive binding assay. Cell proliferation data were obtained using the WST-1 colorimetric assay. DTS inhibited the activity of the C-terminal kinase domain of RSK1 (80% compared to control) with a Kd of 1.3 μM. Anti-proliferative effects of DTS were observed in small lung, pancreatic, breast, and prostate cancer cells with IC50 values ranging from 0.34-0.84 μM. We have identified DTS as a highly selective and isoform-specific RSK1 kinase inhibitor with broad cancer therapeutic potential.

  1. What's your opinion? The experience of therapeutic climate in a treatment facility for adults with mild intellectual disability and severe challenging behavior

    NARCIS (Netherlands)

    Helmond, P.; Vermaes, I.P.R.; Helm, G.H.P. van der

    2014-01-01

    Aim: A therapeutic climate is important so that clients can optimally develop themselves. In a treatment facility for adults with mild intellectual disability and severe challenging behavior we assessed clients’ experiences of therapeutic climate in relation to their internalizing and externalizing

  2. The therapeutic workplace to promote treatment engagement and drug abstinence in out-of-treatment injection drug users: a randomized controlled trial.

    Science.gov (United States)

    Holtyn, August F; Koffarnus, Mikhail N; DeFulio, Anthony; Sigurdsson, Sigurdur O; Strain, Eric C; Schwartz, Robert P; Leoutsakos, Jeannie-Marie S; Silverman, Kenneth

    2014-11-01

    Determine if employment-based reinforcement can increase methadone treatment engagement and drug abstinence in out-of-treatment injection drug users. This study was conducted from 2008 to 2012 in a therapeutic workplace in Baltimore, MD. After a 4-week induction, participants (N=98) could work and earn pay for 26 weeks and were randomly assigned to Work Reinforcement, Methadone & Work Reinforcement, and Abstinence, Methadone & Work Reinforcement conditions. Work Reinforcement participants had to work to earn pay. Methadone & Work Reinforcement and Abstinence, Methadone, & Work Reinforcement participants had to enroll in methadone treatment to work and maximize pay. Abstinence, Methadone, & Work Reinforcement participants had to provide opiate- and cocaine-negative urine samples to maximize pay. Most participants (92%) enrolled in methadone treatment during induction. Drug abstinence increased as a graded function of the addition of the methadone and abstinence contingencies. Abstinence, Methadone & Work Reinforcement participants provided significantly more urine samples negative for opiates (75% versus 54%) and cocaine (57% versus 32%) than Work Reinforcement participants. Methadone & Work Reinforcement participants provided significantly more cocaine-negative samples than Work Reinforcement participants (55% versus 32%). The therapeutic workplace can promote drug abstinence in out-of-treatment injection drug users. Clinical trial registration number: NCT01416584. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Therapeutic doll play in the treatment of a severely impaired psychiatric inpatient: dramatic clinical improvements with a nontraditional nursing intervention.

    Science.gov (United States)

    Birnbaum, Shira; Hanchuk, Hilary; Nelson, Marjorie

    2015-05-01

    Interest has grown in the use of doll therapy, particularly in geropsychiatric and dementia care settings. In a long-term state psychiatric hospital, a dollhouse-play activity was implemented in an effort to engage an acutely disturbed, middle-aged woman undergoing medication trials and whose symptoms had been refractory to conventional treatments. A schedule of nondirective dollhouse-play activities was implemented over an 8-week period. Measures of behavioral change were tracked. Dramatic clinical improvements were seen, including significant reductions in verbal and physical aggression, use of as-needed medications, and need for close one-to-one monitoring. Improvements were seen prior to achievement of therapeutic drug levels. The patient was successfully discharged from the hospital. Doll play has recently been associated with clinical benefits in the care of patients with dementia and has long been deployed in childhood mental health treatment. The current findings suggest doll play may have applications as a time-limited intervention in the treatment of major psychiatric disorders in adults and warrants consideration when achieving therapeutic alliance has proven particularly challenging. Copyright 2015, SLACK Incorporated.

  4. Importance of Therapeutic Drug Monitoring in the Treatment of Active Tuberculosis - A Retrospective Study of 4 Cases

    Directory of Open Access Journals (Sweden)

    Sanaa HAMMI

    2016-06-01

    Full Text Available Background: In the treatment of active tuberculosis, therapeutic drug monitoring (TDM is used to optimize dosing that maximizes therapeutic benefit while minimizing toxicity. In Morocco, TDM is not routinely used, yet low levels of anti-TB drugs can be associated with poorer treatment outcomes.Methods: We retrospectively checked our archives for patients with active TB for whom TDM was performed during 2014. Medical records were reviewed to abstract demographic, clinical, radiographic and microbiological data including time until smear and culture conversion. Then, we looked for cases with delay of TB conversion.Results: In total, 24 patients were identified, for whom TDM was performed, they all had low serum drug levels. Among them, 4 patients showed delayed bacteriological conversion.Conclusions: Our study cases are showing the benefit of serum dosage in the follow-up of the patients showing a delay of sputum examination conversion, both direct and culture, during their evolutions. TDM is potentially useful for the treatment of active TB, but is currently underused in Morocco.

  5. The Therapeutic Potential of Monocyte/Macrophage Manipulation in the Treatment of Chemotherapy-Induced Painful Neuropathy

    Directory of Open Access Journals (Sweden)

    Karli Montague

    2017-11-01

    Full Text Available In cancer treatments a dose-limiting side-effect of chemotherapeutic agents is the development of neuropathic pain, which is poorly managed by clinically available drugs at present. Chemotherapy-induced painful neuropathy (CIPN is a major cause of premature cessation of treatment and so a greater understanding of the underlying mechanisms and the development of novel, more effective therapies, is greatly needed. In some cases, only a weak correlation between chemotherapy-induced pain and neuronal damage is observed both clinically and preclinically. As such, a critical role for non-neuronal cells, such as immune cells, and their communication with neurons in CIPN has recently been appreciated. In this mini-review, we will discuss preclinical evidence for the role of monocytes/macrophages in the periphery in CIPN, with a focus on that which is associated with the chemotherapeutic agents vincristine and paclitaxel. In addition we will discuss the potential mechanisms that regulate monocyte/macrophage–neuron crosstalk in this context. Informed by preclinical data, we will also consider the value of monocytes/macrophages as therapeutic targets for the treatment of CIPN clinically. Approaches that manipulate the signaling pathways discussed in this review show both promise and potential pitfalls. Nonetheless, they are emerging as innovative therapeutic targets with CX3CL1/R1-regulation of monocyte/macrophage–neuron communication currently emerging as a promising front-runner.

  6. Integrative Therapeutic Approaches for the Management and Control of Nausea in Children Undergoing Cancer Treatment: A Systematic Review of Literature.

    Science.gov (United States)

    Momani, Tha'er G; Berry, Donna L

    Chemotherapy-induced nausea and vomiting (CINV) continues to be a common symptom experienced by children undergoing cancer treatment despite the use of contemporary antiemetics. Integrative therapeutic approaches in addition to standard pharmacologic antiemetic regimes offer potential to control CINV. The purpose of this review was to identify current evidence on integrative therapeutic approaches for the control of CINV in children with cancer. Online search engines (PubMed, CINAHL, PsychINFO) were queried using MESH terms. Titles, abstracts, and then full-text articles were reviewed for relevance to the review. The search resulted in 53 studies. Twenty-one studies met our review criteria. Integrative therapies identified included acupuncture/acupressure, aromatherapy, herbal supplements, hypnosis, and other cognitive behavioral interventions. Our review identified little information on the effectiveness and safety of most integrative therapeutic approaches for the control and management of CINV in children with cancer. However, evidence from adult cancer studies and some pediatric studies identify promising interventions for further testing.

  7. Assessing the Therapeutic Environment in Hybrid Models of Treatment: Prisoner Perceptions of Staff

    Science.gov (United States)

    Kubiak, Sheryl Pimlott

    2009-01-01

    Hybrid treatment models within prisons are staffed by both criminal justice and treatment professionals. Because these models may be indicative of future trends, examining the perceptions of prisoners/participants may provide important information. This study examines the perceptions of male and female inmates in three prisons, comparing those in…

  8. Individualized treatment of multidrug-resistant tuberculosis using therapeutic drug monitoring

    Directory of Open Access Journals (Sweden)

    Mathieu S Bolhuis

    2016-01-01

    Conclusion: TDM is highly valuable to individualize and optimize treatment of complex MDR-TB patients. TDM is routinely applied in Tuberculosis Center Beatrixoord, and high success rates for treatment of MDR-TB patients have been achieved. DBS and LSS make implementation of TDM feasible, even in low- and middle-income countries.

  9. Therapeutic Options for the Treatment of Hypertension in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Mary M. Stephens MD, MPH

    2012-01-01

    Full Text Available Primary hypertension in children is increasing in prevalence with many cases likely going undiagnosed. The prevalence is currently estimated at between 3%-5% in the United States and may be higher in certain ethnic groups. Primary hypertension, once felt to be rare in children, is now considered to be about five times more common than secondary hypertension. This review provides information to guide physicians through an organized approach to: 1 screening children and adolescents for hypertension during routine visits; 2 using normative percentile data for diagnosis and classification; 3 performing a clinical evaluation to identify the presence of co-morbidities; 4 initiating a plan of care including subsequent follow-up blood pressure measurements, therapeutic lifestyle changes and pharmacologic therapies.

  10. Herbal cocktail as anti-infective: promising therapeutic for the treatment of viral diseases.

    Science.gov (United States)

    Marathe, Sandhya A; Datey, Akshay A; Chakravortty, Dipshikha

    2012-08-01

    Herbal products have gained considerable interest among the pharmaceutical companies and consumers due to the minimal side effects associated with them. The bioflavanoids present in these products are the key players in modulating their effects. Several therapeutic effects have been attributed to the bioflavanoids present in green tea and turmeric. Antimicrobial activity is one among the spectrum of activities they exhibit. Curcumin and catechins, the principle components of turmeric and green tea respectively have virucidal and virustatic actions. An antimicrobial composition consisting of extracts from green tea and turmeric have shown to be highly potent against various microbes, especially viruses. In the present review, we have discussed the patents and the antiviral effects of curcumin and catechins. The antimalarial effect of curcumin has also been discussed.

  11. The Impact of Interpersonal Style on Ruptures and Repairs in the Therapeutic Alliance Between Offenders and Therapists in Sex Offender Treatment.

    Science.gov (United States)

    Watson, Rachael; Thomas, Stuart; Daffern, Michael

    2017-10-01

    The therapeutic relationship is a critical component of psychological treatment. Strain can occur in the relationship, particularly when working with offenders, and more specifically, those offenders with interpersonal difficulties; strain can lead to a rupture, which may affect treatment participation and performance. This study examined ruptures in the therapeutic relationship in sexual offenders participating in offense-focused group treatment. Fifty-four sex offenders rated the therapeutic alliance at the commencement and completion of treatment; at the completion of treatment, they also reported on the occurrence of ruptures and whether they believed these ruptures were repaired. Ruptures were separated by type, according to severity-Each relationship was therefore characterized as experiencing no rupture, a minor rupture, or a major rupture. Offender characteristics including interpersonal style (IPS) and psychopathy were assessed at the commencement of treatment; their relationship with ruptures was examined. Results revealed that more than half of the offenders (approximately 55%) experienced a rupture in the therapeutic alliance, with one in four of these ruptures remaining unresolved. Offenders who did not report a rupture rated the therapeutic alliance significantly higher at the end of treatment compared with those offenders who reported a rupture that was not repaired. Offenders who reported a major rupture in the therapeutic relationship were higher in interpersonal hostility and hostile-dominance. No interpersonal or offense-specific factors affected the likelihood of a rupture repair.

  12. Assessing therapeutic change in patients with severe dissociative disorders: the progress in treatment questionnaire, therapist and patient measures.

    Science.gov (United States)

    Schielke, Hugo; Brand, Bethany; Marsic, Angelika

    2017-01-01

    Background : Treatment research for dissociative identity disorder (DID) and closely related severe dissociative disorders (DD) is rare, and has been made more difficult by the lack of a reliable, valid measure for assessing treatment progress in these populations. Objective : This paper presents psychometric data for therapist and patient report measures developed to evaluate therapeutic progress and outcomes for individuals with DID and other DD: the Progress in Treatment Questionnaire - Therapist (PITQ-t; a therapist report measure) and the Progress in Treatment Questionnaire - Patient (PITQ-p; a patient self-report measure). Method : We examined the data of 177 patient-therapist pairs (total N  = 354) participating in the TOP DD Network Study, an online psychoeducation programme aimed at helping patients with DD establish safety, regulate emotions, and manage dissociative and posttraumatic symptoms. Results : The PITQ-t and PITQ-p demonstrated good internal consistency and evidence of moderate convergent validity in relation to established measures of emotional dysregulation, dissociation, posttraumatic stress disorder, and psychological quality of life, which are characteristic difficulties for DD patients. The measures also demonstrated significant relationships in the hypothesized directions with positive emotions, social relations, and self-harm and dangerous behaviours. The patient-completed PITQ-p, which may be used as an ongoing assessment measure to guide treatment planning, demonstrated evidence of stronger relationships with established symptom measures than the PITQ-t. Conclusions : The PITQ-t and PITQ-p merit use, additional research, and refinement in relation to the assessment of therapeutic progress with patients with DD.

  13. Study of the therapeutic dose and the clinical effect on Graves' disease with I-131 treatment

    International Nuclear Information System (INIS)

    Dang, Y.

    2005-01-01

    Full text: Graves' disease is being treated with I-131 for more than 40 years in China. Previously the dose of I-131 used to be calculated using the 'Quimby' formula. We have now observed that the dose of I-131 administered to patients is now lower in recent years than the early years. The radioactive iodine uptake by the thyroid gland has also changed significantly over a period of time. In this paper we intend to explore these reasons and to research the relationship between the dose and the effect as well as the main cause of the incidence of the hypothyroidism. The parameters in 'Quimby' formula including I-131 uptake, effective half-life and thyroid weight were analyzed and compared with each year data from 1961 to 1988 and subjected to multiple regression analysis to determine the influence on the calculation of dose in 4465 patients. The therapeutic effects were compared with the data of the clinical follow-up of patients between 1961-1973 and 1978-1988 in 748 patients. The factors which might lead to the hypothyroidism were investigated with the non-condition logistic regression. The I-131 uptake was repeatedly measured within one week in 100 patients to identify the changing pattern of the I-131 uptake and its influence on the administered therapeutic dose. We observed an increase in the value of I-131 uptake. The value of I-131 uptake showed an increase after 1977, as well as a prolongation of effective half-life after 1973. The main reason for these changes being a replacement of the equipment in 1977 (G-M counter tube was replaced by scintillation counter), and the other reason being salt iodization in China in 1973. These two factors resulted in a significant reduction in the administered dose of I-131 during the period 1974-1988 as compared to the previous period 1961-1973; the mean administered doses being 168.35MBq and 330.33MBq respectively. The result of multiple regression analyses suggested that the thyroid weight and the effective half

  14. Differentiated thyroid cancer treatment with therapeutic doses of 131I calculated by dosimetry: our experience

    International Nuclear Information System (INIS)

    Fadel, Ana M.; Chebel, G.M.; Valdivieso, C.M.; Degrossi, Osvaldo J.; Cabrejas, R.; Cabrejas, M.L.

    2006-01-01

    The optimum dose for the differentiated thyroid cancer treatment is a motive of controversy. There exist two ways of deciding the dose to administer: the empirical method (fixed doses) and dosimetric calculation method. The use of fixed doses has demonstrated safety and effectiveness. Nevertheless there are cases in which the use of several small doses not resolves the metastases illness of the patients. Using the Benua-Leeper method for dosimetric calculation we have evaluated the maximum dose treatment that could be administered to 20 patients who showed persistent disease after several treatments with 131 I. (author) [es

  15. THERAPEUTIC CAPABILITIES OF ETHANERCEPT IN TREATMENT OF SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    E.I. Alexeeva

    2011-01-01

    Full Text Available The article presents a clinical case of severe systemic juvenile rheumatoid arthritis, refractory to traditional immunosuppressive treatment and with insufficient efficacy of chimeric homogenous anti-TNF-a antibodies. The patient received 2 courses of anti-Blymphocyte’s- CD20-antibodies that helped to arrest all systemic manifestations of the disease. Articular syndrome was arrested only with the help of soluble receptors to TNF a — ethanercept, given in following dose — 0.4 mg per kg of body mass. The patient has been on treatment with ethanercept for 24 weeks. Joint tenderness and exudation were diminished already after the first 4 weeks of treatment, also there was a dramatic increase in joint motion range. After 6 months of therapy we have managed to improve the patients and his family quality of life.Key words: children, juvenile rheumatoid arthritis, ethanercept, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 141–149

  16. Effect of treatment duration on pharmacokinetic/pharmacodynamic indices correlating with therapeutic efficacy of ceftazidime in experimental Klebsiella pneumoniae lung infection

    NARCIS (Netherlands)

    I.A.J.M. Bakker-Woudenberg (Irma); M.T. ten Kate (Marian); W.H.F. Goessens (Wil); J.W. Mouton (Johan)

    2006-01-01

    textabstractThe pharmacokinetic/pharmacodynamic (PK/PD) indices that define the therapeutic effect of the betalactam ceftazidime in a rat model of Klebsiella pneumoniae lung infection were investigated in relation to treatment duration and treatment endpoint. Treatment was started 24 h after

  17. A therapeutic benefit from combining normobaric carbogen or oxygen with nicotinamide in fractionated X-ray treatments

    International Nuclear Information System (INIS)

    Kjellen, E.; Joiner, M.C.; Collier, J.M.; Johns, H.; Rojas, A.

    1991-01-01

    The ability of normobaric oxygen and carbogen (95 percent O 2 + 5 percent CO 2 ) combined with nicotinamide to enhance the radiosensitivity of two rodent adenocarcinomas and of mouse skin and kidneys was compared with the effects of radiation in air and without the drug. A comparison of the results in tumors and normal tissues showed that significant therapeutic benefit was obtained with normobaric oxygen and carbogen combined with nicotinamide. Toxic side effects of the treatment are unlikely, as prolonged administration of nicotinamide is well tolerated in man. The combination of normobaric carbogen with nicotinamide could be an effective method of enhancing tumor radiosensitivity in clinical radiotherapy where hypoxia limits the outcome of treatment. (author). 45 refs.; 4 fig.; 4 tabs

  18. Veterans in substance abuse treatment program self-initiate box gardening as a stress reducing therapeutic modality.

    Science.gov (United States)

    Lehmann, Lauren P; Detweiler, Jonna G; Detweiler, Mark B

    2018-02-01

    To assess the experiences of a veteran initiated horticultural therapy garden during their 28-day inpatient Substance Abuse Residential Rehabilitation Treatment Program (SARRTP). Retrospective study. Veterans Affairs Medical Center (VAMC), Salem, Virginia, USA INTERVENTIONS: Group interviews with veterans from the last SARRTP classes and individual interviews with VAMC greenhouse staff in summer of 2016. Time spent in garden, frequency of garden visits, types of passive and active garden activities, words describing the veterans' emotional reactions to utilizing the garden. In 3 summer months of 2016, 50 percent of the 56 veterans interviewed visited and interacted with the gardens during their free time. Frequency of visits generally varied from 3 times weekly to 1-2 times a day. Amount of time in the garden varied from 10min to 2h. The veterans engaged in active and/or passive gardening activities during their garden visits. The veterans reported feeling "calm", "serene", and "refreshed" during garden visitation and after leaving the garden. Although data was secured only at the end of the 2016 growing season, interviews of the inpatient veterans revealed that they used their own initiative and resources to continue the horticulture therapy program for 2 successive growing years after the original pilot project ended in 2014. These non-interventionist, therapeutic garden projects suggest the role of autonomy and patient initiative in recovery programs for veterans attending VAMC treatment programs and they also suggest the value of horticulture therapy as a meaningful evidence- based therapeutic modality for veterans. Published by Elsevier Ltd.

  19. Therapeutic potential of paclitaxel-radiation treatment of a murine ovarian carcinoma

    International Nuclear Information System (INIS)

    Milas, Luka; Saito, Yoshihiro; Hunter, Nancy; Milross, Christopher G.; Mason, Kathryn A.

    1996-01-01

    Background. Paclitaxel has been shown to radiosensitize tumor cells in culture by arresting them in the most radiosensitive G 2 and M cell cycle phases. In vivo preclinical studies are now necessary to obtain full insight into the radiopotentiating potential of this drug and its ability to increase the therapeutic gain of radiotherapy. We tested its ability to enhance the tumor radioresponse of an ovarian carcinoma and to influence the normal tissue radioresponse of recipient mice. Methods. Mice bearing 8-mm isotransplants of a syngeneic ovarian carcinoma, designated OCA-I, in their legs were treated with 40 mg/kg paclitaxel i.v., 14-60 Gy single-dose local tumor irradiation, or both; radiation was given under ambient conditions 1-96 h after paclitaxel. Tumor growth delay, tumor cure rate (TCD 50 assay), and delay in tumor recurrences were measured. Normal tissue radioresponse was determined using jejunal crypt cell survival at 3.5 days after exposure of mice to 9-14 Gy single dose of total body irradiation; the mice were untreated or treated with 40 mg/kg i.v. paclitaxel 4-96 h before irradiation. Results. Paclitaxel alone was effective against OCA-I, but its combination with irradiation produced supra-additive tumor growth delay. It also reduced TCD 50 values and delayed tumor recurrences. The enhancement of tumor radioresponse ranged from 1.33 to 1.96; the value increased as the time between paclitaxel administration and tumor irradiation increased up to 48 h, but then decreased again at 96 h. In contrast, paclitaxel protected jejunum against radiation damage by factors of 1.03 to 1.07 when given 24-96 h before irradiation. It showed some potentiation of damage (by a factor of 1.07), but only when given 4 h before irradiation. Conclusions. Paclitaxel potentiated tumor radioresponse if given within 4 days before irradiation, whereas it caused radioprotection of normal tissue (jejunum) at that time. Therefore, paclitaxel significantly increased therapeutic gain

  20. Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer’s disease: Experimental approach and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Jun eWang

    2014-03-01

    Full Text Available Alzheimer’s disease (AD is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol and Concord grape juice extract, with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ-induced long term potentiation (LTP deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.

  1. Nonsurgical treatment of hemifacial microsomia by therapeutic ultrasound and hybrid functional appliance

    Directory of Open Access Journals (Sweden)

    Tarek El-Bialy

    2010-03-01

    Full Text Available Tarek El-Bialy1, Ali Hasan2, Ahmad Janadas3, Tarik Albaghdadi41Division of Orthodontics, Department of Dentistry, University of Alberta, Edmonton, Alberta, Canada; 2Division of Orthodontics, Department of Preventive Dental Sciences, Faculty of Dentistry; 3Division of Oral and Maxillofacial Surgery, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry; 4Division of Radiology, Faculty of Medicine, King Abdul Aziz University, Jeddah, Saudi ArabiaAim: Conventional treatment of patients with hemifacial microsomia involves orthognathic surgery and/or distraction osteogenesis of the mandible. Previous reports showed that low-intensity pulsed ultrasound (LIPUS enhances mandibular growth in growing rabbits and monkeys. In monkeys, LIPUS enhanced mandibular growth when combined with functional jaw orthopedic appliances. The purpose of this pilot study was to investigate if LIPUS could enhance mandibular growth in children with hemifacial microsomia.Methods: Five children (age range 3–11 years with hemifacial microsomia were treated with hybrid jaw orthopedic functional appliances and treatment of the affected mandibular condyle by LIPUS for 20 minutes per day.Results: The results showed that after one year of treatment, significant improvement of the underdeveloped side of patients’ faces and mandibles was recognized both clinically and radiographically.Discussion: Although improvement took a longer time than did a surgical approach, optimizing this technique may achieve better results in a shorter treatment time. A randomized controlled clinical trial to investigate the effect of optimized LIPUS application or functional appliances in the treatment of hemifacial microsomia is warranted.Keywords: hemifacial microsomia, LIPUS, non-surgical treatment, children

  2. Targeting protein neddylation: a novel therapeutic strategy for the treatment of cancer.

    Science.gov (United States)

    Wang, Meng; Medeiros, Bruno C; Erba, Harry P; DeAngelo, Daniel J; Giles, Francis J; Swords, Ronan T

    2011-03-01

    The NEDD8 (neural precursor cell-expressed developmentally downregulated 8) conjugation pathway regulates the post-translational modification of oncogenic proteins. This pathway has important potential for cancer therapeutics. Several proteins vital in cancer biology are regulated by protein neddylation. These observations led to the development of a small molecule inhibitor that disrupts protein neddylation and leads to cancer cell death and important activity in early phase clinical trials. This review provides an extensive coverage of cellular protein homeostasis with particular emphasis on the NEDD8 conjugation pathway. Insights into a new investigational drug that specifically disrupts the NEDD8 pathway are discussed. The clinical data for this agent are also updated. Neddylation controls key cellular pathways found to be dysregulated in many cancers. Protein neddylation is a relatively under-explored pathway for pharmacologic inhibition in cancer. Selective disruption of this pathway has demonstrated clinical activity in patients with myeloid neoplasms and is worth exploring further in combination with other anti-leukemia agents.

  3. Endovenous treatment of primary varicose veins: an effective and safe therapeutic alternative to stripping?

    International Nuclear Information System (INIS)

    Kluner, C.; Fischer, T.; Filimonow, S.; Hamm, B.; Kroencke, T.

    2005-01-01

    Endovenous laser therapy (EVLT) is a new, minimally invasive therapeutic option for treating primary varicose veins and provides an effective and safe alternative to conventional surgical management (stripping). Short-term and intermediate-term outcome is comparable to surgical stripping in terms of elimination of venous reflux (90% - 98%), resolution of visible varices (85%), and improvement of subjective complaints such as sensations of heaviness and tension (96%). Complications occur in 1% - 3% of cases, which is markedly below the rate of conventional surgical management (up to 30%). The intermediate-term incidence of recurrent varicosis in a vein treated by EVLT depends on the laser fluence applied and is reported to range from 7% - 9% compared to 10% - 20% after surgical intervention. Based on a review of the current literature and our own experience, this survey article presents an overview of the indications and contraindications, the technique and pathophysiology of laser-induced venous occlusion, and the results and possible complications of EVLT. (orig.)

  4. Therapeutic Time Window for Edaravone Treatment of Traumatic Brain Injury in Mice

    Science.gov (United States)

    Miyamoto, Kazuyuki; Ohtaki, Hirokazu; Dohi, Kenji; Tsumuraya, Tomomi; Song, Dandan; Kiriyama, Keisuke; Satoh, Kazue; Shimizu, Ai; Aruga, Tohru; Shioda, Seiji

    2013-01-01

    Traumatic brain injury (TBI) is a major cause of death and disability in young people. No effective therapy is available to ameliorate its damaging effects. Our aim was to investigate the optimal therapeutic time window of edaravone, a free radical scavenger which is currently used in Japan. We also determined the temporal profile of reactive oxygen species (ROS) production, oxidative stress, and neuronal death. Male C57Bl/6 mice were subjected to a controlled cortical impact (CCI). Edaravone (3.0 mg/kg), or vehicle, was administered intravenously at 0, 3, or 6 hours following CCI. The production of superoxide radicals (O2 ∙−) as a marker of ROS, of nitrotyrosine (NT) as an indicator of oxidative stress, and neuronal death were measured for 24 hours following CCI. Superoxide radical production was clearly evident 3 hours after CCI, with oxidative stress and neuronal cell death becoming apparent after 6 hours. Edaravone administration after CCI resulted in a significant reduction in the injury volume and oxidative stress, particularly at the 3-hour time point. Moreover, the greatest decrease in O2 ∙− levels was observed when edaravone was administered 3 hours following CCI. These findings suggest that edaravone could prove clinically useful to ameliorate the devastating effects of TBI. PMID:23710445

  5. Therapeutic Time Window for Edaravone Treatment of Traumatic Brain Injury in Mice

    Directory of Open Access Journals (Sweden)

    Kazuyuki Miyamoto

    2013-01-01

    Full Text Available Traumatic brain injury (TBI is a major cause of death and disability in young people. No effective therapy is available to ameliorate its damaging effects. Our aim was to investigate the optimal therapeutic time window of edaravone, a free radical scavenger which is currently used in Japan. We also determined the temporal profile of reactive oxygen species (ROS production, oxidative stress, and neuronal death. Male C57Bl/6 mice were subjected to a controlled cortical impact (CCI. Edaravone (3.0 mg/kg, or vehicle, was administered intravenously at 0, 3, or 6 hours following CCI. The production of superoxide radicals (O2∙- as a marker of ROS, of nitrotyrosine (NT as an indicator of oxidative stress, and neuronal death were measured for 24 hours following CCI. Superoxide radical production was clearly evident 3 hours after CCI, with oxidative stress and neuronal cell death becoming apparent after 6 hours. Edaravone administration after CCI resulted in a significant reduction in the injury volume and oxidative stress, particularly at the 3-hour time point. Moreover, the greatest decrease in O2∙- levels was observed when edaravone was administered 3 hours following CCI. These findings suggest that edaravone could prove clinically useful to ameliorate the devastating effects of TBI.

  6. An Assessment of Prison-Based Drug Treatment; Texas' In-Prison Therapeutic Community Program.

    Science.gov (United States)

    Knight, Kevin; Simpson, D. Dwayne; Chatham, Lois R.; Camacho, L. Mabel

    1997-01-01

    Provides an overview of a comprehensive, prison-based treatment assessment, including a six-month follow-up study. Results show that 80% of the inmates referred to the program graduated. Graduates demonstrated marked reductions in criminal and drug-use activity and had lower relapse and recidivism rates when compared to other parolees. (RJM)

  7. Biofeedback as complementary treatment in patients with epilepsy – an underestimated therapeutic option? Review, results, discussion

    Directory of Open Access Journals (Sweden)

    Uhlmann Carmen

    2016-12-01

    Full Text Available Background. Biofeedback methods represent side effect free complementary options in the treatment of epilepsy. In this paper we review the current status of these methods in terms of clinical study results and their evaluation by systematic review papers. Possible mechanisms of action in biofeedback methods are discussed.

  8. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis

    NARCIS (Netherlands)

    Dorlo, Thomas P. C.; Balasegaram, Manica; Beijnen, Jos H.; de Vries, Peter J.

    2012-01-01

    Miltefosine is an alkylphosphocholine drug with demonstrated activity against various parasite species and cancer cells as well as some pathogenic bacteria and fungi. For 10 years it has been licensed in India for the treatment of visceral leishmaniasis (VL), a fatal neglected parasitic disease. It

  9. Strontium Ranelate Might be a Therapeutic Option for Treatment of CRPS

    OpenAIRE

    Malgorzata Brunner-Palka; Manfred Herold

    2017-01-01

    The postmenopausal osteoporosis of a 66-year-old female with long lasting end stage complex regional pain syndrome on the right hand was treated with strontium ranelate 2 grams daily. After few weeks of treatment an impressive improvement of pain and immobility of the right hand occurred.

  10. Therapeutic outcome after radioiodine and surgery treatment of toxic thyroid adenoma

    International Nuclear Information System (INIS)

    Petrovski, Zlatko P.

    2005-01-01

    Full text: Purpose: The aim of the study was to evaluate late follow-up results in surgery and radioiodine treatment of toxic thyroid adenoma and compare incidence of hypothyroidism and recurrence hyperthyroidism in treated patients. Material and Methods: We observed 93 treated patients (77 female, 26 male, age range 18-76 years) with adenoma toxicum. 29 (32.2 %) patients underwent surgery (adenectomia), while 64 (67.8 %) patients received 131 I therapy (555-1100 MBq).The long term results of the treatment were followed 1-15 years after therapy (median 9,2 years). Results: Recurrent hyperthyroidism occurred in 4/29 (13.8%) patients after surgery adenectomia in comparison to 5/64 (7.8 %) patients after radioiodine therapy. The patients after enucleation of autonomous nodule of the thyroid show increase incidence of late recurrent hyperthyroidism. These results are likely to be due to persistent functional autonomy in the parenchyma surrounding the autonomous adenoma. Apparently this persistent autonomy could be successfully removed by radioiodine. Appear of hypothyroidism was observed in 6/64 (9.3 %) patients treated with 131 I, while after surgery had in 3/29 (10.3 %) patients. Incidence of hypothyroidism between operated patients and radioiodine treated patients was approximately the same. Conclusion: Radioiodine therapy is useful, economical and effective treatment of toxic thyroid adenoma that provides a safe protection in preventing late recurrent hyperthyroidism and is more successful therapy that surgery treatment. (author)

  11. Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    2016-01-01

    Full Text Available Objective. Spinal cord injury (SCI is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI, as well as from master’s dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment.

  12. The effects of treatment adherence and treatment-specific therapeutic competencies on outcome and goal attainment in telephone-based therapy with caregivers of people with dementia.

    Science.gov (United States)

    Schinköthe, Denise; Altmann, Uwe; Wilz, Gabriele

    2015-01-01

    Contradictory results have been found for the impact of therapist's adherence and competence on intervention outcomes. Most studies focus on generic aspects of competence and adherence, rather than taking into account treatment-specific aspects or specific challenges of the clientele. Appropriate analyses are lacking for cognitive behavioral therapy (CBT) with caregivers of people with dementia. In a sample of 43 caregivers, we examined adherence and different competence ratings of 80 complete sessions, as predictors of symptom change and goal attainment. Therapist's competence was evaluated by four raters, using an adapted version of the cognitive therapy scale (CTS) on three subscales of competence: General therapeutic (GT), session-structuring (SS), and treatment-specific CBT technique (CT). Therapist's adherence to the manual was also assessed. The results show that GT competencies were associated with lower post-test depression scores and that CT competencies predicted a decrease in caregiver burden and higher goal attainment, while SS competencies predicted higher post-test burden. Therapist's adherence had no relationship to outcome, but the higher application of modifying dysfunctional thoughts was associated with higher goal attainment. The results suggest the importance of treatment-specific competencies for outcome. Future research should identify empirically what kind of therapeutic behavior is appropriate to the challenges of a specific clientele such as caregivers of people with dementia.

  13. Therapeutic eyelids hygiene in the algorithms of prevention and treatment of ocular surface diseases

    Directory of Open Access Journals (Sweden)

    V. N. Trubilin

    2016-01-01

    Full Text Available When acute inflammation in anterior eye segment of a forward piece of an eye was stopped, ophthalmologists face a problem of absence of acute inflammation signs and at the same time complaints to the remain discomfort feelings. It causes dissatisfaction from the treatment. The complaints are typically caused by disturbance of tears productions. No accidental that the new group of diseases was allocated — the diseases of the ocular surface. Ocular surface is a difficult biologic system, including epithelium of the conjunctiva, cornea and limb, as well as the area costal margin eyelid and meibomian gland ducts. Pathological processes in conjunctiva, cornea and eyelids are linked with tears production. Ophthalmologists prescribes tears substitutions, providing short-term relief to patients. However, in respect that the lipid component of the tear film plays the key role in the preservation of its stability, eyelids hygiene is the basis for the treatment of dry eye associated with ocular surface diseases. Eyelids hygiene provides normal functioning of glands, restores the metabolic processes in skin and ensures the formation of a complete tear film. Protection of eyelids, especially the marginal edge from aggressive environmental agents, infections and parasites and is the basis for the prevention and treatment of blepharitis and dry eye syndrome. The most common clinical situations and algorithms of their treatment and prevention of dysfunction of the meibomian glands; demodectic blepharitis; seborrheic blepharitis; staphylococcal blepharitis; allergic blepharitis; barley and chalazion are discussed in the article. The prevention keratoconjunctival xerosis (before and postoperative period, caused by contact lenses, computer vision syndrome, remission after acute conjunctiva and cornea inflammation is also presented. The first part of the article presents the treatment and prevention algorithms for dysfunction of the meibomian glands, as well as

  14. A Novel Therapeutic Strategy for the Treatment of Glioma, Combining Chemical and Molecular Targeting of Hsp90α

    International Nuclear Information System (INIS)

    Mehta, Adi; Shervington, Leroy; Munje, Chinmay; Shervington, Amal

    2011-01-01

    Hsp90α's vital role in tumour survival and progression, together with its highly inducible expression profile in gliomas and its absence in normal tissue and cell lines validates it as a therapeutic target for glioma. Hsp90α was downregulated using the post-transcriptional RNAi strategy (sihsp90α) and a post-translational inhibitor, the benzoquinone antibiotic 17-AAG. Glioblastoma U87-MG and normal human astrocyte SVGp12 were treated with sihsp90α, 17-AAG and concurrent sihsp90α/17-AAG (combined treatment). Both Hsp90α gene silencing and the protein inhibitor approaches resulted in a dramatic reduction in cell viability. Results showed that sihsp90α, 17-AAG and a combination of sihsp90α/17-AAG, reduced cell viability by 27%, 75% and 88% (p < 0.001), respectively, after 72 h. hsp90α mRNA copy numbers were downregulated by 65%, 90% and 99% after 72 h treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG, respectively. The relationship between Hsp90α protein expression and its client Akt kinase activity levels were monitored following treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG. Akt kinase activity was downregulated as a direct consequence of Hsp90α inhibition. Both Hsp90α and Akt kinase levels were significantly downregulated after 72 h. Although, 17-AAG when used as a single agent reduces the Hsp90α protein and the Akt kinase levels, the efficacy demonstrated by combinatorial treatment was found to be far more effective. Combination treatment reduced the Hsp90α protein and Akt kinase levels to 4.3% and 43%, respectively, after 72 h. hsp90α mRNA expression detected in SVGp12 was negligible compared to U87-MG, also, the combination treatment did not compromise the normal cell viability. Taking into account the role of Hsp90α in tumour progression and the involvement of Akt kinase in cell signalling and the anti-apoptotic pathways in tumours, this double targets treatment infers a novel therapeutic strategy

  15. Therapeutic plasma exchange: an effective treatment in ethylene dibromide poisoning cases.

    Science.gov (United States)

    Pahwa, Naresh; Bharani, Rajesh; Jain, Manish; Argal, Suarabh; Soni, Harish; Kosta, Susmit; Kumar, Ravindra

    2013-10-01

    Ethylene dibromide (EDB) poisoning is very common in Central India and has fatal outcome. EDB is highly protein bound and, therefore, it is suggested that therapeutic plasma exchange (TPE) may be useful in removing drug from body shortly after ingestion before EDB metabolizes and causes severe end organ damage. The aim of our study is to find the effect of time of start of TPE on survival outcome of EDB poisoning cases. Fifty-eight cases of EDB poisoning were reviewed from 2007 to 2012 in Department of critical care medicine in tertiary care hospitals at Indore. Five patients were discharged against medical advice and lost to follow up. TPE was done in 47 patients as early as possible and irrespective of appearance of clinical symptoms. TPE was not performed in six cases as they were hypotensive at admission. The patients with EDB poisoning were 15-45 yrs old with 3:2 male to female ratio. Out of 47 who received TPE, 39 patients survived. TPE had started within 24 h of ingestions of EDB in 36 out of 39 survived patients. Survival outcome was nine times higher in patients who received TPE within 24 h than after 24 h of ingestion. Survival rate was increased to 100% in patients where TPE was done within 12 h of ingestion of EDB. Early TPE help to remove plasma protein bound toxin with significant mortality reduction. However, delay in start of TPE after ingestion of poison has significant poor survival outcome. Copyright © 2013 Wiley Periodicals, Inc.

