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Sample records for agent ii clinical

  1. RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials.

    Science.gov (United States)

    Oronsky, Bryan; Paulmurugan, Ramasamy; Foygel, Kira; Scicinski, Jan; Knox, Susan J; Peehl, Donna; Zhao, Hongjuan; Ning, Shoucheng; Cabrales, Pedro; Summers, Thomas A; Reid, Tony R; Fitch, William L; Kim, Michelle M; Trepel, Jane B; Lee, Min-Jung; Kesari, Santosh; Abrouk, Nacer D; Day, Regina M; Oronsky, Arnold; Ray, Carolyn M; Carter, Corey A

    2017-01-01

    According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes. Areas covered: This article summarizes the characteristics of the macrophage-stimulating agent RRx-001, a molecular iconoclast, sourced from the aerospace industry, with a particular emphasis on the cell-to-cell transfer mechanism of action (RBCs to TAMs) underlying its antitumor activity as well as its chemo and radioprotective properties, consolidated from various preclinical and clinical studies. Expert opinion: RRx-001 is macrophage-stimulating agent with the potential to synergize with chemotherapy, radiotherapy and immunotherapy while simultaneously protecting normal tissues from their cytotoxic effects. Given the promising indications of activity in multiple tumor types and these normal tissue protective properties, RRx-001 may be used to treat a broad spectrum of malignancies, if it is approved in the future.

  2. Radioimmunotherapy (II): clinical application

    International Nuclear Information System (INIS)

    Cheon, Gi Jeong; Kang, Hye Jin; Lim, Sang Moo

    2006-01-01

    Molecular targeting may be defined as the specific concentration of a diagnostic or therapeutic tracer by its interaction with a molecular species that is distinctly present or absent in a disease state. Monoclonal antibody (mAb) is one of the successful agents for targeted therapy in cancer. To enhance the therapeutic effect. the concept of targeting radionuclides to tumors using radiolabeled mAbs against tumor-associated antigens, radioimmunotherapy, was proposed. The efficacy of radioimmunotherapy, however, has to be further optimized. Several strategies to improve targeting of tumors with radiolabeled mAbs have been developed, such as the use of mAb fragments, the use of high-affinity mAbs, the use of labeling techniques that are stable in vivo, active removal of the radiolabeled mAb from the circulation, and pretargeting strategies. Until now, however, there are many kinds of obstacles to be solved in the use of mAb for the targeted therapy. Major technical challenges to molecular targeting are related to the rapid and specific delivery of tracers to the target, the elimination of unwanted background activity, and the development of more specific targets to create a cytocidal effect. Further development of this field will be determined by success in solving these challenges

  3. Embodied Conversational Agents in Clinical Psychology

    DEFF Research Database (Denmark)

    Provoost, Simon; Lau, Ho Ming; Ruwaard, Jeroen

    2017-01-01

    BACKGROUND: Embodied conversational agents (ECAs) are computer-generated characters that simulate key properties of human face-to-face conversation, such as verbal and nonverbal behavior. In Internet-based eHealth interventions, ECAs may be used for the delivery of automated human support factors....... OBJECTIVE: We aim to provide an overview of the technological and clinical possibilities, as well as the evidence base for ECA applications in clinical psychology, to inform health professionals about the activity in this field of research. METHODS: Given the large variety of applied methodologies, types...... applications in the treatment of mood, anxiety, psychotic, autism spectrum, and substance use disorders were conducted in databases in the fields of psychology and computer science, as well as in interdisciplinary databases. Studies were included if they conveyed primary research findings on an ECA application...

  4. Phase II clinical development of new drugs

    CERN Document Server

    Ting, Naitee; Ho, Shuyen; Cappelleri, Joseph C

    2017-01-01

    This book focuses on how to appropriately plan and develop a Phase II program, and how to design Phase II clinical trials and analyze their data. It provides a comprehensive overview of the entire drug development process and highlights key questions that need to be addressed for the successful execution of Phase II, so as to increase its success in Phase III and for drug approval. Lastly it warns project team members of the common potential pitfalls and offers tips on how to avoid them.

  5. The clinical use of contrast agents in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Bydder, G.M.

    1987-01-01

    Interest in the use of external agents to increase tissue contrasts has come from many sources dating back to the earliest work in NMR, to animal studies and to the widespread use of contrast agents in conventional radiological practice. The first clinical magnetic resonance images were published in 1980 and in the following year a brief account of the use of the paramagnetic agents in human volunteers was established. It was apparent relatively early in the development of magnetic resonance imaging (MRI) that a high level of soft tissue contrast was available de novo and the need for externally administered agents might therefore be small. This observation was tempered by the fact that separation of tumour from oedema was frequently better with contrast enhanced CT X-ray than with unenhanced MRI and that of a contrast agent might therefore be needed for MRI. At the end of 1983 the first parenteral agent gadoliminum diethylene triamine pentaacetic acid (Gd-DTPA) was used in volunteers and clinical studies began in 1984. At the present time only molecular O/sub 2/, oral iron compounds and Gd-DTPA are in clinical use although there are a number of other agents which have been used in animals and some of these may become available for clinical use in the foreseeable future