  16. Therapeutic effect of minimally invasive intracranial hematoma evacuation in the treatment of hypertensive cerebral hemorrhage and TCD evaluation

    Directory of Open Access Journals (Sweden)

    Zi-Hao Zhang

    2017-06-01

    Full Text Available Objective: To explore the therapeutic effect of minimally invasive intracranial hematoma evacuation in the treatment of hypertensive cerebral hemorrhage and the value of dynamic TCD monitoring in predicting the neurological function recovery. Methods: A total of 70 patients with hypertensive cerebral hemorrhage who were admitted in our hospital were included in the study and divided into the minimally invasive group and conservative group with 35 cases in each group according to different treatment protocols. The patients in the two groups were given drug conservative treatments. On this basis, the patients in the minimally invasive group were given urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle. TCD was performed before treatment, 1 d, 5 d, 10 d, and 21 d after treatment. The hematoma and edema volume was calculated. NIHSS was used to evaluate the neurological function recovery. Results: Vs, Vd, and Vm after treatment in the minimally invasive group were significantly elevated, while PI was significantly reduced. Vs, Vd, and Vm after treatment in the conservative group were reduced first and elevated later, while PI was elevated first and reduced later, and reached the lowest/peak 10d after treatment. Vs, Vd, and Vm 5 d, 10 d, and 21 d after treatment in the minimally invasive group were significantly higher than those in the conservative group, while PI was significantly lower than that in the conservative group. The hematoma and edema volume after treatment in the two groups was significantly reduced. The hematoma and edema volume at each timing point was significantly lower than that in the conservative group. NIHSS score after treatment in the minimally invasive group was significantly reduced. NIHSS score in the conservative group was elevated first and reduced later, reached the peak 10d after treatment, and at each timing point was higher than that in the minimally invasive group. Conclusions: The

  17. A Comparison of Therapeutic and Anti-inflammatory Properties of Triamcinolone and Placebo (Vitamin A in Treatment of Paederus Dermatitis

    Directory of Open Access Journals (Sweden)

    Seyed Hasan Nikookar

    2014-09-01

    Full Text Available Abstract Background and purpose: Paederus associated dermatitis has always been considered as a health problem in the northern of Iran. Since until now, the traditional method and some corticosteroids have been used in the treatment of Paederus dermatitis (PD and no comprehensive studies have been carried out on the new method of treatment. Therefore, this study was aimed to compare the anti-inflammatory effects of triamcinolone with placebo in treatment of PD. Materials and Methods: This randomized double-blind clinical trial was performed during 6 months period in the clinics of Sari and Neka, Iran. Experimental group received triamcinolone and control group received placebo. The therapeutic effects of topically applied triamcinolone in 15 dermatitis patients and 15 control subjects were compared. The study subjects were visited in three separate times in the 1st, 7th and 14th day of the treatment. The data were collected in the questionnaire and compared in both groups by introducing the data into SPSS 11 software and analyzed by means of χ 2 test. Results: A total of 15 patients, 10 and 5 cases were undertaken for treatment in the Sari and Neka Townships, respectively. 40% and 50% of the patients from Sari and Neka Townships had lesion size 6-10 cm2, respectively. In this study, 90% and 100% of the patients from Sari and Neka had complete recovery 7 days after treatment, respectively. Statistical analysis indicated a significant difference between the case and control groups (P < 0.05. Conclusion: Insignificant difference was observed for treatment between the patients from the two Townships under study.

  18. Therapeutic Potential of Cholera Toxin B Subunit for the Treatment of Inflammatory Diseases of the Mucosa

    Directory of Open Access Journals (Sweden)

    Joshua M. Royal

    2017-11-01

    Full Text Available Cholera toxin B subunit (CTB is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine and vaccine development for decades. On the other hand, several studies have investigated CTB’s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn’s disease and asthma. Furthermore, we recently found that a variant of CTB could induce colon epithelial wound healing in mouse colitis models. This review summarizes the possible mechanisms behind CTB’s anti-inflammatory activity and discuss how the protein could impact mucosal inflammatory disease treatment.

  19. Dosimetric verification of a software for planning of radio therapeutical treatments

    International Nuclear Information System (INIS)

    Alfonso, R.; Huerta, U.; Alfonso, J.L.; Torres, M.

    1995-01-01

    A software for radiation treatment planning was recently developed by medical physicists at the Hermanos Ameijeiras Hospital in Havana. Selected locations in head and neck region were used to evaluate the reliability of calculated dose distributions in patients, taking as a reference the results of dosimetric measurements with TLD-700 powder in a RANDO type phantom. The different options is shown. Causes of discrepancies are analyzed and recommendations are made for the use of data acquisitions options

  20. Therapeutic Potential of Curcumin in Treatment of Pancreatic Cancer: Current Status and Future Perspectives.

    Science.gov (United States)

    Hosseini, Mina; Hassanian, Seyed Mahdi; Mohammadzadeh, Elham; ShahidSales, Soodabeh; Maftouh, Mina; Fayazbakhsh, Hasan; Khazaei, Majid; Avan, Amir

    2017-07-01

    Pancreatic cancer is among the leading cause of deaths due to cancer with extremely poor prognosis. Gemcitabine is being used in the treatment of patient with pancreatic ductal adenocarcinoma (PDAC), although, the response rate is bellow 12%. A recent phase III trial revealed that FOLFIRINOX could be an option for the treatment of metastatic PDAC patients, although it is associated with increased toxicity. Therefore, identification of novel agents that either improves gemcitabine activity, within novel combinatorial approaches, or with a better efficacy than gemcitabine is warranted. The antitumor activity of curcumin in several tumors, including prostate, breast and colorectal cancers have investigated. A recent phase II trial explored the effects of curcumin in advanced pancreatic cancer patient. They found that oral curcumin was well tolerated. Another trial showed the activity of 8,000 mg of curcumin in combination with gemcitabine in patients with advanced pancreatic cancer. This review summarizes the current knowledge about possible molecular mechanisms of curcumin in PDAC with particular emphasis on preclinical/clinical studies in pancreatic cancer treatment. J. Cell. Biochem. 118: 1634-1638, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Current and developing therapeutic agents in the treatment of Chagas disease

    Directory of Open Access Journals (Sweden)

    Werner Apt

    2010-09-01

    Full Text Available Werner AptUniversity of Chile, Faculty of Medicine, Santiago, ChileAbstract: Chagas disease must be treated in all its stages: acute, indeterminate, chronic, and initial and middle determinant chronic, due to the fact that DNA of the parasite can be demonstrated by PCR in chronic cases, where optical microscopy does not detect parasites. Nifurtimox (NF and benznidazole (BNZ are the drugs accepted to treat humans based upon ethical considerations and efficiency. However, both the drugs produce secondary effects in 30% of the cases, and the treatment must be given for at least 30–60 days. Other useful drugs are itraconazole and posaconazole. The latter may be the drug to treat Chagas disease in the future when all the investigations related to it are finished. At present, there is no criterion of cure for chronic cases since in the majority, the serology remains positive, although it may decrease. In acute cases, 70% cure with NF and 75% with BNZ is achieved. In congenital cases, 100% cure is obtained if the treatment is performed during the first year of life. In chronic acquired cases, 20% cure and 50% improvement of the electrocardiographic changes are obtained with itraconazole.Keywords: Chagas disease, treatment, nifurtimox, benznidazole, allopurinol, itraconazole, posaconazole

  2. [Clinical and therapeutical considerations regarding the diagnosis and treatment in meconial disease].

    Science.gov (United States)

    Sabetay, C; Ciobanu, O; Zavate, A; Ciucă, M; Malos, A; Marin-Diu, B

    2010-01-01

    The meconium disease represents a problem of great impact over the vital prognosis of the newborn, the mortality of this disease being rated in various studies between 30 and 50%. The meconial disease that reunites the meconial ileus and the meconial peritonitis is often associated with cystic fibrosis a disease of general impact over the entire organism increasing the gravity and influencing the vital prognosis of these patients. The authors' purpose is to evaluate the results obtained after the treatment of the meconial disease in the Pediatric Surgery Clinic of the Emergency Hospital of Craiova over a period of 10 years. The study has been made on a number of 16 cases of meconial ileus, plug and peritonitis analising the difficulty of the diagnostic process, the preoperative care as well as the possibilities of surgical treatment. The surgical treatment is composed of multiple procedures including simple suture of the bowel defect and segmentary bowel resections with primary anastomosis and/or secondary anastomosis after ileostoma. The mortality on the studied cases was of 37.5% despite recent progresses achieved in postoperative care of these type of patients.

  3. Pathogenesis and therapeutic approaches for improved topical treatment in localized scleroderma and systemic sclerosis.

    Science.gov (United States)

    Badea, I; Taylor, M; Rosenberg, A; Foldvari, M

    2009-03-01

    SSc is a chronic progressive disorder of unknown aetiology characterized by excess synthesis and deposition of collagen and other extracellular matrix components in a variety of tissues and organs. Localized scleroderma (LS) differs from SSc in that with LS only skin and occasionally subcutaneous tissues are involved. Although rarely life threatening, LS can be disfiguring and disabling and, consequently, can adversely affect quality of life. There is no known effective treatment for LS, and various options, including, as examples, corticosteroids and other immunomodulatory agents, ultraviolet radiation and vitamin D analogues, are of unproven efficacy. Clinical trials evaluating combination therapy such as corticosteroids with MTX or UVA1 exposure with psoralens have not been established as consistently effective. New immunomodulators such as tacrolimus and thalidomide are also being evaluated. A better understanding of the molecular and cellular mechanisms of LS has led to evaluation of new treatments that modulate profibrotic cytokines such as TGF-beta and IL-4, regulate assembly and deposition of extracellular matrix components, and restore Th1/Th2 immune balance by administering IL-12 or IFN-gamma. IFN-gamma acts by directly inhibiting collagen synthesis and by restoring immune balance. In this review, we evaluate current and future treatment options for LS and cutaneous involvement in SSc. Recent advances in therapy focus mainly on anti-fibrotic agents. Delivery of these drugs into the skin as the target tissue might be a key factor in developing more effective and safer therapy.

  4. Glycogen Synthase Kinase 3β Inhibition as a Therapeutic Approach in the Treatment of Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Liang Ma

    2013-08-01

    Full Text Available Alternative strategies beyond current chemotherapy and radiation therapy regimens are needed in the treatment of advanced stage and recurrent endometrial cancers. There is considerable promise for biologic agents targeting the extracellular signal-regulated kinase (ERK pathway for treatment of these cancers. Many downstream substrates of the ERK signaling pathway, such as glycogen synthase kinase 3β (GSK3β, and their roles in endometrial carcinogenesis have not yet been investigated. In this study, we tested the importance of GSK3β inhibition in endometrial cancer cell lines and in vivo models. Inhibition of GSK3β by either lithium chloride (LiCl or specific GSK3β inhibitor VIII showed cytostatic and cytotoxic effects on multiple endometrial cancer cell lines, with little effect on the immortalized normal endometrial cell line. Flow cytometry and immunofluorescence revealed a G2/M cell cycle arrest in both type I (AN3CA, KLE, and RL952 and type II (ARK1 endometrial cancer cell lines. In addition, LiCl pre-treatment sensitized AN3CA cells to the chemotherapy agent paclitaxel. Administration of LiCl to AN3CA tumor-bearing mice resulted in partial or complete regression of some tumors. Thus, GSK3β activity is associated with endometrial cancer tumorigenesis and its pharmacologic inhibition reduces cell proliferation and tumor growth.

  5. Prevention and treatment of allergic asthma in pregnancy: from conventional drugs to new therapeutical approaches.

    Science.gov (United States)

    Cadavid, Angela P; Bannenberg, Gérard L; Arck, Petra C; Fitzgerald, Justine S; Markert, Udo R

    2011-05-01

    Different conventional anti-asthmatic and anti-allergic drugs are commonly used in pregnancy, including inhaled corticosteroids, long- and short-acting β-agonists, leukotriene modifiers, cromolyn, and theophylline. Alternatively, immunotherapy with allergens before and during pregnancy is accepted as a causal treatment of allergies, but the allergy specifity and severity in combination with a variety of application protocols and procedures cause wide heterogenity of this treatment principle. Furthermore, the pharmacokinetic characteristics and the US Food and Drug Administration (FDA) classification of conventional anti-allergic drugs and immunological implications of immunotherapy are summarized in this review, and insights on fetal programming of allergies are introduced. We propose a potential perspective of treatment with anti-inflammatory and pro-resolving mediators, such as lipoxins, resolvins and protectins; these are lipid mediators physiologically generated during the immune response from arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid. This proposal fits with the recently appreciated approaches to allergy prevention for the newborn child by a balanced maternal nutrition and omega-3 long-chain polyunsaturated fatty acid consumption.

  6. Study and evaluation of radiometry in photo therapeutic treatment of the neonatal hyperbilirubinaemia; Estudo e avaliacao da radiometria no tratamento fototerapico da hiperbilirrubinemia neonatal

    Energy Technology Data Exchange (ETDEWEB)

    Caly, Jose Pucci

    2009-07-01

    Phototherapy is a procedure established more than 50 years ago in the treatment of the newborn jaundice. However there is no a standard method to quantify the photo therapeutic dose in published clinical studies, hindering the comparison of previous studies on photo therapeutic effectiveness, as well as the establishment of safe and predictable doses. The photo therapeutic dose depends, among other factors, on the effective mean irradiance produced by the photo therapeutic unit. There are no standard procedures, however, neither to quantify the effective irradiance, nor to estimate the mean effective irradiance. As a consequence, large measurement variations in a same photo therapeutic unit are observed using different commercially available radiometers, as a consequence of the vast diversity of spectral responsivities of the instruments. An objective of this work was to adapt and to apply the bases of the wideband ultraviolet radiometry to quantify the available irradiance from photo therapeutic units, establishing procedures that allow us to compare measured irradiances from different sources, using radiometers presenting different spectral responsivities. Another objective was to characterize samples of photo therapeutic units commonly used, focusing the problem of the estimation of the effective mean irradiance from photo therapeutic units, proposing a method to estimate of the effective irradiance from focused sources. The experimental results allow us to conclude that it is not only necessary to standardize the photo therapeutic radiometry, but also the method of estimation of the effective mean irradiance. (author)

  7. Robustness of solvent/detergent treatment of plasma derivatives: a data collection from Plasma Protein Therapeutics Association member companies.

    Science.gov (United States)

    Dichtelmüller, Herbert O; Biesert, Lothar; Fabbrizzi, Fabrizio; Gajardo, Rodrigo; Gröner, Albrecht; von Hoegen, Ilka; Jorquera, Juan I; Kempf, Christoph; Kreil, Thomas R; Pifat, Dominique; Osheroff, Wendy; Poelsler, Gerhard

    2009-09-01

    Solvent/detergent (S/D) treatment is an established virus inactivation technology that has been applied in the manufacture of medicinal products derived from human plasma for more than 20 years. Data on the inactivation of enveloped viruses by S/D treatment collected from seven Plasma Protein Therapeutics Association member companies demonstrate the robustness, reliability, and efficacy of this virus inactivation method. The results from 308 studies reflecting production conditions as well as technical variables significantly beyond the product release specification were evaluated for virus inactivation, comprising different combinations of solvent and detergent (tri(n-butyl) phosphate [TNBP]/Tween 80, TNBP/Triton X-100, TNBP/Na-cholate) and different products (Factor [F]VIII, F IX, and intravenous and intramuscular immunoglobulins). Neither product class, process temperature, protein concentration, nor pH value has a significant impact on virus inactivation. A variable that did appear to be critical was the concentration of solvent and detergent. The data presented here demonstrate the robustness of virus inactivation by S/D treatment for a broad spectrum of enveloped test viruses and process variables. Our data substantiate the fact that no transmission of viruses such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or of other enveloped viruses was reported for licensed plasma derivatives since the introduction of S/D treatment.

  8. Sexuality issues in gynaecological oncology patients: post treatment symptoms and therapeutic options.

    Science.gov (United States)

    Iavazzo, C; Johnson, K; Savage, H; Gallagher, S; Datta, M; Winter-Roach, B A

    2015-03-01

    According to recent studies up to 80% of patients would like to receive more information about how cancer treatments can affect their sexual functioning. Moreover, 75 % of them would not feel comfortable being the first to bring up the subject. Our Gynaecological Advice Clinic was established in 2006 at the Christie Hospital and offers support to cancer patients who face sexuality issues. A previous evaluation established that the service sees approximately, 200 patients per year. The aims of this study are to evaluate the service by collecting data relating to levels of attendance, type and amount of clinical activity and to explore further patients' experiences and management. This is a retrospective study which was carried out in 2012-2013. Different models are used to evaluate our patients including history taking integrated therapy model, consultations to understand the normal anatomy and physiology with the use of diagrams and photographs, psycho-education and the international classification "Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition" (DSMV). The treatment options advised include medications such as hormone replacement treatment, testosterone, antidepressant, local oestrogen, tibolone, aqueous cream, lubrication to introitus, diprobase, dermal cream and advice for massage to areas of discomfort. Moreover, the use of vaginal dilators, the role of pelvic floor exercises, vulval care and self examination are explained. The team works closely with the psycho-oncology department. The most frequently discussed topics that were covered during the consultation are analysed. 41 outpatient clinics were held between 2012 and 2013. 194 patients attended those clinics during the study period. Single and not group therapy was offered to all the participants. 216 patients were offered appointments while 194 patients actually attended (90%). Patients' age ranged from 24 to 91 years with a mean age of 59 years. 45% had endometrial and 32% cervical

  9. Assessment of therapeutic response and treatment planning for brain tumors using metabolic and physiological MRI.

    Science.gov (United States)

    Nelson, Sarah J

    2011-07-01

    MRI is routinely used for diagnosis, treatment planning and assessment of response to therapy for patients with glioma. Gliomas are spatially heterogeneous and infiltrative lesions that are quite variable in terms of their response to therapy. Patients classified as having low-grade histology have a median overall survival of 7 years or more, but need to be monitored carefully to make sure that their tumor does not upgrade to a more malignant phenotype. Patients with the most aggressive grade IV histology have a median overall survival of 12-15 months and often undergo multiple surgeries and adjuvant therapies in an attempt to control their disease. Despite improvements in the spatial resolution and sensitivity of anatomic images, there remain considerable ambiguities in the interpretation of changes in the size of the gadolinium-enhancing lesion on T(1) -weighted images as a measure of treatment response, and in differentiating between treatment effects and infiltrating tumor within the larger T(2) lesion. The planning of focal therapies, such as surgery, radiation and targeted drug delivery, as well as a more reliable assessment of the response to therapy, would benefit considerably from the integration of metabolic and physiological imaging techniques into routine clinical MR examinations. Advanced methods that have been shown to provide valuable data for patients with glioma are diffusion, perfusion and spectroscopic imaging. Multiparametric examinations that include the acquisition of such data are able to assess tumor cellularity, hypoxia, disruption of normal tissue architecture, changes in vascular density and vessel permeability, in addition to the standard measures of changes in the volume of enhancing and nonenhancing anatomic lesions. This is particularly critical for the interpretation of the results of Phase I and Phase II clinical trials of novel therapies, which are increasingly including agents that are designed to have anti-angiogenic and anti

  10. [Comparison of the therapeutic effects of PTBD and PTBS in treatment of malignant obstructive jaundice].

    Science.gov (United States)

    Bai, Ai-Guo; Zheng, Chuan-Sheng; Zhou, Guo-Feng; Liang, Hui-Min; Feng, Gan-Sheng

    2010-06-01

    To summarize and compare the short-term and long-term clinical efficacy of percutaneous transhepatic biliary drainage (PTBD) and percutaneous transhepatic biliary stent (PTBS) in the treatment of malignant obstructive jaundice. 210 cases of malignant obstructive jaundice underwent interventional therapy, of which 161 cases of drainage catheters placement and 49 cases of metallic stent implantation. Follow-up information was obtained through telephone review or check-up records. The technical success rate of technique was 100%. At 3 - 5 days after treatment, the serum total bilirubin in 15 metallic stent-treated patients was decreased by (178.04 +/- 42.32) micromol/L, and direct bilirubin by (83.97 +/- 23.63) micromol/L. Compared with those of 28 cases treated with drainage catheters: (95.67 +/- 34.28) micromol/L and (49.84 +/- 28.21) micromol/L, there were statistically significant differences between the two groups (P = 0.017 and P = 0.035). At 6 - 9 days after treatment, the serum total bilirubin in 28 cases of metallic stent group was decreased by (188.22 +/- 79.90) micromol/L, and that in 126 cases of drainage catheter group decreased by (141.39 +/- 65.32) micromol/L. The difference was statistically significant (P = 0.014). But the decline value of direct bilirubin had no significant difference. The median patency period and the median survival time of the drainage catheter group were 60 and 148 days, respectively, those of metallic stent group were 197 days and 245 days. There were statistically significant differences between the two groups (P < 0.05). The results of this study indicate that the short-term and long-term efficacies of metallic stent implantation are better than those of catheter drainage technique.

  11. Oral soft tissue infections: causes, therapeutic approaches and microbiological spectrum with focus on antibiotic treatment.

    Science.gov (United States)

    Götz, Carolin; Reinhart, Edeltraud; Wolff, Klaus-Dietrich; Kolk, Andreas

    2015-11-01

    Intraoral soft tissue infections (OSTI) are a common problem in dentistry and oral surgery. These abscesses are mostly exacerbated dental infections (OIDC), and some emerge as postoperative infections (POI) after tooth extraction (OITR) or apicoectomy (OIRR). The main aim of this study was to compare OIDC with POI, especially looking at the bacteria involved. An additional question was, therefore, if different antibiotic treatments should be used with OSTI of differing aetiologies. The impact of third molars on OSTI was evaluated and also the rates of POI after removal of third molars were specified. Patient data was collected from the patients' medical records and the results were statistically evaluated with SPSS (SPSS version 21.0; SPSS, IBM; Chicago, IL, USA). The inclusion criterion was the outpatient treatment of a patient with an exacerbated oral infection; the exclusion criteria were an early stage of infiltration without abscess formation; and a need for inpatient treatment. Periapical exacerbated infections, especially in the molar region were the commonest cause of OIDC. In the OITR group, mandibular tooth removal was the commonest factor (p=0.016). Remarkably, retained lower wisdom teeth led to significant number of cases in the OITR group (p=0.022). In our study we could not define differences between the causal bacteria found in patients with OIDC and POI. Due to resistance rates we conclude that amoxicillin combined with clavulanic acid seems to be the antibiotic standard for exacerbated intraoral infections independent of their aetiology. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  12. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.

    Science.gov (United States)

    Langdahl, Bente; Ferrari, Serge; Dempster, David W

    2016-12-01

    The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that

  13. The therapeutic potential of escitalopram in the treatment of panic disorder

    Directory of Open Access Journals (Sweden)

    Mark H Townsend

    2007-01-01

    Full Text Available Mark H Townsend, Erich J ConradDepartment of Psychiatry, Louisiana State University Health Sciences Center New Orleans, New Orleans, Louisiana, USAAbstract: Panic disorder is a chronic and disabling condition that is often accompanied by other psychiatric and medical conditions. The serotonin reuptake inhibitors (SSRIs and serotoninnorepinephrine reuptake inhibitors (SNRIs have been used effectively with panic disorder (PD and conditions in which panic attacks frequently occur. Escitalopram is the most selective SSRI and a variety of evidence suggests it is of great value in the treatment of panic disorder. In this paper, we review the theoretical and practical implications of its use.Keywords: panic disorder, escitalopram, antidepressant, serotonin

  14. Treatment of acquired arteriovenous fistula with severe hemodynamic effects: therapeutic challenge

    Directory of Open Access Journals (Sweden)

    Bruna Ferreira Pilan

    2014-03-01

    Full Text Available A 34-year-old female patient with severe heart failure and pulmonary hypertension was diagnosed late with a high-output acquired arteriovenous fistula between the right common iliac vein and artery. The most probable cause was an iatrogenic vascular injury inflicted during a prior laparoscopic cholecystectomy. Treatment was conducted by placement of an endoprosthesis in the common iliac artery, achieving total exclusion of the fistula and complete remission of symptoms. Considering the options available for treating this type of lesion, endovascular techniques are becoming ever more effective and are now the option of first-choice for management of this pathology.

  15. Curcumin as therapeutics for the treatment of head and neck squamous cell carcinoma by activating SIRT1

    Science.gov (United States)

    Hu, An; Huang, Jing-Juan; Li, Rui-Lin; Lu, Zhao-Yang; Duan, Jun-Li; Xu, Wei-Hua; Chen, Xiao-Ping; Fan, Jing-Ping

    2015-01-01

    SIRT1 is one of seven mammalian homologs of Sir2 that catalyzes NAD+-dependent protein deacetylation. The aim of the present study is to explore the effect of SIRT1 small molecule activator on the anticancer activity and the underlying mechanism. We examined the anticancer activity of a novel oral agent, curcumin, which is the principal active ingredient of the traditional Chinese herb Curcuma Longa. Treatment of FaDu and Cal27 cells with curcumin inhibited growth and induced apoptosis. Mechanistic studies showed that anticancer activity of curcumin is associated with decrease in migration of HNSCC and associated angiogenesis through activating of intrinsic apoptotic pathway (caspase-9) and extrinsic apoptotic pathway (caspase-8). Our data demonstrating that anticancer activity of curcumin is linked to the activation of the ATM/CHK2 pathway and the inhibition of nuclear factor-κB. Finally, increasing SIRT1 through small molecule activator curcumin has shown beneficial effects in xenograft mouse model, indicating that SIRT1 may represent an attractive therapeutic target. Our studies provide the preclinical rationale for novel therapeutics targeting SIRT1 in HNSCC. PMID:26299580

  16. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

    Full Text Available Objective. Layered double hydroxide (LDH nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML, 5-FU/LDH (FL, and (MTX + 5-FU/LDH (MFL nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

  17. Combination Therapy With Histone Deacetylase Inhibitors (HDACi for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi

    Directory of Open Access Journals (Sweden)

    Amila Suraweera

    2018-03-01

    Full Text Available Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi, a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, HDACi have shown limited success in treating solid tumors. The combination of HDACi with standard chemotherapeutic drugs has demonstrated promising anticancer effects in both preclinical and clinical studies. In this review, we summarize the research thus far on HDACi in combination therapy, with other anticancer agents and their translation into preclinical and clinical studies. We additionally highlight the side effects associated with HDACi in cancer therapy and discuss potential biomarkers to either select or predict a patient’s response to these agents, in order to limit the off-target toxicity associated with HDACi.

  18. Evaluation of outpatient therapeutic programme (OTP) for treatment of severe acute malnutrition in Yemen: a focus on treatment default and its risk factors.

    Science.gov (United States)

    Al Amad, Mohammed; Al-Eryani, Lina; Al Serouri, Abdulwahed; Khader, Yousef S

    2017-12-01

    This study aimed to measure the treatment default rate among children with severe acute malnutrition (SAM) who were admitted to the outpatient therapeutic programme (OTP) in Yemen and determine its risk factors. A prospective study was conducted among children with SAM who were newly admitted to the 11 OTPs in primary health centres of Sana'a city. A pretested semistructured questionnaire was used for data collection at admission and at after 2 months of admission to the OTP. Univariate and multivariate analysis using binary logistic regression were used to analyse the risk factors of treatment default. This study included 339 SAM children. Of those, 186 (55%) children discharged as defaulters, 141 (42%) were cured, and 12 (3%) were transferred to other treatment sites. Many factors related to poor accessibility, poor satisfaction with staff and system, and treatment and acceptability of OTP services factors were significantly associated with treatment default. Having difficulty to attend OTP every week (OR 8.4), unavailability of medication during follow-up visits (OR 5.0), not liking to eat Plumpy'Nut (OR 5.8), and not gaining weight since the start of treatment (OR 9.3) were the strongest predictors of treatment default. This study showed a high default rate among SAM children in Sana'a city. Factors related to poor accessibility, poor satisfaction with staff and system, and factors related to treatment and acceptability of OTP services were significantly associated with high default rate. Expansion of OTP services and training OTPs staff on SAM treatment protocols are highly recommended. © 2017 John Wiley & Sons, Ltd.

  19. Therapeutic Potentials of Microalgae in the Treatment of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Tosin A. Olasehinde

    2017-03-01

    Full Text Available Current research is geared towards the discovery of new compounds with strong neuroprotective potential and few or no side effects compared to synthetic drugs. This review focuses on the potentials of extracts and biologically active compounds derived from microalgal biomass for the treatment and management of Alzheimer’s disease (AD. Microalgal research has gained much attention recently due to its contribution to the production of renewable fuels and the ability of alga cells to produce several secondary metabolites such as carotenoids, polyphenols, sterols, polyunsaturated fatty acids and polysaccharides. These compounds exhibit several pharmacological activities and possess neuroprotective potential. The pathogenesis of Alzheimer’s disease (AD involves complex mechanisms that are associated with oxidative stress, cholinergic dysfunction, neuronal damage, protein misfolding and aggregation. The antioxidant, anticholinesterase activities as well as the inhibitory effects of some bioactive compounds from microalgae extracts on β-amyloid aggregation and neuronal death are discussed extensively. Phytochemical compounds from microalgae are used as pharmaceuticals, nutraceuticals and food supplements, and may possess neuroprotective potentials that are relevant to the management and/or treatment of AD.

  20. Effectiveness of hydroplasty and therapeutic exercise for treatment of frozen shoulder.

    Science.gov (United States)

    Callinan, Nancy; McPherson, Scott; Cleaveland, Susan; Voss, Debra Gardiner; Rainville, Darcel; Tokar, Nancy

    2003-01-01

    The purpose of this retrospective review was to evaluate the effectiveness of a hydraulic distention technique (hydroplasty) combined with a therapy program for treatment of idiopathic frozen shoulder. Over a two-year period, 60 patients with idiopathic frozen shoulder were identified as having undergone the hydroplasty procedure and therapy protocol at the authors' hand center. Distention of the glenohumeral joint was achieved by an injection of a 10-mL combination of bupivacaine (Marcaine), lidocaine (Xylocaine), and corticosteroid followed by injection of 30 mL of chilled sterile normal saline. Therapy was initiated immediately after the surgeon had completed the hydroplasty. The mean active range of motion improvement was as follows: flexion 28 degrees, abduction 42 degrees, internal rotation 22 degrees, and external rotation 26 degrees. There was no significant difference in outcomes between diabetics and nondiabetics or subjects with symptoms less than six months' duration compared with subjects with symptom duration greater than six months. At discharge, only two (3%) of the subjects reported persistent pain during sleep. The hydroplasty procedure combined with a therapy program is a successful treatment for idiopathic frozen shoulder.

  1. [Therapeutic effects of a combination treatment with flomoxef and tobramycin against infections complicated with hematological disorders].

    Science.gov (United States)

    Yamane, T; Tanaka, K; Hasuike, T; Hirai, M; Misu, K; Ota, K; Ohira, H; Nakao, Y; Yasui, Y; Inoue, T

    1992-08-01

    The efficacy and safety of a combination regimen using flomoxef (FMOX) and tobramycin (TOB) were evaluated in the treatment of infections complicated with hematological disorders. The primary diseases in 40 patients included acute leukemia, malignant lymphoma and others. Complicated infections included 35 cases with suspected septicemia, 4 cases with septicemia and 1 case with pleuritis. Clinical responses were excellent in 10 (25.0%), good in 14 (35.0%), fair in 2 (5.0%) and poor in 14 (35.0%). The efficacy rate was 73.1% in patients with neutrophil counts higher than 501/microliters after administration, but it was 35.7% in patients with counts less than 501/microliters; the difference was statistically significant. No side effects were observed in any of the 40 patients. Abnormal laboratory data in liver functions were identified in 1 patient (2.5%). Degree of this abnormality was very slight, and the continuation of treatment was not disturbed. In conclusion, this combination therapy of FMOX and TOB thus appears to be useful and safe in therapies for infections complicated with hematological disorders.

  2. Optimization of radio-therapeutic treatment and the program of quality assurance in ionizing radiation therapy

    International Nuclear Information System (INIS)

    Rosca, A.; Bahnarel, I.; Coretchi, L.

    2015-01-01

    The Program of Quality Assurance (PQA) in Ionizing Radiation Therapy (IRT) addresses the most important problems of assuring the quality of IRT utilization in the treatment of patients with neoplasm. In this context, the IRT value grows considerably, hence the implementation of PQA is of great significance. The study concentrates on a detailed description of the PQA as concerns the activity involving IRT devices applied in the IRT departments (rooms) of public medical/sanitary institutions, science research institutions etc., where IRT is employed using technogenic sources and ionizing radiation generators. For the performing of the study, annual statistics reports about the activity of the IRT, and data of Cancer Registry of the Oncologic Institute of the Republic of Moldova were analyzed. The work also includes an in-depth description of the personnel categories involved in PQA, possible errors in radiotherapy, the responsibilities of the bioengineer in this program, importance of source calibration, the impact of the quality control in PQA, the role of topometric training, the interaction between the medical and technical personnel and the patient. Optimization of IRT is very important and necessary in the Republic of Moldova. PQA incontestably contributes to reducing specialist's errors in planning correct treatment, dictates the need of team work and proper delegation of the responsibilities in co-optation of other professionals, performance of duty of bioengineering, the influence of quality control of profile installations, meaning accurate topographic planning, applying several methods of work, quality assurance program assuming the major importance. (authors)

  3. [SGLT2 inhibitors: a new therapeutic class for the treatment of type 2 diabetes mellitus].

    Science.gov (United States)

    Dagan, Amir; Dagan, Bracha; SegaL, Gad

    2015-03-01

    SGLT2 (Sodium Glucose co-Transporter 2 Inhibitors) inhibitors are a new group of oral medications for the treatment of type 2 diabetes mellitus patients. These medications interfere with the process of glucose reabsorption in the proximal convoluted tubules in the kidneys, therefore increasing both glucose and water diuresis. SGLT2 inhibitors were found to be effective in lowering HbA1c levels in double-blinded studies, both as monotherapy and in combination with other oral hypoglycemic medications of various other mechanisms of action. SGLT2 Inhibitors are not a risk factor for hypoglycemia and are suitable for combination with insulin therapy. Their unique mode of action, relying on glomerular filtration, make these medication unsuitable for usage as treatment for type 2 diabetes patients who are also suffering from moderate to severe renal failure. Their main adverse effects are increased risk for urinary and genital tract infections. The following review describes the relevant pathophysiology addressed by these novel medications, evidence for efficacy and the safety profile of SGLT2 Inhibitors.

  4. Advances in the treatment of pancreatic cancer. Limitations of surgery and evaluation of new therapeutic strategies

    International Nuclear Information System (INIS)

    Yokoyama, Yukihiro; Nagino, Masato; Nimura, Yuji

    2009-01-01

    Pancreatic ductal carcinoma is one of the most dismal malignancies of the gastrointestinal system. Even after curative resection, the actual 5-year survival is only 10%-20%. Of all the treatments used against pancreatic cancer, surgery is still the only one that can achieve complete cure. Pancreatic cancer spreads easily to the adjacent tissues and distant metastasis is common. Typically, this cancer invades the retropancreatic neural tissue, duodenum, portal vein (PV), and superior mesenteric vein (SMV), or regional lymph nodes. For this reason, aggressive surgery that removes the cancerous lesion completely is recommended. Several retrospective and prospective studies have been conducted to validate the usefulness of aggressive surgery for pancreatic cancer in the past few decades. Surprisingly, the survival benefits of aggressive surgery have been denied by most randomized controlled trials (RCTs). This implies that surgery alone is not enough. Thus, adjuvant therapy, such as radiotherapy and chemotherapy, has been given in combination with surgery to improve survival. Although the benefits of radiotherapy alone are limited, the results of chemotherapy are promising. Other newly evolving molecular targeting drugs may also improve the treatment outcomes of pancreatic cancer. (author)

  5. [Novel therapeutic approach for the treatment of post-traumatic stress disorder (PTSD): facilitating fear extinction].

    Science.gov (United States)

    Fujita, Yosuke; Yamamoto, Shigeto; Morinobu, Shigeru

    2012-08-01

    Pharmacological agents enhancing fear extinction may be promising tools for the treatment of PTSD. Histone acetylation is involved in memory formation, and histone deacetylase (HDAC) inhibitors increase histone acetylation and subsequently enhance fear extinction. In this study, we examined whether vorinostat, an HDAC inhibitor, facilitated fear extinction, using a contextual fear conditioning (FC) paradigm. We found that vorinostat facilitated fear extinction. Next, the levels of global acetylated histone were measured by Western blotting. We also assessed the effect of vorinostat on the hippocampal levels of NMDA receptor mRNA by real-time quantitative PCR (RT-PCR). The levels of acetylated histone and NR2B mRNA, but not NR1 or NR2A mRNA, were elevated in the hippocampus 2 h after administration of vorinostat. We investigated the levels of acetylated histones and phospho-CREB (p-CREB) binding at the promoter of the NR2B gene using the chromatin immunoprecipitation (ChIP) assay followed by RT-PCR. The levels of acetylated histone and the binding of p-CREB to its binding site at the promoter of the NR2B gene were increased. These findings suggest that vorinostat in conjunction with exposure therapy can be a promising new avenue for the treatment of PTSD.

  6. SGLT2 inhibitors – an insulin-independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin

    Directory of Open Access Journals (Sweden)

    Seufert J

    2015-11-01

    Full Text Available Jochen SeufertDepartment of Endocrinology and Diabetology, Clinic for Internal Medicine II, Freiburg University Hospital, Freiburg, GermanyAbstract: Despite the availability of a great variety of medications, a significant proportion of people with type 2 diabetes mellitus (T2DM are not able to achieve or maintain adequate glycemic control. Beyond improved glucose control, novel treatments would ideally provide a reduction of cardiovascular risk, with a favorable impact on excess weight, and a low intrinsic hypoglycemia risk, as well as a synergistic mechanism of action for broad combination therapy. With the development of sodium glucose cotransporter 2 (SGLT2 inhibitors, an antidiabetic pharmacologic option has recently become available that comes close to meeting these requirements. For the first time, SGLT2 inhibitors offer a therapeutic approach acting directly on the kidneys without requiring insulin secretion or action. Canagliflozin, dapagliflozin, and empagliflozin are the SGLT2 inhibitors approved to date. Taken once a day, these medications can be combined with all other antidiabetic medications including insulin, due to their insulin-independent mechanism of action, with only a minimal risk of hypoglycemia. SGLT2 inhibitors provide additional reductions in body weight and blood pressure due to the therapeutically induced excretion of glucose and sodium through the kidneys. These "concomitant effects" are particularly interesting with regard to the increased cardiovascular risk in T2DM. In many cases, T2DM treatment requires a multidimensional approach where the treatment goals have to be adapted to the individual patient. While there is a consensus on the use of metformin as a first-line drug therapy, various antidiabetics are used for treatment intensification. New mechanisms of action like that of SGLT2 inhibitors such as canagliflozin, which can be used both in early and late stages of diabetes, are a welcome addition to expand

  7. Sole stenting treatment for small wide-necked saccular intracranial aneurysms:a clinical therapeutic analysis

    International Nuclear Information System (INIS)

    Cheng Jiyong; Hong Bo; Xu Yi; Huang Qinghai; Yang Pengfei; Zhao Wenyuan; Liu Jianmin

    2010-01-01

    Objective: To discuss the feasibility, safety and efficacy of sole stenting technique for the treatment of small wide-necked saccular intracranial aneurysms. Methods: Between February 2001 and November 2009, 36 consecutive patients with small wide-necked saccular intracranial aneurysms (18 males and 18 females, aged 19-75 years,with a mean age of 52.3 years) were treated with stenting technique only. Of 36 patients, the Grade 0 of Hunt and Hess classification was seen in 22,Grade I in 8, Grade II in 5 and Grade III in 1. The aneurysmal diameter ranged from 1.8 mm to 5.0 mm,with a mean diameter of 3.6 mm. The aneurysms were located at the anterior communicating artery (n=1), posterior communicating artery (n=11), intradural paraclinoid internal carotid artery (n=18), basilar artery (n=1), anterior choroidal artery (n=4) or middle cerebral artery (n=1). The clinical manifestations, the angiographic findings and the follow-up observations were analyzed and the results were evaluated by means of the Modified Rankin Scale, magnetic resonance angiography and digital subtraction angiography. Results: Sole stenting treatment was performed in 36 patients with small wide-necked saccular intracranial aneurysms. A total of 37 stents were successfully delivered and deployed at the targeted location. Immediate post-procedural angiography showed that complete occlusion was obtained in one aneurysm, a sluggish intra-aneurysmal vortex motion in 3 aneurysms and a correction of the angle of the parent vessel in two cases, whereas no change was seen in the remaining 30 aneurysms. Angiographic follow-up was carried out in 22 of the 36 patients (61%) during a mean following-up period of 16 months (ranged from 3 to 59 months). The follow-up angiography showed that the complete occlusion was seen in 11 cases, narrowed aneurysmal neck with shrinkage of the aneurysm in 9 cases, narrowed aneurysmal neck only in 1 case, and shrinkage of the aneurysm only in 1 case.All the patients remained

  8. Therapeutic effect of transcatheter arterial infusion chemotherapy in the treatment of advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Lin Junhua; Song Mingzhi; Zhang Yuanyuan; Xu Yiyu; Chen Jing

    2001-01-01

    Objective: To evaluate the clinical efficacy of transcatheter arterial infusion (TAI) or transcatheter arterial chemo-embolization (TACE) in the treatment of advanced pancreatic cancer. Methods: 36 cases of advanced pancreatic cancer were divided into two groups, 18 cases were treated with TAI or TACE (group A), other 18 cases were treated with systemic chemotherapy (group B). Results: The clinical benefit response rate of the group A was 55.6% (10/18) and that of the group B was 16.7%(3/18), respectively (P 0.05). Conclusions: In the transcatheter arterial infusion group, no survival advantage could be demonstrated when compared with the controls, but TAI could effectively increase clinical benefit response and improve the quality of life of advanced pancreatic cancer

  9. Targeting kit activation: a potential therapeutic approach in the treatment of allergic inflammation

    DEFF Research Database (Denmark)

    Jensen, Bettina M; Metcalfe, Dean D; Gilfillan, Alasdair M

    2007-01-01

    The prevalence of allergic diseases is increasing worldwide. Hence, there is continued need for novel pharmacological therapies for the treatment of these disorders. As the mast cell is one of the essential cells that contributes to the inflammation associated with allergic diseases, this cell type......E-receptor) on the cell surface. These mediators also contribute to the late and chronic stages of allergic inflammation. Thus, the IgE/antigen response has been a major focus in the development of new drugs targeting mast cells. The essential role that stem cell factor (SCF) and its receptor, Kit, play in mast cell...... remains an attractive target for such pharmacological intervention. Mast cells are major players in the early phase of the allergic response since they generate and release a variety of inflammatory mediators following antigen-dependent aggregation of IgE-bound FcepsilonRI (high affinity Ig...

  10. Rapid Treatment of Leukostasis in Leukemic Mantle Cell Lymphoma Using Therapeutic Leukapheresis: A Case Report

    Directory of Open Access Journals (Sweden)

    Xuan Duc Nguyen

    2011-01-01

    Full Text Available We describe a case of severe leukocytosis caused by leukemic mantle cell lymphoma (MCL, complicated by leukostasis with myocardial infarction in which leukapheresis was used in the initial management. A 73-year-old male presented to the emergency department because of fatigue and thoracic pain. Blood count revealed 630 × 109/L WBC (white blood cells. The electrocardiogram showed ST-elevation with an increase of troponin and creatinine kinase. The diagnosis was ST-elevation myocardial infarction (STEMI induced and complicated by leukostasis. Immunophenotyping, morphology, cytogenetic and fluorescence-in-situ-hybridization analysis revealed the diagnosis of a blastoid variant of MCL. To remove leukocytes rapidly, leukapheresis was performed in the intensive care unit. Based on the differential blood count with 95% blasts, which were assigned to the lymphocyte population by the automatic hematology analyzer, leukapheresis procedures were then performed with the mononuclear cell standard program on the Spectra cell separator. The patient was treated with daily leukapheresis for 3 days. The WBC count decreased to 174 × 109/L after the third leukapheresis, with a 72% reduction. After the second apheresis, treatment with vincristine, cyclophosphamide, and prednisolone was started. The patient fully recovered in the further course of the treatment. To the best of our knowledge, this is the first report on blastoid MCL with leukostasis associated with a STEMI that was successfully treated by leukapheresis. Effective harvest of circulating lymphoma cells by leukapheresis requires adaptation of instrument settings based on the results of the differential blood count prior to apheresis.

  11. Cancer treatment-induced bone loss in premenopausal women: a need for therapeutic intervention?

    Science.gov (United States)

    Hadji, P; Gnant, M; Body, J J; Bundred, N J; Brufsky, A; Coleman, R E; Guise, T A; Lipton, A; Aapro, M S

    2012-10-01

    Current clinical treatment guidelines recommend cytotoxic chemotherapy, endocrine therapy, or both (with targeted therapy if indicated) for premenopausal women with early-stage breast cancer, depending on the biologic characteristics of the primary tumor. Some of these therapies can induce premature menopause or are specifically designed to suppress ovarian function and reduce circulating estrogen levels. In addition to bone loss associated with low estrogen levels, cytotoxic chemotherapy may have a direct negative effect on bone metabolism. As a result, cancer treatment-induced bone loss poses a significant threat to bone health in premenopausal women with breast cancer. Clinical trials of antiresorptive therapies, such as bisphosphonates, have demonstrated the ability to slow or prevent bone loss in this setting. Current fracture risk assessment tools are based on data from healthy postmenopausal women and do not adequately address the risks associated with breast cancer therapy, especially in younger premenopausal women. We therefore recommend that all premenopausal women with breast cancer be informed about the potential risk of bone loss prior to beginning anticancer therapy. Women who experience amenorrhea should have bone mineral density assessed by dual-energy X-ray absorptiometry and receive regular follow-up to monitor bone health. Regular exercise and daily calcium and vitamin D supplementation are recommended. Women with a Z-score <-2.0 or Z-score ≤-1.0 and/or a 5-10% annual decrease in bone mineral density should be considered for bisphosphonate therapy in addition to calcium and vitamin D supplements. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi from Ghana and Gabon

    Directory of Open Access Journals (Sweden)

    Kreuels Benno

    2008-10-01

    Full Text Available Abstract Background Intermittent preventive treatment in infants (IPTi with sulphadoxine-pyrimethamine (SP reduces the incidence of malaria episodes in young children. The exact mechanism by which the protective effect is mediated needs to be defined. This study aimed to investigate therapeutic, prophylactic, and possible exceeding effects of SP-based IPTi in two clinical trials. Methods Protective efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambaréné, Gabon, were assessed for overlapping time series of 61 days. For six-months periods after each of three IPTi doses a multivariate Poisson regression model with the respective cohort as co-variate was generated and effect modification of protective efficacy with time strata was evaluated by log-likelihood tests. Results Protective efficacies were not significantly different between the two study cohorts. Study-cohort corrected protective efficacy was highest for the first 61 days after each IPTi application and decreased continuously. For the first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%, 44%, and 43%, respectively. A reduction of the malaria incidence rate was detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug application, respectively. After IPTi-3 a higher risk for malaria could be seen after day 60. This effect was mainly based on the overwhelming influence of the Kumasi cohort. Conclusion The results suggest that SP-based IPTi mainly works through a therapeutic and prophylactic effect over 30 to 60 days after drug application and that a sustained effect beyond post-treatment prophylaxis might be very low. Trial registration Data analysis from clinical trials NCT ID # 00206739 (Kumasi Trial and NCT ID # 00167843 (Lambaréné Trial, http://www.clinicaltrials.gov.

  13. Congruence of therapeutic bond perceptions and its relation to treatment outcome: Within- and between-dyad effects.

    Science.gov (United States)

    Rubel, Julian A; Bar-Kalifa, Eran; Atzil-Slonim, Dana; Schmidt, Sebastian; Lutz, Wolfgang

    2018-04-01

    The present study investigates the association between congruence of patients' and therapists' perceptions of the therapeutic bond and symptom improvement. Bond congruence-outcome associations were examined on the within- and between-dyad level for 580 patients (mainly depression and anxiety) receiving cognitive-behavioral therapy. Symptom change was assessed on a session-to-session level as well as from pre- to posttreatment. For the between-dyad analyses, the truth and bias model was applied. For the within-dyad analyses, polynomial regression and response surface analysis were conducted. On the between-dyad level, higher temporal congruence between patients' and therapists' bond ratings (i.e., their correlation) was associated with better treatment outcomes. Additionally, the average discrepancy between therapists' and patients' bond ratings showed a significant quadratic association with treatment outcome. A tendency for therapists to moderately rate the bond lower than their patients' showed lowest posttreatment symptom scores. On the within-dyad level, we found that when patients' and therapists' ratings were in "agreement," higher bond scores were associated with fewer next-session symptoms. For "disagreement," the results showed that if therapists rated the bond as weak, whereas their patients rated it as strong, higher subsequent symptom distress was observed than if patients rated the bond as weak and their therapists rated it as strong. The present study highlights the importance of therapists being vigilant to session-to-session changes in the therapeutic bond to adjust their interventions accordingly. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  14. The Relationship Between Brain Oscillatory Activity and Therapeutic Effectiveness of Transcranial Magnetic Stimulation in the Treatment of Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Andrew Francis Leuchter

    2013-02-01

    Full Text Available Major Depressive Disorder (MDD is marked by disturbances in brain functional connectivity. This connectivity is modulated by rhythmic oscillations of brain electrical activity, which enable coordinated functions across brain regions. Oscillatory activity plays a central role in regulating thinking and memory, mood, cerebral blood flow, and neurotransmitter levels, and restoration of normal oscillatory patterns is associated with effective treatment of MDD. Repetitive Transcranial Magnetic Stimulation (rTMS is a robust treatment for MDD, but the mechanism of action (MOA of its benefits for mood disorders remains incompletely understood. Benefits of rTMS have been tied to enhanced neuroplasticity in specific brain pathways. We summarize here the evidence that rTMS entrains and resets thalamocortical oscillators, normalizes regulation and facilitates reemergence of intrinsic cerebral rhythms, and through this mechanism restores normal brain function. This entrainment and resetting may be a critical step in engendering neuroplastic changes and the antidepressant effects of rTMS. It may be possible to modify the method of rTMS administration to enhance this mechanism of action and achieve better antidepressant effectiveness. We propose that rTMS can be administered: 1 synchronized to a patient’s individual alpha rhythm (IAF, or synchronized rTMS (sTMS; 2 as a low magnetic field strength sinusoidal wave form; and, 3 broadly to multiple brain areas simultaneously. We present here the theory and evidence indicating that these modifications could enhance the therapeutic effectiveness of rTMS for the treatment of MDD.

  15. Treatment outcome and factors affecting time to recovery in children with severe acute malnutrition treated at outpatient therapeutic care program

    Directory of Open Access Journals (Sweden)

    Melkamu Merid Mengesha

    2016-07-01

    Full Text Available Background: The outpatient therapeutic care program (OTP of children with severe acute malnutrition (SAM has been decentralized to health post level in Ethiopia since 2008–2009. However, there is a lack of evidence regarding treatment outcomes and factors related to the duration of stay on treatment after its decentralization to health post level. Objective: This study was aimed to assess treatment outcome and factors affecting time to recovery in children with SAM treated at OTP. Design: Health facility–based retrospective cohort study was conducted using data from 348 patient cards. The outcome variable was time to recovery. Descriptive analysis was done using percentages for categorical data and mean/median for continuous variables. A robust method of analyzing time to event data, the Cox proportional-hazard regression, was used. All statistical tests in this study are declared significant at p<0.05. Result: 89.1% of children with kwashiorkor and 69.4% of children with marasmus were recovered. Of the total children studied, 22% were readmitted cases. The median time of recovery was 35 days for children with kwashiorkor and 49 days for children with marasmus. Children older than 3 years were 33% less likely to achieve nutritional recovery [adjusted hazard ratio, AHR=0.67, 95% confidence interval, CI (0.46, 0.97]. Similarly, marasmic children stayed longer on treatment [AHR=0.42, 95% CI (0.32, 0.56]. However, children who gained Mid-Upper Arm Circumference (MUAC ≥ 0.24 mm/day were 59% more likely to recover faster [AHR=1.59, 95% CI (1.23, 2.06]. Conclusions: Close monitoring of weight and MUAC gain to assess nutritional improvement with due emphasis given to children with lower admission weight, children of age 3 years and above and marasmic children will have a positive effect on treatment duration and outcome.

  16. Weekly therapist ratings of the therapeutic relationship and patient introject during the course of dialectical behavioral therapy for the treatment of borderline personality disorder.

    Science.gov (United States)

    Bedics, Jamie D; Atkins, David C; Comtois, Katherine Anne; Linehan, Marsha M

    2012-06-01

    The purpose of the present study was to examine theory-driven hypotheses of the therapeutic relationship and patient introject in dialectical behavior therapy (DBT; Linehan, 1993) for the treatment of borderline personality disorder. A total of 14 DBT therapists provided weekly ratings of the therapeutic relationship and patient introject (N=41) during the course of a randomized controlled trial of DBT for the treatment of borderline personality disorder. Using hierarchical linear modeling (Raudenbush & Bryk, 2002), we tested four hypotheses of the therapeutic relationship as predicted by DBT and behavioral theory. Results supported three of our four predicted hypotheses of the therapeutic relationship, including the effective use of balancing autonomy and control in the therapeutic relationship, the importance of therapists' maintaining a nonpejorative stance toward the patient, and the use of therapist warmth and autonomy as a contingency for improved intrapsychic outcome. Results did not support a modeling hypothesis of the therapeutic relationship. The study supported a DBT and behavioral model of the therapeutic relationship from the perspective of the treating clinician. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  17. Therapeutic use of human mesenchymal stem cells (MSC) for the treatment of radio-induced diseases

    International Nuclear Information System (INIS)

    Mouiseddine, Moubarak

    2008-05-01

    Ionising radiation can induce toxic effects on body. They provoke physiological modifications of tissues and organs which can be lethal. Total body irradiation or local abdominal irradiation can induce serious complications. Intestine is the first tissue concerned by these side effects. Radiation induces malabsorption of the intestine and lost of it integrity. Radio-induced physiopathological effects on intestine could lead to distant effects on other tissues and organs such as liver. The actual treatments have a limited efficiency or are not adapted to gastrointestinal damages. Indeed, in this type of lesions, the heterogeneous systems which are concerned and the gravity of lesions complicates the medical care. Our purpose is to show that cell therapy using human mesenchymal stem cells (MSC) constitutes resolution in this type of illness. The works which are presented in this thesis show that MSC are multi-potent and have heterogeneous expression of molecules. These cells are able to establish themselves in many organs and tissues after injection into irradiated body. Thus we have shown that MSC can prevent the small intestine from radio-induced damages. Indeed we demonstrate that through their actions on gut, MSC can indirectly restore hepatic integrity. (author)

  18. Therapeutic effect of 60Co teletherapy and radium treatment to various malignant neoplasm

    International Nuclear Information System (INIS)

    Kim, Jin Yong; Park, Sang Sook; Chung, Jin Woo

    1970-01-01

    In radiation therapy, a complete study of patients on the indication of radiotherapy, delicate consideration during the radiotherapy, adequate after-care, the follow-up study and reconsideration are necessary. The radiotherapy patients are quite different in treatment and care. It takes, time to evaluate. Sometimes the misjudgement of patients last several years. However, the great endurance and efforts are vital necessity for the radiotherapy evaluation and improvement of radiotherapy techniques. At the Radiological Research Institute, all the radiotherapy patients from November 23, 1963 to December 31, 1968 were observed, and among them, those who survived three years after radiotherapy were analyzed in order to report the difficulty in follow-up study and to help formulate a better method of radiotherapy. All the follow-up study was done by questionnaire form. We have sent 8,470 letters, and received 2,084 Positive answers (24.6%) and the returned and no-reply were 6,386 (75.4%). As a sample case, 121 patients, who reside in Chongro-ku Seoul, were selected for home-visiting by our staffs. 67 patients (48.6%) could be located easily where as 71 patients (51.4%) could not be located. The results of follow-up correspondences were analyzed and categorized by the international classification of disease. Three-years survivors and the surviving rate are listed

  19. Treatment-resistant Lennox-Gastaut syndrome: therapeutic trends, challenges and future directions

    Directory of Open Access Journals (Sweden)

    Ostendorf AP

    2017-04-01

    Full Text Available Adam P Ostendorf,1 Yu-Tze Ng2 1Department of Pediatrics, Neurology Section, Nationwide Children’s Hospital, The Ohio State University, Columbus, OH, 2Department of Pediatrics, Baylor College of Medicine, The Children’s Hospital of San Antonio, San Antonio, TX, USA Abstract: Lennox-Gastaut syndrome is a severe, childhood-onset electroclinical syndrome comprised of multiple seizure types, intellectual and behavioral disturbances and characteristic findings on electroencephalogram of slow spike and wave complexes and paroxysmal fast frequency activity. Profound morbidity often accompanies a common and severe seizure type, the drop attack. Seizures often remain refractory, or initial treatment efficacy fades. Few individuals are seizure free despite the development of multiple generations of antiseizure medications over decades and high-level evidence on several choices. Approved medications such as lamotrigine, topiramate, rufinamide, felbamate and clobazam have demonstrated efficacy in reducing seizure burden. Cannabidiol has emerged as a promising investigational therapy with vast social interest yet lacks a standard, approved formulation. Palliative surgical procedures, such as vagal nerve stimulation and corpus callosotomy may provide reduction in total seizures and drop attacks. Emerging evidence suggests that complete callosotomy provides greater improvement in seizures without additional side effects. Etiologies such as dysplasia or hypothalamic hamartoma may be amenable for focal resection and thus offer potential to reverse this devastating epileptic encephalopathy. Keywords: Lennox-Gastaut syndrome, epilepsy, epilepsy surgery, cannabidiol, epileptic encephalopathy

  20. Therapeutic efficacy of atorvastatin in treatment of non-alcoholic fatty liver disease in patients with type Ⅱ diabetes mellitus

    Directory of Open Access Journals (Sweden)

    FENG Mengdie

    2013-07-01

    Full Text Available ObjectiveTo observe the therapeutic efficacy of atorvastatin in the treatment of non-alcoholic fatty liver disease (NAFLD in patients with type Ⅱ diabetes mellitus. MethodsA total of 118 patients with type Ⅱ diabetes mellitus complicated by NAFLD, who visited the outpatient department of internal medicine or were hospitalized in our hospital from January 2010 to March 2012, were divided randomly into treatment group (n=61 and control group (n=57. Both groups received liver protection therapy and blood glucose control, and atorvastatin (20 mg/d was administered as an addition in the treatment group. The clinical symptoms, body mass index (BMI, blood levels of total cholesterol (TC, triglyceride (TG, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C, alanine aminotransferase (ALT, and aspartate aminotransferase (AST, and liver B-mode ultrasound findings were evaluated before and after 6 months of treatment. The enumeration data were analysed by chi-square test, the indices before and after treatment were compared by t-test. ResultsAfter 6 months of treatment, the treatment group had a significantly decreased clinical symptom score (t=21.07, P=0.0000, significantly decreased blood levels of TC ((6.80±1.20 vs (5.24±0.67 mmol/L, t=8.87, P=0000, LDL-C ((4.38±0.75 vs (3.45±0.68 mmol/L, t=7.17, P=0.0000, TG ((2.14±0.56 vs (1.69±0.34 mmol/L, t=5.36, P=0.0000, ALT ((61±11 vs (46±9 U/L, t=8.24, P=0.0000, and AST ((53±14 vs (41±12 U/L, t=5.08, P=0.0000, and increased blood HDL-C level (t=1.95, P>0.05, but there was no significant change in BMI (t=1.84, P=0.0683. No significant changes in these indices were found in the control group (P>0.05. Both groups showed changes in liver density as measured by B-mode ultrasound, but there was no significant difference between them (P>0.05. No adverse events occurred in either group. ConclusionAtorvastatin can markedly relieve clinical symptoms and lower

  1. [Therapeutic education of elderly patients under antivitamin - K treatment: evaluation of the program after 5 years].

    Science.gov (United States)

    Thiriat, N; Peyron, I; Bernard-Charrière, S; Monti, A; Pariel, S; Pautas, E

    2014-09-01

    Elderly people with vitamin K antagonists (VKA) have a higher risk of potentially serious hemorrhagic complications. An education program for patients (EPP) aged > or = 75 years with VKA was set up in 2008 in a French geriatric hospital. It includes individual and group sessions conducted by a nurse and a geriatrician. The aim of this study was to assess this EPP after 5 years. Strengths, weaknesses and difficulties of implementation were highlighted, and some improvements were proposed. This study is an external audit conducted by a pharmacist trained in EPP. Files of consecutive patients included in the program between may 2008 and March 2013 were reviewed allowing the data collection of patients characteristics and results of the different sessions. The educational objectives were assessed by the rate of correct responses to the questionnaires during the program. The results are presented taking into account the changes made during the 5 years of the program. One hundred forty-three patients, mean age 83.3 +/- 6.5 years, were included in the EPP. 51 sessions were conducted (2.8 patients/session on average). 58% of selected patients were hospitalized. The mean time between the start of anticoagulant treatment and the incLusion in the program was 48.9 +/- 71 months. For 95 patients (66.4%) the medication management at home required a caregiver who was present for sessions in 82 cases (57.3%). The questionnaires form and the organisation of the sessions were gradually improved between 2008 and the end of 2010. Thus, the impact of the EPP has been estimated from November 2010 to March 2013. The correct responses rates before and after the sessions were respectively: 47.8% vs 91.3% for knowledge of INR target values, 25.4% vs 91.3% for knowledge of hemorrhagic signs, 14.9% vs 87.0% for knowledge of the situations or the medications that may disturb the INR equilibrium. Furthermore, the mean number of correct responses, for the 23 patients participating in the entire

  2. Therapeutic Effect of Activated Carbon-Induced Constipation Mice with Lactobacillus fermentum Suo on Treatment

    Directory of Open Access Journals (Sweden)

    Huayi Suo

    2014-11-01

    Full Text Available The aim of this study was to investigate the effects of Lactobacillus fermentum Suo (LF-Suo on activated carbon-induced constipation in ICR (Institute of Cancer Research mice. ICR mice were orally administered with lactic acid bacteria for 9 days. Body weight, diet intake, drinking amount, defecation status, gastrointestinal transit and defecation time, and the serum levels of MTL (motilin, Gas (gastrin, ET (endothelin, SS (somatostatin, AChE (acetylcholinesterase, SP (substance P, VIP (vasoactive intestinal peptide were used to evaluate the preventive effects of LF-Suo on constipation. Bisacodyl, a laxative drug, was used as a positive control. The normal, control, 100 mg/kg bisacodyl treatment, LB (Lactobacillus bulgaricus-, LF-Suo (L- and LF-Suo (H-treated mice showed the time to the first black stool defecation at 90, 218, 117, 180, 155 and 137 min, respectively. By the oral administration of LB-, LF-Suo (L, LF-Suo (H or bisacodyl (100 mg/kg, the gastrointestinal transit was reduced to 55.2%, 72.3%, 85.5% and 94.6%, respectively, of the transit in normal mice, respectively. In contrast to the control mice, the serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Suo (p < 0.05. By the RT-PCR (reverse transcription–polymerase chain reaction and western blot assays, LF-Suo increased the c-Kit, SCF (stem cell factor, GDNF (glial cell line-derived neurotrophic factor and decreased TRPV1 (transient receptor potential vanilloid 1, NOS (nitric oxide synthase expressions of small intestine tissue in mice. These results demonstrate that lactic acid bacteria has preventive effects on mouse constipation and LF-Suo demonstrated the best functional activity.

  3. Therapeutic treatment plan optimization with probability density-based dose prescription

    International Nuclear Information System (INIS)

    Lian Jun; Cotrutz, Cristian; Xing Lei

    2003-01-01

    The dose optimization in inverse planning is realized under the guidance of an objective function. The prescription doses in a conventional approach are usually rigid values, defining in most instances an ill-conditioned optimization problem. In this work, we propose a more general dose optimization scheme based on a statistical formalism [Xing et al., Med. Phys. 21, 2348-2358 (1999)]. Instead of a rigid dose, the prescription to a structure is specified by a preference function, which describes the user's preference over other doses in case the most desired dose is not attainable. The variation range of the prescription dose and the shape of the preference function are predesigned by the user based on prior clinical experience. Consequently, during the iterative optimization process, the prescription dose is allowed to deviate, with a certain preference level, from the most desired dose. By not restricting the prescription dose to a fixed value, the optimization problem becomes less ill-defined. The conventional inverse planning algorithm represents a special case of the new formalism. An iterative dose optimization algorithm is used to optimize the system. The performance of the proposed technique is systematically studied using a hypothetical C-shaped tumor with an abutting circular critical structure and a prostate case. It is shown that the final dose distribution can be manipulated flexibly by tuning the shape of the preference function and that using a preference function can lead to optimized dose distributions in accordance with the planner's specification. The proposed framework offers an effective mechanism to formalize the planner's priorities over different possible clinical scenarios and incorporate them into dose optimization. The enhanced control over the final plan may greatly facilitate the IMRT treatment planning process

  4. Antibacterial therapeutics for the treatment of chytrid infection in amphibians: Columbus’s egg?

    Science.gov (United States)

    2012-01-01

    Background The establishment of safe and effective protocols to treat chytridiomycosis in amphibians is urgently required. In this study, the usefulness of antibacterial agents to clear chytridiomycosis from infected amphibians was evaluated. Results Florfenicol, sulfamethoxazole, sulfadiazine and the combination of trimethoprim and sulfonamides were active in vitro against cultures of five Batrachochytrium dendrobatidis strains containing sporangia and zoospores, with minimum inhibitory concentrations (MIC) of 0.5-1.0 μg/ml for florfenicol and 8.0 μg/ml for the sulfonamides. Trimethoprim was not capable of inhibiting growth but, combined with sulfonamides, reduced the time to visible growth inhibition by the sulfonamides. Growth inhibition of B. dendrobatidis was not observed after exposure to clindamycin, doxycycline, enrofloxacin, paromomycin, polymyxin E and tylosin. Cultures of sporangia and zoospores of B. dendrobatidis strains JEL423 and IA042 were killed completely after 14 days of exposure to 100 μg/ml florfenicol or 16 μg/ml trimethoprim combined with 80 μg/ml sulfadiazine. These concentrations were, however, not capable of efficiently killing zoospores within 4 days after exposure as assessed using flow cytometry. Florfenicol concentrations remained stable in a bathing solution during a ten day period. Exposure of Discoglossus scovazzi tadpoles for ten days to 100 μg/ml but not to 10 μg florfenicol /ml water resulted in toxicity. In an in vivo trial, post metamorphic Alytes muletensis, experimentally inoculated with B. dendrobatidis, were treated topically with a solution containing 10 μg/ml of florfenicol during 14 days. Although a significant reduction of the B. dendrobatidis load was obtained, none of the treated animals cleared the infection. Conclusions We thus conclude that, despite marked anti B. dendrobatidis activity in vitro, the florfenicol treatment used is not capable of eliminating B. dendrobatidis infections

  5. Antibacterial therapeutics for the treatment of chytrid infection in amphibians: Columbus's egg?

    Science.gov (United States)

    Muijsers, Mariska; Martel, An; Van Rooij, Pascale; Baert, Kris; Vercauteren, Griet; Ducatelle, Richard; De Backer, Patrick; Vercammen, Francis; Haesebrouck, Freddy; Pasmans, Frank

    2012-09-25

    The establishment of safe and effective protocols to treat chytridiomycosis in amphibians is urgently required. In this study, the usefulness of antibacterial agents to clear chytridiomycosis from infected amphibians was evaluated. Florfenicol, sulfamethoxazole, sulfadiazine and the combination of trimethoprim and sulfonamides were active in vitro against cultures of five Batrachochytrium dendrobatidis strains containing sporangia and zoospores, with minimum inhibitory concentrations (MIC) of 0.5-1.0 μg/ml for florfenicol and 8.0 μg/ml for the sulfonamides. Trimethoprim was not capable of inhibiting growth but, combined with sulfonamides, reduced the time to visible growth inhibition by the sulfonamides. Growth inhibition of B. dendrobatidis was not observed after exposure to clindamycin, doxycycline, enrofloxacin, paromomycin, polymyxin E and tylosin. Cultures of sporangia and zoospores of B. dendrobatidis strains JEL423 and IA042 were killed completely after 14 days of exposure to 100 μg/ml florfenicol or 16 μg/ml trimethoprim combined with 80 μg/ml sulfadiazine. These concentrations were, however, not capable of efficiently killing zoospores within 4 days after exposure as assessed using flow cytometry. Florfenicol concentrations remained stable in a bathing solution during a ten day period. Exposure of Discoglossus scovazzi tadpoles for ten days to 100 μg/ml but not to 10 μg florfenicol /ml water resulted in toxicity. In an in vivo trial, post metamorphic Alytes muletensis, experimentally inoculated with B. dendrobatidis, were treated topically with a solution containing 10 μg/ml of florfenicol during 14 days. Although a significant reduction of the B. dendrobatidis load was obtained, none of the treated animals cleared the infection. We thus conclude that, despite marked anti B. dendrobatidis activity in vitro, the florfenicol treatment used is not capable of eliminating B. dendrobatidis infections from amphibians.

  6. Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety.

    Directory of Open Access Journals (Sweden)

    Eva M Marco

    Full Text Available Anxiety disorders are among the most prevalent psychiatric diseases with high personal costs and a remarkable socio-economic burden. However, current treatment of anxiety is far from satisfactory. Novel pharmacological targets have emerged in the recent years, and attention has focused on the endocannabinoid (eCB system, given the increasing evidence that supports its central role in emotion, coping with stress and anxiety. In the management of anxiety disorders, drug development strategies have left apart the direct activation of type-1 cannabinoid receptors to indirectly enhance eCB signalling through the inhibition of eCB deactivation, that is, the inhibition of the fatty acid amide hydrolase (FAAH enzyme. In the present study, we provide evidence for the anxiolytic-like properties of a novel, potent and selective reversible inhibitor of FAAH, ST4070, orally administered to rodents. ST4070 (3 to 30 mg/kg per os administered to CD1 male mice induced an increase of time spent in the exploration of the open arms of the elevated-plus maze. A partial reduction of anxiety-related behaviour by ST4070 was also obtained in Wistar male rats, which moderately intensified the time spent in the illuminated compartment of the light-dark box. ST4070 clearly inhibited FAAH activity and augmented the levels of two of its substrates, N-arachidonoylethanolamine (anandamide and N-palmitoylethanolamine, in anxiety-relevant brain regions. Altogether, ST4070 offers a promising anxiolytic-like profile in preclinical studies, although further studies are warranted to clearly demonstrate its efficacy in the clinic management of anxiety disorders.

  7. Antibacterial therapeutics for the treatment of chytrid infection in amphibians: Columbus’s egg?

    Directory of Open Access Journals (Sweden)

    Muijsers Mariska

    2012-09-01

    Full Text Available Abstract Background The establishment of safe and effective protocols to treat chytridiomycosis in amphibians is urgently required. In this study, the usefulness of antibacterial agents to clear chytridiomycosis from infected amphibians was evaluated. Results Florfenicol, sulfamethoxazole, sulfadiazine and the combination of trimethoprim and sulfonamides were active in vitro against cultures of five Batrachochytrium dendrobatidis strains containing sporangia and zoospores, with minimum inhibitory concentrations (MIC of 0.5-1.0 μg/ml for florfenicol and 8.0 μg/ml for the sulfonamides. Trimethoprim was not capable of inhibiting growth but, combined with sulfonamides, reduced the time to visible growth inhibition by the sulfonamides. Growth inhibition of B. dendrobatidis was not observed after exposure to clindamycin, doxycycline, enrofloxacin, paromomycin, polymyxin E and tylosin. Cultures of sporangia and zoospores of B. dendrobatidis strains JEL423 and IA042 were killed completely after 14 days of exposure to 100 μg/ml florfenicol or 16 μg/ml trimethoprim combined with 80 μg/ml sulfadiazine. These concentrations were, however, not capable of efficiently killing zoospores within 4 days after exposure as assessed using flow cytometry. Florfenicol concentrations remained stable in a bathing solution during a ten day period. Exposure of Discoglossus scovazzi tadpoles for ten days to 100 μg/ml but not to 10 μg florfenicol /ml water resulted in toxicity. In an in vivo trial, post metamorphic Alytes muletensis, experimentally inoculated with B. dendrobatidis, were treated topically with a solution containing 10 μg/ml of florfenicol during 14 days. Although a significant reduction of the B. dendrobatidis load was obtained, none of the treated animals cleared the infection. Conclusions We thus conclude that, despite marked anti B. dendrobatidis activity in vitro, the florfenicol treatment used is not capable of eliminating B

  8. The Impeding Role of Self-Critical Perfectionism on Therapeutic Alliance During Treatment and Eating Disorder Symptoms at Follow-up in Patients with an Eating Disorder

    Directory of Open Access Journals (Sweden)

    Jolene van der Kaap-Deeder

    2016-04-01

    Full Text Available This study examines the impeding role of self-critical perfectionism at onset of treatment on therapeutic alliance during treatment and eating disorder symptoms at follow-up in patients with an eating disorder. Participants were 53 female patients with a mean age of 21.1 years treated for an eating disorder in a specialized inpatient treatment unit. Self-critical perfectionism was assessed at admission, therapeutic alliance was assessed during treatment (after three months of treatment, and eating disorder symptoms were assessed at admission, after three months and one year later. Self-critical perfectionism negatively related to treatment alliance with the therapist. Although self-critical perfectionism was not directly predictive of subsequent changes in eating disorder symptoms, it was indirectly related to less reduction in body dissatisfaction through the therapeutic alliance. These results point to the importance of self-critical perfectionism in the therapeutic alliance and in changes in body image problems. Treatment implications are discussed.