  6. Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor

    Directory of Open Access Journals (Sweden)

    Sachiko Ezoe

    2012-07-01

    Full Text Available Etoposide is an anticancer agent, which is successfully and extensively used in treatments for various types of cancers in children and adults. However, due to the increases in survival and overall cure rate of cancer patients, interest has arisen on the potential risk of this agent for therapy-related secondary leukemia. Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL gene on chromosome 11q23, which is associated with secondary leukemia. The prognosis is extremely poor for leukemias associated with rearrangements in the MLL gene, including etoposide-related secondary leukemias. It is of great importance to gain precise knowledge of the clinical aspects of these diseases and the mechanism underlying the leukemogenesis induced by this agent to ensure correct assessments of current and future therapy strategies. Here, I will review current knowledge regarding the clinical aspects of etoposide-related secondary leukemia, some probable mechanisms, and strategies for treating etoposide-induced leukemia.

  7. Agent-Based Health Monitoring System, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose combination of software intelligent agents to achieve decentralized reasoning, with fault detection and diagnosis using PCA, neural nets, and maximum...

  8. Ambulatory blood pressure monitoring in clinical trials with antihypertensive agents

    NARCIS (Netherlands)

    A.H. van den Meiracker (Anton)

    1995-01-01

    textabstractAmbulatory blood pressure monitoring (ABPM) is being used increasingly for the evaluation of antihypertensive agents in clinical trials. In this brief review several aspects of ABPM are discussed. In particular, attention is paid to the extent to which ABPM is subject to a placebo

  9. Coordinated Control of Multi-Agent Systems in Rapidly Varying Environments, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The main objective of this Phase II STTR project is to develop advanced control algorithms that enable multiple autonomous agents to perform complex tasks in rapidly...

  10. Clinical Pharmacology of Chemotherapy Agents in Older People with Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoye He

    2011-01-01

    Full Text Available Populations around the world are aging, and the associated increase in cancer incidence has led to the recognition of the importance of geriatric oncology. Chronological age is a poor determinant of pharmacological response to cancer chemotherapy agents. Age-associated changes in physiology and organ function have a significant impact on the clinical pharmacology of cancer chemotherapy agents used in cancer treatment. Altered response to medicines in older people is a consequence of changes in body composition, organ function, concomitant pathophysiology, multiple medications, genetic determinants of drug response, and patient's clinical status. These issues highlight the need to individualize the management of cancer in the older people with consideration of age-related changes in the clinical pharmacology of cancer drugs, analgesics, and adjunctive therapies.

  11. Advance directives: the clinical nurse specialist as a change agent.

    Science.gov (United States)

    Meehan, Karen Anne

    2009-01-01

    The purpose of this article is to describe the impact the clinical nurse specialist (CNS) has on the advance directive process within the cardiac surgery patient population. As a change agent, the CNS needs to be able to increase the number of advance directives obtained and increase the provision of dignified, self-directed, quality patient care. With requirements from The Joint Commission and the Patient Self-determination Act, the change in process must take place to ensure that healthcare professionals are doing all they can do to carry out a patient's wishes. The 6-Source Influencer Model is applied to a case study to illustrate the role of the CNS as a change agent. Following this model, the CNS can facilitate lasting institutional change in the advance directive process. Based on the example, it is possible that a CNS can act as a change agent for other patient populations within the healthcare setting.

  12. Keratin sponge/hydrogel II, active agent delivery

    Science.gov (United States)

    Keratin sponge/hydrogels from oxidation and reduction hydrolysis of fine and coarse wool fibers were formed to behave as cationic hydrogels to swell and release active agents in the specific region of the gastro-intestinal (GI) tract. Their porous, interpenetrating networks (IPN) were effective for...

  13. Synthesis and biological activity of imidazopyridine anticoccidial agents: Part II.

    Science.gov (United States)

    Scribner, Andrew; Dennis, Richard; Lee, Shuliang; Ouvry, Gilles; Perrey, David; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

    2008-06-01

    Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Recently, we reported the synthesis and biological activity of potent imidazo[1,2-a]pyridine anticoccidial agents. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we report the synthesis and anticoccidial activity of a second set of such compounds, focusing on derivatization of the amine side chain at the imidazopyridine 7-position. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

  14. Clinical Perspectives of Urocortin and Related Agents for the Treatment of Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2012-01-01