  9. Single-dose radiosurgical treatment for hepatic metastases - therapeutic outcome of 138 treated lesions from a single institution

    International Nuclear Information System (INIS)

    Habermehl, Daniel; Herfarth, Klaus K; Bermejo, Justo Lorenzo; Hof, Holger; Rieken, Stefan; Kuhn, Sabine; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

    2013-01-01

    Local ablative therapies such as stereotactically guided single-dose radiotherapy or helical intensity-modulated radiotherapy (tomotherapy) with high single-doses are successfully applied in many centers in patients with liver metastasis not suitable for surgical resection. This study presents results from more than 10 years of clinical experience and evaluates long-term outcome and efficacy of this therapeutic approach. From 1997 to 2009 a total of 138 intrahepatic tumors of 90 patients were irradiated with single doses of 17 to 30 Gy (median dose 24 Gy). Median age of the patients was 64 years (range 31–89 years). Most frequent underlying tumor histologies were colorectal adenocarcinoma (70 lesions) and breast cancer (27 lesions). In 35 treatment sessions multiple targets were simultaneously irradiated (up to four lesions at once). Local progression-free (PFS) and overall survival (OS) after treatment were investigated using uni- and multiple survival regression models. Median overall survival of all patients was 24.3 months. Local PFS was 87%, 70% and 59% after 6, 12 and 18 months, respectively. Median time to local progression was 25.5 months. Patients with a single lesion and no further metastases at time of RT had a favorable median PFS of 43.1 months according to the Kaplan-Meier estimator. The type of tumor showed a statistical significant influence on local PFS, with a better prognosis for breast cancer histology than for colorectal carcinoma in uni- and multiple regression analysis (p = 0.05). Multiple regression analysis revealed no influence of planning target volume (PTV), patient age and radiation dose on local PFS. Treatment was well tolerated with no severe adverse events. This study confirms safety of SBRT in liver lesions, with 6- and 12 months local control of 87% and 70%. The dataset represents the clinical situation in a large oncology setting, with many competing treatment options and heterogeneous patient characteristics

  10. Is TNF-a-targeted short hairpin RNA (shRNA) a novel potential therapeutic tool in psoriasis treatment?

    DEFF Research Database (Denmark)

    Stenderup, Karin; Jakobsen, Maria; Rosada, Cecilia

    2008-01-01

      TNF-α is a well known target in psoriasis treatment and biological treatments targeting TNF-a are already clinically used against psoriasis and psoriasis arthritis. Attention is however given to a novel therapeutic tool: RNA interference that controls gene silencing. This study investigates...... the efficiency of targeting TNF-a with specific short hairpin RNA (shRNA) and explores its potential in treating psoriasis. ShRNAs targeting human TNF-α mRNA were generated. Their efficiency in down-regulating TNF-a protein expression was evaluated using a Renilla luciferase screening-assay and a transient co...... TNF-a shRNA was used to transduce HEK293 cells and verify vector-derived TNF-a knockdown in vitro. In vivo, psoriasis skin was exposed to lentiviral TNF-a shRNAs by a single intra-dermal injection. Psoriasis skin for the in vivo study was obtained from psoriatic plaque skin biopsies that were...

  11. Therapeutic Potential of Dental Pulp Stem Cell Secretome for Alzheimer’s Disease Treatment: An In Vitro Study

    Directory of Open Access Journals (Sweden)

    Nermeen El-Moataz Bellah Ahmed

    2016-01-01

    Full Text Available The secretome obtained from stem cell cultures contains an array of neurotrophic factors and cytokines that might have the potential to treat neurodegenerative conditions. Alzheimer’s disease (AD is one of the most common human late onset and sporadic neurodegenerative disorders. Here, we investigated the therapeutic potential of secretome derived from dental pulp stem cells (DPSCs to reduce cytotoxicity and apoptosis caused by amyloid beta (Aβ peptide. We determined whether DPSCs can secrete the Aβ-degrading enzyme, neprilysin (NEP, and evaluated the effects of NEP expression in vitro by quantitating Aβ-degrading activity. The results showed that DPSC secretome contains higher concentrations of VEGF, Fractalkine, RANTES, MCP-1, and GM-CSF compared to those of bone marrow and adipose stem cells. Moreover, treatment with DPSC secretome significantly decreased the cytotoxicity of Aβ peptide by increasing cell viability compared to nontreated cells. In addition, DPSC secretome stimulated the endogenous survival factor Bcl-2 and decreased the apoptotic regulator Bax. Furthermore, neprilysin enzyme was detected in DPSC secretome and succeeded in degrading Aβ1–42 in vitro in 12 hours. In conclusion, our study demonstrates that DPSCs may serve as a promising source for secretome-based treatment of Alzheimer’s disease.

  12. Therapeutic evaluation of prolonged infusions of β-lactam antibiotics in the treatment and management of critically ill patients

    Directory of Open Access Journals (Sweden)

    Jorge S. Amador

    2017-04-01

    Full Text Available Context: Critically ill patients has a large number of pathophysiological changes product of commitment and organ systems. Therefore, knowledge of the pharmacological properties of antimicrobials is essential to choose the best treatment. In order to optimize the response of antibiotic therapy and these drugs, new strategies have been proposed dosage, the most used drug application of the model, called: Pharmacokinetics/Pharmacodynamics (PK/PD. In the case of β-lactam antibiotics, the PK/PD model is known as time-dependent on the Minimum Inhibitory Concentration (Time > MIC. For optimal concentrations in β-lactam antibiotics, prolonged or continuous infusions, thus exposing the drug on the pathogen is achieved in a longer optimal concentrations through are used. Aims: To evaluate the therapeutic response of β-lactam antibiotics in critically ill patients with prolonged infusions by applying the model PK/ PD. Methods: Prospective observational study (concurrent cohort, taking as a control non-concurrent historic cohort, conducted for a period of seven months in the intensive care unit of the Hospital Clínico San Borja Arriarán (HCSBA, Santiago, Chile. Results: It was found a significant difference in number of days of hospitalization in ICU for the group bolus versus infusion group (12.5 ± 5.4 vs. 18 ± 9.7 days, IC: 1.5-9.5; p = 0.009. Conclusions: This study suggests that there would be a therapeutic advantage in the use of prolonged infusion in ICU stay duration.

  13. Internet-based treatment for PTSD reduces distress and facilitates the development of a strong therapeutic alliance: a randomized controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Maercker Andreas

    2007-04-01

    Full Text Available Abstract Background The present study was designed to evaluate the efficacy of an internet-based therapy (Interapy for Posttraumatic Stress Disorder (PTSD in a German speaking population. Also, the quality of the online therapeutic relationship, its development and its relevance as potential moderator of the treatment effects was investigated. Method Ninety-six patients with posttraumatic stress reactions were allocated at random to ten sessions of Internet-based cognitive behavioural therapy (CBT conducted over a 5-week period or a waiting list control group. Severity of PTSD was the primary outcome. Secondary outcome variables were depression, anxiety, dissociation and physical health. Follow-up assessments were conducted at the end of treatment and 3 months after treatment. Results From baseline to post-treatment assessment, PTSD severity and other psychopathological symptoms were significantly improved for the treatment group (intent-to-treat group × time interaction effect size d = 1.40. Additionally, patients of the treatment condition showed significantly greater reduction of co-morbid depression and anxiety as compared to the waiting list condition. These effects were sustained during the 3-months follow-up period. High ratings of the therapeutic alliance and low drop-out rates indicated that a positive and stable therapeutic relationship could be established online. Significant improvement of the online working alliance in the course of treatment and a substantial correlation between the quality of the online relationship at the end of treatment and treatment outcome emerged. Conclusion Interapy proved to be a viable treatment alternative for PTSD with large effect sizes and sustained treatment effects. A stable and positive online therapeutic relationship can be established through the Internet which improved during the treatment process. Trial registration Australian Clinical Trials Registry ACTRN012606000401550

  14. Treatment differences in the therapeutic relationship and introject during a 2-year randomized controlled trial of dialectical behavior therapy versus nonbehavioral psychotherapy experts for borderline personality disorder.

    Science.gov (United States)

    Bedics, Jamie D; Atkins, David C; Comtois, Katherine A; Linehan, Marsha M

    2012-02-01

    The present study explored the role of the therapeutic relationship and introject during the course of dialectical behavior therapy (DBT; Linehan, 1993) for the treatment of borderline personality disorder. Women meeting DSM-IV criteria for borderline personality disorder (N = 101) were randomized to receive DBT or community treatment by experts. The Structural Analysis of Social Behavior (Benjamin, 1974) was used to measure both the therapeutic relationship and introject. Relative to community treatment by experts, DBT participants reported the development of a more positive introject, including significantly greater self-affirmation, self-love, self-protection, and less self-attack, during the course of treatment and 1-year follow-up. The therapeutic relationship did not have an independent effect on intrapsychic or symptomatic outcome but did interact with treatment. DBT participants who perceived their therapist as affirming and protecting reported less frequent occurrences of nonsuicidal self-injury. The study showed positive intrapsychic change during DBT and emphasized the importance of affirmation and control in the therapeutic relationship. Results are discussed in the context of understanding the mechanisms of change in DBT. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  15. Interventional embolization with coils for the treatment of surgical stoma bleeding caused by portal hypertension: a therapeutic analysis

    International Nuclear Information System (INIS)

    Chen Feng; Chen Shiwei; Qiao Delin; Tang Zhen

    2010-01-01

    Objective: To assess the feasibility and safety of interventional embolization with coils in treating surgical stoma bleeding caused by portal hypertension. Methods: From February 2008 to May 2010, the authors treated eight patients with surgical stoma bleeding associated with portal hypertension. The patients included 5 females and 3 males, with a mean age of 57 years. The diagnosis was confirmed preoperatively by enhanced CT scanning and vascular reconstruction, and was further verified by angiography after operation. All patients were treated with coil embolization. The percutaneous transhepatic catheterization was performed, after that the catheter was manipulated to pass portal vein into the tortuous dilated mesenteric vein. The bleeding veins were occluded with gelatin sponge, and the spleen was embolized at the same time. The patients were followed up for two months to two years. Based on CT angiographic manifestations, color-Doppler ultrasound findings and clinical conditions the therapeutic results were evaluated. Results: Technical success with single procedure was achieved in all eight patients, the hemostasis rate was 100%. No serious complications occurred. During the follow-up period no recurrent bleeding of the surgical stoma was seen. Conclusion: For the treatment of surgical stoma bleeding caused by portal hypertension interventional embolization with coils is a safe and effective technique. It is worth popularizing this method in clinical practice. (authors)

  16. Minimally invasive myotomy for the treatment of esophageal achalasia: evolution of the surgical procedure and the therapeutic algorithm.

    Science.gov (United States)

    Bresadola, Vittorio; Feo, Carlo V

    2012-04-01

    Achalasia is a rare disease of the esophagus, characterized by the absence of peristalsis in the esophageal body and incomplete relaxation of the lower esophageal sphincter, which may be hypertensive. The cause of this disease is unknown; therefore, the aim of the therapy is to improve esophageal emptying by eliminating the outflow resistance caused by the lower esophageal sphincter. This goal can be accomplished either by pneumatic dilatation or surgical myotomy, which are the only long-term effective therapies for achalasia. Historically, pneumatic dilatation was preferred over surgical myotomy because of the morbidity associated with a thoracotomy or a laparotomy. However, with the development of minimally invasive techniques, the surgical approach has gained widespread acceptance among patients and gastroenterologists and, consequently, the role of surgery has changed. The aim of this study was to review the changes occurred in the surgical treatment of achalasia over the last 2 decades; specifically, the development of minimally invasive techniques with the evolution from a thoracoscopic approach without an antireflux procedure to a laparoscopic myotomy with a partial fundoplication, the changes in the length of the myotomy, and the modification of the therapeutic algorithm.

  17. Therapeutic paint of cidofovir/sucralfate gel combination topically administered by spraying for treatment of orf virus infections.

    Science.gov (United States)

    Sonvico, Fabio; Colombo, Gaia; Gallina, Laura; Bortolotti, Fabrizio; Rossi, Alessandra; McInnes, Colin J; Massimo, Gina; Colombo, Paolo; Scagliarini, Alessandra

    2009-06-01

    The aim of the research was to study a new cidofovir/sucralfate drug product to be used as a spray for treating the mucosal and/or skin lesions. The product, i.e., a water suspension of sucralfate (15% w/w) and cidofovir (1% w/w), combines the potent antiviral activity of the acyclic nucleoside phosphonate cidofovir ((S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) and the wound healing properties of sucralfate gel (sucrose octasulphate basic aluminum salt). The product was characterized in vitro with respect to compatibility between drug and carrier, spray particle size, spray deposition, drying kinetics, and drug content and release. An interaction between the two active substances was found. The interaction between sucralfate and cidofovir was counteracted by introducing sodium dihydrogen phosphate (16% w/w) in the preparation. The spray formulation containing cidofovir/sucralfate gel painted the skin and dried quickly to a scab, remaining firmly adhered to the lesions. The therapeutic paint was tested in vivo on lambs infected with orf virus by treating the animals with different cidofovir/sucralfate formulations (0.5% or 1% cidofovir + sucralfate 15% + NaH(2)PO(4) 16% w/w) and with sucralfate gel suspension alone as control. The treatment with formulations containing cidofovir and phosphate salt for four consecutive days resulted in a rapid resolution of the lesions, with scabs containing significantly lower amounts of viable virus when compared with untreated lesions and lesions treated with sucralfate suspension alone.

  18. The therapeutic efficacy of sacroiliac joint blocks with triamcinolone acetonide in the treatment of sacroiliac joint dysfunction without spondyloarthropathy.

    Science.gov (United States)

    Liliang, Po-Chou; Lu, Kang; Weng, Hui-Ching; Liang, Cheng-Loong; Tsai, Yu-Duan; Chen, Han-Jung

    2009-04-20

    Prospective case series. The study aimed to investigate the therapeutic efficacy of sacroiliac joint (SIJ) blocks with triamcinolone acetonide in patients with SIJ pain without spondyloarthropathy. Numerous studies have demonstrated that SIJ blocks with corticosteroid/anesthetic provide long-term pain relief in seronegative spondyloarthropathy. However, only one report on SIJ dysfunction patients without spondyloarthropathy shows promising results. We conducted a prospective observational study of patients at a University Spine Center from March 2005 to May 2006. The above mentioned SIJ blocks were performed in 150 patients, and dual SIJ blocks confirmed SIJ pain in 39 patients (26%). Twenty-six patients (66.7%) experienced significant pain reduction for more than 6 weeks; the overall mean duration of pain reduction in these responders was 36.8 +/- 9.9 weeks. SIJ blocks were ineffective in 13 patients (33.3%); the mean duration of pain reduction in these patients was 4.4 +/- 1.8 weeks. Univariate analysis revealed that treatment failure was significantly associated with a history of lumbar/lumbosacral fusion (P = 0.03). SIJ blocks with triamcinolone acetonide are beneficial for some patients with SIJ pain without spondyloarthropathy. The SIJ blocks showed a long-lasting efficacy in two-thirds of the patients; however, the duration of its efficacy was shorter in patients with a history of lumbar/lumbosacral fusion. These findings suggest the need for further studies.

  19. Preclinical Development of a Subcutaneous ALAS1 RNAi Therapeutic for Treatment of Hepatic Porphyrias Using Circulating RNA Quantification

    Directory of Open Access Journals (Sweden)

    Amy Chan

    2015-01-01

    Full Text Available The acute hepatic porphyrias are caused by inherited enzymatic deficiencies in the heme biosynthesis pathway. Induction of the first enzyme 5-aminolevulinic acid synthase 1 (ALAS1 by triggers such as fasting or drug exposure can lead to accumulation of neurotoxic heme intermediates that cause disease symptoms. We have demonstrated that hepatic ALAS1 silencing using siRNA in a lipid nanoparticle effectively prevents and treats induced attacks in a mouse model of acute intermittent porphyria. Herein, we report the development of ALN-AS1, an investigational GalNAc-conjugated RNAi therapeutic targeting ALAS1. One challenge in advancing ALN-AS1 to patients is the inability to detect liver ALAS1 mRNA in the absence of liver biopsies. We here describe a less invasive circulating extracellular RNA detection assay to monitor RNAi drug activity in serum and urine. A striking correlation in ALAS1 mRNA was observed across liver, serum, and urine in both rodents and nonhuman primates (NHPs following treatment with ALN-AS1. Moreover, in donor-matched human urine and serum, we demonstrate a notable correspondence in ALAS1 levels, minimal interday assay variability, low interpatient variability from serial sample collections, and the ability to distinguish between healthy volunteers and porphyria patients with induced ALAS1 levels. The collective data highlight the potential utility of this assay in the clinical development of ALN-AS1, and in broadening our understanding of acute hepatic porphyrias disease pathophysiology.

  20. Pharmacological Targeting SHP-1-STAT3 Signaling Is a Promising Therapeutic Approach for the Treatment of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Li-Ching Fan

    2015-09-01

    Full Text Available STAT3 activation is associated with poor prognosis in human colorectal cancer (CRC. Our previous data demonstrated that regorafenib (Stivarga is a pharmacological agonist of SH2 domain-containing phosphatase 1 (SHP-1 that enhances SHP-1 activity and induces apoptosis by targeting STAT3 signals in CRC. This study aimed to find a therapeutic drug that is more effective than regorafenib for CRC treatment. Here, we showed that SC-43 was more effective than regorafenib at inducing apoptosis in vitro and suppressing tumorigenesis in vivo. SC-43 significantly increased SHP-1 activity, downregulated p-STAT3Tyr705 level, and induced apoptosis in CRC cells. An SHP-1 inhibitor or knockdown of SHP-1 by siRNA both significantly rescued the SC-43–induced apoptosis and decreased p-STAT3Tyr705 level. Conversely, SHP-1 overexpression increased the effects of SC-43 on apoptosis and p-STAT3Tyr705 level. These data suggest that SC-43–induced apoptosis mediated through the loss of p-STAT3Tyr705 was dependent on SHP-1 function. Importantly, SC-43–enhanced SHP-1 activity was because of the docking potential of SC-43, which relieved the autoinhibited N-SH2 domain of SHP-1 and inhibited p-STAT3Tyr705 signals. Importantly, we observed that a significant negative correlation existed between SHP-1 and p-STAT3Tyr705expression in CRC patients (P = .038. Patients with strong SHP-1 and weak p-STAT3Tyr705 expression had significantly higher overall survival compared with patients with weak SHP-1 and strong p-STAT3Tyr705 expression (P = .029. In conclusion, SHP-1 is suitable to be a useful prognostic marker and a pharmacological target for CRC treatment. Targeting SHP-1-STAT3 signaling by SC-43 may serve as a promising pharmacotherapy for CRC.

  1. Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G.

    Directory of Open Access Journals (Sweden)

    Shohei Ogata

    Full Text Available Although intravenous immunoglobulin (IVIG is highly effective in Kawasaki disease (KD, mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I, the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient's own endogenous IgG.We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (sST6Gal-I levels were measured by ELISA.There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p <0.001, respectively.Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals.

  2. The Prevalence of Sexual Abuse and Its Impact on the Onset of Drug Use among Adolescents in Therapeutic Community Drug Treatment.

    Science.gov (United States)

    Hawke, Josephine M.; Jainchill, Nancy; De Leon, George

    2000-01-01

    Describes the prevalence of sexual abuse among adolescents (N=938) admitted to residential therapeutic communities for treatment of substance abuse and related disorders. Results indicate that approximately one-third of the sample reported histories of sexual abuse. Prevalence rates were significantly higher for girls than for boys. History of…

  3. Treatment Differences in the Therapeutic Relationship and Introject during a 2-Year Randomized Controlled Trial of Dialectical Behavior Therapy versus Nonbehavioral Psychotherapy Experts for Borderline Personality Disorder

    Science.gov (United States)

    Bedics, Jamie D.; Atkins, David C.; Comtois, Katherine A.; Linehan, Marsha M.

    2012-01-01

    Objective: The present study explored the role of the therapeutic relationship and introject during the course of dialectical behavior therapy (DBT; Linehan, 1993) for the treatment of borderline personality disorder. Method: Women meeting "DSM-IV" criteria for borderline personality disorder (N = 101) were randomized to receive DBT or community…

  4. A therapeutic workplace for the long-term treatment of drug addiction and unemployment: eight-year outcomes of a social business intervention.

    Science.gov (United States)

    Aklin, Will M; Wong, Conrad J; Hampton, Jacqueline; Svikis, Dace S; Stitzer, Maxine L; Bigelow, George E; Silverman, Kenneth

    2014-01-01

    This study evaluated the long-term effects of a therapeutic workplace social business on drug abstinence and employment. Pregnant and postpartum women (N = 40) enrolled in methadone treatment were randomly assigned to a therapeutic workplace or usual care control group. Therapeutic workplace participants could work weekdays in training and then as employees of a social business, but were required to provide drug-free urine samples to work and maintain maximum pay. Three-year outcomes were reported previously. This paper reports 4- to 8-year outcomes. During year 4 when the business was open, therapeutic workplace participants provided significantly more cocaine- and opiate-negative urine samples than controls; reported more days employed, higher employment income, and less money spent on drugs. During the 3 years after the business closed, therapeutic workplace participants only reported higher income than controls. A therapeutic workplace social business can maintain long-term abstinence and employment, but additional intervention may be required to sustain effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. A Therapeutic Workplace for the Long-Term Treatment of Drug Addiction and Unemployment: Eight-Year Outcomes of a Social Business Intervention

    Science.gov (United States)

    Aklin, Will M.; Wong, Conrad J.; Hampton, Jacqueline; Svikis, Dace S.; Stitzer, Maxine L.; Bigelow, George E.; Silverman, Kenneth

    2014-01-01

    This study evaluated the long-term effects of a Therapeutic Workplace social business on drug abstinence and employment. Pregnant and postpartum women (N=40) enrolled in methadone treatment were randomly assigned to a Therapeutic Workplace or Usual Care Control group. Therapeutic Workplace participants could work weekdays in training and then as employees of a social business, but were required to provide drug-free urine samples to work and maintain maximum pay. Three-year outcomes were reported previously. This paper reports 4- to 8- year outcomes. During year 4 when the business was open, Therapeutic Workplace participants provided significantly more cocaine- and opiate-negative urine samples than controls; reported more days employed, higher employment income, and less money spent on drugs. During the 3 years after the business closed, Therapeutic Workplace participants only reported higher income than controls. A Therapeutic Workplace social business can maintain long-term abstinence and employment, but additional intervention may be required to sustain effects. PMID:25124257

  6. Farmer knowledge and a priori risk analysis: pre-release evaluation of genetically modified Roundup Ready wheat across the Canadian prairies.

    Science.gov (United States)

    Mauro, Ian J; McLachlan, Stéphane M; Van Acker, Rene C

    2009-09-01

    corporations, previous experience with GM canola, and a strong belief in the importance of community and environment. Farmers were critical of expert-based risk assessment, particularly RRW field trials, and believed that their LK was valuable for assessing agbiotechnology as a whole. Over 90% of canola production across the Canadian prairies makes use of herbicide-tolerant (HT) varieties. Yet, respondents were generally uniform in their criticism of RRW, regardless whether they were HT users, non-HT-users, conservation tillage or organic in approach. They had a sophisticated understanding of how GM trait confinement was intrinsically tied to grain system segregation and, ultimately, market accessibility, and were concerned that gene flow in RRW would not be contained. Organic farmers were particularly critical of RRW, in large part because certification standards prohibit the presence of GM traits. Farmers practicing conservation tillage were also at relatively great risk, in part because their dependence on glyphosate to control weeds increases the likelihood that RRW volunteer would become more difficult and costly to control. This research is the first of its kind to include farmer knowledge in the a priori risk analysis of GM crops and, arguably, given its prairie-wide scope, is the largest scale, independent-farmer-focused study on GM crops ever conducted. The surprising uniformity in attitudes between users and non-users of GM technology and among organic, conventional, conservation tillage and GM using farmers speaks to the ability of farmers to discriminate among HT varieties. Our results clearly show that prairie farmers recognize that the risks associated with RRW commercialization outweigh any benefits. Farmer knowledge systems are holistic in nature, incorporating socioeconomic, cultural, political, and agroecological factors that all can contribute meaningfully to the pre-release evaluation of GM crops. The inclusion of farmers and other stakeholders in risk

  7. A Thermally Stable Form of Bacterial Cocaine Esterase: A Potential Therapeutic Agent for Treatment of Cocaine Abuse

    Energy Technology Data Exchange (ETDEWEB)

    Brim, Remy L.; Nance, Mark R.; Youngstrom, Daniel W.; Narasimhan, Diwahar; Zhan, Chang-Guo; Tesmer, John J.G.; Sunahara, Roger K.; Woods, James H. (Michigan); (Michigan-Med); (Kentucky)

    2010-09-03

    Rhodococcal cocaine esterase (CocE) is an attractive potential treatment for both cocaine overdose and cocaine addiction. CocE directly degrades cocaine into inactive products, whereas traditional small-molecule approaches require blockade of the inhibitory action of cocaine on a diverse array of monoamine transporters and ion channels. The usefulness of wild-type (wt) cocaine esterase is hampered by its inactivation at 37 C. Herein, we characterize the most thermostable form of this enzyme to date, CocE-L169K/G173Q. In vitro kinetic analyses reveal that CocE-L169K/G173Q displays a half-life of 2.9 days at 37 C, which represents a 340-fold improvement over wt and is 15-fold greater than previously reported mutants. Crystallographic analyses of CocE-L169K/G173Q, determined at 1.6-{angstrom} resolution, suggest that stabilization involves enhanced domain-domain interactions involving van der Waals interactions and hydrogen bonding. In vivo rodent studies reveal that intravenous pretreatment with CocE-L169K/G173Q in mice provides protection from cocaine-induced lethality for longer time periods before cocaine administration than wt CocE. Furthermore, intravenous administration (pretreatment) of CocE-L169K/G173Q prevents self-administration of cocaine in a time-dependent manner. Termination of the in vivo effects of CoCE seems to be dependent on, but not proportional to, its clearance from plasma as its half-life is approximately 2.3 h and similar to that of wt CocE (2.2 h). Taken together these data suggest that CocE-L169K/G173Q possesses many of the properties of a biological therapeutic for treating cocaine abuse but requires additional development to improve its serum half-life.

  8. Peroxisome proliferator-activated receptor-gamma as a potential therapeutic target in the treatment of preeclampsia.

    LENUS (Irish Health Repository)

    McCarthy, Fergus P

    2012-01-31

    Preeclampsia is a multisystemic disorder of pregnancy characterized by hypertension, proteinuria, and maternal endothelial dysfunction. It is a major cause of maternal and perinatal morbidity and mortality and is thought to be attributable, in part, to inadequate trophoblast invasion. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor expressed in trophoblasts, and the vasculature of which activation has been shown to improve endothelium-dependent vasodilatation in hypertensive conditions. We investigated the effects of the administration of a PPAR-gamma agonist using the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. The selective PPAR-gamma agonist, rosiglitazone, was administered to pregnant rats that had undergone RUPP surgery. To investigate whether any observed beneficial effects of PPAR-gamma activation were mediated by the antioxidant enzyme, heme oxygenase 1, rosiglitazone was administered in combination with the heme oxygenase 1 inhibitor tin-protoporphyrin IX. RUPP rats were characterized by hypertension, endothelial dysfunction, and elevated microalbumin:creatinine ratios. Rosiglitazone administration ameliorated hypertension, improved vascular function, and reduced the elevated microalbumin:creatinine ratio in RUPP rats. With the exception of microalbumin:creatinine ratio, these beneficial effects were abrogated in the presence of the heme oxygenase 1 inhibitor. Administration of a PPAR-gamma agonist prevented the development of several of the pathophysiological characteristics associated with the RUPP model of preeclampsia, via a heme oxygenase 1-dependent pathway. The findings from this study provide further insight into the underlying etiology of preeclampsia and a potential therapeutic target for the treatment of preeclampsia.

  9. Therapeutic potential of ex vivo expansion of haematopoietic precursors for the treatment of accidental irradiation-induced aplasia

    International Nuclear Information System (INIS)

    Nguyen-Neildez, T.M.A.; Vetillard, J.; Thierry, D.; Nenot, J.C.; Parmentier, C.

    1996-01-01

    After whole body overexposure, the key issue is the therapeutic decision, i.e. the choice between bone marrow transplantation and other strategies. The indications of bone marrow transplantation cover only a short range of doses, provided the exposure is distributed uniformly within the body; a rare event in accidental settings. The results of the clinical trials for Granulocyte-Colony Stimulating Factor: G-CSF, Granulocyte/Macrophage Colony Stimulating Factor: GM-CSF or Interleukin 3: IL-3, in vivo and in vitro radiobiology experiments suggest that growth factor therapy could be of use after most accidental overexposures to evidence and to stimulate the remaining haematopoietic stem cells in order to shorten the duration of aplasia, although questions have been raised about growth factor infusion real clinical efficiency. Ex vivo expansion of haematopoietic precursor, stem cells and differentiated cells is a new approach of growth factor therapy, which may be of interest for the treatment of patients with accidental radiation-induced aplasia. These studies aim to expand the pool of progenitors and stem cells for transplantation or to expand differentiated cells (mainly granulocytes but also megakaryocytes) for transfusion. This is made possible due to the development of techniques allowing the selection of a population of haematopoietic progenitors and stem cells from the blood (with stimulation by growth factors prior stem cell harvesting) or bone marrow using immature cell positive selection. The next step consisting in their culture with combination of growth factors or additional stroma cells is also under development. Autologous progenitor cells generated ex vivo has been recently used with some success for reconstitution of haematopoiesis after high-dose chemotherapy. (author)

  10. Therapeutic effectiveness and safety parathyroid adenoma ablation with percutaneous ethanol injection under sonographic guidance in patients with chronic renal failure and secondary hyperparathyroidism refractory to medical treatment

    International Nuclear Information System (INIS)

    De Nubila, Eduardo; Vega, Jose; Garcia Luz; Murillo, Marlyn; Mercado, Jaime

    2010-01-01

    Secondary hyperparathyroidism unresponsive to medical treatment is a common complication in patients with chronic renal failure and prolonged dialysis therapy, which requires surgery of the parathyroid glands, with the risks and costs of surgery. Objective: To evaluate the therapeutic effectiveness and safety of ablation of parathyroid adenomas by percutaneous ethanol injection under ultrasound guidance. Method: After approval by the institutional medical ethics committee, informed written consent was obtained in 15 patients who met the inclusion criteria. Sonographically guided ethanol was injected consecutively into adenomas, with an interval of time less than six months. Results: Size, Doppler vascularity of adenomas, and the levels of parathyroid hormone, calcium and phosphorus were measured before and after ablation as criteria for treatment response in 15 patients. Of all patients, six (40%) had no therapeutic response. Therapeutic response was observed in nine patients (60%). In the latter group, five patients (33.3%) had successful response and symptomatic improvement, in two patients (13.3%), therapeutic response was suboptimal, and in two patients (13.3%), the response was unsatisfactory. The procedure was safe. Local pain, transient dysphonia and cough were considered minor complications and were the most common, with resolution in all cases. There were no major complications. Conclusion: Ablation of parathyroid adenomas with percutaneous ethanol injection and ultrasound guidance, in uremic patients with secondary hyperparathyroidism unresponsive to medical treatment is an effective and safe therapy. Studies involving more patients and longer follow up are needed in order to stablish more conclusive results

  11. A Retrospective Analysis of 5,195 Patient Treatment Sessions in an Integrative Veterinary Medicine Service: Patient Characteristics, Presenting Complaints, and Therapeutic Interventions

    Directory of Open Access Journals (Sweden)

    Justin Shmalberg

    2015-01-01

    Full Text Available Integrative veterinary medicine, the combination of complementary and alternative therapies with conventional care, is increasingly prevalent in veterinary practice and a focus of clinical instruction in many academic teaching institutions. However, the presenting complaints, therapeutic modalities, and patient population in an integrative medicine service have not been described. A retrospective analysis of 5,195 integrative patient treatment sessions in a veterinary academic teaching hospital demonstrated that patients most commonly received a combination of therapeutic modalities (39% of all treatment sessions. The 274 patients receiving multiple modalities were most frequently treated for neurologic and orthopedic disease (50.7% versus 49.6% of all presenting complaints, resp.. Older neutered or spayed dogs (mean age = 9.0 years and Dachshunds were treated more often than expected based on general population statistics. Acupuncture, laser therapy, electroacupuncture, and hydrotherapy were frequently administered (>50% patients. Neurologic patients were more likely to receive acupuncture, electroacupuncture, and therapeutic exercises but less likely than orthopedic patients to receive laser, hydrotherapy, or therapeutic ultrasound treatments (P<0.05. The results suggest that the application of these specific modalities to orthopedic and neurologic diseases should be subjected to increased evidence-based investigations. A review of current knowledge in core areas is presented.

  12. Development of a methodology to determine optimized therapeutic doses of {sup 131}I for the treatment of hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, Francisco de; Santas, Bernardo Maranhao; Dantas, Ana Leticia Almeida; Lucena, Eder Augusto [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)]. E-mail: faraujo@ird.gov.br; Melo, Rossana Corbo de; Rebelo, Ana Maria de Oliveira [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina

    2007-07-01

    Several methods can be used to determine the activity of {sup 131}I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology to evaluate therapeutic doses through the determination of biokinetic parameters and the activity of {sup 131}I deposited in the thyroid of patients submitted to the treatment of hyperthyroidism with {sup 131}I. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of {sup 131}I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The calculation of the calibration factor of the scintillation camera allows the determination of activities in the thyroid of patients in pre-established time periods through a 48-hours uptake curve. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were 39.3 {+-} 0.8 and 4.3 {+-} 0.2 respectively. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use

  13. Therapeutic ultrasound

    International Nuclear Information System (INIS)

    Crum, Lawrence A

    2004-01-01

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

  14. Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection

    OpenAIRE

    Chu, Dafeng; Gao, Jin; Wang, Zhenjia

    2015-01-01

    Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute...

  15. [The spa and health resort-based treatment of metabolic syndrome with the application of the therapeutic courses of different duration: the evaluation according long-term results].

    Science.gov (United States)

    Chalaya, E N; Botvineva, L A; Tsallagova, L V; Ahkubekova, N K; Efimenko, N V; Kaysinova, A S; Amiyants, V Yu; Vasin, V A

    The objective of the present study was to estimate the effectiveness of the new therapeutic modalities for the spa and health resort-based treatment of metabolic syndrome based on the results of the long-term follow-up observations. A total of 100 patients presenting with metabolic syndrome were recruited for the participation in the study. All of them underwent a shortened course of mineral water intake in the combination with the use of the herbal medicinal products. The results of the study give evidence of the more favorable changes in the clinical and instrumental characteristics of the patients with metabolic syndrome treated with the use of the proposed approach in comparison the patients treated by the conventional methods. Moreover, the beneficial effects of the proposed approach persisted during a longer period. The basal treatment given to our patients was supplemented by dietary therapy, therapeutic physical exercise, narzan baths, intake of mineral water having a temperature of 35-37 °С in conjunction with sulphate mineral water (narzan) cooled to 13-15 °С, and a phytococktail. The results of the long-term observations confirmed the enhanced effectiveness of the spa and health resort-based treatment of metabolic syndrome including the therapeutic courses with the intake of cooled narzan mineral water in the combination with phytococktails. This therapeutic modality increased the duration of the favorable changes of various parameters that characterize metabolic syndrome. Specifically, they persisted during 5-6 months after the application of the standard methods, were still apparent within 6-7 months after the two-week course of the treatment with cold narzan and phytococktails, and during 8-9 months when the duration of the treatment course was extended up to 3 weeks.

  16. Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson's Disease, Glioma, and Schwannoma.

    Science.gov (United States)

    Hall, Justin; Prabhakar, Shilpa; Balaj, Leonora; Lai, Charles P; Cerione, Richard A; Breakefield, Xandra O

    2016-04-01

    Extracellular vesicles present an attractive delivery vehicle for therapeutic proteins. They intrinsically contain many proteins which can provide information to other cells. Advantages include reduced immune reactivity, especially if derived from the same host, stability in biologic fluids, and ability to target uptake. Those from mesenchymal stem cells appear to be intrinsically therapeutic, while those from cancer cells promote tumor progression. Therapeutic proteins can be loaded into vesicles by overexpression in the donor cell, with oligomerization and membrane sequences increasing their loading. Examples of protein delivery for therapeutic benefit in pre-clinical models include delivery of: catalase for Parkinson's disease to reduce oxidative stress and thus help neurons to survive; prodrug activating enzymes which can convert a prodrug which crosses the blood-brain barrier into a toxic chemotherapeutic drug for schwannomas and gliomas; and the apoptosis-inducing enzyme, caspase-1 under a Schwann cell specific promoter for schwannoma. This therapeutic delivery strategy is novel and being explored for a number of diseases.

  17. COMPARATIVE STUDY OF THE THERAPEUTIC EFFICIENCY OF OXITETRACICLINE, IMIDOCARB AND DIMINAzENE, USED IN THE TREATMENT OF EQUINE THOROUGBREED HEMOPARASITES

    OpenAIRE

    Comerma Steffensen, Simon Gabriel; Arrieta-Mendoza, D.; Morales, A; Viloria, D; Romero, N.; Morales, G.; Kassar, M.

    2012-01-01

    It presents a comparative study of the therapeutic efficacy of oxytetracycline, imidocarb and diminaze- ne, used in the treatment of equine hemoparasitosis Thoroughbreds. We studied a total of 105 horses, Tho- roughbreds, all under 2 years old, during the quarantine period November to December 2011. They practice a clinical examination, blood samples were taken for a complete blood count and blood smear for disposal of taxon. They were then medicated with single dose intramuscular (IM) as fol...

  18. Kompleksowe postepowanie leczenicze nowotowrów gruczołu sutkowego = Comprehensive therapeutic treatments methods of mammary gland carcinoma

    Directory of Open Access Journals (Sweden)

    Jan Paweł Mieszkowski

    2015-07-01

    terapii nowotworów piersi ze szczególnym  skupieniem się na kompleksowym podejściem do problemu klinicznego jakim są nowotwory piersi. Ma to na celu lepszego zrozumienie roli wczesnej diagnostyki w przeciwdziałaniu rozwojowi nowotworów piersi oraz konieczności prowadzenia kompleksowych działań leczniczych (współdziałania metod leczenia z zakresu farmacji, fizjoterapii, psychologii w terapii tego schorzenia.   Summary             Breast cancers are now the most commonly diagnosed cancer amongst worldwide women, with the number of newly diagnosed cases 1 670 000 patients (in 2012. Among deaths due to cancer, breast cancer is the first cause of women death in less developed countries and the second (after lung cancer in developed countries. In Poland continuous increase of breast cancer incidences is being observed. Breast cancers are mostly diagnosed in 50 - 69 years women, but recently the number of breast cancer rates in younger women is increasing.             In the last two decades, new prevention strategies allow the detection of the disease development in its early stages, significantly increasing the chance of patients longer life or full  recovery. However, the treatment of breast cancer remains a long-term process which not gives a guarantee for the inhibition and recovery. The therapeutic efficacy of therapy methods is very diverse and always requires customization, and uses separate treatment strategies (surgery, pharmacotherapy, physiotherapy, psychotherapy, which will improve patient general health, slowing down the disease progression or improving the quality of life.             This article is an attempt to systematize the available diagnosis and treatment methods of breast cancer with a particular focus on a comprehensive approach to this clinical problem. The aim is to better understand the role of early diagnosis in prevention of breast cancer development and the need of a comprehensive approach

  19. Local production and provision of ready-to-use therapeutic food (RUTF) spread for the treatment of severe childhood malnutrition

    Science.gov (United States)

    Ready-to-use therapeutic food (RUTF) spread has been shown to be very effective in the rehabilitation of severely malnourished children and facilitates home-based therapy of these children. RUTF spread is an edible lipid-based paste that is energy dense, resists bacterial contamination, and requires...

  20. Mobile Software as a Medical Device (SaMD) for the Treatment of Epilepsy: Development of Digital Therapeutics Comprising Behavioral and Music-Based Interventions for Neurological Disorders.

    Science.gov (United States)

    Afra, Pegah; Bruggers, Carol S; Sweney, Matthew; Fagatele, Lilly; Alavi, Fareeha; Greenwald, Michael; Huntsman, Merodean; Nguyen, Khanhly; Jones, Jeremiah K; Shantz, David; Bulaj, Grzegorz

    2018-01-01

    Digital health technologies for people with epilepsy (PWE) include internet-based resources and mobile apps for seizure management. Since non-pharmacological interventions, such as listening to specific Mozart's compositions, cognitive therapy, psychosocial and educational interventions were shown to reduce epileptic seizures, these modalities can be integrated into mobile software and delivered by mobile medical apps as digital therapeutics. Herein, we describe: (1) a survey study among PWE about preferences to use mobile software for seizure control, (2) a rationale for developing digital therapies for epilepsy, (3) creation of proof-of-concept mobile software intended for use as an adjunct digital therapeutic to reduce seizures, and (4) broader applications of digital therapeutics for the treatment of epilepsy and other chronic disorders. A questionnaire was used to survey PWE with respect to preferred features in a mobile app for seizure control. Results from the survey suggested that over 90% of responders would be interested in using a mobile app to manage their seizures, while 75% were interested in listening to specific music that can reduce seizures. To define digital therapeutic for the treatment of epilepsy, we designed and created a proof-of-concept mobile software providing digital content intended to reduce seizures. The rationale for all components of such digital therapeutic is described. The resulting web-based app delivered a combination of epilepsy self-care, behavioral interventions, medication reminders and the antiseizure music, such as the Mozart's sonata K.448. To improve long-term patient engagement, integration of mobile medical app with music and multimedia streaming via smartphones, tablets and computers is also discussed. This work aims toward development and regulatory clearance of software as medical device (SaMD) for seizure control, yielding the adjunct digital therapeutic for epilepsy, and subsequently a drug-device combination

  1. The shorter the better? A follow-up analysis of 10-session psychiatric treatment including the motive-oriented therapeutic relationship for borderline personality disorder.

    Science.gov (United States)

    Kramer, Ueli; Stulz, Niklaus; Berthoud, Laurent; Caspar, Franz; Marquet, Pierre; Kolly, Stéphane; De Roten, Yves; Despland, Jean-Nicolas

    2017-05-01

    There is little research on short-term treatments for borderline personality disorder (BPD). While the core changes may occur only in long-term treatments, short-term treatments may enable the study of early generic processes of engagement in therapy and thus inform about effective treatment components. It was shown that a 10-session version of a psychiatric treatment was effective in reducing borderline symptoms at the end of this treatment [Kramer, U., Kolly, S., Berthoud, L., Keller, S., Preisig, M., Caspar, F., … Despland, J.-N. (2014). Effects of motive-oriented therapeutic relationship in a ten-session general psychiatric treatment for borderline personality disorder: A randomized controlled trial. Psychotherapy and Psychosomatics, 83, 176-186.]. Also, it was demonstrated in a randomized design that adding the motive-oriented therapeutic relationship (MOTR), following an individualized case formulation based on Plan Analysis, further increased general outcome after session 10 and had a positive effect on the early changes in self-esteem and alliance. The present study focuses on the follow-up period after this initial treatment, examining treatment density and outcomes after 6 months and service utilization after 12 months. Outcome was measured using the OQ-45. Results on a sub-sample of N = 40 patients with available OQ-45 data at follow-up (n = 21 for MOTR-treatment, n = 19 for comparison treatment) showed maintenance of gains over the follow-up period, which did not differ between both conditions. It appeared for this sample that MOTR treatments, while using the same number of sessions, lasted more weeks (i.e., lower treatment density, defined as the number of sessions per week), when compared to the treatments without MOTR. Density marginally predicted symptom reduction at follow-up. Patients in MOTR treatments had a greater likelihood of entering structured psychotherapy after the initial sessions than patients in the comparison

  2. [Effectiveness of aftercare treatment after release from prison: A first evaluation of the forensic therapeutic outpatient clinic for serious violent and sexual offenders in Berlin].

    Science.gov (United States)

    Sauter, J; Voss, T; Dahle, K-P

    2015-05-01

    The Forensic Therapeutic Outpatient Clinic (FTA) in Berlin targets the professional aftercare treatment of classified high-risk violent and sexual offenders released from prison or forensic psychiatric hospitals. A comparison sample (n = 32) matched to the patients of the FTA (complete survey n = 32) according to similar criminal histories and diagnoses (ICD-10) was collected from offenders released from prison and forensic psychiatry at a time before the FTA was established. The focus of the study was on recidivism measured by complaints received by police departments during the follow-up period. Sexual recidivism occurred significantly later in the case of released offenders with aftercare treatment compared to those without. Moreover, for the duration of aftercare treatment the general risk of recidivism was approximately 85 % lower; however, after termination of treatment the recidivism rates of both samples converged to almost the same level. Individually adapted measures should be maintained after finishing aftercare treatment; however, because prisoners released from prison are frequently less prepared than patients from forensic psychiatric hospitals, the therapeutic work often reaches its limits in these cases. Therefore, social work should be taken into account right from the start.

  3. Functionalized bioengineered spider silk spheres improve nuclease resistance and activity of oligonucleotide therapeutics providing a strategy for cancer treatment.

    Science.gov (United States)

    Kozlowska, Anna Karolina; Florczak, Anna; Smialek, Maciej; Dondajewska, Ewelina; Mackiewicz, Andrzej; Kortylewski, Marcin; Dams-Kozlowska, Hanna

    2017-09-01

    Cell-selective delivery and sensitivity to serum nucleases remain major hurdles to the clinical application of RNA-based oligonucleotide therapeutics, such as siRNA. Spider silk shows great potential as a biomaterial due to its biocompatibility and biodegradability. Self-assembling properties of silk proteins allow for processing into several different morphologies such as fibers, scaffolds, films, hydrogels, capsules and spheres. Moreover, bioengineering of spider silk protein sequences can functionalize silk by adding peptide moieties with specific features including binding or cell recognition domains. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel oligonucleotide delivery system that can be utilized to improve pharmacokinetics of RNA-based therapeutics, such as CpG-siRNA. The MS2 bioengineered silk was functionalized with poly-lysine domain (KN) to generate hybrid silk MS2KN. CpG-siRNA efficiently bound to MS2KN in contrary to control MS2. Both MS2KN complexes and spheres protected CpG-siRNA from degradation by serum nucleases. CpG-siRNA molecules encapsulated into MS2KN spheres were efficiently internalized and processed by TLR9-positive macrophages. Importantly, CpG-STAT3siRNA loaded in silk spheres showed delayed and extended target gene silencing compared to naked oligonucleotides. The prolonged Stat3 silencing resulted in the more pronounced downregulation of interleukin 6 (IL-6), a proinflammatory cytokine and upstream activator of STAT3, which limits the efficacy of TLR9 immunostimulation. Our results demonstrate the feasibility of using spider silk spheres as a carrier of therapeutic nucleic acids. Moreover, the modified kinetic and activity of the CpG-STAT3siRNA embedded into silk spheres is likely to improve immunotherapeutic effects in vivo. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel

  4. Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.

    Science.gov (United States)

    Ashizawa, Nobuyuki; Tsuji, Yasuhiro; Kawago, Koyomi; Higashi, Yoshitsugu; Tashiro, Masato; Nogami, Makiko; Gejo, Ryuichi; Narukawa, Munetoshi; Kimura, Tomoatsu; Yamamoto, Yoshihiro

    2016-05-01

    Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  5. Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatment, and Therapeutic Modalities

    Science.gov (United States)

    2011-02-01

    Therapeutic and Imaging Agents to Lung Cancer (PI and co-PI: Renata Pasqualini , Ph.D., Wadih Arap, M.D., Ph.D.) The studies outlined in this proposal...with Drs. Pasqualini , Arap, and Wistuba. The IHC staining of lung cancer TMAs (390 cases) has been completed. We are working with investigators to...Project 3, R. Pasqualini ). This project was completed and a manuscript is in preparation by Dr. Pasqualini’s lab. b) Molecular abnormalities

  6. Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection.

    Science.gov (United States)

    Chu, Dafeng; Gao, Jin; Wang, Zhenjia

    2015-12-22

    Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute lung inflammation, we demonstrated that intravenously (iv) infused NPs made from denatured bovine serum albumin (BSA) were specifically internalized by activated neutrophils, and subsequently, the neutrophils containing NPs migrated across blood vessels into inflammatory tissues. When neutrophils were depleted using anti-Gr-1 in a mouse, the transport of albumin NPs across blood vessel walls was robustly abolished. Furthermore, it was found that albumin nanoparticle internalization did not affect neutrophil mobility and functions. Administration of drug-loaded albumin NPs markedly mitigated the lung inflammation induced by LPS (lipopolysaccharide) or infection by Pseudomonas aeruginosa. These results demonstrate the use of an albumin nanoparticle platform for in situ targeting of activated neutrophils for delivery of therapeutics across the blood vessel barriers into diseased sites. This study demonstrates our ability to hijack neutrophils to deliver nanoparticles to targeted diseased sites.

  7. An assessment of the utilization of the preclinical rodent model literature in clinical trials of putative therapeutics for the treatment of alcohol use disorders.

    Science.gov (United States)

    Barajaz, Ashley M; Kliethermes, Christopher L

    2017-12-01

    Rodent models of Alcohol Use Disorders (AUD) are used extensively by preclinical researchers to develop new therapeutics for the treatment of AUD. Although these models play an important role in the development of novel, targeted therapeutics, their role in bringing therapeutics to clinical trials is unclear, as off-label use of existing medications not approved for the treatment of AUD is commonly seen in the clinic and clinical trials. In the current study, we used the Clinicaltrials.gov database to obtain a list of drugs that have been tested for efficacy in a clinical trial between 1997 and 2017. We then conducted a set of literature searches to determine which of the 98 unique drugs we identified had shown efficacy in a rodent model of an AUD prior to being tested in a clinical trial. We found that slightly less than half of the drugs tested in clinical trials (48%) had shown prior efficacy in any rodent model of an AUD, while the remaining 52% of drugs were used off-label, or in some cases, following non-published studies. This study raises the question of how clinical researchers incorporate results from preclinical studies in the decision to bring a drug to a clinical trial. Our results underscore the need for ongoing communication among preclinical and clinical researchers. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Developing Optimized Treatment Plans for Patients with Dyslipidemia in the Era of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Therapeutics.

    Science.gov (United States)

    Underberg, James A; Blaha, Michael J; Jackson, Elizabeth J; Jones, Peter H

    2017-10-01

    This educational content was derived from a live satellite symposium at the American College of Physicians Internal Medicine Meeting 2017 in San Diego, California (online at http://courses.elseviercme.com/acp/702e). This activity will focus on optimized treatment plans for patients with dyslipidemia in the era of proprotein convertase subtilisin/kexin type 9 inhibitor therapeutics. Low-density lipoprotein cholesterol has been identified as an important therapeutic target to prevent the progression of atherosclerotic disease; however, only 1 of every 3 adults with high low-density lipoprotein cholesterol has the condition under control. Expert faculty on this panel will discuss the science of proprotein convertase subtilisin/kexin type 9 inhibitors and aid physicians in the best practices to achieve low-density lipoprotein cholesterol target in their patients. Copyright © 2017. Published by Elsevier Inc.

  9. Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy

    Science.gov (United States)

    Ahn, James; Ahn, Hyung Seok; Cheong, Jae Hoon; dela Peña, Ike

    2016-01-01

    Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a “safer” approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments. PMID:26966583

  10. Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease.

    Science.gov (United States)

    Toledo-Sherman, Leticia M; Prime, Michael E; Mrzljak, Ladislav; Beconi, Maria G; Beresford, Alan; Brookfield, Frederick A; Brown, Christopher J; Cardaun, Isabell; Courtney, Stephen M; Dijkman, Ulrike; Hamelin-Flegg, Estelle; Johnson, Peter D; Kempf, Valerie; Lyons, Kathy; Matthews, Kimberly; Mitchell, William L; O'Connell, Catherine; Pena, Paula; Powell, Kendall; Rassoulpour, Arash; Reed, Laura; Reindl, Wolfgang; Selvaratnam, Suganathan; Friley, Weslyn Ward; Weddell, Derek A; Went, Naomi E; Wheelan, Patricia; Winkler, Christin; Winkler, Dirk; Wityak, John; Yarnold, Christopher J; Yates, Dawn; Munoz-Sanjuan, Ignacio; Dominguez, Celia

    2015-02-12

    We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochemical and cellular assays and their selectivity against other kynurenine pathway enzymes. We describe the optimization process that led to the identification of a program lead compound with a suitable ADME/PK profile for therapeutic development. We demonstrate that systemic inhibition of KMO in vivo with this lead compound provides pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in the periphery and in the central nervous system.

  11. Preliminary comparison of the therapeutic efficacy of accelerated relative to conventional fractionation radiotherapy by treatment of spontaneous canine malignancies

    International Nuclear Information System (INIS)

    Denman, David L.; Levin, Rebecca; Buncher, C. Ralph; Aron, Bernard S.

    1996-01-01

    Purpose/Objective: This study's ultimate goals involve development of an accelerated fractionation (AF) regimen with an integrated final concomitant boost (CB) and examination of factors prognostic of the CB's therapeutic efficacy which could be measured during the initial AF portion to determine for which patients CB should be used. These endpoints can be accurately determined quickly by evaluating the treatment (tx) of spontaneous canine veterinary patient tumors. Because surviving tumor clonogen growth rate increases after radiotherapy (RT) begins, this accelerated repopulation (AR) should be reduced by AF. Furthermore, CB using a small field encompassing only the tumor bed, given as a second daily tx during the last week of RT, should further reduce AR. The initial portion of this project which is nearing completion was designed to determine if incidentally treated normal tissues could tolerate the AF regimen and project whether addition of the tumor bed CB would also be tolerated. Materials and Methods: Currently 20 canine patients with biopsy proven localized tumors have received canine AF radiotherapy given as 3.2Gy/fraction(fx) administered 5 days a week (Mon-Fri) to a total of 15 fxs (48Gy) within 18 elapsed days. RT is given with a 60 Co teletherapy unit. Their tumor response, control, survival, and acute normal tissue responses are being directly compared to results we previously obtained from canines receiving a nearly equivalent dose/fx and total dose conventional fractionation (CF) regimen which was given alone or with adjuvant hyperthermia (HT). In that study the canines were stratified by tumor histology and anatomic site and randomly assigned to receive canine CF (3.5Gy/fx, 3 fxs/week [Mon-Wed-Fri] to 14 fxs (49Gy) in an elapsed time of approx. 30 days) either alone or followed weekly by local HT (44 deg. +/- 2 deg. C) for 30 minutes (5 HT fxs). As is currently done, these CF+/-HT patients were followed up to 3 years to quantitate the magnitudes

  12. Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, Fingolimod will change therapeutic paradigm approach

    Directory of Open Access Journals (Sweden)

    Gasperini C

    2012-07-01

    Full Text Available Claudio Gasperini,1 Serena Ruggieri21Department of Neurosciences, S Camillo Forlanini Hospital, 2Department of Neurology and Psychiatry, University of Rome “Sapienza,” Rome, ItalyAbstract: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720.Keywords: multiple sclerosis, oral compounds, fingolimod, fty720, sphingosine 1, phosphate, patient satisfaction

  13. Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials.

    Science.gov (United States)

    Zimran, Ari; Elstein, Deborah; Gonzalez, Derlis E; Lukina, Elena A; Qin, Yulin; Dinh, Quinn; Turkia, Hadhami Ben

    2018-02-01

    Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively. Consistent with the goal for bone mineral density, lumbar spine bone density improved in 87% of patients ≥18years of age. At year 4, compared with clinical ranges for healthy individuals, 86% of patients with a low baseline hemoglobin concentration had normalized, 60% with a low baseline platelet count had normalized, 67% with baseline splenomegaly had normalized, 58% with hepatomegaly had normalized, and lumbar spine bone density had normalized in 53% of adults. The decade-old therapeutic goals do not reflect the potential for normalization of clinical parameters in ERT-treated patients. Goals consistent with normalization or near-normalization should be considered. ClinicalTrials.gov identifiers: NCT00430625, NCT00553631, NCT00635427. Copyright © 2016 Shire Human Genetic Therapies, Inc. Published by Elsevier Inc. All rights reserved.

  14. Web-Based Treatment Program Using Intensive Therapeutic Contact for Patients With Eating Disorders : Before-After Study

    NARCIS (Netherlands)

    ter Huurne, E.D.; Postel, Marloes Gerda; de Haan, H.A.; Drossaert, Constance H.C.; Jong, C.A.J.

    2013-01-01

    Background: Although eating disorders are common in the Netherlands, only a few patients are treated by mental health care professionals. To reach and treat more patients with eating disorders, Tactus Addiction Treatment developed a web-based treatment program with asynchronous and intensive

  15. Response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient's therapeutic CPAP requirement.

    Science.gov (United States)

    Landry, Shane A; Joosten, Simon A; Sands, Scott A; White, David P; Malhotra, Atul; Wellman, Andrew; Hamilton, Garun S; Edwards, Bradley A

    2017-08-01

    Upper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility. Therapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (P crit ) and ventilation at CPAP level of 0 cmH 2 O (V passive )) were retrospectively analysed from a randomized controlled trial (n = 20) comparing the combination of oxygen and eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index (AHI) plus an AHICPAP requirement compared with non-responders (6.6 (5.4-8.1)  cmH 2 O vs 8.9 (8.4-10.4) cmH 2 O, P = 0.007), consistent with their reduced collapsibility (lower P crit , P = 0.017, higher V passive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve (AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both P crit (AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and V passive (AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cmH 2 O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies. Therapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and

  16. Therapeutic results after ultrasound-guided intratissue percutaneous electrolysis (EPI®) in the treatment of rectus abdominis-related groin pain in professional footballers: a pilot study.

    Science.gov (United States)

    Moreno, Carlos; Mattiussi, Gabriele; Núñez, Francisco J

    2016-10-01

    Rectus abdominis-related groin pain (RAGP) is one of the possible clinical patterns that determine pubalgia. RAGP is one of the typical patterns in footballers and is due to the degeneration and tendinopathy of the distal tendon, at the level of the two pubic tubercles. Intratissue percutaneous electrolysis (EPI) is a novel technique used in the treatment of tendinopathies. The aim of this study was to examine the therapeutic benefits of EPI by contrasting the two basic components that characterize RAGP: painful symptoms and resultant functional deficits. Eight professional footballers at Udinese Calcio Spa Football Club underwent ultrasound-guided EPI intervention. No other type of treatment was combined with EPI. Pain was monitored with the Verbal Rating Scale, while functional deficit was monitored using the Patient Specific Functional Scale. The scales implementation took place before treatment, then 24 hours, 1 week, 1 month and 6 months after the end of treatment. Treatment with EPI produced a complete reduction of pain symptoms in one month and enabled excellent functional recovery for walking and jogging in one week; for getting out of bed, running, jumping and kicking within one month from the end of the treatment. Treatment with ultrasound-guided EPI has shown encouraging clinical results for RAGP. Data are preliminary: considering the limitations of this study more complex design studies are necessary to test the efficacy of the technique. This study introduces the EPI technique for the first time in the treatment of professional footballers suffering from RAGP. Its future use is proposed as a treatment solution, including complementary to conservative treatment.

  17. A novel therapeutic approach for the treatment of central sleep apnea: The remedē{sup ®} system

    Energy Technology Data Exchange (ETDEWEB)

    Germany, Robin, E-mail: rgermany@respicardia.com [University of Oklahoma School of Medicine (United States); Joseph, Susan [Washington University School of Medicine (United States); James, Kristofer [Respicardia, Inc., Hopkins, MN (United States); Kao, Andrew [University of Missouri School of Medicine, Kansas City (United States); St. Luke' s Mid-America Heart Institute, Kansas City, MO (United States)

    2014-06-15

    Central sleep apnea (CSA) occurs primarily in cardiovascular patients and is associated with high morbidity and mortality. The disorder often is unrecognized due to the overlap of symptoms with those of the underlying cardiac disease. CSA can be easily diagnosed with a sleep study. Following optimization of all co-morbidities, the therapeutic approach available currently focuses on mask-based therapies which suffer from poor patient adherence. A new therapy, the remedē{sup ®} System, has been developed; it utilizes a transvenous, fully implantable system providing phrenic nerve stimulation intended to restore a more normal breathing pattern. The therapy demonstrated promising results based on an initial chronic study and a randomized trial is underway to further evaluate safety and efficacy of this novel system in patients with CSA.

  18. A novel therapeutic approach for the treatment of central sleep apnea: The remedē® system

    International Nuclear Information System (INIS)

    Germany, Robin; Joseph, Susan; James, Kristofer; Kao, Andrew

    2014-01-01

    Central sleep apnea (CSA) occurs primarily in cardiovascular patients and is associated with high morbidity and mortality. The disorder often is unrecognized due to the overlap of symptoms with those of the underlying cardiac disease. CSA can be easily diagnosed with a sleep study. Following optimization of all co-morbidities, the therapeutic approach available currently focuses on mask-based therapies which suffer from poor patient adherence. A new therapy, the remedē ® System, has been developed; it utilizes a transvenous, fully implantable system providing phrenic nerve stimulation intended to restore a more normal breathing pattern. The therapy demonstrated promising results based on an initial chronic study and a randomized trial is underway to further evaluate safety and efficacy of this novel system in patients with CSA

  19. Role of Therapeutic Plasma Exchange in Treatment of Tumefactive Multiple Sclerosis-Associated Low CD4 and CD8 Levels

    Directory of Open Access Journals (Sweden)

    Kristen Lew

    2016-08-01

    Full Text Available We report a 35-year-old healthy male who developed central nervous system inflammatory demyelinating disease consistent with tumefactive multiple sclerosis. About 2 weeks after onset of symptoms and prior to initiation of therapy, the patient had lymphopenia and low CD4 and CD8 levels. His lymphocyte count was 400 cells/µl (850–3,900 cells/µl, CD4 was 193 cells/µl (490–1,740 cells/µl and CD8 was 103 cells/µl (180–1,170 cells/µl. He was treated with intravenous methylprednisolone followed by therapeutic plasma exchange, the levels of CD4 and CD8 normalized, and ultimately, he recovered completely.

  20. Clinical study of fetal liver transplantation in treatment of four cases of accidental or therapeutic acute radiation sickness

    International Nuclear Information System (INIS)

    1989-01-01

    This report summarized the clinical experience of fetal liver transplantation (FLT) in the medical handling of accidental (case 1) or therapeutic (cases 2-4) acute radiation sickness of severe haemopoietic form. In addition to receiving 80 mg/kg of cyclophosphamide, cases 2, 3 and 4 were exposed to total body single irradiation of 5.5, 5.0 and 5.0 Gy, respectively; while case 1 was exposed to whole body irradiation of 5.2 Gy only. The total number of nucleated fetal liver cells transplanted was 2.26-4.1 x 10 8 /kg. Only 2-5% of peripheral blood cells of cases 2, 3 and 4 were found to have allogeneic marker. The author points out that FLT may be beneficial in those cases of accidental irradiation or patients with acute leukemia when there were no HLA-identical bone marrow donors available

  1. Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

    Science.gov (United States)

    Peluso, Michael J; Spudich, Serena

    2014-09-01

    The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

  2. Cortical hemorrhage-associated neurological deficits and tissue damage in mice are ameliorated by therapeutic treatment with nicotine.

    Science.gov (United States)

    Anan, Junpei; Hijioka, Masanori; Kurauchi, Yuki; Hisatsune, Akinori; Seki, Takahiro; Katsuki, Hiroshi

    2017-09-01

    Intracerebral hemorrhage (ICH) is associated with diverse sets of neurological symptoms and prognosis, depending on the site of bleeding. Relative rate of hemorrhage occurring in the cerebral cortex (lobar hemorrhage) has been increasing, but there is no report on effective pharmacotherapeutic approaches for cortical hemorrhage either in preclinical or clinical studies. The present study aimed to establish an experimental model of cortical hemorrhage in mice for evaluation of effects of therapeutic drug candidates. Type VII collagenase at 0.015 U, injected into the parietal cortex, induced hemorrhage expanding into the whole layer of the posterior parts of the sensorimotor cortex in male C57BL/6 mice. Mice with ICH under these conditions exhibited significant motor deficits as revealed by beam-walking test. Daily administration of nicotine (1 and 2 mg/kg), with the first injection given at 3 hr after induction of ICH, improved motor performance of mice in a dose-dependent manner, although nicotine did not alter the volume of hematoma. Immunohistochemical examinations revealed that the number of neurons was drastically decreased within the hematoma region. Nicotine at 2 mg/kg partially but significantly increased the number of remaining neurons within the hematoma at 3 days after induction of ICH. ICH also resulted in inflammatory activation of microglia/macrophages in the perihematoma region, and nicotine (1 and 2 mg/kg) significantly attenuated the increase of microglia. These results suggest that nicotine can provide a therapeutic effect on cortical hemorrhage, possibly via its neuroprotective and anti-inflammatory actions. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Revision muduloblastoma and treatment of posterior fossa ependinoma analysis of new therapeutic strategies; Revision de tratamiento de meduloblastoma y ependinoma de fosa posterior analisis de nuevas estrategias terapeuticas

    Energy Technology Data Exchange (ETDEWEB)

    Mara, C.; Rodríguez, R.; Torres, M.; Roldán, G.; Ferreira, V. [Depto. de Oncologia del Hospital de Clínicas, Facultad de Medicina, Universidad de la Republica, Montevideo (Uruguay); Instituto Nacional de Oncología, Ministerio de Salud Pública, Montevideo (Uruguay)

    2010-12-15

    Fulltext: In general the primary tumors of S.n.c. required at some stage in their treatment, use of radiotherapy, usually as postoperative treatment or exclusively in the case that the surgery is not possible, in turn for treatment of some of these tumors association with chemotherapy has shown to be beneficial. In the case of medulloblastomas, ependymomas of the posterior fossa tumors of the choroid plexus and the pineal gland, irradiation technique that used for their particular spread is the total craniospinal irradiation. In this paper a review of the treatment techniques are performed, the overall survival and disease-free survival and complications treatments, in patients with medulloblastoma and ependymomas treated in the Department. Oncology Hospital and Clinics in INDO period of approximately 30 years. Results were compared with the international literature and analysis was performed new perspectives on the therapeutic radiation treatment (radiotherapy 3D shaped for example) and its association with chemotherapy. The results will be analyzed in Congress.

  4. Botulinum toxin as treatment for focal dystonia : a systematic review of the pharmaco-therapeutic and pharmaco-economic value

    NARCIS (Netherlands)

    Zoons, E.; Dijkgraaf, M. G. W.; Dijk, J. M.; van Schaik, I. N.; Tijssen, M. A.

    2012-01-01

    Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the

  5. Botulinum toxin as treatment for focal dystonia: a systematic review of the pharmaco-therapeutic and pharmaco-economic value

    NARCIS (Netherlands)

    Zoons, E.; Dijkgraaf, M. G. W.; Dijk, J. M.; van Schaik, I. N.; Tijssen, M. A.

    2012-01-01

    Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the

  6. Imbalanced Protein Expression Patterns of Anabolic, Catabolic, Anti-Catabolic and Inflammatory Cytokines in Degenerative Cervical Disc Cells: New Indications for Gene Therapeutic Treatments of Cervical Disc Diseases

    Science.gov (United States)

    Mern, Demissew S.; Beierfuß, Anja; Fontana, Johann; Thomé, Claudius; Hegewald, Aldemar A.

    2014-01-01

    Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix

  7. PirocarbotrateTM: A new radiopharamaceutical labelled with 32P for the treatment of solid tumours. Therapeutic action and radiodosimetric calculations

    International Nuclear Information System (INIS)

    Zubillaga, M.; Boccio, J.; Calmanovici, G.; Goldman, C.; Caro, R.; Nicolini, J.; Ughetti, R.; Sapia, S.; Frahm, I.; Gamboni, M.

    2001-01-01

    Pirocarbotrat TM is a gelatin protected charcoal suspension labelled with chromic [ 32 P] pyrophosphate. To evaluate its effectiveness as a therapeutic agent for the treatment of solid tumours, studies of therapeutic action and dose calculations, were carried out after an intratumoural single dose of this radiopharmaceutical. We used 28 female Sprague Dawley rats in which experimental mammary adenocarcinomas were induced. The tumours were injected with a single dose of 18.5 MBq. Once the experiment was finished, animals were sacrificed to extract their organs and the injected tumours, the activity of which were measured by the Bremsstrahlung photons of 32 P. Representative pieces of tissues from the treated and control tumours were selected for histolopathological examination. The results show that after 32 days of treatment, the percentage of activity found in the tumour was 84.50 ± 2.60%, while the percentage of activity found in the other evaluated organs was almost negligible. The therapeutic action was evaluated by the percentage of tumour regression (P.T.R.) which was 78.3%. The treated tumours showed closely packed black charcoal particles at the injection point, which are shown always in sharply demarcated big clusters, always associated with necrotic debris from the neoplastic tissue. The extension of the necrotic tissue in the tumour vicinity is variable, ranging from 1 to 4 mm. Radiodosimetric calculations, carried out according to the Medical Internal Radiation Dose Committee (MIRD) of the Society of Nuclear Medicine, demonstrate that the dose absorbed by the tumours was 6200 Gy. The dose absorbed by the rest of the organism is 0.533 Gy. The ratio dose to the tumour/dose to the rest of the organism is 1.17x10 4 . We can conclude that Pirocarbotrat TM , a non-sealed beta radiation source, behaves very closely to a sealed beta radiation source when it is intratumourally injected into solid tumours. (author)

  8. "They Treat Us Like Human Beings"--Experiencing a Therapeutic Sex Offenders Prison: Impact on Prisoners and Staff and Implications for Treatment.

    Science.gov (United States)

    Blagden, Nicholas; Winder, Belinda; Hames, Charlie

    2016-03-01

    Research evidence demonstrates that sex offender treatment programmes (SOTPs) can reduce the number of sex offenders who are reconvicted. However, there has been much less empirical research exploring the experiences and perspectives of the prison environment within which treatment takes place. This is important, particularly for sexual offenders, as they often face multiple stigmas in prison. This study used a mixed-methods approach to explore the experiences of prisoners and staff at a therapeutically orientated sexual offenders' prison to understand whether the prison environment was conducive to rehabilitation. The quantitative strand of the research sampled prisoners (n = 112) and staff (n = 48) from a therapeutically orientated sex offenders prison. This strand highlighted that both prisoners and staff had positive attitudes toward offenders and high beliefs that offenders could change. Importantly, the climate was rated positively and, in particular, participants had very high ratings of "experienced safety." The qualitative strand of the research consisted of semistructured interviews with prisoners (n = 15) and a range of prison staff (n = 16). The qualitative analysis revealed positive prisoner views toward staff relationships, with most participants articulating that the prison and its staff had contributed to positive change in prisoners. Crucially, the environment was perceived as safe and allowed prisoners "headspace" to work through problems and contemplate change. This research offers some support to the notion that context is important for sex offender rehabilitation. © The Author(s) 2014.

  9. Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction.

    Science.gov (United States)

    Xue, Xiaodong; Liu, Yu; Zhang, Jian; Liu, Tao; Yang, Zhonglu; Wang, Huishan

    2015-01-01

    Objectives. Low survival rate of mesenchymal stem cells (MSCs) severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI). Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs) or empty vector (vector-MSCs). MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and plate-derived growth factor (PDGF) increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

  10. [Migration biography and culture as determinants of diagnostic and therapeutic processes in mentally ill immigrants. A systematic differentiation based on a qualitative content analysis of treatment courses].

    Science.gov (United States)

    Behrens, Katharina; Calliess, Iris Tatjana

    2008-01-01

    A systematic differentiation of culture- in contrast to migration-related influence factors in diagnostic and therapeutic processes is introduced. "Culture-related" refers to characteristics caused by values, behavior norms and religious attitudes of the ethnic community a person belongs to. "Migration-specific" refers to consequences of moving one's residence from one country to another (e. g., absence of family, trouble with authorities concerning the legal status or ambivalence with respect to returning to the home country). Based on a theoretic background of these determinants, categories for a content analysis were defined and applied to the treatment records of n = 55 first generation immigrants treated in a psychiatric day clinic of an university hospital. The results suggest that migration biography should not only be considered as affecting vulnerability in the genesis of a mental illness, but rather be classified as a factor of at least as much relevance for therapeutic situations as the usually named cultural diversity: summarizing the results of the qualitative content analysis of the entire treatment courses more cases were influenced by migration specific aspects rather than culture specific aspects.

  11. Clinical utility of therapeutic drug monitoring in biological disease modifying anti-rheumatic drug treatment of rheumatic disorders: a systematic narrative review.

    Science.gov (United States)

    Van Herwaarden, Noortje; Van Den Bemt, Bart J F; Wientjes, Maike H M; Kramers, Cornelis; Den Broeder, Alfons A

    2017-08-01

    Biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) have improved the treatment outcomes of inflammatory rheumatic diseases including Rheumatoid Arthritis and spondyloarthropathies. Inter-individual variation exists in (maintenance of) response to bDMARDs. Therapeutic Drug Monitoring (TDM) of bDMARDs could potentially help in optimizing treatment for the individual patient. Areas covered: Evidence of clinical utility of TDM in bDMARD treatment is reviewed. Different clinical scenarios will be discussed, including: prediction of response after start of treatment, prediction of response to a next bDMARD in case of treatment failure of the first, prediction of successful dose reduction or discontinuation in case of low disease activity, prediction of response to dose-escalation in case of active disease and prediction of response to bDMARD in case of flare in disease activity. Expert opinion: The limited available evidence does often not report important outcomes for diagnostic studies, such as sensitivity and specificity. In most clinical relevant scenarios, predictive value of serum (anti-) drug levels is absent, therefore the use of TDM of bDMARDs cannot be advocated. Well-designed prospective studies should be done to further investigate the promising scenarios to determine the place of TDM in clinical practice.

  12. Therapeutic effects of strontium-89 combined with endocrine therapy for treatment of bone metastasis in patients with prostate cancer

    International Nuclear Information System (INIS)

    Guo Deming

    2009-01-01

    Objective: To evaluate the effects of strontium-89 ( 89 Sr) combined with endocrine therapy for the treatment of bone metastasis in patients with advanced prostate cancer. Methods: 45 cases of prostate cancer with bone metastasis were randomly divided into 2 groups: patients in study group (23 cases) were given 89 Sr combined with endocrine therapy while patients in control group (22 cases) were given endocrine therapy only. The effect on pain relief, the serum PSA level, hemogram and biochemical indicators of hepatic and renal function were observed. Results: The pain degree was not statistically significant between two groups before treatment (P>0.05) and was statistically significant after treatment (P 89 Sr radionuclide combined with endocrine therapy was more effective than endocrine therapy alone in relief of the pain from bone metastasis and reduction of metastasis size in patients with advaced prostatic cancer. (authors)

  13. Screening vs. non-screening detected colorectal cancer: Differences in pre-therapeutic work up and treatment.

    Science.gov (United States)

    Saraste, D; Martling, A; Nilsson, P J; Blom, J; Törnberg, S; Janson, M

    2017-06-01

    Objectives To compare preoperative staging, multidisciplinary team-assessment, and treatment in patients with screening detected and non-screening detected colorectal cancer. Methods Data on patient and tumour characteristics, staging, multidisciplinary team-assessment and treatment in patients with screening and non-screening detected colorectal cancer from 2008 to 2012 were collected from the Stockholm-Gotland screening register and the Swedish Colorectal Cancer Registry. Results The screening group had a higher proportion of stage I disease (41 vs. 15%; p team-assessed than the non-screening group ( p team-assessed than patients with surgically resected cancers ( p team assessed more extensively than patients with non-screening detected cancers. Staging and multidisciplinary team assessment prior to endoscopic resection was less complete compared with surgical resection. Extensive surgical and (neo)adjuvant treatment was given in stage I disease. Participation in screening reduced the risk of emergency surgery for colorectal cancer.

  14. Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review.