    Full Text Available The effects of corticotropin-releasing hormone, also known as corticotropin-releasing factor (CRF, on the cardiovascular system have been intensively researched since its discovery. Moreover, the actions of urocortin (Ucn I on the cardiovascular system have also been intensively scrutinized following the cloning and identification of its receptor, CRF receptor type 2 (CRFR2, in peripheral tissues including the heart. Given the cardioprotective actions of CRFR2 ligands, the clinical potential of not only Ucn I but also Ucn II and III, which were later identified as more specific ligands for CRFR2, has received considerable attention from researchers. In addition, recent work has indicated that CRF type 1 receptor may be also involved in cardioprotection against ischemic/reperfusion injury. Here we provide a historical overview of research on Ucn I and related agents, their effects on the cardiovascular system, and the clinical potential of the use of such agents to treat cardiovascular diseases.

  15. SMART II : the spot market agent research tool version 2.0.

    Energy Technology Data Exchange (ETDEWEB)

    North, M. J. N.

    2000-12-14

    Argonne National Laboratory (ANL) has worked closely with Western Area Power Administration (Western) over many years to develop a variety of electric power marketing and transmission system models that are being used for ongoing system planning and operation as well as analytic studies. Western markets and delivers reliable, cost-based electric power from 56 power plants to millions of consumers in 15 states. The Spot Market Agent Research Tool Version 2.0 (SMART II) is an investigative system that partially implements some important components of several existing ANL linear programming models, including some used by Western. SMART II does not implement a complete model of the Western utility system but it does include several salient features of this network for exploratory purposes. SMART II uses a Swarm agent-based framework. SMART II agents model bulk electric power transaction dynamics with recognition for marginal costs as well as transmission and generation constraints. SMART II uses a sparse graph of nodes and links to model the electric power spot market. The nodes represent power generators and consumers with distinct marginal decision curves and varying investment capital as well individual learning parameters. The links represent transmission lines with individual capacities taken from a range of central distribution, outlying distribution and feeder line types. The application of SMART II to electric power systems studies has produced useful results different from those often found using more traditional techniques. Use of the advanced features offered by the Swarm modeling environment simplified the creation of the SMART II model.

  16. Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor

    OpenAIRE

    Sachiko Ezoe

    2012-01-01

    Etoposide is an anticancer agent, which is successfully and extensively used in treatments for various types of cancers in children and adults. However, due to the increases in survival and overall cure rate of cancer patients, interest has arisen on the potential risk of this agent for therapy-related secondary leukemia. Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL<...

  17. Pharmacokinetic studies of neuromuscular blocking agents: Good Clinical Research Practice (GCRP)

    DEFF Research Database (Denmark)

    Viby-Mogensen, J.; Østergaard, D.; Donati, F.

    2000-01-01

    Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design......Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design...

  18. Polydisulfide Manganese(II) Complexes as Non-Gadolinium Biodegradable Macromolecular MRI Contrast Agents

    Science.gov (United States)

    Ye, Zhen; Jeong, Eun-Kee; Wu, Xueming; Tan, Mingqian; Yin, Shouyu; Lu, Zheng-Rong

    2011-01-01

    Purpose To develop safe and effective manganese(II) based biodegradable macromolecular MRI contrast agents. Materials and Methods In this study, we synthesized and characterized two polydisulfide manganese(II) complexes, Mn-DTPA cystamine copolymers and Mn-EDTA cystamine copolymers, as new biodegradable macromolecular MRI contrast agents. The contrast enhancement of the two manganese based contrast agents were evaluated in mice bearing MDA-MB-231 human breast carcinoma xenografts, in comparison with MnCl2. Results The T1 and T2 relaxivities were 4.74 and 10.38 mM−1s−1 per manganese at 3T for Mn-DTPA cystamine copolymers (Mn=30.50 kDa) and 6.41 and 9.72 mM−1s−1 for Mn-EDTA cystamine copolymers (Mn= 61.80 kDa). Both polydisulfide Mn(II) complexes showed significant liver, myocardium and tumor enhancement. Conclusion The manganese based polydisulfide contrast agents have a potential to be developed as alternative non-gadolinium contrast agents for MR cancer and myocardium imaging. PMID:22031457

  19. Multi-Agent System for Recruiting Patients for Clinical Trials

    Science.gov (United States)

    2014-05-01

    Managing Agent: The Trial Managing Agent has been implemented in Java , with support from a MySQL back-end database. This is used to conveniently exchange...these principles via simulation. • Recruitment Agent: The Recruitment Agent has been imple- mented in Java and has been used by 124 GPs so far

  20. DNA alkylating agents alleviate silencing of class II transactivator gene expression in L1210 lymphoma cells.

    Science.gov (United States)

    Murphy, Shawn P; Holtz, Renae; Lewandowski, Nicole; Tomasi, Thomas B; Fuji, Hiroshi