    Science.gov (United States)

    Campagnolo, N; Johnston, S; Collatz, A; Staines, D; Marshall-Gradisnik, S

    2017-06-01

    Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is characterised by unexplained fatigue for at least 6 months accompanied by a diverse but consistent set of symptoms. Diet modification and nutritional supplements could be used to improve patient outcomes, such fatigue and quality of life. We reviewed and discussed the evidence for nutritional interventions that may assist in alleviating symptoms of CFS/ME. Medline, Cinahl and Scopus were systematically searched from 1994 to May 2016. All studies on nutrition intervention were included where CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing). Seventeen studies were included that meet the inclusion criteria. Of these, 14 different interventions were investigated on study outcomes. Many studies did not show therapeutic benefit on CFS/ME. Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10. This review identified insufficient evidence for the use of nutritional supplements and elimination or modified diets to relieve CFS/ME symptoms. Studies were limited by the number of studies investigating the interventions, small sample sizes, study duration, variety of instruments used, and studies not reporting dietary intake method. Further research is warranted in homogeneous CFS/ME populations. © 2017 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.

  15. Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection

    Science.gov (United States)

    Stohr, Thomas; Palomo, Concepción; Piedra, Pedro A.; Gilbert, Brian E.; Mas, Vicente; Millar, Andrena; Power, Ultan F.; Stortelers, Catelijne; Allosery, Koen; Melero, José A.; Depla, Erik

    2015-01-01

    Respiratory syncytial virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly individuals. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanized monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F protein with subnanomolar affinity. ALX-0171 demonstrated in vitro neutralization superior to that of palivizumab against prototypic RSV subtype A and B strains. Moreover, ALX-0171 completely blocked replication to below the limit of detection for 87% of the viruses tested, whereas palivizumab did so for 18% of the viruses tested at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease. PMID:26438495

  16. Preparation of (177Lu-DOTAn-PAMAM-[Nimotuzumab-F(ab’2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Titis Sekar Humani

    2017-12-01

    Full Text Available Intact monoclonal antibodies with a high molecular weight tend to have a poor pharmacokinetic profile and tumor penetration, and potential for eliciting host antibody responses. F(ab’2 fragments smaller than intact monoclonal antibodies that still maintain antigen binding could solve this problem. The objective of this study was to optimize the digestion process of nimotuzumab, an anti-EGFR monoclonal antibody, into its F(ab’2 fragment and investigate its potential as a therapeutic radioimmunoconjugate. Optimal conditions for digestion of nimotuzumab to its F(ab’2 fragment were found to be 6 hours of digestion time with a pH of 3.5 and 1:100 mol ratio of pepsin to nimotuzumab. The purity of the F(ab’2-nimotuzumab was confirmed by SDS-PAGE and HPLC analysis. Prior to its labeling with lutetium-177 radionuclide, the nimotuzumab-F(ab’2 was conjugated to DOTA-PAMAM dendrimer [DOTA denotes 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, PAMAM denotes poly(amidoamine] to form conjugate of (DOTAn-PAMAM-[nimotuzumab-F(ab’2]. Radiolabeling of DOTA-PAMAM-[nimotuzumab-F(ab’2] conjugate with 177Lu resulted in (177Lu-DOTAn-PAMAM-[nimotuzumab-F(ab’2] with radiochemical purity > 99% after purification with a PD-10 column. Further studies still need to be performed in order to confirm the potential of this radioimmunoconjugate as a radioimmunotherapeutic agent for EGFR overexpressed cancers.

  17. Evaluation of psoriasis patients’ attitudes toward benefit–risk and therapeutic trade-offs in their choice of treatments

    Directory of Open Access Journals (Sweden)

    Eliasson L

    2017-02-01

    Full Text Available Lina Eliasson,1 Anthony P Bewley,2 Farhan Mughal,3 Karissa M Johnston,4 Andreas Kuznik,5 Chloe Patel,1 Andrew J Lloyd1 1Clinical Outcomes Assessment, ICON Clinical Research UK Ltd, 2Department of Dermatology, Whipps Cross University Hospital, Barts Health National Health Service Trust, London, 3Health Economics Outcomes Research, Celgene Ltd, Uxbridge, UK; 4Epidemiology, ICON Commercialisation and Outcomes, Vancouver, BC, Canada; 5Global Health Economics and Outcomes Research, Celgene Corporation, Summit, NJ, USA Objective: Treatment options for psoriasis offer trade-offs in terms of efficacy, convenience, and risk of adverse events. We evaluated patients’ preferences with respect to benefit–risk in the treatment of psoriasis. Methods: A discrete choice experiment was conducted in adults from the UK with moderate-to-severe psoriasis using an orthogonal design with 32 hypothetical choice sets. Participants were randomly assigned to one of two surveys with 16 choice sets. Patients’ preferences were investigated with respect to the following attributes: reduction in body surface area affected by psoriasis, treatment administration (frequency and mode of delivery, short-term diarrhea or nausea risk, and 10-year risk of developing melanoma or nonmelanoma skin cancer, tuberculosis, or serious infections. A mixed effects logistic regression model generated relative preferences between treatment profiles. Results: Participants (N=292 had a strong preference to avoid increased risk of melanoma or nonmelanoma skin cancer (odds ratio [OR]: 0.44 per 5% increased 10-year risk and increased risks of tuberculosis and serious infections (both ORs: 0.73 per 5% increased 10-year risk and preferred once-weekly to twice-daily tablets (OR: 0.76 and weekly (OR: 0.56 or fortnightly (OR: 0.65 injections. Participants preferred avoiding treatments that may cause diarrhea or nausea in the first 2 weeks (OR: 0.87 per 5% increase and preferred treatments that

  18. AD-venture program: therapeutic biking for the treatment of depression in long-term care residents with dementia.

    Science.gov (United States)

    Buettner, Linda L; Fitzsimmons, Suzanne

    2002-01-01

    This project tested an innovative intervention in a controlled clinical investigation of a nonpharmacological treatment of depression in long-term care residents with dementia. This treatment utilized a wheelchair bicycle in a recreation therapy protocol, which combined small group activity therapy and one-to-one bike rides with a staff member. Depression levels were significantly reduced in the two-week portion of the study with levels maintained in the 10-week maintenance period. Improvements were also found in sleep and levels of activity engagement.

  19. Therapeutic Effects of Topical Minoxidil or Rosemary and the Combination of Both on the treatment of Alopecia areata

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Lohrasb

    2015-02-01

    Full Text Available Background & Objectives: Considering the prevalence of Alopecia areata, , failure of treatment, and the unknown pathogenesis of this illness, a comparative study was performed by using topical Minoxidil 2% and topical rosemary solution alone and in combination to treatment this disease. Materials & Methods: This study is a clinical trial performed on 200 patients with Alopecia areata referring to Hamzeh clinic of Fasa during the years 2012 and 2013. They were divided into four groups by random permutation, each group contained 50 patients. Group one received the combination of topical Minoxidil 2% and topical rosemary, group two received only topical Minoxidil 2% solution, group three received only topical rosemary solution and the fourth group, the case-control group, did not receive any medication and were just advised to rub the site of the disease for the same period of time. The patients were under observation for one year. Results: The Results of this investigation showed that the best remissions after treatments were as follow (respectively: combination of topical Minoxidil 2% and topical rosemary (27 patient=54 %, Minoxidil 2% solution (23 patients =46%, rosemary solution (21 patients =42%, and case- control group (9 patients =18%. These results showed that despite better response to the combination of rosemary and Minoxidil solutions in comparison to the two other treated groups, the changes were minimal and statistically insignificant (P-value =0.0411. Conclusion: Using the combination of both rosemary and Minoxidil is more effective than the individual one on treatment of Alopecia areata.

  20. Examining the Relation between the Therapeutic Alliance, Treatment Adherence, and Outcome of Cognitive Behavioral Therapy for Children with Anxiety Disorders

    Science.gov (United States)

    Liber, Juliette M.; McLeod, Bryce D.; Van Widenfelt, Brigit M.; Goedhart, Arnold W.; van der Leeden, Adelinde J. M.; Utens, Elisabeth M. W. J.; Treffers, Philip D. A.

    2010-01-01

    Little is known about the contribution of technical and relational factors to child outcomes in cognitive behavioral therapy (CBT) for children with anxiety disorders. This study investigated the association between treatment adherence, the child-therapist alliance, and child clinical outcomes in manual-guided individual- and group-based CBT for…

  1. Examining the relation between the therapeutic alliance, treatment adherence, and outcome of cognitive behavioral therapy for children with anxiety disorders

    NARCIS (Netherlands)

    Liber, Juliette M.; McLeod, Bryce D.; van Widenfelt, Brigit M.; Goedhart, Arnold W.; van der Leeden, Adelinde J. M.; Utens, Elisabeth M. W. J.; Treffers, Philip D. A.

    2010-01-01

    Little is known about the contribution of technical and relational factors to child outcomes in cognitive behavioral therapy (CBT) for children with anxiety disorders. This study investigated the association between treatment adherence, the child-therapist alliance, and child clinical outcomes in

  2. MO-AB-BRA-06: Dynamic FLT PET for Investigating Potential Synergistic Therapeutic Targets During Anti-Angiogenic Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Scarpelli, M; Perlman, S; Liu, G [University of Wisconsin-Madison, Madison, WI (United States); Simoncic, U [Jozef Stefan Institute, Ljubljana (Slovenia); Jeraj, R [University of Wisconsin-Madison, Madison, WI (United States); Jozef Stefan Institute, Ljubljana (Slovenia)

    2016-06-15

    Purpose: Novel treatment strategies for metastatic cancer patients involve synergistically combining treatments with the hope of improving outcomes. This study investigated changes in tumor proliferative and vascular characteristics derived from dynamic [F-18]FLT PET during antiangiogenic treatment with the goal of identifying synergistic treatment opportunities. Methods: Patients with various solid cancers underwent continuous three-week cycles of anti-angiogenic treatment with intermittent dosing (two-weeks-on/one-week-off). Patients received up to six dynamic FLT PET/CT scans (days 0, 14, and 21 of cycle 1 (C1) and cycle 3 (C3)). Tumor proliferative (Kflt, net uptake rate) and vascular parameters (K1 blood-to-tissue transfer; Vb, vascular fraction) were calculated using a two-tissue compartment four-rate parameter kinetic model. Relative changes in these parameters, from day 0 to 14 (TxResp) and day 14 to 21 (offTxResp), were calculated. Significant differences were tested using Wilcoxon signed-rank test and significant correlations were tested using Spearman correlation. Results: Thirty patients were evaluable for C1 offTxResp with median values for Kflt, K1, and Vb of +30%, +35% and +30%, respectively. The fractions of patients with positive C1 offTxResp were: 21/30 for Ki, 24/30 for K1, 21/30 for Vb, and 12/30 had positive offTxResp for all three kinetic parameters. The offTxResp in C3 was not significantly different from C1 for any of the kinetic parameters. Significant correlations were found between TxResp and offTxResp in C1 for Kflt (ρ=-0.52, p=0.014), K1 (ρ=−0.61, p=0.003) and Vb (ρ=−0.80, p<0.001). Similar correlations were found for Kflt (ρ=-1, p=0.017) and K1 (ρ=−1, p=0.017) for the five patients evaluable in C3. Conclusion: Dynamic FLT PET showed evidence of distinct vascular and proliferative increases during off treatment weeks that could potentially be targeted with synergistic therapy. Early changes in kinetic parameters were

  3. NGO-provided free HIV treatment and services in Burkina Faso: scarcity, therapeutic rationality and unfair process

    Directory of Open Access Journals (Sweden)

    Ridde Valéry

    2012-03-01

    Full Text Available Abstract Until 2010, Burkina Faso was an exception to the international trend of abolishing user fees for antiretroviral treatment (ART. Patients were still expected to pay 1,500F CFA (2 Euros per month for ART. Nevertheless, many non-governmental organizations (NGOs exempted patients from payment. The objective of this study was to investigate how NGOs selected the beneficiaries of payment exemptions for government-provided ART and rationed out complementary medical and psychosocial services. For this qualitative study, we conducted 13 individual interviews and three focus group discussions (n = 13 persons with program staff in nine NGOs (4,000 patients, two NGO coordinating structures and one national program. These encounters were recorded and transcribed, and their content was thematically analyzed. The results were presented to the NGOs for feedback. Results indicate that there are no concrete guidelines for identifying patients warranting payment exemptions. Formerly, ART was scarce in Burkina Faso and the primary criterion for treatment selection was clinical. Our results suggest that this scarcity, mediated by an approach we call sociotherapeutic rationality (i.e. maximization of clinical success, may have led to inequities in the provision of free ART. This approach may be detrimental to assuring equity since the most impoverished lack resources to pay for services that maximize clinical success (e.g. viral load that would increase their chances of being selected for treatment. However, once selected into treatment, attempts were made to ration-out complementary services more equitably. This study demonstrates the risks entailed by medication scarcity, which presents NGOs and health professionals with impossible choices that run counter to the philosophy of equity in access to treatment. Amid growing concerns of an international funding retreat for ART, it is important to learn from the past in order to better manage the potentially

  4. NGO-provided free HIV treatment and services in Burkina Faso: scarcity, therapeutic rationality and unfair process.

    Science.gov (United States)

    Ridde, Valéry; Somé, Paul Andre; Pirkle, Catherine M

    2012-03-06

    Until 2010, Burkina Faso was an exception to the international trend of abolishing user fees for antiretroviral treatment (ART). Patients were still expected to pay 1,500F CFA (2 Euros) per month for ART. Nevertheless, many non-governmental organizations (NGOs) exempted patients from payment. The objective of this study was to investigate how NGOs selected the beneficiaries of payment exemptions for government-provided ART and rationed out complementary medical and psychosocial services. For this qualitative study, we conducted 13 individual interviews and three focus group discussions (n = 13 persons) with program staff in nine NGOs (4,000 patients), two NGO coordinating structures and one national program. These encounters were recorded and transcribed, and their content was thematically analyzed. The results were presented to the NGOs for feedback. Results indicate that there are no concrete guidelines for identifying patients warranting payment exemptions. Formerly, ART was scarce in Burkina Faso and the primary criterion for treatment selection was clinical. Our results suggest that this scarcity, mediated by an approach we call sociotherapeutic rationality (i.e. maximization of clinical success), may have led to inequities in the provision of free ART. This approach may be detrimental to assuring equity since the most impoverished lack resources to pay for services that maximize clinical success (e.g. viral load) that would increase their chances of being selected for treatment. However, once selected into treatment, attempts were made to ration-out complementary services more equitably.This study demonstrates the risks entailed by medication scarcity, which presents NGOs and health professionals with impossible choices that run counter to the philosophy of equity in access to treatment. Amid growing concerns of an international funding retreat for ART, it is important to learn from the past in order to better manage the potentially inequitable consequences

  5. Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study.

    Science.gov (United States)

    Wallach, Joshua D; Ciani, Oriana; Pease, Alison M; Gonsalves, Gregg S; Krumholz, Harlan M; Taylor, Rod S; Ross, Joseph S

    2018-03-21

    The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product's actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01-2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95

  6. Review article: the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease.

    Science.gov (United States)

    Woodhouse, C A; Patel, V C; Singanayagam, A; Shawcross, D L

    2018-01-01

    Mortality from chronic liver disease is rising exponentially. The liver is intimately linked to the gut via the portal vein, and exposure to gut microbiota and their metabolites translocating across the gut lumen may impact upon both the healthy and diseased liver. Modulation of gut microbiota could prove to be a potential therapeutic target. To characterise the changes in the gut microbiome that occur in chronic liver disease and to assess the impact of manipulation of the microbiome on the liver. We conducted a PubMed search using search terms including 'microbiome', 'liver' and 'cirrhosis' as well as 'non-alcoholic fatty liver disease', 'steatohepatitis', 'alcohol' and 'primary sclerosing cholangitis'. Relevant articles were also selected from references of articles and review of the ClinicalTrials.gov website. Reduced bacterial diversity, alcohol sensitivity and the development of gut dysbiosis are seen in several chronic liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease and primary sclerosing cholangitis. Perturbations in gut commensals could lead to deficient priming of the immune system predisposing the development of immune-mediated diseases. Furthermore, transfer of stool from an animal with the metabolic syndrome may induce steatosis in a healthy counterpart. Patients with cirrhosis develop dysbiosis, small bowel bacterial overgrowth and increased gut wall permeability, allowing bacterial translocation and uptake of endotoxin inducing hepatic and systemic inflammation. Manipulation of the gut microbiota with diet, probiotics or faecal microbiota transplantation to promote the growth of "healthy" bacteria may ameliorate the dysbiosis and alter prognosis. © 2017 John Wiley & Sons Ltd.

  7. Review on the Potential Therapeutic Roles of Nigella sativa in the Treatment of Patients with Cancer: Involvement of Apoptosis

    Directory of Open Access Journals (Sweden)

    Hamid Mollazadeh

    2017-09-01

    Full Text Available Nigella sativa (N. sativa, family Ranunculaceae is a medicinal plant that has been widely used for centuries throughout the world as a natural remedy. A wide range of chemical compounds found in N. sativa expresses its vast therapeutic effects. Thymoquinone (TQ is the main component (up to 50% in the essential oil of N. sativa. Also, pinene (up to 15%, p-cymene (40%, thymohydroquinone (THQ, thymol (THY, and dithymoquinone (DTQ are other pharmacologically active compounds of its oil. Other terpenoid compounds, such as carvacrol, carvone, 4-terpineol, limonenes, and citronellol, are also found in small quantities in its oil. The main pharmacological characteristics of this plant are immune system stimulatory, anti- inflammatory, hypotensive, hepatoprotective, antioxidant, anti-cancer, hypoglycemic, anti- tussive, milk production, uricosuric, choleretic, anti-fertility, and spasmolytic properties. In this regard, we have searched the scientific databases PubMed, Web of Science, and Google Scholar with keywords of N. sativa, anti-cancer, apoptotic effect, antitumor, antioxidant, and malignancy over the period from 2000 to 2017. The effectiveness of N. sativa against cancer in the blood system, kidneys, lungs, prostate, liver, and breast and on many malignant cell lines has been shown in many studies, but the molecular mechanisms behind that anti-cancer role are still not clearly understood. From among the many effects of N. sativa, including its anti-proliferative effect, cell cycle arrest, apoptosis induction, ROS generation, anti-metastasis/anti-angiogenesis effects, Akt pathway control, modulation of multiple molecular targets, including p53, p73, STAT-3, PTEN, and PPAR-γ, and activation of caspases, the main suggestive anti-cancer mechanisms of N. sativa are its free radical scavenger activity and the preservation of various anti-oxidant enzyme activities, such as glutathione peroxidase, catalase, and glutathione-S- transferase. In this review

  8. Macromolecular therapeutics.

    Science.gov (United States)

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Adherence to recommendations of the Therapeutic Positioning Report about treatment with oral anticoagulants in elderly patients with atrial fibrillation. The ESPARTA study.

    Science.gov (United States)

    Suárez Fernández, Carmen; Mostaza, Jose María; Castilla Guerra, Luis; Cantero Hinojosa, Jesus; Suriñach, Josep Maria; Acosta de Bilbao, Fernando; Tamarit, Juan José; Diaz Diaz, José Luis; Hernandez, Jose Luis; Cazorla, Daniel; Ràfols, Carles

    2017-10-06

    To evaluate the adherence to the recommendations in clinical practice performed by the Therapeutic Positioning Report (TPR) of the Spanish Agency of Medicines and Sanitary Products about the treatment with oral anticoagulants in patients aged≥75 years old with nonvalvular atrial fibrillation (NVAF) treated in Internal Medicine departments in Spain. Observational, cross-sectional and multicenter study in which 837 patients aged≥75 years old with NVAF, with stable treatment with oral anticoagulants at least 3 months before inclusion, and that had started treatment with oral anticoagulants before the inclusion period were included. Mean age was 83.0±5.0 years old, mean CHADS 2 score 3.2±1.2, mean CHA 2 DS 2 -VASc score 5.0±1.4, and mean HAS-BLED score 2.1±0.9. A percentage of 70.8 of patients were treated with vitamin K antagonists (VKA) and the rest of patients with direct oral anticoagulants (DOACs). A percentage of 65.6 of patients treated with VKA did not follow the recommendations made by the TPR compared with 43.0% of patients treated with DOACs (P<.0001). In the case of VKA, the main reason for being considered as not appropriate according to the TPR was having poor control of anticoagulation and not switching to DOACs, whereas in the case of DOACs, it was not receiving the adequate dose according to the TPR. In a high proportion of anticoagulated elderly patients with NVAF in Spain, the recommendations performed by the TPR are not followed, particularly with VKA, since patients are not switched to DOACs despite time in therapeutic range. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  10. Chronic myeloid leukemia: an overview of the determinants of effectiveness and therapeutic response in the first decade of treatment with imatinib mesylate in a Brazilian hospital

    Directory of Open Access Journals (Sweden)

    Danielle Maria Camelo Cid

    2013-01-01

    Full Text Available Background: In the last decade, there has been a revolution in chronic myeloid leukemia treatment with the introduction of tyrosine kinase inhibitors with imatinib mesylate becoming the frontline therapy. Objective: To evaluate the therapeutic efficacy of imatinib mesylate in treating chronic myeloid leukemia patients and to identify factors related to therapeutic efficacy. Methods: This retrospective study was based on information obtained from patients'records in the Hematology Service of Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará (HUWC / UFC. All patients diagnosed with chronic myeloid leukemia that took imatinib mesylate for a minimum of 12 months in the period from January 2001 to January 2011 were included. From a population of 160 patients, 100 were eligible for analysis. Results: The study population consisted of 100 patients who were mostly male (51% with ages rangingbetween 21 and 40 years (42%, from the countryside (59%, in the chronic phase (95%, with high-riskprognostic factors (40%; the prognosis of high risk was not associated with complete hematologic responseor complete cytogenetic response, but correlated to complete molecular response or major molecularresponse. Reticulin condensation was associated with complete hematologic response and completecytogenetic response. It was found that 53% of patients had greater than 90% adherence to treatment. Thehigh adherence was correlated to attaining complete cytogenetic response in less than 12 months. Moreover,20% of patients had good response. Conclusion: Significant changes are indispensable in the monitoring of patients with chronic myeloid leukemia. Thus, the multidisciplinary team is important as it provides access to the full treatment and not just to medications.

  11. [Cost-effectiveness of the clinical treatment of Grave's disease in a public University Hospital: a retrospective analysis and prospective projection for a therapeutic approach].

    Science.gov (United States)

    Lima, Nicolau; Knobel, Meyer; Camargo, Rosalinda Y; Tomimori, Eduardo; Medeiros-Neto, Geraldo

    2005-08-01

    The aim of the present study was to evaluate a new proposal for increasing compliance to the clinical management of patients with Graves' disease (GD) in a large and public University Hospital. The patients were carefully selected (no previous GD treatment, goiter volume less than 6 mL must be living in the metro area of São Paulo), received medication at no cost, were contacted frequently by the social worker and alerted for the date of consultation and only referred to a single endocrinologist during all phases of treatment. We recruited 229 patients with GD that were initially treated with methimazole (MMI--60 mg q.d) in a single daily dose followed by a combination of MMI (20 mg) plus L-T4 (100 microg) daily for 24 months. Only 83 patients (36.2%) completed the protocol and were subdivided in: Group 1 (n= 34) that were in remission for 3 years after discontinuation of the MMI and Group 2 (n= 49) that presented recurrence of GD between 2 and 36 months without MMI. Predictive factors associated with remission were: decrease of the glandular volume, serum TG< 40 ng/mL and normal TRAb values. We concluded that in spite of a careful protocol planned to increase compliance, more than 60% of patients with GD did not complete the therapeutic trial and were referred for radioiodine treatment. The solution for this low therapeutic success for GD should be the possible identification of factors that would indicate patients that are not inclined to follow a long period of clinical therapy.

  12. Short-term effects of manipulative treatment versus a therapeutic home exercise protocol for chronic cervical pain

    DEFF Research Database (Denmark)

    Galindez-Ibarbengoetxea, Xabier; Setuain, Igor; Ramírez-Velez, Robinson

    2018-01-01

    BACKGROUND: While both manipulative treatment and physical exercises are used to treat cervical pain, it remains unclear which is most effective. OBJECTIVE: To compare the short-term effects of high-velocity, low-amplitude manipulation techniques (MT) with those of home-exercise (HE) with stretch......BACKGROUND: While both manipulative treatment and physical exercises are used to treat cervical pain, it remains unclear which is most effective. OBJECTIVE: To compare the short-term effects of high-velocity, low-amplitude manipulation techniques (MT) with those of home-exercise (HE...... scale (VAS); neck disability index (NDI); pressure pain thresholds; cervical spine range of motion and electromyography during the cranio-cervical flexion test was measured before and one week after the intervention. RESULTS: After the intervention, both groups showed improved (P

  13. State-of-the-Art Treatment of Irritable Bowel Syndrome – Recent Advances and Emerging Therapeutic Alternatives

    Directory of Open Access Journals (Sweden)

    Magnus Simrén

    2013-11-01

    Full Text Available Irritable bowel syndrome (IBS is a highly prevalent functional disorder characterised by chronic and recurrent abdominal pain and altered bowel habit. Numerous pharmacological and non pharmacological treatment options have proven to have some benefit in the condition, and a multidisciplinary approach should ensure that treatment is tailored to the individual. Recently, an enhanced understanding of the pathophysiological processes underlying the condition has led to the development of new therapies, including prokinetic agents targeting serotonin (5-HT pathways, and pro-secretory agents. Many are still at an early stage of clinical development, however, some have demonstrated improved outcomes in clinical trials and have gained regulatory approval. Lubiprostone, a calcium channel activator and linaclotide, a novel secretagogue that activates the guanylate cyclase C receptor, have demonstrated improvement of abdominal pain as well as improved bowel function in patients with IBS with constipation (IBS-C in a series of randomised, placebo-controlled studies.

  14. Therapeutic result of radioactive nuclide 90Sr/90Y treatment in patients with benign prostatic hypertrophy (BPH)

    International Nuclear Information System (INIS)

    Chen Hanchao; Li Yuying

    2008-01-01

    Objective: To study the effect of radioactive nuclide 90 Sr/ 90 Y treatment in patients with benign prostatic hypertrophy (BPH). Methods: Sixty patients with BPH were treated with a course of transurethral radioactive nuclide 90 Sr/ 90 Y therapy. Results: The severity of BPH was assessed with four parameters: maximal flow rate (MFR), volume of residual urine (VRU), international prostatic symptom score (IPSS) and volume (size) of prostate. In this series, the total effective rate was 93.33% with no treatment- related mortality. Favorable changes of the parameters after a course of radioactive nuclide therapy were significant. Conclusion: Radioactive nuclide 90 Sr/ 90 Y therapy for patients with BPH was safe, easily performed and quite effective. This procedure is worth popularizing in appropriate patients. (authors)

  15. Planning and Evaluation of Radio-Therapeutic Treatment of Head-and-Neck Cancer Using PET/CT scanning

    DEFF Research Database (Denmark)

    Hollensen, Christian

    represent a work within the automatic definition of organs and tumours. The thesis includes a summary of the prior methods employed for automatic segmentation and 3 articles describing segmentation algorithms of different areas of application for radiation therapy. Variation within and between manual...... and automatic segmentation methods is documented in the thesis. The last article of the thesis analyses treatment outcome difference due to manual delineation variation....

  16. Therapeutic Efficacy with Treatment-related Toxicities of 177Lu-labeled Bombesin Derivative for the Peptide Receptor Radiotherapy

    International Nuclear Information System (INIS)

    Lim, Jae Cheong; Cho, Eun Ha; Lee, So Young

    2015-01-01

    The gastrin-releasing peptide receptor (GRPR) has been shown to be overexpressed in many human tumours, including breast cancer, prostate cancer, small cell lung cancer, ovarian cancers, endometrial cancers, and gastrointestinal stromal tumors. In particular, GRPR expression is high in 83 % of invasive primary prostatic carcinomas. These results suggest that 177 Lu-labeled bombesin derivative has promising characteristics as a novel nuclear medicine, especially for the treatment of GRPR over-expressing prostate tumors

  17. Therapeutic Phlebotomy is Safe in Children with Sickle Cell Anaemia and can be Effective Treatment for Transfusional Iron Overload

    OpenAIRE

    Aygun, Banu; Mortier, Nicole A.; Kesler, Karen; Lockhart, Alexandre; Schultz, William H.; Cohen, Alan R.; Alvarez, Ofelia; Rogers, Zora R.; Kwiatkowski, Janet L.; Miller, Scott T.; Sylvestre, Pamela; Iyer, Rathi; Lane, Peter A.; Ware, Russell E.

    2015-01-01

    Serial phlebotomy was performed on sixty children with sickle cell anaemia, stroke and transfusional iron overload randomized to hydroxycarbamide in the Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy procedures with only 33 adverse events, all of which were grade 2. Among 23 children completing 30 months of study treatment, the net iron balance was favourable (−8.7 mg Fe/kg) with significant decrease in ferritin, although liver iron concentration remained un...

  18. UFT and leucovorin: a review of its clinical development and therapeutic potential in the oral treatment of cancer.

    Science.gov (United States)

    Hoff, P M; Pazdur, R; Benner, S E; Canetta, R

    1998-07-01

    UFT is an oral antineoplastic drug combining uracil and tegafur in a 4:1 molar ratio. Tegafur acts as a prodrug of 5-fluorouracil (5-FU), being slowly metabolized by cytochrome P450 to 5-FU. Uracil competitively inhibits the metabolism of 5-FU, resulting in increased plasma and tumor 5-FU concentrations. At equimolar doses, higher peak plasma 5-FU concentrations are achieved with UFT plus oral leucovorin with similar systemic 5-FU exposure compared with low-dose continuous 5-FU infusions. The elimination half-life of 5-FU following UFT administration is approximately 7 h compared with 0.2 h with i.v. 5-FU. In phase II studies of UFT plus oral leucovorin for the treatment of advanced colorectal cancer, response rates ranged from 25 to 42%. UFT plus oral leucovorin is well tolerated, with manageable diarrhea being the only dose-limiting toxicity; the regimen is not associated with significant myelosuppression, mucositis, hand-foot syndrome or alopecia. UFT, with or without leucovorin, has also been evaluated alone or in combination with other cytotoxic agents for the treatment of advanced lung, breast and gastric cancers. UFT has also been evaluated as adjuvant therapy for colorectal, breast, gastric, head and neck, and superficial bladder cancers. UFT plus leucovorin offers patients an entirely oral cancer treatment, and appears to provide potential advantages over bolus 5-FU regimens with regard to toxicity and convenience of administration. These benefits should be advantageous in the adjuvant setting, as well as in advanced disease settings in which palliation is an important consideration. Ongoing clinical trials will further define the role of this promising oral treatment regimen.

  19. Id-1 gene and gene products as therapeutic targets for treatment of breast cancer and other types of carcinoma

    Science.gov (United States)

    Desprez, Pierre-Yves; Campisi, Judith

    2014-08-19

    A method for treatment of breast cancer and other types of cancer. The method comprises targeting and modulating Id-1 gene expression, if any, for the Id-1 gene, or gene products in breast or other epithelial cancers in a patient by delivering products that modulate Id-1 gene expression. When expressed, Id-1 gene is a prognostic indicator that cancer cells are invasive and metastatic.

  20. Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G.

    Science.gov (United States)

    Ogata, Shohei; Shimizu, Chisato; Franco, Alessandra; Touma, Ranim; Kanegaye, John T; Choudhury, Biswa P; Naidu, Natasha N; Kanda, Yutaka; Hoang, Long T; Hibberd, Martin L; Tremoulet, Adriana H; Varki, Ajit; Burns, Jane C

    2013-01-01

    Although intravenous immunoglobulin (IVIG) is highly effective in Kawasaki disease (KD), mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia) content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I), the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient's own endogenous IgG. We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (s)ST6Gal-I levels were measured by ELISA. There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals.

  1. Characterization of the interaction between therapeutical carbon ions and bone-like materials and related impact on treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Eichhorn, Anna; Durante, Marco [GSI Helmholtzzentrum fuer Schwereionen, Darmstadt (Germany); TU Darmstadt (Germany); Carlino, Antonio [University of Palermo (Italy); Kaderka, Robert; Kraemer, Michael; La Tessa, Chiara; Scifoni, Emanuele [GSI Helmholtzzentrum fuer Schwereionen, Darmstadt (Germany)

    2013-07-01

    Radiotherapy is one of the most common and effective therapies for cancer. The treatment planning system for ions TRiP98 was developed at GSI, Darmstadt. In TRiP98, the interaction between primary radiation and tissue is modeled from experimental data measured in water and rescaled to other tissue. This approximation is not accurate enough for biological materials whose elemental composition besides density deviates significantly from water. The nuclear attenuation of carbon beams in bone-like materials was measured and an estimation of the fragmentation cross section was done. In parallel, the dose profile inhomogeneity predicted by TRiP98 at the interface between water and bones was investigated and measured at HIT (Heidelberg). A 3D treatment plan was delivered in a water phantom equipped with bone targets. Pin-point ionization chambers and X-ray dosimetric films were used for measuring the dose at different positions. As a further step, the measured cross sections of carbon ions in bone have been implemented in TRiP98. The comparison of the dose profiles calculated with the standard and benchmarked versions of the treatment planning will give an estimate of the improvement.

  2. Hataedock treatment has preventive therapeutic effects for atopic dermatitis through skin barrier protection in Dermatophagoides farinae-induced NC/Nga mice.

    Science.gov (United States)

    Cha, Ho-Yeol; Ahn, Sang-Hyun; Cheon, Jin-Hong; Park, Sun-Young; Kim, Kibong

    2017-07-12

    Hataedock treatment is traditionally used for the purpose of preventing the future skin disease by feeding herbal extracts to the newborn in traditional Chinese and Korean medicine. This study investigated the preventive therapeutic effects of Hataedock (HTD) treatment for atopic dermatitis (AD) through skin barrier protection in Dermatophagoides farinae-induced NC/Nga mice. To the HTD treatment group, the extract of Coptis japonica Makino and Glycyrrhiza uralensis Fischer, which analyzed with High Performance Liquid Chromatography (HPLC)-fingerprint for quality consistency, was administered orally to the 3-week-old mice before inducing AD. After that, Dermatophagoides farinae was applied except the control group to induce AD-like skin lesions. We confirmed the effects of HTD on morphological changes, protection of skin barrier, regulation of Th2 differentiation, inflammation regulation and induction of apoptosis through histochemistry, immunohistochemistry, and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. HTD effectively reduced edema, angiogenesis and skin lesion. HTD also increased the levels of liver X receptor (LXR) and filaggrin but decreased the level of protein kinase C (PKC) (pprotection of skin barrier. Therefore, HTD may have potential applications for alternative and preventive treatment in the management of AD. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  3. Role of CTA1R7K-COL-DD as a novel therapeutic mucosal tolerance-inducing vector for treatment of collagen-induced arthritis.

    Science.gov (United States)

    Hasselberg, Annemarie; Schön, Karin; Tarkowski, Andrej; Lycke, Nils

    2009-06-01

    To determine whether a cholera toxin-derived, novel immunomodulating fusion protein, CTA1R7K-COL-DD, carrying the class II major histocompatibility complex H-2q-restricted type II collagen peptide aa 259-274, can induce therapeutic tolerance and prevent collagen-induced arthritis (CIA) when administered intranasally in DBA/1 mice, and to assess whether ADP-ribosylation at the mucosal membranes exerts a regulatory function such that the outcome of tolerance or immune enhancement can be controlled. DBA/1 mice with CIA were treated intranasally with CTA1R7K-COL-DD. The therapeutic effect was monitored for 46 days after the onset of disease. Clinical scoring of disease, histologic examination of inflammation, and bone erosion were assessed, and cytokine levels were determined in the serum or supernatants from splenocytes stimulated with recall antigen. The protective effect of CTA1R7K-COL-DD resulted in roughly 60% of the mice having no clinical signs or histologic evidence of disease after treatment, and those with CIA had significantly milder disease with less bone erosion. The protective status was associated with lower serum titers of IgG1, IgG2a, IgG2b, and IgG3 anticollagen and a substantial decrease in the production of interleukin-6 (IL-6), IL-17, and interferon-gamma, while levels of IL-10 were markedly up-regulated both in the serum and at the T cell level. The enzymatically inactive mutant fusion protein CTA1R7K-COL-DD provided substantial therapeutic protection against CIA following intranasal administration. The mechanism behind the effect appears to be mediated by peptide-specific regulatory T cells induced by mucosal exposure to the peptide containing CTA1R7K-COL-DD vector. In addition, ADP-ribosylation at the mucosal membranes acts as a key regulator controlling mucosal tolerance or immunity.

  4. Steps Toward Creating A Therapeutic Community for Inpatients Suffering from Chronic Ulcers: Lessons from Allada Buruli Ulcer Treatment Hospital in Benin.

    Directory of Open Access Journals (Sweden)

    Arnaud Setondji Amoussouhoui

    2016-07-01

    Full Text Available Reducing social distance between hospital staff and patients and establishing clear lines of communication is a major challenge when providing in-patient care for people afflicted by Buruli ulcer (BU and chronic ulcers. Research on hospitals as therapeutic communities is virtually non-existent in Africa and is currently being called for by medical anthropologists working in the field of health service and policy planning. This paper describes a pioneering attempt to establish a therapeutic community for patients suffering from BU and other chronic ulcers requiring long term hospital care in Benin.A six-month pilot project was undertaken with the objectives of establishing a therapeutic community and evaluating its impact on practitioner and patient relations. The project was designed and implemented by a team of social scientists working in concert with the current and previous director of a hospital serving patients suffering from advanced stage BU and other chronic ulcers. Qualitative research initially investigated patients' understanding of their illness and its treatment, identified questions patients had about their hospitalization, and ascertained their level of social support. Newly designed question-answer health education sessions were developed. Following these hospital wide education sessions, open forums were held each week to provide an opportunity for patients and hospital staff to express concerns and render sources of discontent transparent. Patient group representatives then met with hospital staff to problem solve issues in a non-confrontational manner. Psychosocial support for individual patients was provided in a second intervention which took the form of drop-in counseling sessions with social scientists trained to serve as therapy facilitators and culture brokers.Interviews with patients revealed that most patients had very little information about the identity of their illness and the duration of their treatment. This

  5. Therapeutic Nanodevices

    Science.gov (United States)

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

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

  6. Comparison of the effect of low-power laser with therapeutic ultrasound on the treatment of rotator cuff tendonitis

    Directory of Open Access Journals (Sweden)

    asghar Akbari

    2009-01-01

    Full Text Available Akbari A1 1. Assistant Professor, Department of Physiotherapy, Faculty of Medicine, Zahedan University of Medical Sciences Abstract Background: Shoulder pain is the third most prevalent cause of musculoskeletal disorder after low back and cervical pains. Most of the shoulder symptoms are attributed to the rotator cuff. The objective of this study was to compare the effects of low-power laser therapy with ultrasound therapy on the patients with rotator cuff tendonitis. Materials and methods: This clinical trial was performed in Zahedan university of medical sciences in 2006. Thirty patients with rotator cuff tendonitis were randomly assigned to either a low-power laser therapy group (15 patients or an ultrasound therapy group (15 patients. Strength (kg of shoulder abductor, and internal and external rotator muscles, as well as range (degree of shoulder abduction, and internal and external rotation were measured before and after intervention using hand-held dynamometer and goniometer respectively. The pain was evaluated using the visual analogue scale. In the laser group, a low-level Ga-As laser was applied with a 100 mw point probe (average power, wave length of 905 nm, pulse duration of 200 ns, 6 J/cm2 dosage, 5 KHz frequency, and lasting 3 minutes. The ultrasound treatment was applied with a power of 1 W/cm2, a frequency of 1 MHz, pulse mode of 1:4, and lasting 10 minutes on each occasion. The treatment was carried out 3 times weekly for 10 days. The data were analyzed using independent sample t-test and paired t-test. Results: The pain in the laser group was significantly decreased from 6.06±1.6 to 5±1.3 in abduction, from 5.3±1.5 to 4.7±1.3 in internal rotation, and from 5.06±1.4 to 4.3±1.44 in external rotation (p0.05. A significant improvement after treatment was observed in the laser group in measures of shoulder abductor, internal rotator and external rotator muscles strength compared to those of the ultrasound therapy group (p<0

  7. Systems approach for the selection of micro-RNAs as therapeutic biomarkers of anti-EGFR monoclonal antibody treatment in colorectal cancer

    Science.gov (United States)

    Deyati, Avisek; Bagewadi, Shweta; Senger, Philipp; Hofmann-Apitius, Martin; Novac, Natalia

    2015-01-01

    miRNA plays an important role in tumourgenesis by regulating expression of oncogenes and tumour suppressors. Thus affects cell proliferation and differentiation, apoptosis, invasion and angiogenesis. miRNAs are potential biomarkers for diagnosis, prognosis and therapies of different forms of cancer. However, relationship between response of cancer patients towards targeted therapy and the resulting modifications of the miRNA transcriptome in the context of pathway regulation is poorly understood. With ever-increasing pathways and miRNA-mRNA interaction databases, freely available mRNA and miRNA expression data in multiple cancer therapy have produced an unprecedented opportunity to decipher the role of miRNAs in early prediction of therapeutic efficacy in diseases. Efficient translation of -omics data and accumulated knowledge to clinical decision-making are of paramount scientific and public health interest. Well-structured translational algorithms are needed to bridge the gap from databases to decisions. Herein, we present a novel SMARTmiR algorithm to prospectively predict the role of miRNA as therapeutic biomarker for an anti-EGFR monoclonal antibody i.e. cetuximab treatment in colorectal cancer.

  8. RNA interference-based therapeutics for human immunodeficiency virus HIV-1 treatment: synthetic siRNA or vector-based shRNA?

    Science.gov (United States)

    Subramanya, Sandesh; Kim, Sang-Soo; Manjunath, N; Shankar, Premlata

    2010-02-01

    Despite the clinical benefits of highly active antiretroviral therapy (HAART), the prospect of life-long antiretroviral treatment poses significant problems, which has spurred interest in developing new drugs and strategies to treat HIV infection and eliminate persistent viral reservoirs. RNAi has emerged as a therapeutic possibility for HIV. We discuss progress in overcoming hurdles to translating transient and stable RNAi enabling technologies to clinical application for HIV; covering the past 2 - 3 years. HIV inhibition can be achieved by transfection of chemically or enzymatically synthesized siRNAs or by DNA-based vector systems expressing short hairpin RNAs (shRNAs) that are processed intracellularly into siRNA. We compare these approaches, focusing on technical and safety issues that will guide the choice of strategy for clinical use. Introduction of synthetic siRNA into cells or its stable endogenous production using vector-driven shRNA have been shown to suppress HIV replication in vitro and, in some instances, in vivo. Each method has advantages and limitations in terms of ease of delivery, duration of silencing, emergence of escape mutants and potential toxicity. Both appear to have potential as future therapeutics for HIV, once the technical and safety issues of each approach are overcome.

  9. Combined therapeutic use of oral alitretinoin and narrowband ultraviolet-B therapy in the treatment of Hailey-Hailey disease

    Directory of Open Access Journals (Sweden)

    Kaitlin A. Vanderbeck

    2014-11-01

    Full Text Available Hailey-Hailey disease (HHD is a chronic familial bullous disease characterized by recurrent blisters and erosions typically at friction-prone areas of the body accompanied by acantholysis upon histologic examination. There are a number of therapies used in the management of HHD. Its symptoms have been effectively treated with antimicrobial therapies, corticosteroids and other agents such as cyclosporine and prednisone. However, such treatments are not always effective. Therefore, there is a need for new treatments for the management of HHD. In this report, a patient with long-standing HHD responsive only to high levels of prednisone is described. After the successful tapering and cessation of oral prednisone the patient began a new combination therapy of complementary doses of oral alitretinoin, and narrowband UVB therapy, which yielded a favorable response within 2-3 weeks. After 6 weeks, a mono-therapy of daily (30 mg oral alitretinoin was sufficient to maintain successful near-complete remission of the disease.

  10. Safety and therapeutic efficacy of artesunate suppositories for treatment of malaria in children in Papua New Guinea.

    Science.gov (United States)

    Karunajeewa, Harin A; Kemiki, Adedayo; Alpers, Michael P; Lorry, Kerry; Batty, Kevin T; Ilett, Kenneth F; Davis, Timothy M

    2003-03-01

    Although suppositories of artemisinin derivatives may be a valuable option for treatment of malaria in children when circumstances prevent oral and parenteral therapy, few confirmatory data have been published. We assessed the safety and efficacy of rectal artesunate in 47 children ages 5 to 10 years with uncomplicated malaria acquired in a hyperendemic area of Papua New Guinea. Thirty were symptomatic and had Plasmodium falciparum parasitemia >2000/microl (Group 1), 12 had and either a parasitemia suppositories were well-tolerated. After 24 h only one child (from Group 1) had persistent parasitemia, and only one (from Group 3) had not defervesced. These two children received intramuscular quinine and recovered uneventfully. Three Group 2 children redeveloped fever and tachycardia at 24 h, but each responded to simple supportive measures and remained aparasitemic. Intrarectal artesunate is safe, effective initial treatment for uncomplicated malaria in children. A transient fever spike can sometimes occur after parasite clearance. We recommend that children with uncomplicated malaria receive two doses of > or =10 mg/kg rectal artesunate within the first 24 h.

  11. Combined embolization with multiple materials for the treatment of esophagogastric varices: an analysis of clinical therapeutic effect

    International Nuclear Information System (INIS)

    Lu Yanping; Qin Haopu; Zhang Mengzeng

    2011-01-01

    Objective: To evaluate the clinical efficacy of percutaneous transhepatic combined embolization with multiple materials in treating esophagogastric varices. Methods: A total of 48 patients with esophagogastric varices complicated by bleeding due to ruptured varices were enrolled in this study. Percutaneous transhepatic combined embolization with Gelfoam, ethanol and stainless steel coils was carried out in all patients. The clinical results were analyzed. Results: Superselective catheterization and subsequent combined embolization procedure were successfully completed in all patients. In 17 patients with acute upper gastrointestinal bleeding, one died seven days after the treatment because of general failure. Postoperative gastroscopic examination was performed in 33 patients, which showed that esophagogastric varices were completely obliterated in 27 patients and markedly improved in six patients. A total of 35 patients were followed up for 4-36 months. During the follow-up period rebleeding occurred in 5 and death in 2 patients. Conclusion: For the treatment of esophagogastric varices, combined embolization with multiple materials is mini-invasive, safe and effective. It is of value to popularize this technique in clinical practice. (authors)

  12. Post-evaluation of the neurophaties treatment post-trauma with therapeutic laser. Model in sciatic nerve of frog

    International Nuclear Information System (INIS)

    Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernandez, Maria G. H.; Jasso, Jose L. C.; Lira, Maricela O. F.; Flores, Mariana A.; Balderrama, Vicente L.

    2010-01-01

    The purpose of this study was to evaluate the compound nerve action potential amplitude and latency measured to determine the degree of myelination and the number of fibers stimulated in a model of stimulated frog sciatic nerve laser at 810 nm as perioperative treatment after injury. It used 30 bullfrogs (Rana catesbeiana) to obtain 60 sciatic nerves forming four groups, groups 1 and 2 worked with nerves in vitro, were dissected in humid chambers for placing isolated organ, was recorded on compound nerve action potential, the second group laser was applied at 24, 48, 72, 96 and 120 hours and at the same time were placed in 10% formalin. Groups 3 and 4 are worked in vivo localizing the nerve and causing damage through compression, occurred over the compound nerve action potential to assess the degree of myelination and the number of fibers stimulated, the group 4 was applied to 810 nm laser (500 Hz, 10 J, 200 mW) after injury, after 48 hours, three frogs were sacrificed by introducing the nerves in 10% formalin. The latency recorded by stimulating the sciatic nerve of frog to 0.5 mA and 100 ms in groups 1 and 2 show significant differences (p 000), as to the extent, if any statistically significant difference. (p<0.001 and p<0.000). The laser produces a favorable response in the treatment of paresthesia (post-traumatic neuropathy).

  13. Rethinking Therapeutic Misconception in Biobanking

    DEFF Research Database (Denmark)

    Tupasela, Aaro; Snell, Karoliina; Cañada, Jose

    2017-01-01

    Some authors have noted that in biobank research participants may be guided by what is called therapeutic misconception, whereby participants attribute therapeutic intent to research procedures.This article argues that the notion of therapeutic misconception is increasingly less justified when...... underpinnings for the need to separate research and treatment, and thus the notion of therapeutic misconception in the fi rst place. We call this tension between research and treatment ambivalent research advancement to highlight the difficulties that various actors have in managing such shifts within...

  14. Hypertension Treatment in Patients with Metabolic Syndrome and/or Type 2 Diabetes Mellitus: Analysis of the Therapy Effectivity and the Therapeutic Inertia in Outpatient Study.

    Science.gov (United States)

    Farský, Štefan; Strišková, Andrea; Borčin, Marián

    2018-01-01

    We have analysed the database of 1,595 consecutive patients visiting our department of cardiology and internal medicine clinic in 2005-2014. The analysis included 13,990 visit records, and the average number of visits per patient was 8.5 ± 7.0. Our goals were to evaluate the effectivity of hypertension treatment as for drug choice, decrease of sBP and dBP associated with a certain drug, a drug combination, and therapeutic inertia in patients with metabolic syndrome and/or diabetes mellitus. The final number of patients for analysis who fulfilled the inclusion criteria for interpenetration of both diagnostic circles was 570. Results . 15% of patients were treated using hypertension monotherapy, 70% of patients were treated using 2- to 4-drug combination therapy, and 15% of patients were treated using 5- to 6-drug combination. The drugs used most frequently were perindopril (perin), nitrendipine (nitre), amlodipine (amlo), telmisartan (telmi), hydrochlorothiazide (hydro), rilmenidine, and nebivolol (used in >100 patients). The most significant decrease of sBP was associated with treatment by nitre, hydro, telmi, and urapidil (>19 mmHg). The most significant decrease of dBP was associated with treatment by nitre, hydro, telmi, and verapamil (>10 mmHg). The most significant decrease of both sBP and dBP was associated with treatment using 3-drug combination of telmi + hydro + spironolactone (41 and 16 mmHg, resp.), telmi + hydro + nitre (34 and 15 mmHg, resp.), and telmi + hydro + urapidil (34 and 15 mmHg, resp.). At the last visit, 281 out of 413 patients at the first visit had sBP >140 mmHg (68%); that is, sBP control was 32%. At the last visit, 76 patients out of 217 at the first visit had dBP >90 mmHg (35%); that is, dBP control was 65%. Therapeutic inertia was calculated by evaluating the proportion of visits at which sBP was above the target for eligible visits minus the proportion of visits where the change was made in

  15. The therapeutic effect and possible harm of puerarin for treatment of stage III diabetic nephropathy: a meta-analysis.

    Science.gov (United States)

    Wang, Bin; Chen, Shibo; Yan, Xiufeng; Li, Mingdi; Li, Daqi; Lv, Pin; Ti, Guixiang

    2015-01-01

    Diabetic nephropathy (DN) is the main cause of end-stage kidney disease in developed countries. Current therapy can slow the rate of progression of DN, but eventually end-stage renal failure will occur in a proportion of patients. Identification of new strategies and additional complementary and alternative therapies for treating DN are important. The research team wanted to assess the beneficial and harmful effects of using puerarin plus angiotensin converting enzyme inhibitor (ACEI) compared with using only ACEI for treatment of individuals with stage III DN. The research team performed a meta-analysis of randomized, controlled trials (RCTs) by searching the following electronic databases: (1) the Cochrane Database of Systematic Reviews, (2) the Cochrane Central Register of Controlled Trials (CENTRAL), (3) PubMed, (4) EMBASE (Elsevier), (5) the Allied and Complementary Medicine Database (AMED), (6) the Chinese Biomedicine Database (CBM), (7) the China National Knowledge Infrastructure (CNKI), and (8) the Chinese Biomedical Journals (VIP), with no language restrictions, as well as databases of clinical trials. Measured outcomes included (1) urinary protein measured as urinary albumin excretion rate (UAER) (μg/min) and 24-h urine protein (24-h UP) (mg/24 h); (2) renal function measured as blood urea nitrogen (BUN) (mmol/L) and serum creatinine (SCr) (μmol/L); (3) α1-microglobulin (α1-MG) (mg/24 h) and endothelin-1 (ET-1) (ng/24 h); (4) end points (EPs); and (5) adverse events (AEs). Ten RCTs involving 669 participants were included. All trials were conducted and published in China. Treatment of DN with puerarin plus ACEI significantly decreased the UAER-P < .0001, MD = -23.43 (95% CI, -33.95 to -12.91), and had no effect on 24-h UP-P = .09, MD = -56.76 (95% CI, -122.65 to 9.12); BUN-P = .17, MD = -0.51 (95% CI, -1.24 to 0.21); and SCr-P = .26, MD = -4.43 (95% CI, -12.05 to 3.20). One trial reported abdominal discomfort and nausea (2 cases) in the treatment

  16. MODELLING OF RING-SHAPED ULTRASONIC WAVEGUIDES FOR TESTING OF MECHANICAL PROPERTIES AND THERAPEUTIC TREATMENT OF BIOLOGICAL TISSUES

    Directory of Open Access Journals (Sweden)

    V. T. Minchenya

    2011-01-01

    Full Text Available The article presents results of modelling of ring-shaped waveguide tool for ultrasonic treatment of biological materials, particularly malignant tumours, and testing of their mechanical properties. Harmonic analysis of forced flexural vibration of the waveguide using ANSYS software and APDL programming language was implemented for determination of waveguide geometric parameters providing its resonance for the given excitation frequency. The developed finite element model accounts for interaction between the waveguide and tumour tissue as well as initial prestressing of tissue radially compressed by the waveguide. Resonant curves of the waveguide in terms of its thickness and diameter are calculated and presented. Principle of application of the developed modeling technique for extraction of diagnostic data on mechanical properties of biological tissues is described.

  17. Evaluation of therapeutic potential of VB-001, a leave-on formulation, for the treatment of moderate adherent dandruff.

    Science.gov (United States)

    Bhattacharyya, Anamika; Jain, Nilu; Prasad, Sudhanand; Jain, Shilpi; Yadav, Vishal; Ghosh, Shamik; Sengupta, Shiladitya

    2017-05-03

    Dandruff is a common scalp condition characterized by excessive scaling and itch. Aberrant colonization of the scalp by commensal Malassezia spp. is a major contributor in the multifactorial etiology of dandruff. Literature based understanding of Malassezia linked pathophysiology of dandruff allowed us to comprehend a strategy to potentiate the efficacy of a known antifungal agent used in dandruff therapy. The aim of this study was to determine the efficacy and skin safety of VB-001 antidandruff leave-on formulation in comparison with marketed antidandruff ZPTO shampoo in patients with moderate adherent dandruff of the scalp. Healthy males or females aged ≥ 15 years and ≤ 65 with a clinical diagnosis of moderate adherent dandruff of the scalp were recruited for the study to monitor the effects of topical VB-001 versus those of marketed antidandruff ZPTO shampoo. 168 subjects were randomized to the treatment (VB-001, n = 84) and control (ZPTO shampoo, n = 84) groups. The efficacy of each product was evaluated by comparing proportion of subjects who have shown reduction in flaking by ASFS (adherent scalp flaking score) and pruritus by IGA (investigator global assessment) score. VB-001 imparted consistently better reduction in ASFS and enabled early reduction of pruritus in comparison to marketed ZPTO shampoo. VB-001, a leave-on formulation with ingredients chosen to selectively disturb the Malassezia niche on dandruff scalp by denying extra nutritional benefits to the microbe, provides unique advantages over existing best in class ZPTO shampoo therapy. It has the potential to emerge as an attractive novel treatment for moderate adherent dandruff. CTRI Registration number: CTRI/2013/01/003283 . Registered on: 02/01/2013.

  18. Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence

    Energy Technology Data Exchange (ETDEWEB)

    Campana, Davide; Nori, Francesca; Cacciari, Giulia; Tomassetti, Paola [University of Bologna, Department of Medical and Surgical Sciences, Bologna (Italy); Capurso, Gabriele; Panzuto, Francesco; Delle Fave, Gianfranco [University of Rome, Digestive and Liver Disease Unit, Rome (Italy); Partelli, Stefano [Sacro Cuore Don Calabria Hospital, Department of Surgery, Negrar (Italy); University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy); Tamburrino, Domenico; Falconi, Massimo [University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy)

    2013-08-15

    Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment modality for patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs). The aim of this study was to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response. Patients with sporadic GEP NETs prospectively treated with PRRT were retrospectively analysed. The primary end point was progression-free survival (PFS). A total of 69 patients (37 men and 32 women; 45 with pancreatic and 24 with gastrointestinal lesion; 22 NET G1 and 41 NET G2) were treated with {sup 90}Y or {sup 177}Lu. The objective response rate was 27.5 % (partial response, PR), while 50.7 % had stable disease and 23.2 % had progressive disease. Significant differences in PFS were observed in relationship to the stage of the disease (44 months for stage III, 23 months for stage IV), the evidence of a PR 6 months after the end of the PRRT (39 months in patients with a PR, 22 months in patients without a PR) and previous transarterial chemoembolization (TACE, yes 13 months vs no 31 months). Stage IV, NET G2 and previous TACE were found to be significant factors for tumour progression at multivariate analysis. Low tumour burden and a low proliferation index represent independent prognostic factors for long PFS, while previous chemoembolization techniques represent independent prognostic factors for early tumour progression and shorter PFS. Our data suggest that chemoembolization techniques to reduce the hepatic tumour burden should be avoided. (orig.)

  19. 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

  20. Determination of the biodistribution and biokinetics of radiopharmaca like 166Ho-ferric-hydroxide or 153Sm-EDTMP used for therapeutic treatment by energy dispersive measurements

    International Nuclear Information System (INIS)

    Fischer, H.; Poljanc, K.; Aiginger, H.; Pruefert, U.; Granegger, S.; Ofluoglu, S.; Pirich, Ch.; Sinzinger, H.; Dudczak, R.; Steger, F.

    2003-01-01

    The activity distribution of beta-emitting radionuclides in the human body and the respective therapeutic dose distribution in the target and the unwanted leakage in the other organs was determined by measurement of corresponding gamma-lines. The measurement was done by scanning in a whole-body counter in the General Hospital Vienna. It is possible to localize activity and dose distribution by means of the detected activity profiles of the four detectors. Two typical treatments are reported: the treatment of synovitis using radiation of 166 Ho-Ferric-Hydroxide (characteristic gamma-line: 81 keV) and radionuclide therapy focused at the palliative treatment of bone metastases with 153 Sm-EDTMP, a bone seeking beta-emitting radionuclide (characteristic gamma-line: 103 keV). For the determination of the applied dose, the leakage and the quality assurance spectroscopic data of a clinical whole-body counter can be a useful tool for controlling and monitoring in health care. (authors)

  1. Short-Term Therapeutic Efficacy of the Isobar TTL Dynamic Internal Fixation System for the Treatment of Lumbar Degenerative Disc Diseases.

    Science.gov (United States)

    Qian, Jiale; Bao, Zhaohua; Li, Xuefeng; Zou, Jun; Yang, Huilin

    2016-07-01

    At present, posterior interbody fusion surgery with pedicle internal fixation is the gold standard for the treatment of lumbar degenerative disc diseases. However, an increasing number of studies have shown that because fused lumbar vertebrae lose their physiological activity, the compensatory range of motion (ROM) of the adjacent levels increases. To address this issue, dynamic internal fixation systems have been developed. Our goal was to investigate the short-term therapeutic efficacy of the Isobar TTL dynamic internal fixation system for the treatment of lumbar degenerative disc diseases and its effect on the ROM of the surgical segments. Retrospective Evaluation. Tertiary hospital setting in China. Twenty-four lumbar degenerative disc disease patients who underwent posterior lumbar decompression and single-segment Isobar TTL dynamic internal fixation at our hospital between January 2013 and July 2014 were retrospectively analyzed. The preoperative and one month, 3 month, and 12 month postoperative visual analog scale (VAS) pain scores, Japanese Orthopedic Association (JOA) scores, and Oswestry Disability Index (ODI) scores were observed and recorded to assess the clinical therapeutic effect; the lumbar ROM was measured preoperatively and at the last follow-up to evaluate the preservation of functional movement in the dynamically stabilized segment. All patients underwent the operation successfully without complications during hospitalization and were followed for 12 to 27 months, with an average of 18 months. The patients' preoperative and one month, 3 month, and 12 month postoperative VAS scores were 6.42 ± 0.72, 1.71 ± 0.86, 1.38 ± 0.65, and 1.37 ± 0.58, respectively, and their JOA scores were 9.54 ± 1.89, 21.21 ± 1.98, 22.50 ± 1.47, and 23.46 ± 1.32, respectively. The preoperative ODI score was 42.04 ± 2.63; the one month, 3 month, and 12 month postoperative ODI scores were 22.79 ± 1.61, 18.63 ± 1.61, and 15.08 ± 1.21, respectively. These

  2. Comparison of Efficacy and Safety of Different Therapeutic Regimens as 
Second-line Treatment for Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Zhihua LI

    2015-05-01

    Full Text Available Background and objective Small-cell lung cancer (SCLC is an aggressive disease for which the mainstay of treatment is cytotoxic chemotherapy. Despite good initial responses most patients will relapse or progress after the first-line therapy. The evidence of a benefit from second-line chemotherapy is limited in patients with relapsed/advanced SCLC. Some drugs are recommended by guidelines, but more regimens are formulated based on experience in clinical. So we conducted this retrospective study in order to compare the efficacy and safety of different second-line treatment regimens. Methods We totally analyzed 309 patients received second-line treatment in our retrospective study. 157 patients received best supportive care (BSC, and the rest 152 patients received second-line chemotherapy. The Kaplan-Meier method survival curves and Log-rank test were used to analysis the differences among different groups. The endpoints were objective response rate (ORR, disease control rate (DCR, progression-free survival (PFS, and overall survival (OS. Results Patients administered second-line chemotherapy lived significantly longer, with a total OS from first-line therapy of 11.5 mo compared to 6.0 mo in patients with best supportive care alone (P<0.001, and the ORR, DCR, PFS and OS of the former (including the sensitive disease and resistance/refractory disease patients were obviously better than that of the latter. The ORR and DCR of the patients who received second-line chemotherapy is 39.5% and 59.2%, respectively. The median PFS and OS from second-line chemotherapy were 3.3 mo and 5.3 mo. The patients who received second-line chemotherapy were divided by types of second-line regimens. The sensitive disease patients were from group A (VP-16-based rechallenge and group B1 (CPT-11-based regimen. The ORR of the two groups were 48.6% and 35.3%, and the DCR were 68.6% and 58.8%, respectively. There was no statistically significant difference (P=0.264; P=0

  3. Somatic Experiencing® Informed Therapeutic Group for the Care and Treatment of Biopsychosocial Effects upon a Gender Diverse Identity.

    Science.gov (United States)

    Briggs, Paul C; Hayes, Sage; Changaris, Michael

    2018-01-01

    Somatic Experiencing ® (SE™) is a resiliency-based treatment for autonomic nervous systems dysregulation syndromes, such as posttraumatic stress disorder, anxiety, depression, and physical syndromes like chronic pain, migraines, and fibromyalgia. "Transgender/gender non-conforming/gender variant" describes people whose gender identity/expression is different, at least part of the time, from the sex assigned at birth. Research indicates transgender individuals have a higher incidence of depression, anxiety, victimization, and discrimination. SE™ tools may support transgender/gender non-conforming individuals to increase resilience in the face of discrimination and social injustice. This study is a pretest posttest within group ( N  = 7) pilot study assessing the impact of a 10 session SE™ based group treatment on depression (PHQ-9), anxiety (GAD-7), somatic symptoms (PHQ-15), quality of life (QoL) (WHOQoL-BREF), and coping with discrimination (CDS) for a cohort of seven individuals identifying as transgender/gender non-conforming. Materials were created in collaboration with members of the LGBTQIA community. Care was taken to be inclusive of gender non-conforming identities and culturally responsive in design. Participants described their gender identities as: non-binary, female to male, male to female, and gender fluid. Participants had significant increase in psychological QoL (psychological well-being) (WHOQoL-BREF) p  = 0.004, SD = 2.31, with a modest effect size of d  = 0.71. Some likely impacts of historical effect discussed. No other clinical or QoL outcomes were statistically significant. However, one outlier was identified in the dataset. When this outlier was excluded there was a trend toward significant reduction in depression symptoms (PhQ-9) p  = 0.097, SD = 3.31 and a modest effect size of d  = 0.68; somatic symptoms (PhQ-15) p  = 0.093, SD = 3.52 and a modest effect size of d  = 0.72. These data indicate

  4. Development of a methodology to determine optimized therapeutic doses of {sup 131}I for the treatment of hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, F.; Moura, M.B.; Pereira, A.C., E-mail: faraujo@ird.gov.br [Instituto de Medicna Nuclear (IMEN), Goiania, GO (Brazil); Dantas, B.M.; Dantas, A.L.A.; Lucena, E.A. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Melo, R.C.; Rebelo, A.M.O. [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Faculdade de Medicina

    2008-07-01

    Several methods can be used to determine the activity of {sup 131}I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with {sup 131}I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of {sup 131}I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and Instituto de Medicina Nuclear - IMEN, of Goiania. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were (39.3 ± 0.78), (58.1 ± 2.38) to uptake probe SCT-13004 e 13002, respectively and 4.3 ± 0.17 to scintillation camera. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use of diagnose equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable procedure in terms of effectiveness, simplicity and cost

  5. Somatic Experiencing® Informed Therapeutic Group for the Care and Treatment of Biopsychosocial Effects upon a Gender Diverse Identity

    Directory of Open Access Journals (Sweden)

    Paul C. Briggs

    2018-02-01

    Full Text Available BackgroundSomatic Experiencing® (SE™ is a resiliency-based treatment for autonomic nervous systems dysregulation syndromes, such as posttraumatic stress disorder, anxiety, depression, and physical syndromes like chronic pain, migraines, and fibromyalgia. “Transgender/gender non-conforming/gender variant” describes people whose gender identity/expression is different, at least part of the time, from the sex assigned at birth. Research indicates transgender individuals have a higher incidence of depression, anxiety, victimization, and discrimination. SE™ tools may support transgender/gender non-conforming individuals to increase resilience in the face of discrimination and social injustice.MethodsThis study is a pretest posttest within group (N = 7 pilot study assessing the impact of a 10 session SE™ based group treatment on depression (PHQ-9, anxiety (GAD-7, somatic symptoms (PHQ-15, quality of life (QoL (WHOQoL-BREF, and coping with discrimination (CDS for a cohort of seven individuals identifying as transgender/gender non-conforming. Materials were created in collaboration with members of the LGBTQIA community. Care was taken to be inclusive of gender non-conforming identities and culturally responsive in design.ResultsParticipants described their gender identities as: non-binary, female to male, male to female, and gender fluid. Participants had significant increase in psychological QoL (psychological well-being (WHOQoL-BREF p = 0.004, SD = 2.31, with a modest effect size of d = 0.71. Some likely impacts of historical effect discussed. No other clinical or QoL outcomes were statistically significant. However, one outlier was identified in the dataset. When this outlier was excluded there was a trend toward significant reduction in depression symptoms (PhQ-9 p = 0.097, SD = 3.31 and a modest effect size of d = 0.68; somatic symptoms (PhQ-15 p = 0.093, SD = 3.52 and a modest effect size of d = 0

  6. Development of a methodology to determine optimized therapeutic doses of 131I for the treatment of hyperthyroidism

    International Nuclear Information System (INIS)

    Araujo, F.; Moura, M.B.; Pereira, A.C.; Dantas, B.M.; Dantas, A.L.A.; Lucena, E.A.; Melo, R.C.; Rebelo, A.M.O.

    2008-01-01

    Several methods can be used to determine the activity of 131 I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with 131 I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of 131 I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and Instituto de Medicina Nuclear - IMEN, of Goiania. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were (39.3 ± 0.78), (58.1 ± 2.38) to uptake probe SCT-13004 e 13002, respectively and 4.3 ± 0.17 to scintillation camera. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use of diagnose equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable procedure in terms of effectiveness, simplicity and cost. (author)

  7. Therapeutic role of calcium and vitamin K3 in chemically induced hepatocarcinogenesis - new tools for cancer treatment.

    Science.gov (United States)

    Anwar, Firoz; Khan, Ruqaiyah; Sachan, Richa; Kazmi, Imran; Rawat, Alisha; Sabih, Abdullah; Singh, Rajbala; Afzal, Muhammad; Ahmad, Aftab; Al-Orab, Abdulaziz S; Al-Abbasi, F A; Bhatt, Prakash Chandra; Kumar, Vikas

    2018-04-17

    HCC has been reported to be immensely occurring carcinoma worldwide. Recent days the mortality occurred due to liver cancer has also been found to be increased at an alarming speed affecting mostly the young patients. The aim of the current study was to decipher the role of calcium and vitamin K3 in the treatment of chemically induced hepatocarcinogenesis in the male Wistar rats. Liver cancer was induced via a subnecrogenic dose of 160 mg/kg body weight, diethylnitrosamine (DENA) when associated with fasting/refeeding in male Wistar rats. It elevated the serum glutamate oxaloacetate (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), bilirubin, total cholesterol (CH), triglycerides (TG), alfa-fetoprotein (AFP) and reduced high-density lipoprotein (HDL). Histopathological examination of liver tissue showed marked carcinogenicity of the chemical carcinogen. Food, water intake and animal weights were also assessed, respectively. The animals exposed to DENA showed a significant decrease in the body weight. The elevated levels of serum SGOT, SGPT, ALP, AFP, TC and TG were restored by administration of calcium and Vit K (ad libitum) combination at higher dose than the normal dietary requirement (3 mg/kg) daily for 12 weeks p.o. Physiological and biochemical analysis showed the beneficial effects of calcium and vitamin K3 combination in the animals exposed to DENA. The results deciphered the beneficial effects of calcium and vitamin K3 in combination.

  8. Optimization of Bicomponent Electrospun Fibers for Therapeutic Use: Post-Treatments to Improve Chemical and Biological Stability

    Directory of Open Access Journals (Sweden)

    Antonio Papa

    2017-10-01

    Full Text Available Bicomponent electrospun nanofibers based on the combination of synthetic (i.e., aliphatic polyesters such as polycaprolactone (PCL and natural proteins (i.e., gelatin have been extensively investigated as temporary platforms to instruct cells by the release of molecular/pharmaceutical signals for the regeneration of several tissues. Here, water soluble proteins (i.e., gelatin, strictly embedded to PCL, act as carriers of bioactive molecules, thus improving bioavailability and supporting cell activities during in vitro regeneration. However, these proteins are rapidly digested by enzymes, locally produced by many different cell types, both in vitro and in vivo, with significant drawbacks in the control of molecular release. Hence, we have investigated three post-processing strategies based on the use of different crosslinking agents—(1-ethyl-3-(3-dimethylaminopropylcarbodiimide hydrochloride (EDC, glyceraldehyde (GC, and 1,4-butanediol diglycidyl ether (BDDGE—to delay the dissolution time of gelatin macromolecules from bicomponent fibers. All of the qualitative (i.e., SEM, TGA and quantitative (i.e., Trinitrobenzene sulfonate (TNBS and bicinchoninic acid (BCA assays morphological/chemical analyses as well as biocompatibility assays indicate that EDC crosslinking improves the chemical stability of bicomponent fibers at 37 °C and provides a more efficient encapsulation and controlled sustained release of drug, thus resulting in the best post-treatment to design bio-inspired fibrous platforms for the extended in vitro release of drugs.

  9. Optimization of Bicomponent Electrospun Fibers for Therapeutic Use: Post-Treatments to Improve Chemical and Biological Stability.

    Science.gov (United States)

    Papa, Antonio; Guarino, Vincenzo; Cirillo, Valentina; Oliviero, Olimpia; Ambrosio, Luigi

    2017-10-16

    Bicomponent electrospun nanofibers based on the combination of synthetic (i.e., aliphatic polyesters such as polycaprolactone (PCL)) and natural proteins (i.e., gelatin) have been extensively investigated as temporary platforms to instruct cells by the release of molecular/pharmaceutical signals for the regeneration of several tissues. Here, water soluble proteins (i.e., gelatin), strictly embedded to PCL, act as carriers of bioactive molecules, thus improving bioavailability and supporting cell activities during in vitro regeneration. However, these proteins are rapidly digested by enzymes, locally produced by many different cell types, both in vitro and in vivo, with significant drawbacks in the control of molecular release. Hence, we have investigated three post-processing strategies based on the use of different crosslinking agents-(1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride) (EDC), glyceraldehyde (GC), and 1,4-butanediol diglycidyl ether (BDDGE)-to delay the dissolution time of gelatin macromolecules from bicomponent fibers. All of the qualitative (i.e., SEM, TGA) and quantitative (i.e., Trinitrobenzene sulfonate (TNBS) and bicinchoninic acid (BCA) assays) morphological/chemical analyses as well as biocompatibility assays indicate that EDC crosslinking improves the chemical stability of bicomponent fibers at 37 °C and provides a more efficient encapsulation and controlled sustained release of drug, thus resulting in the best post-treatment to design bio-inspired fibrous platforms for the extended in vitro release of drugs.

  10. Post-evaluation of the neurophaties treatment post-trauma with therapeutic laser. Model in sciatic nerve of frog

    Science.gov (United States)

    Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernández, María G. H.; Jasso, José L. C.; Lira, Maricela O. F.; Flores, Mariana A.; Balderrama, Vicente L.

    2010-05-01

    The purpose of this study was to evaluate the compound nerve action potential amplitude and latency measured to determine the degree of myelination and the number of fibers stimulated in a model of stimulated frog sciatic nerve laser at 810 nm as perioperative treatment after injury. It used 30 bullfrogs (Rana catesbeiana) to obtain 60 sciatic nerves forming four groups, groups 1 and 2 worked with nerves in vitro, were dissected in humid chambers for placing isolated organ, was recorded on compound nerve action potential, the second group laser was applied at 24, 48, 72, 96 and 120 hours and at the same time were placed in 10% formalin. Groups 3 and 4 are worked in vivo localizing the nerve and causing damage through compression, occurred over the compound nerve action potential to assess the degree of myelination and the number of fibers stimulated, the group 4 was applied to 810 nm laser (500 Hz, 10 J, 200 mW) after injury, after 48 hours, three frogs were sacrificed by introducing the nerves in 10% formalin. The latency recorded by stimulating the sciatic nerve of frog to 0.5 mA and 100 ms in groups 1 and 2 show significant differences (p000), as to the extent, if any statistically significant difference. (pparesthesia (post-traumatic neuropathy).

  11. Increased therapeutic efficacy of a newly synthesized tyrosinase inhibitor by solid lipid nanoparticles in the topical treatment of hyperpigmentation

    Directory of Open Access Journals (Sweden)

    Al-Amin M

    2016-12-01

    Full Text Available Md Al-Amin, Jiafu Cao, Muhammad Naeem, Hasanul Banna, Min-Soo Kim, Yunjin Jung, Hae Young Chung, Hyung Ryong Moon, Jin-Wook Yoo College of Pharmacy, Pusan National University, Busan, South Korea Abstract: Hyperpigmentation caused by melanin overproduction is a major skin disorder in humans. Inhibition of tyrosinase, a key regulator of melanin production, has been used as an effective strategy to treat hyperpigmentation. In this study, we investigated the use of solid lipid nanoparticles (SLNs as a highly effective and nontoxic means to deliver a newly synthesized potent tyrosinase inhibitor, MHY498, and to target melanocytes through the skin. MHY498-loaded SLNs (MHY-SLNs were prepared by an oil-in-water emulsion solvent-evaporation method, and their morphological and physicochemical properties were characterized. MHY-SLNs showed a prolonged drug-release profile and higher skin permeation than that of MHY solution. In an in vivo evaluation of antimelanogenic activity, MHY-SLNs showed a prominent inhibitory effect against ultraviolet B-induced melanogenesis, resulting in no change in the skin color of C57BL/6 mouse, compared with that observed in an MHY solution-treated group and an untreated control group. The antimelanogenic effect of MHY-SLNs was further confirmed through Fontana–Masson staining. Importantly, MHY-SLNs did not induce any toxic effects in the L929 cell line. Overall, these data indicate that MHY-SLNs show promise in the topical treatment of hyperpigmentation. Keywords: melanogenesis, hyperpigmentation, MHY498, solid lipid nanoparticles, skin delivery

  12. [Prognostic and therapeutic value of D2 lymphadenectomy in the treatment of gastric cancer: experience of an Italian team].