    2002-09-15

    MHC class II (Ia) Ag expression is inversely correlated with tumorigenicity and directly correlated with immunogenicity in clones of the mouse L1210 lymphoma (1 ). Understanding the mechanisms by which class II Ag expression is regulated in L1210 lymphoma may facilitate the development of immunotherapeutic approaches for the treatment of some types of lymphoma and leukemia. This study demonstrates that the variation in MHC class II Ag expression among clones of L1210 lymphoma is due to differences in the expression of the class II transactivator (CIITA). Analysis of stable hybrids suggests that CIITA expression is repressed by a dominant mechanism in class II-negative L1210 clones. DNA-alkylating agents such as ethyl methanesulfonate and the chemotherapeutic drug melphalan activate CIITA and class II expression in class II negative L1210 cells, and this effect appears to be restricted to transformed cell lines derived from the early stages of B cell ontogeny. Transient transfection assays demonstrated that the CIITA type III promoter is active in class II(-) L1210 cells, despite the fact that the endogenous gene is not expressed, which suggests that these cells have all of the transacting factors necessary for CIITA transcription. An inverse correlation between methylation of the CIITA transcriptional regulatory region and CIITA expression was observed among L1210 clones. Furthermore, 5-azacytidine treatment activated CIITA expression in class II-negative L1210 cells. Collectively, our results suggest that 1) CIITA gene expression is repressed in class II(-) L1210 cells by methylation of the CIITA upstream regulatory region, and 2) treatment with DNA-alkylating agents overcomes methylation-based silencing of the CIITA gene in L1210 cells.

  1. Trichorhinophalangeal syndrome II, expanding the clinical spectrum

    African Journals Online (AJOL)

    Rabah M. Shawky

    2014-06-17

    Jun 17, 2014 ... an autosomal dominant fashion, most cases of TRPS II are sporadic [1]. TRPS III, is a form of brachydactyly due to short metacarpals and severe .... and broad on both sides (black asterisk), the fifth metacarpal bone has similar yet less pronounced appearance (white asterisk). Langer–Giedion syndrome. 91 ...

  2. Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells

    International Nuclear Information System (INIS)

    Tanaka, Mamoru; Kamiya, Takeshi; Joh, Takashi; Kataoka, Hiromi; Yano, Shigenobu; Ohi, Hiromi; Kawamoto, Keisuke; Shibahara, Takashi; Mizoshita, Tsutomu; Mori, Yoshinori; Tanida, Satoshi

    2013-01-01

    Cisplatin (CDDP) is the most frequently used chemotherapeutic agent for various types of advanced cancer, including gastric cancer. However, almost all cancer cells acquire resistance against CDDP, and this phenomenon adversely affects prognosis. Thus, new chemotherapeutic agents that can overcome the CDDP-resistant cancer cells will improve the survival of advanced cancer patients. We synthesized new glycoconjugated platinum (II) and palladium (II) complexes, [PtCl 2 (L)] and [PdCl 2 (L)]. CDDP-resistant gastric cancer cell lines were established by continuous exposure to CDDP, and gene expression in the CDDP-resistant gastric cancer cells was analyzed. The cytotoxicity and apoptosis induced by [PtCl 2 (L)] and [PdCl 2 (L)] in CDDP-sensitive and CDDP-resistant gastric cancer cells were evaluated. DNA double-strand breaks by drugs were assessed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established and antitumor effects were also examined in vivo. CDDP-resistant gastric cancer cells exhibit ABCB1 and CDKN2A gene up-regulation, as compared with CDDP-sensitive gastric cancer cells. In the analyses of CDDP-resistant gastric cancer cells, [PdCl 2 (L)] overcame cross-resistance to CDDP in vitro and in vivo. [PdCl 2 (L)] induced DNA double-strand breaks. These results indicate that [PdCl 2 (L)] is a potent chemotherapeutic agent for CDDP-resistant gastric cancer and may have clinical applications

  3. Mitochondrial complex II, a novel target for anti-cancer agents

    Czech Academy of Sciences Publication Activity Database

    Klučková, Katarína; Bezawork-Geleta, A.; Rohlena, Jakub; Dong, L.; Neužil, Jiří

    2013-01-01

    Roč. 1827, č. 5 (2013), s. 552-564 ISSN 0005-2728 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP301/12/1851 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitochondrion * Complex II * Anti-cancer agent Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.829, year: 2013

  4. A New Clinical HIFU System (Teleson II)

    Science.gov (United States)

    Ma, Yixin; Symonds-Tayler, Richard; Rivens, Ian H.; ter Haar, Gail R.

    2007-05-01

    Previous clinical trials with our first prototype HIFU system (Teleson I) for the treatment of liver tumors, demonstrated a major challenge to be treatment of those tumors located behind the ribs. We have designed a new multi-element transducer for rib sparing. Initial simulation and experimental results (using a single channel power amplifier) are very encouraging. A new clinical HIFU system which can drive the multi-element transducer and control each channel independently is being designed and constructed. This second version of a clinical prototype HIFU system consists of a 3D motorised gantry, a multi-channel signal generator, a multi-channel power amplifier, a user interface PC, an embedded controller and auxiliary circuits for real-time interleaving/synchronization control and a to-be-implemented safety monitoring and data logging unit. For multi-element transducers, each element can be individually switched on and off for rib sparing, and phase and amplitude modulated for potential phased array applications. The multi-channel power amplifier can be switched on/off very rapidly at required intervals to interleave with ultrasound B-Scan imaging for HIFU monitoring or radiation force elastography imaging via a dedicated interleaving/timing module. The gantry movement can also be synchronised with power amplifier on/off and phase/amplitude updating for lesion generation under a wide variety of conditions including single lesions, lesion arrays and lesions "tracks" created whilst translating the active transducer. Results from testing the system using excised tissue will be presented.

  5. Magnesium ionophore II as an extraction agent for trivalent europium and americium

    Energy Technology Data Exchange (ETDEWEB)

    Makrlik, Emanuel [Czech Univ. of Life Sciences, Prague (Czech Republic). Faculty of Environmental Sciences; Vanura, Petr [Univ. of Chemistry and Technology, Prague (Czech Republic). Dept. of Analytical Chemistry

    2016-11-01

    Solvent extraction of microamounts of trivalent europium and americium into nitrobenzene by using a mixture of hydrogen dicarbollylcobaltate (H{sup +}B{sup -}) and magnesium ionophore II (L) was studied. The equilibrium data were explained assuming that the species HL{sup +}, HL{sup +}{sub 2}, ML{sup 3+}{sub 2}, and ML{sup 3+}{sub 3} (M{sup 3+} = Eu{sup 3+}, Am{sup 3+}; L=magnesium, ionophore II) are extracted into the nitrobenzene phase. Extraction and stability constants of the cationic complex species in nitrobenzene saturated with water were determined and discussed. From the experimental results it is evident that this effective magnesium ionophore II receptor for the Eu{sup 3+} and Am{sup 3+} cations could be considered as a potential extraction agent for nuclear waste treatment.

  6. Clinical evaluation of the Non-Contact Tonometer Mark II.

    Science.gov (United States)

    Chauhan, B C; Henson, D B

    1988-09-01

    The purpose of this investigation was to test the reliability of the American Optical Non-Contact Tonometer Mark II (NCT II) using the Goldmann Applanation Tonometer (GAT) as the validating instrument. The sample contained 102 consecutive patients from our University Eye Clinic, of whom one-half had 4 NCT II measurements first, followed by 4 GAT measurements; the other one-half had 4 GAT measurements first, followed by 4 NCT II measurements. No significant change in intraocular pressure (IOP) was noted over the measurement sequence with either instrument. There was no significant difference between paired NCT II and GAT readings when the NCT II was used first; however, a highly significant difference between paired readings was obtained when the GAT was used first, indicating that the GAT measurement produced a delayed reduction in the IOP. This effect did not occur with the NCT II. Although the NCT II is shown to have a good overall reliability when compared to the GAT in both protocols, the agreement between any two tonometers may be influenced greatly by the very process of taking a measurement and by the dynamic nature of the IOP.

  7. 77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

    Science.gov (United States)

    2012-10-01

    ...] Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public Workshop... to the clinical development of disease-modifying agents for the treatment of peripheral neuropathy... disease-modifying products for the management of peripheral neuropathy. Date and Time: The public workshop...

  8. Clinical Benefits of Memantine Treatment for Alzheimer's Disease in the Okayama Memantine Study II (OMS II).

    Science.gov (United States)

    Matsuzono, Kosuke; Yamashita, Toru; Ohta, Yasuyuki; Hishikawa, Nozomi; Koike, Makoto; Sato, Kota; Kono, Syoichiro; Deguchi, Kentaro; Nakano, Yumiko; Abe, Koji

    2015-01-01

    The clinical benefits of memantine, depending on the baseline cognitive and affective conditions in real world dementia clinics, have not been completely examined. We performed the "Okayama Memantine Study II (OMS II)" to retrospectively evaluate the clinical effects of memantine monotherapy (n = 38) in Alzheimer's disease (AD) patients using seven batteries to assess dementia at the baseline, at 3, 6, and 12 months. Additionally, we divided 163 AD patients treated with memantine into two subgroups depending on the baseline cognitive score of the Mini-Mental State Examination (MMSE): the MMSE OMS II showed that memantine monotherapy improved BPSD until 12 months. The higher baseline cognitive subgroup (MMSE ≥15) and the worse baseline BPSD subgroup were expected to show better effects with memantine.

  9. Mononuclear Pd(II) complex as a new therapeutic agent: Synthesis, characterization, biological activity, spectral and DNA binding approaches

    Science.gov (United States)

    Saeidifar, Maryam; Mirzaei, Hamidreza; Ahmadi Nasab, Navid; Mansouri-Torshizi, Hassan

    2017-11-01

    The binding ability between a new water-soluble palladium(II) complex [Pd(bpy)(bez-dtc)]Cl (where bpy is 2,2‧-bipyridine and bez-dtc is benzyl dithiocarbamate), as an antitumor agent, and calf thymus DNA was evaluated using various physicochemical methods, such as UV-Vis absorption, Competitive fluorescence studies, viscosity measurement, zeta potential and circular dichroism (CD) spectroscopy. The Pd(II) complex was synthesized and characterized using elemental analysis, molar conductivity measurements, FT-IR, 1H NMR, 13C NMR and electronic spectra studies. The anticancer activity against HeLa cell lines demonstrated lower cytotoxicity than cisplatin. The binding constants and the thermodynamic parameters were determined at different temperatures (300 K, 310 K and 320 K) and shown that the complex can bind to DNA via electrostatic forces. Furthermore, this result was confirmed by the viscosity and zeta potential measurements. The CD spectral results demonstrated that the binding of Pd(II) complex to DNA induced conformational changes in DNA. We hope that these results will provide a basis for further studies and practical clinical use of anticancer drugs.

  10. Reações tegumentares adversas relacionadas aos agentes antineoplásicos: parte II Adverse mucocutaneous reactions related to chemotherapeutic agents: part II

    Directory of Open Access Journals (Sweden)

    Paulo Ricardo Criado

    2010-10-01

    Full Text Available Os eventos e reações envolvendo quimioterapia são frequentes na prática oncológica. Agentes quimioterápicos são uma modalidade de tratamento amplamente utilizada. Efeitos colaterais podem variar de frequência e também ser confundidos com outras manifestações tegumentares do tratamento oncológico. Este artigo objetiva expor as informações sobre reações cutâneas à quimioterapia, em especial, aqueles para os quais o dermatologista é requisitado a emitir parecer e a comentar sobre a segurança e a viabilidade da readministração de uma droga específica. Os autores descrevem os aspectos associados a esses eventos, fazendo uma análise detalhada de cada um deles.Events and reactions involving chemotherapy are common in clinical oncology. Chemotherapeutic agents are widely used in therapy. Side effects range from the common to the rare and may be confused with other mucocutaneous manifestations resulting from the oncological treatment. The objective of this paper was to present data on skin reactions to chemotherapy, particularly those cases in which the dermatologist is requested to issue a report and asked to comment on the safety and viability of readministration of a specific drug. The authors describe aspects associated with these events, presenting a detailed analysis of each one of them.

  11. The SafeBoosC Phase II Randomised Clinical Trial

    DEFF Research Database (Denmark)

    Pellicer, Adelina; Greisen, Gorm; Benders, Manon

    2013-01-01

    Near-infrared spectroscopy-derived regional tissue oxygen saturation of haemoglobin (rStO2) reflects venous oxygen saturation. If cerebral metabolism is stable, rStO2 can be used as an estimate of cerebral oxygen delivery. The SafeBoosC phase II randomised clinical trial hypothesises that the bur...

  12. The SafeBoosC phase II clinical trial

    DEFF Research Database (Denmark)

    Riera, Joan; Hyttel-Sorensen, Simon; Bravo, María Carmen

    2016-01-01

    BACKGROUND: The SafeBoosC phase II randomised clinical trial recently demonstrated the benefits of a combination of cerebral regional tissue oxygen saturation (rStO2) by near-infrared spectroscopy (NIRS) and a treatment guideline to reduce the oxygen imbalance in extremely preterm infants. AIMS: ...

  13. Embodied Conversational Agents in Clinical Psychology : A Scoping Review

    NARCIS (Netherlands)

    Provoost, Simon; Lau, Ho Ming; Ruwaard, Jeroen; Riper, Heleen

    2017-01-01

    BACKGROUND: Embodied conversational agents (ECAs) are computer-generated characters that simulate key properties of human face-to-face conversation, such as verbal and nonverbal behavior. In Internet-based eHealth interventions, ECAs may be used for the delivery of automated human support factors.

  14. Clinical bacterial isolates from hospital environment as agents of ...

    African Journals Online (AJOL)

    The relationship between bacteria isolated from the hospital environment and those from wounds of operated patients was investigated to determine the causal agents of surgical site nosocomial infections. The study was carried out on bacterial species isolated from the theatre, surgical ward and patients' surgical wounds ...

  15. Platinum(II)-gadolinium(III) complexes as potential single-molecular theranostic agents for cancer treatment.

    Science.gov (United States)

    Zhu, Zhenzhu; Wang, Xiaoyong; Li, Tuanjie; Aime, Silvio; Sadler, Peter J; Guo, Zijian

    2014-11-24

    Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. 4-aminoquinoline analogues and its platinum (II) complexes as antimalarial agents.

    Science.gov (United States)

    de Souza, Nicolli Bellotti; Carmo, Arturene M L; Lagatta, Davi C; Alves, Márcio José Martins; Fontes, Ana Paula Soares; Coimbra, Elaine Soares; da Silva, Adilson David; Abramo, Clarice

    2011-07-01

    The high incidence of malaria and drug-resistant strains of Plasmodium have turned this disease into a problem of major health importance. One of the approaches used to control it is to search for new antimalarial agents, such as quinoline derivates. This class of compounds composes a broad group of antimalarial agents, which are largely employed, and inhibits the formation of β-haematin (malaria pigment), which is lethal to the parasite. More specifically, 4-aminoquinoline derivates represent potential sources of antimalarials, as the example of chloroquine, the most used antimalarial worldwide. In order to assess antimalarial activity, 12 4-aminoquinoline derived drugs were obtained and some of these derivatives were used to obtain platinum complexes platinum (II). These compounds were tested in vivo in a murine model and revealed remarkable inhibition of parasite multiplication values, whose majority ranged from 50 to 80%. In addition they were not cytotoxic. Thus, they may be object of further research for new antimalarial agents. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  17. State and development of new clinical contrast agents for MR diagnosis of liver diseases

    International Nuclear Information System (INIS)

    Rummeny, E.J.; Peters, P.E.

    1992-01-01

    MR contrast agents are developed for pharmaceutical manipulation of tissue signal intensities. Today it is widely recognized that MR contrast agents will play an increasingly important role in MR imaging of the liver. Contrast-enhanced MR-imaging allows to obtain simultaneously dynamic physiologic information and high anatomci detail. Up to now three major classes of MR contrast agents are available for clinical MR-imaging of the liver. These include paramagnetic perfusion agents, hepatobiliary agents, and superparamagnetic RES-specific iron oxide particles. A fourth class of contrast agents now in use for animal experiments includes ultrasmall superparamagnetic particles which can be targeted to extrareticuloendothelial structures such as asialoglycoprotein receptors of hepatocytes. In this article, we review recent advances in the development of MR contrast media and the clinical of contrast-enhanced MR imaging of the liver. (orig.) [de

  18. Design of clinical trials Phase I and II with radiopharmaceuticals

    International Nuclear Information System (INIS)

    Giannone, C.A.; Soroa, V.E.

    2015-01-01

    We presented some usual designs for clinical studies in Phase I and Phase II. For Phase I we considered the 3 + 3 Classic design, designs with accelerated titration and those with dose escalation schemes with overdose control (EWOC). For Phase II designs with efficacy outcomes are presented. The design proposed by Fleming is discussed as well as those with inclusion of patients in two stages: Gehan’s design and the Optimal two–stage Simon’s design. We also discussed the design of combined endpoints of efficacy and safety of Bryant and Day with an application example of therapeutically Lu-177. Finally some proposals for phase II trials with control group are considered. (authors) [es

  19. Phase II cancer clinical trials for biomarker-guided treatments.

    Science.gov (United States)

    Jung, Sin-Ho

    2018-01-01

    The design and analysis of cancer clinical trials with biomarker depend on various factors, such as the phase of trials, the type of biomarker, whether the used biomarker is validated or not, and the study objectives. In this article, we demonstrate the design and analysis of two Phase II cancer clinical trials, one with a predictive biomarker and the other with an imaging prognostic biomarker. Statistical testing methods and their sample size calculation methods are presented for each trial. We assume that the primary endpoint of these trials is a time to event variable, but this concept can be used for any type of endpoint.

  20. Reassessing Phase II Heart Failure Clinical Trials: Consensus Recommendations

    Science.gov (United States)

    Butler, Javed; Hamo, Carine E.; Udelson, James E.; O’Connor, Christopher; Sabbah, Hani N.; Metra, Marco; Shah, Sanjiv J.; Kitzman, Dalane W.; Teerlink, John; Bernstein, Harold S.; Brooks, Gabriel; Depre, Christophe; DeSouza, Mary M.; Dinh, Wilfried; Donovan, Mark; Frische-Danielson, Regina; Frost, Robert J.; Garza, Dahlia; Gohring, Udo-Michael; Hellawell, Jennifer; Hsia, Judith; Ishihara, Shiro; Kay-Mugford, Patricia; Koglin, Joerg; Kozinn, Marc; Larson, Christopher J.; Mayo, Martha; Gan, Li-Ming; Mugnier, Pierrre; Mushonga, Sekayi; Roessig, Lothar; Russo, Cesare; Salsali, Afshin; Satler, Carol; Shi, Victor; Ticho, Barry; van der Laan, Michael; Yancy, Clyde; Stockbridge, Norman; Gheorghiade, Mihai

    2017-01-01

    The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue regarding the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17th 2016 represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions. PMID:28356300

  1. New Drug Formulary Will Help Expedite Use of Agents in Clinical Trials

    Science.gov (United States)

    NCI launched the “NCI Formulary” that will enable investigators at NCI-designated Cancer Centers to have quicker access to approved and investigational agents for use in preclinical studies and cancer clinical trials.

  2. Adjuvant Chemotherapy for Stage II Colon Cancer: A Clinical Dilemma.

    Science.gov (United States)

    Kannarkatt, Joseph; Joseph, Joe; Kurniali, Peter C; Al-Janadi, Anas; Hrinczenko, Borys

    2017-04-01

    The decision to treat a patient with stage II colon cancer with adjuvant chemotherapy can be challenging. Although the benefit of treatment is clear in most patients with stage III disease, the decision to provide chemotherapy after surgical resection in stage II disease must be made on an individual basis. Several trials have demonstrated the small but absolute benefits of receiving adjuvant chemotherapy for stage II colon cancer for disease-free survival and overall survival. In an attempt to better understand the role of chemotherapy, several studies were performed that identified high-risk characteristics that can be used prognostically and predictively to aid in the clinical decision making process. ASCO, the National Comprehensive Cancer Network, and the European Society of Medical Oncology have published guidelines describing these high-risk characteristics. Since then, several other molecular markers have emerged that may offer more information on a given patient's risk for recurrence. The decision to treat a patient with stage II colon cancer must be made on an individual basis, considering the risks and benefits of treatment. In this short review, we will present the available evidence and offer possible directions for future study.

  3. Type I-II laryngeal cleft: clinical course and outcome.

    Science.gov (United States)

    Slonimsky, Guy; Carmel, Eldar; Drendel, Michael; Lipschitz, Noga; Wolf, Michael

    2015-04-01

    Laryngeal cleft (LC) is a rare congenital anomaly manifesting in a variety of symptoms, including swallowing disorders and aspirations, dyspnea, stridor and hoarseness. The mild forms (types I-II) may be underdiagnosed, leading to protracted symptomatology and morbidity. To evaluate the diagnostic process, clinical course, management and outcome in children with type I-II laryngeal clefts. We conducted a retrospective case analysis for the years 2005-2012 in a tertiary referral center. Seven children were reviewed: five boys and two girls ranging in age from birth to 5 years. The most common presenting symptoms were cough, aspirations and pneumonia. Evaluation procedures included fiber-optic laryngoscopy (FOL), direct laryngoscopy (DL) and videofluoroscopy. Other pathologies were seen in three children. Six children underwent successful endoscopic surgery and one child was treated conservatively. The postoperative clinical course was uneventful in most of the cases. Types I-II LC should be considered in the differential diagnosis of children presenting with protracted cough and aspirations. DL is crucial for establishing the diagnosis. Endoscopic surgery is safe and should be applied promptly when conservative measures fail.

  4. Hepatobiliary contrast agents for contrast-enhanced MRI of the liver: properties, clinical development and applications

    International Nuclear Information System (INIS)

    Reimer, Peter; Schneider, Guenter; Schima, Wolfgang

    2004-01-01

    Hepatobiliary contrast agents with uptake into hepatocytes followed by variable biliary excretion represent a unique class of cell-specific MR contrast agents. Two hepatobiliary contrast agents, mangafodipir trisodium and gadobenate dimeglumine, are already clinically approved. A third hepatobiliary contrast agent, Gd-EOB-DTPA, is under consideration. The purpose of this review is to provide an overview on the properties, clinical development and application of these three hepatobiliary contrast agents. Bolus injectable paramagnetic hepatobiliary contrast agents combine established features of extracellular agents with the advantages of hepatocyte specificity. The detection and characterisation of focal liver disease appears to be improved compared to unenhanced MRI, MRI with unspecific contrast agents and contrast-enhanced CT. To decrease the total time spent by a patient in the MR scanner, it is advisable to administer the agent immediately after acquisition of unenhanced T1-w MRI. After infusion or bolus injection (with dynamic FS-T1-w 2D or 3D GRE) of the contrast agent, moderately and heavily T2w images are acquired. Post-contrast T1-w MRI is started upon completion of T2-w MRI for mangafodipir trisodium and Gd-EOB-DTPA as early as 20 min following injection, while gadobenate dimeglumine scans are obtained >60 min following injection. Post-contrast acquisition techniques with near isotropic 3D pulse sequences with fat saturation parallel the technical progress made by MSCT combined with an unparalleled improvement in tumour-liver contrast. The individual decision that hepatobiliary