    Science.gov (United States)

    Candela, Giancarlo; Sergio, Varriale; Di Libero, Lorenzo; Manetta, Fiorenza; Giordano, Marco; Lanza, Michele; Scetta, Giovanni; Pizza, Alessandra; Sciascia, Valerio; Napolitano, Salvatore; D'Aniello, Francesco; Casaburi, Vincenzo; Esposito, Daniela; Sarno, Gerardo; Santini, Luigi

    2008-01-01

    Recently, the incidence of gastric cancer and the related percentage of mortality have been decreasing world-wide, especially in the industrialised countries. Surgery has commonly been opted for as primary treatment of this disease. However, the optimal extent of surgical intervention is still debated. Japanese surgeons have been the pioneers of perigastric and celiac tripod lymphadenectomies in an attempt to improve long-term survival and the postoperative disease-free period. In recent years, D2 resection has been compared with D1 resection, which consists in excision of the stomach along with its locoregional nodes. From March 2002 to January 2007, 70 interventions for gastric cancer were performed at the VII Division of General Surgery of the Second University of Naples. All patients underwent excision of the lymph nodes from stations 1 to 6 (D1) combined with excision of stations 7 to 12 (D2). In 32 cases (45.7%) there were no metastatic lymph nodes (NO), in 28 patients (40%) 1 to 6 nodes proved metastatic (N1), and in 10 cases (14.3%) from 7 to 15 nodes were metastasised (N2). The incidence of metastatic lymph nodes was 54.3% and the prevalence 13.6%. Metastatic lymph nodes were found mostly in T3 (15/24) and T4 (14/20) stage tumours rather than in T1 (3/12) and T2 (6/14) neoplasms. Two patients (2.86%) died within 60 days of the intervention. The overall postoperative morbidity and mortality rates were 21.43% and 2.86%, respectively. D2 gastrectomies without pancreatic resections present distinct advantages in terms of long-term survival and are associated with postoperative morbidity and mortality rates which are similar to those obtained after D1 node resection.

  13. Therapeutic potential and adverse events of everolimus for treatment of hepatocellular carcinoma – systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Yamanaka, Kenya; Petrulionis, Marius; Lin, Shibo; Gao, Chao; Galli, Uwe; Richter, Susanne; Winkler, Susanne; Houben, Philipp; Schultze, Daniel; Hatano, Etsuro; Schemmer, Peter

    2013-01-01

    Everolimus is an orally administrated mammalian target of rapamycin (mTOR) inhibitor. Several large-scale randomized controlled trials (RCTs) have demonstrated the survival benefits of everolimus at the dose of 10 mg/day for solid cancers. Furthermore, mTOR-inhibitor-based immunosuppression is associated with survival benefits for patients with hepatocellular carcinoma (HCC) who have received liver transplantation. However, a low rate of tumor reduction and some adverse events have been pointed out. This review summarizes the antitumor effects and adverse events of everolimus and evaluates its possible application in advanced HCC. For the meta-analysis of adverse events, we used the RCTs for solid cancers. The odds ratios of adverse events were calculated using the Peto method. Manypreclinical studies demonstrated that everolimus had antitumor effects such as antiproliferation and antiangiogenesis. However, some differences in the effects were observed among in vivo animal studies for HCC treatment. Meanwhile, clinical studies demonstrated that the response rate of single-agent everolimus was low, though survival benefits could be expected. The meta-analysis revealed the odds ratios (95% confidence interval [CI]) of stomatitis: 5.42 [4.31–6.73], hyperglycemia: 3.22 [2.37–4.39], anemia: 3.34 [2.37–4.67], pneumonitis: 6.02 [3.95–9.16], aspartate aminotransferase levels: 2.22 [1.37–3.62], and serum alanine aminotransferase levels: 2.94 [1.72–5.02], respectively. Everolimus at the dose of 10 mg/day significantly increased the risk of the adverse events. In order to enable its application to the standard conventional therapies of HCC, further studies are required to enhance the antitumor effects and manage the adverse events of everolimus

  14. Serial assessment of the physiological status of leatherback turtles (Dermochelys coriacea) during direct capture events in the northwestern Atlantic Ocean: comparison of post-capture and pre-release data.

    Science.gov (United States)

    Innis, Charles J; Merigo, Constance; Cavin, Julie M; Hunt, Kathleen; Dodge, Kara L; Lutcavage, Molly

    2014-01-01

    The physiological status of seven leatherback turtles (Dermochelys coriacea) was assessed at two time points during ecological research capture events in the northwestern Atlantic Ocean. Data were collected as soon as possible after securing each turtle onboard the capture vessel and again immediately prior to release. Measured parameters included sea surface temperature, body temperature, morphometric data, sex, heart rate, respiratory rate and various haematological and blood biochemical variables. Results indicated generally stable physiological status in comparison to previously published studies of this species. However, blood pH and blood potassium concentrations increased significantly between the two time points (P = 0.0018 and P = 0.0452, respectively). Turtles were affected by a mild initial acidosis (mean [SD] temperature-corrected pH = 7.29 [0.07]), and blood pH increased prior to release (mean [SD] = 7.39 [0.07]). Initial blood potassium concentrations were considered normal (mean [SD] = 4.2 [0.9] mmol/l), but turtles experienced a mild to moderate increase in blood potassium concentrations during the event (mean [SD] pre-release potassium = 5.9 [1.7] mmol/l, maximum = 8.5 mmol/l). While these data support the general safety of direct capture for study of this species, the observed changes in blood potassium concentrations are of potential concern due to possible adverse effects of hyperkalaemia on cardiac function. The results of this study highlight the importance of physiological monitoring during scientific capture events. The results are also likely to be relevant to unintentional leatherback capture events (e.g. fisheries interactions), when interactions may be more prolonged or extreme.

  15. High intensity focused ultrasound treatment of adenomyosis: The relationship between the features of magnetic resonance imaging on T2 weighted images and the therapeutic efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Chunmei [State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Haifu Hospital, College of Biomedical Engineering, Chongqing Medical University, Chongqing (China); Setzen, Raymond [Department of Obstetrics and Gynecology, Chris Hani Baragwanath Academic Hospital, Johannesburg (South Africa); Liu, Zhongqiong; Liu, Yunchang [State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Haifu Hospital, College of Biomedical Engineering, Chongqing Medical University, Chongqing (China); Xie, Bin [Department of Ultrasound, Huanggang Central Hospital, Huanggang City, Hubei 438000 (China); Aili, Aixingzi, E-mail: 1819483078@qq.com [Shanghai First Maternity and Infant Health Hospital, Shanghai (China); Zhang, Lian, E-mail: lianwzhang@yahoo.com [State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Haifu Hospital, College of Biomedical Engineering, Chongqing Medical University, Chongqing (China)

    2017-04-15

    Objectives: To investigate the relationship between the features of magnetic resonance imaging (MRI) on T2 weighted images (T2WI) and the therapeutic efficacy of high intensity focused ultrasound (HIFU) on adenomyosis. Materials and methods: From January 2011 to November 2015, four hundred and twenty-eight patients with symptomatic adenomyosis were treated with HIFU. Based on the signal intensity and the number of hyperintense foci in the adenomyotic lesions on T2WI, the patients were classified into groups. The day after HIFU ablation patients underwent contrast-enhanced MRI and a comparison was made of non-perfused volume (NPV) ratio, energy efficiency factor (EEF), treatment time, sonication time, and adverse effects. Results: No significant difference in terms of HIFU treatment settings and results was observed between the group of patients with hypointense adenomyotic lesions and the group with isointense adenomyotic lesions (P > 0.05). However, the sonication time and EEF were significantly higher in the group with multiple hyperintense foci compared to the group with few hyperintense foci. The NPV ratio achieved in the lesions with multiple hyperintenese foci was significantly lower than that in the lesions with few hyperintense foci (P < 0.05). No significant difference was observed in the rate of adverse effects between the two groups. Conclusions: Based on our results, the response of the adenomyotic lesions to HIFU treatment is not related to the signal intensity of adenomyotic lesions on T2WI. However, the number of the high signal intensity foci in the adenomyotic lesions on T2WI can be considered as a predictive factor to help select patients for HIFU treatment.

  16. High intensity focused ultrasound treatment of adenomyosis: The relationship between the features of magnetic resonance imaging on T2 weighted images and the therapeutic efficacy

    International Nuclear Information System (INIS)

    Gong, Chunmei; Setzen, Raymond; Liu, Zhongqiong; Liu, Yunchang; Xie, Bin; Aili, Aixingzi; Zhang, Lian

    2017-01-01

    Objectives: To investigate the relationship between the features of magnetic resonance imaging (MRI) on T2 weighted images (T2WI) and the therapeutic efficacy of high intensity focused ultrasound (HIFU) on adenomyosis. Materials and methods: From January 2011 to November 2015, four hundred and twenty-eight patients with symptomatic adenomyosis were treated with HIFU. Based on the signal intensity and the number of hyperintense foci in the adenomyotic lesions on T2WI, the patients were classified into groups. The day after HIFU ablation patients underwent contrast-enhanced MRI and a comparison was made of non-perfused volume (NPV) ratio, energy efficiency factor (EEF), treatment time, sonication time, and adverse effects. Results: No significant difference in terms of HIFU treatment settings and results was observed between the group of patients with hypointense adenomyotic lesions and the group with isointense adenomyotic lesions (P > 0.05). However, the sonication time and EEF were significantly higher in the group with multiple hyperintense foci compared to the group with few hyperintense foci. The NPV ratio achieved in the lesions with multiple hyperintenese foci was significantly lower than that in the lesions with few hyperintense foci (P < 0.05). No significant difference was observed in the rate of adverse effects between the two groups. Conclusions: Based on our results, the response of the adenomyotic lesions to HIFU treatment is not related to the signal intensity of adenomyotic lesions on T2WI. However, the number of the high signal intensity foci in the adenomyotic lesions on T2WI can be considered as a predictive factor to help select patients for HIFU treatment.

  17. Intra-arterial embolization with pingyangmycin-lipiodol emulsion for the treatment of hepatic cavernous hemangioma: an analysis of factors affecting therapeutic results

    International Nuclear Information System (INIS)

    Zeng Qingle; Chen Yong; Zhao Jianbo; Zhang Kewei; Li Yanhao

    2009-01-01

    Objective: To analyze the factors that might affect the therapeutic results of pingyangmycin-lipiodol emulsion intra-arterial sclerosing embolization (PLE-IASE) in treating symptomatic cavernous hemangioma of liver (SCHL). Methods: PLE-IASE was performed in 89 patients with SCHL (32 males and 57 females). Before treatment the mean diameter of the hemangioma was (8.3±3.8) cm. Of 89 patients, 53 experienced anxiety, 35 suffered from right upper abdominal pain and the remaining one developed Kasabach-Merrit syndrome. Before PLE-IASE, the arteriographic classification was conducted based on hepatic arteriographic findings. Then pingyangmycin-lipiodol emulsion (PLE) was injected through the feeding artery. The dosage of pingyangmycin (PYM) was (9.8 ± 4.4) mg and the dosage of lipiodol (LP) was (5.9 ± 2.9) ml. The lipiodol deposition status was judged by the follow-up spot film taken immediately after PLE-IASE. The observations of the occurrence of complications, the relief of symptoms and the minification of SCHL were followed for 6-72 months after PLE-IASE. The linear regression analysis statistics was conducted by taking the minification as dependent variable and taking the arteriographic classification, lipiodol deposition status, the dosage of PYM, the dosage of lipiodol and the preoperative SCHL diameter as independent variable. Results: Of all 89 cases of SCHL, hypervascular type was seen in 51, hypovascular type in 26 and arteriovenous shunt (AVS) type in 12. Good lipiodol deposition status was found in 64 patients and poor deposition in 25 patients after PLE-IASE. After PLE-IASE, the symptom of anxiety in 53 patients was relieved and the right upper abdominal pain was reduced in 33 cases although intermittent pain still remained in 2 patients. The blood platelet count of the patient with Kasabach-Merrit syndrome returned to normal after the treatment. The symptomatic relieve rate was 98.7%. No serious complications occurred in the follow-up period. The linear

  18. Targeting the PD-1/PD-L1 Immune Evasion Axis With DNA Aptamers as a Novel Therapeutic Strategy for the Treatment of Disseminated Cancers.

    Science.gov (United States)

    Prodeus, Aaron; Abdul-Wahid, Aws; Fischer, Nicholas W; Huang, Eric H-B; Cydzik, Marzena; Gariépy, Jean

    2015-04-28

    Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a number of other tumor types as both a monotherapy and as part of combination regimens. Here, we report the development of DNA aptamers as synthetic, nonimmunogenic antibody mimics, which bind specifically to the murine extracellular domain of PD-1 and block the PD-1:PD-L1 interaction. One such aptamer, MP7, functionally inhibits the PD-L1-mediated suppression of IL-2 secretion in primary T-cells. A PEGylated form of MP7 retains the ability to block the PD-1:PD-L1 interaction, and significantly suppresses the growth of PD-L1+ colon carcinoma cells in vivo with a potency equivalent to an antagonistic anti-PD-1 antibody. Importantly, the anti-PD-1 DNA aptamer treatment was not associated with off-target TLR-9-related immune responses. Due to the inherent advantages of aptamers including their lack of immunogenicity, low cost, long shelf life, and ease of synthesis, PD-1 antagonistic aptamers may represent an attractive alternative over antibody-based anti PD-1 therapeutics.

  19. Therapeutic value of 3-D printing template-assisted 125I-seed implantation in the treatment of malignant liver tumors

    Directory of Open Access Journals (Sweden)

    Han T

    2017-07-01

    Full Text Available Tao Han,1,* Xiaodan Yang,1,* Ying Xu,2,* Zhendong Zheng,1,* Ying Yan,2 Ning Wang2 1Department of Oncology, 2Department of Radiotherapy, General Hospital of Shenyang Military Region, Shenyang, China *These authors contributed equally to this work Objective: To explore the therapeutic value of 3-D printing template-assisted 125I-seed implantation in the treatment of malignant liver tumors.Materials and methods: Fifteen liver cancer patients with 47 total lesions were treated with 3-D printing template-assisted radioactive seed implantation (group A, and 25 liver-tumor patients with 66 total lesions were treated with 125I-seed implantation without a template auxiliary (group B. Operation time, in-hospital time, operation complications, dose distribution, and response rate (number were compared between the two groups. Results: Shorter operation times and better dose distribution were observed in group A than in group B, and the differences were statistically significant. The response rate after 2 months was 86.7% (13 of 15 in group A and 84% (21 of 25 in group B; differences between the two groups were not significant.Conclusion: Application of 3-D printing template-assisted radioactive seed implantation in the treatment of malignant liver tumors can help shorten operation time and optimize radiation-dose distribution, is worthy of further study, and has clinical significance. Keywords: brachytherapy, stereotactic techniques, iodine isotopes, liver, carcinoma 

  20. Hyperthermic treatment at 56 °C induces tumour-specific immune protection in a mouse model of prostate cancer in both prophylactic and therapeutic immunization regimens.

    Science.gov (United States)

    De Sanctis, Francesco; Sandri, Sara; Martini, Matteo; Mazzocco, Marta; Fiore, Alessandra; Trovato, Rosalinda; Garetto, Stefano; Brusa, Davide; Ugel, Stefano; Sartoris, Silvia

    2018-06-14

    Most active cancer immunotherapies able to induce a long-lasting protection against tumours are based on the activation of tumour-specific cytotoxic T lymphocytes (CTLs). Cell death by hyperthermia induces apoptosis followed by secondary necrosis, with the production of factors named "danger associated molecular pattern" (DAMP) molecules (DAMPs), that activate dendritic cells (DCs) to perform antigen uptake, processing and presentation, followed by CTLs cross priming. In many published studies, hyperthermia treatment of tumour cells is performed at 42-45 °C; these temperatures mainly promote cell surface expression of DAMPs. Treatment at 56 °C of tumour cells was shown to induce DAMPs secretion rather than their cell surface expression, improving DC activation and CTL cross priming in vitro. Thus we tested the relevance of this finding in vivo on the generation of a tumour-specific memory immune response, in the TRAMP-C2 mouse prostate carcinoma transplantable model. TRAMP-C2 tumour cells treated at 56 °C were able not only to activate DCs in vitro but also to trigger a tumour-specific CTL-dependent immune response in vivo. Prophylactic vaccination with 56 °C-treated TRAMP-C2 tumour cells alone provided protection against TRAMP-C2 tumour growth in vivo, whilst in the therapeutic regimen, control of tumour growth was achieved combining immunization with adjuvant chemotherapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Clinical, Etiological and Therapeutic Features of Jaw-opening and Jaw-closing Oromandibular Dystonias: A Decade of Experience at a Single Treatment Center

    Directory of Open Access Journals (Sweden)

    Pedro Gonzalez-Alegre

    2014-04-01

    Full Text Available Background: Dystonia is a heterogeneous hyperkinetic disorder. The anatomical location of the dystonia helps clinicians guide their evaluation and treatment plan. When dystonia involves masticatory, lingual, and pharyngeal muscles, it is referred to as oromandibular dystonia (OMD.Methods: We identified patients diagnosed with OMD in a Movement Disorders Clinic and Laryngeal Movement Disorders Clinic from a single institution. Demographic, etiological, clinical, and therapeutic information was retrospectively reviewed for patients with jaw‐opening (O‐OMD and jaw‐closing (C‐OMD OMD.Results: Twenty‐seven patients were included. Their average age of onset was in the sixth decade of life and there was a female predominance. Etiological factors linked in this study to OMD included a family history of dystonia or essential tremor, occupation, cerebellar disease, a dental disorder, and tardive syndrome. Clinically, patients with C‐OMD presented with more prominent feeding difficulties, but seemed to respond better to therapy than those with O‐OMD. In addition to the known benefits of botulinum toxin therapy, patients who described sensory tricks obtained benefit from the use of customized dental prosthesis.Discussion: This works provides useful information on potential etiological factors for OMD and its response to therapy, and highlights the potential benefit of dental prosthesis for the treatment of OMD.

  2. Targeting the PD-1/PD-L1 Immune Evasion Axis With DNA Aptamers as a Novel Therapeutic Strategy for the Treatment of Disseminated Cancers

    Directory of Open Access Journals (Sweden)

    Aaron Prodeus

    2015-01-01

    Full Text Available Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a number of other tumor types as both a monotherapy and as part of combination regimens. Here, we report the development of DNA aptamers as synthetic, nonimmunogenic antibody mimics, which bind specifically to the murine extracellular domain of PD-1 and block the PD-1:PD-L1 interaction. One such aptamer, MP7, functionally inhibits the PD-L1-mediated suppression of IL-2 secretion in primary T-cells. A PEGylated form of MP7 retains the ability to block the PD-1:PD-L1 interaction, and significantly suppresses the growth of PD-L1+ colon carcinoma cells in vivo with a potency equivalent to an antagonistic anti-PD-1 antibody. Importantly, the anti-PD-1 DNA aptamer treatment was not associated with off-target TLR-9-related immune responses. Due to the inherent advantages of aptamers including their lack of immunogenicity, low cost, long shelf life, and ease of synthesis, PD-1 antagonistic aptamers may represent an attractive alternative over antibody-based anti PD-1 therapeutics.

  3. Therapeutic Effects of a Traditional Chinese Medicine Formula Plus Tamoxifen vs. Tamoxifen for the Treatment of Mammary Gland Hyperplasia: A Meta-Analysis of Randomized Trials

    Science.gov (United States)

    Li, Hao-Tian; Liu, Hong-Hong; Yang, Yu-Xue; Wang, Tao; Zhou, Xue-Lin; Yu, Yang; Li, Su-Na; Zheng, Yi; Zhang, Ping; Wang, Rui-Lin; Li, Jian-Yu; Wei, Shi-Zhang; Li, Kun; Li, Peng-Yan; Qian, Li-Qi

    2018-01-01

    As a common disorder that accounts for over 70% of all breast disease cases, mammary gland hyperplasia (MGH) causes a severe problem for the quality of patients' life, and confers an increased risk of breast carcinoma. However, the etiology and pathogenesis of MGH remain unclear, and the safety and efficacy of current western drug therapy for MGH still need to be improved. Therefore, a meta-analysis was conducted by our team to determine whether a TCM formula named Ru-Pi-Xiao in combination with tamoxifen or Ru-Pi-Xiao treated alone can show more prominent therapeutic effects against MGH with fewer adverse reactions than that of tamoxifen. Studies published before June 2017 were searched based on standardized searching rules in several mainstream medical databases. A total of 27 articles with 4,368 patients were enrolled in this meta-analysis. The results showed that the combination of Ru-Pi-Xiao and tamoxifen could exhibit better therapeutic effects against MGH than that of tamoxifen (OR: 3.79; 95% CI: 3.09–4.65; P < 0.00001) with a lower incidence of adverse reactions (OR: 0.35; 95% CI: 0.28–0.43; P < 0.00001). The results also suggested that this combination could improve the level of progesterone (MD: 2.22; 95% CI: 1.72–2.71; P < 0.00001) and decrease the size of breast lump (MD: −0.67; 95% CI: −0.86 to −0.49; P < 0.00001) to a greater extent, which might provide a possible explanation for the pharmacodynamic mechanism of Ru-Pi-Xiao plus tamoxifen. In conclusion, Ru-Pi-Xiao and related preparations could be recommended as auxiliary therapy combined tamoxifen for the treatment of MGH. PMID:29456506

  4. [Analysis of the therapeutic effects of different treatment modalities on the outcomes of 87 patients with lung oligometastasis from nasopharyngeal carcinoma after radiotherapy].

    Science.gov (United States)

    Tang, Q; Hu, Q Y; Piao, Y F; Hua, Y H; Chen, X Z

    2016-03-23

    The aim of the present study was to evaluate the efficacy of three different modalities in treatment of lung oligometastases from nasopharyngeal carcinoma (NPC) after radiotherapy and to identify a more appropriate treatment modality. The clinical data of 87 cases of lung oligometastases from NPC were analyzed retrospectively. Among them, 33 patients underwent local small-field irradiation+ /- chemotherapy, 28 underwent whole-lung irradiation+ chemotherapy, and 26 underwent simple chemotherapy. The survival rates were calculated using Kaplan-Meier analysis. The differences among the modalities were evaluated using the log-rank test. Cox univariate and multivariate analyses were performed to determine the influencing factors. The 3-year lung metastasis survival (LMS) rates of patients with lung metastasis undergoing the three treatment modalities (local small-field irradiation+ /-chemotherapy, whole-lung irradiation+ chemotherapy and chemotherapy alone) were 89.3%, 72.7%, and 72.4%, respectively, showing a significant difference between the groups (P=0.003). Further subgroup analysis showed that the 5-year LMS rate was significantly higher in the local small-field irradiation+ /-chemotherapy group than that in the whole-lung irradiation+ chemotherapy group and chemotherapy alone group (P=0.001). The 2-year progression-free survival (PFS) rates of the three groups were 57.1%, 25.8% and 3.8%, respectively, showing significant intergroup differences (P=0.002 and P<0.001). Multivariate analysis indicated that compared with the whole lung irradiation group and the chemotherapy alone group, the local irradiation+ /- chemotherapy is an independent favorable prognostic factor for LMS and PFS (P<0.05). Local radiotherapy combined with systemic chemotherapy is the best therapeutic modality for lung oligometastases derived from NPC after radiotherapy, improving the LMS and prolonging the PFS.

  5. Systematic review of clinical trials assessing the therapeutic efficacy of visceral leishmaniasis treatments: A first step to assess the feasibility of establishing an individual patient data sharing platform.

    Directory of Open Access Journals (Sweden)

    Jacob T Bush

    2017-09-01

    Full Text Available There are an estimated 200,000 to 400,000 cases of visceral leishmaniasis (VL annually. A variety of factors are taken into account when considering the best therapeutic options to cure a patient and reduce the risk of resistance, including geographical area, malnourishment and HIV coinfection. Pooled analyses combine data from many studies to answer specific scientific questions that cannot be answered with individual studies alone. However, the heterogeneity of study design, data collection, and analysis often makes direct comparison difficult. Individual Participant Data (IPD files can be standardised and analysed, allowing detailed analysis of this merged larger pool, but only a small fraction of systematic reviews and meta-analyses currently employ pooled analysis of IPD. We conducted a systematic literature review to identify published studies and studies reported in clinical trial registries to assess the feasibility of developing a VL data sharing platform to facilitate an IPD-based analysis of clinical trial data. Studies conducted between 1983 to 2015 that reported treatment outcome were eligible.From the 2,271 documents screened, 145 published VL clinical trials were identified, with data from 26,986 patients. Methodologies varied for diagnosis and treatment outcomes, but overall the volume of data potentially available on different drugs and dose regimens identified hundreds or possibly thousands of patients per arm suitable for IPD pooled meta-analyses.A VL data sharing platform would provide an opportunity to maximise scientific use of available data to enable assessment of treatment efficacy, contribute to evidence-based clinical management and guide optimal prospective data collection.

  6. WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

    International Nuclear Information System (INIS)

    Chang, S; Rivera, J; Tian, H; Price, A; Santos, C; Zhang, Y

    2016-01-01

    Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression and cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may provide

  7. WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

    Energy Technology Data Exchange (ETDEWEB)

    Chang, S [Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, NC (United States); Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina (United States); Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States); Rivera, J [Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina (United States); Tian, H [Xuzhou Medical College, Xuzhou, Jiangsu (China); Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States); Price, A [Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, NC (United States); Santos, C [Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States); Zhang, Y [Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, NC (United States); Xuzhou Medical College, Xuzhou, Jiangsu (China); Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States)

    2016-06-15

    Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression and cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may provide

  8. Radiosynoviorthesis in hemophilic arthropathy: pathologic blood pool imaging on pre-therapeutic bone scintigraphy is not a predictor of treatment success

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir [University Duisburg-Essen, Department of Nuclear Medicine, Essen (Germany); University Hospital, Department of Nuclear Medicine, Bonn (Germany); Strauss, Andreas Christian; Schmolders, Jan; Bornemann, Rahel; Pennekamp, Peter Hans [University of Bonn, Department of Orthopaedics and Trauma Surgery, Bonn (Germany); Sabet, Amin; Biersack, Hans Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Oldenburg, Johannes [University of Bonn, Department of Experimental Hematology and Transfusion Medicine, Bonn (Germany); Ezziddin, Samer [University Duisburg-Essen, Department of Nuclear Medicine, Essen (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2017-03-15

    Increased articular {sup 99m}Tc MDP uptake on blood pool imaging (BPI) of patients with rheumatologic conditions is indicative of active inflammatory changes, and has been suggested as a strong predictor of response to radiosynoviorthesis (RSO). In this study, we aimed to assess the value of pretreatment BPI positivity (i.e. scintigraphic-apparent hyperemia) for successful RSO in hemophilic arthropathy. Thirty-four male patients with painful hemophilic arthropathy underwent RSO after failure of conservative treatment. Treated joints comprised the knee in eight, elbow in five, and ankle in 21 patients. Pretreatment triple-phase bone scintigraphy showed hyperemic joints (pathologic BPI) in 17 patients, whereas 17 patients had no increased tracer uptake on BPI. Response to RSO was evaluated 6 months post-treatment by measuring changes in intensity of arthralgia according to the visual analog scale (VAS), bleeding frequency, and range of motion. The association between hyperemia (pathologic BPI) and treatment outcome was examined using nonparametric tests for independent samples. Clinically evident pain relief occurred in 26 patients (76.5 %), and the mean VAS decreased from 7.7 ± 1.1 to 4.6 ± 2.7 (p < 0.001). Joint bleeding frequency (hemarthrosis) decreased from 4.5 ± 0.6 to 2.1 ± 0.4 during the first 6 months after RSO (p < 0.001). For both parameters (pain relief and bleeding frequency), patients experienced a similar benefit from RSO regardless of pretreatment BPI: arthralgia (p = 0.312) and frequency of hemarthrosis (p = 0.396). No significant improvement was observed for range of motion, but it was significantly more restricted in hyperemic joints both before (p = 0.036) and after treatment (p = 0.022). Hemophilic arthropathy can be effectively treated with RSO regardless of pre-therapeutic BPI. Patients in whom articular hyperemia is not detectable by scintigraphy may have similar (outstanding) outcomes, and thus should not be excluded from treatment. (orig.)

  9. Treatment differences in the therapeutic relationship and introject during a 2-year randomized controlled trial of dialectical behavior therapy versus non-behavioral psychotherapy experts for borderline personality disorder

    Science.gov (United States)

    Bedics, Jamie D.; Atkins, David C.; Comtois, Katherine A.; Linehan, Marsha M.

    2011-01-01

    Objective The purpose of the present study was to explore the role of the therapeutic relationship and introject during the course of dialectical behavior therapy (DBT; Linehan, 1993) for the treatment of borderline personality disorder. Method Women meeting DSM-IV criteria for borderline personality disorder (N = 101) were randomized to receive DBT or community treatment by experts. The Structural Analysis of Social Behavior (SASB; Benjamin, 1974) was used to measure both the therapeutic relationship and introject. Results Using hierarchical linear modeling, DBT patients reported the development of a more positive introject including significantly greater self-affirmation, self-love, self-protection, and less self-attack during the course of treatment and one-year follow-up relative to community treatment by experts. The therapeutic relationship did not have an independent effect on intrapsychic or symptomatic outcome but did interact with treatment. DBT patients who perceived their therapist as affirming and protecting reported less frequent occurrences of non-suicidal self-injury. Conclusions The study showed positive intrapsychic change during DBT while emphasizing the importance of affirmation and control in the therapeutic relationship. Results are discussed in the context of understanding the mechanisms of change in DBT. PMID:22061867

  10. Medical therapeutic effect of hyperthyroidism

    International Nuclear Information System (INIS)

    Lee, K.B.

    1980-01-01

    In order to compare the therapeutic effect as well as side effects between antithyroid therapy and radioiodine therapy in hyperthyroidism, the author evaluated 111 cases of hyperthyroidism which were composed of 57 patients with antithyroid treatment, 23 patients with combined treatment comprising of antithyroid and radioactive iodine ( 131 I) and 31 patients with treatment of 131 I alone. (author)

  11. Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism.

    Science.gov (United States)

    Wendt, Daniel J; Dvorak-Ewell, Melita; Bullens, Sherry; Lorget, Florence; Bell, Sean M; Peng, Jeff; Castillo, Sianna; Aoyagi-Scharber, Mika; O'Neill, Charles A; Krejci, Pavel; Wilcox, William R; Rimoin, David L; Bunting, Stuart

    2015-04-01

    Achondroplasia (ACH), the most common form of human dwarfism, is caused by an activating autosomal dominant mutation in the fibroblast growth factor receptor-3 gene. Genetic overexpression of C-type natriuretic peptide (CNP), a positive regulator of endochondral bone growth, prevents dwarfism in mouse models of ACH. However, administration of exogenous CNP is compromised by its rapid clearance in vivo through receptor-mediated and proteolytic pathways. Using in vitro approaches, we developed modified variants of human CNP, resistant to proteolytic degradation by neutral endopeptidase, that retain the ability to stimulate signaling downstream of the CNP receptor, natriuretic peptide receptor B. The variants tested in vivo demonstrated significantly longer serum half-lives than native CNP. Subcutaneous administration of one of these CNP variants (BMN 111) resulted in correction of the dwarfism phenotype in a mouse model of ACH and overgrowth of the axial and appendicular skeletons in wild-type mice without observable changes in trabecular and cortical bone architecture. Moreover, significant growth plate widening that translated into accelerated bone growth, at hemodynamically tolerable doses, was observed in juvenile cynomolgus monkeys that had received daily subcutaneous administrations of BMN 111. BMN 111 was well tolerated and represents a promising new approach for treatment of patients with ACH. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Therapeutic potential of novel formulated forms of curcumin in the treatment of breast cancer by the targeting of cellular and physiological dysregulated pathways.

    Science.gov (United States)

    Tajbakhsh, Amir; Hasanzadeh, Malihe; Rezaee, Mehdi; Khedri, Mostafa; Khazaei, Majid; ShahidSales, Soodabeh; Ferns, Gordon A; Hassanian, Seyed Mahdi; Avan, Amir

    2018-03-01

    Breast cancer is among the most important causes of cancer related death in women. There is a need for novel agents for targeting key signaling pathways to either improve the efficacy of the current therapy, or reduce toxicity. There is some evidence that curcumin may have antitumor activity in breast cancer. Several clinical trials have investigated its activity in patients with breast cancer, including a recent trial in breast cancer patients receiving radiotherapy, in whom it was shown that curcumin reduced the severity of radiation dermatitis, although it is associated with low bioavailability. Several approaches have been developed to increase its absorption rate (e.g., nano crystals, liposomes, polymers, and micelles) and co-delivery of curcumin with adjuvants as well as different conjugation to enhance its bioavailability. In particular, micro-emulsions is an option for transdermal curcumin delivery, which has been reported to increase its absorption. Lipid-based nano-micelles is another approach to enhance curcumin absorption via gastrointestinal tract, while polymer-based nano-formulations (e.g., poly D, L-lactic-co-glycolic [PLGA]) allows the release of curcumin at a sustained level. This review summarizes the current data of the therapeutic potential of novel formulations of curcumin with particular emphasis on recent preclinical and clinical studies in the treatment of breast cancer. © 2017 Wiley Periodicals, Inc.

  13. Comparison of Therapeutic Efficacies of Norethisterone, Tranexamic Acid and Levonorgestrel-Releasing Intrauterine System for the Treatment of Heavy Menstrual Bleeding: A Randomized Controlled Study.

    Science.gov (United States)

    Kiseli, Mine; Kayikcioglu, Fulya; Evliyaoglu, Ozlem; Haberal, Ali

    2016-01-01

    Our aim was to compare the therapeutic efficacies of norethisterone acid (NETA), tranexamic acid and levonorgestrel-releasing intrauterine system (LNG-IUS) in treating idiopathic heavy menstrual bleeding (HMB). Women with heavy uterine bleeding were randomized to receive NETA, tranexamic acid or LNG-IUS for 6 months. The primary outcome was a decrease in menstrual bleeding as assessed by pictorial blood loss assessment charts and hematological parameters analyzed at the 1st, 3rd and 6th months. Health-related quality of life (QOL) variables were also recorded and analyzed. Twenty-eight patients were enrolled in each treatment group, but the results of only 62 were evaluated. NETA, tranexamic acid, and LNG-IUS reduced menstrual blood loss (MBL) by 53.1, 60.8, and 85.8%, respectively, at the 6th month. LNG-IUS was more effective than NETA and tranexamic acid in decreasing MBL. LNG-IUS was also more efficient than tranexamic acid in correcting anemia related to menorrhagia. Satisfaction rates were comparable among the NETA (70%), tranexamic acid (63%) and LNG-IUS (77%) groups. QOL in physical aspects increased significantly in the tranexamic acid and LNG-IUS groups. The positive effect of LNG-IUS on QOL parameters, as well as its high efficacy, makes it a first-line option for HMB. © 2016 S. Karger AG, Basel.

  14. Subretinal fibrosis and uveitis: a spectral domain OCT study of its evolution and the minimal therapeutic effect of the off-label treatment with ranibizumab.

    Science.gov (United States)

    Symeonidis, Chrysanthos; Dastiridou, Anna; Konidaris, Vasilis; Brazitikos, Periklis; Androudi, Sofia

    2014-12-01

    The subretinal fibrosis and uveitis (SFU) syndrome is a rare multifocal posterior uveitis characterized by progressive subretinal fibrosis and significant visual loss. Slit-lamp examination, dilated fundoscopy, fluorescein angiography, Spectral Domain-Optical Coherence Tomography (SD-OCT) and laboratory testing were employed. A 52-year-old male presented with bilateral (best-corrected visual acuity: 2/10) visual loss. Clinical examination revealed bilateral anterior uveitis with posterior synechiae and posterior uveitis. Medical workup revealed no pathologic findings. Treatment included 1 gr intravenous prednisone followed by oral prednisone, immunosuppresive therapy and three ranibizumab injections in the right eye with no improvement. One year later, there was significant subretinal fibrosis. In the second year follow-up, the picture was slightly worse, with persisting bilateral macular edema and fibrosis. This is the first SFU syndrome report monitored with SD-OCT. This novel imaging modality can localize the lesion level, guide the therapeutic approach and may prove helpful in assessing disease prognosis.

  15. Functional Neurosurgery in the Treatment of Severe Obsessive Compulsive Disorder and Major Depression: Overview of Disease Circuits and Therapeutic Targeting for the Clinician

    Science.gov (United States)

    Shah, Dhwani B.; Pesiridou, Angeliki; Baltuch, Gordon H.; Malone, Donald A.; O’Reardon, John P.

    2008-01-01

    Over the past 20 years, there has been a concerted effort to expand our understanding of the neural circuitry involved in the pathogenesis of psychiatric disorders. Distinct neuronal circuits and networks have been implicated in obsessive compulsive disorder (OCD) and major depressive disorder (MDD) involving feedback loops between the cortex, striatum, and thalamus. When neurosurgery is used as a therapeutic tool in severe OCD and MDD, the goal is to modulate specific targets or nodes within these networks in an effort to produce symptom relief. Currently, four lesioning neurosurgical procedures are utilized for treatment refractory OCD and MDD: cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy. Deep brain stimulation (DBS) is a novel neurosurgical approach that has some distinct advantages over lesioning procedures. With DBS, the desired clinical effect can be achieved by reversible, high frequency stimulation in a nucleus or at a node in the circuit without the need to produce an irreversible lesion. Recent trials of deep brain stimulation in both OCD and MDD at several neuroanatomical targets have reported promising early results in highly refractory patients and with a good safety profile. Future definitive trials in MDD and OCD are envisaged. PMID:19727257

  16. Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritabl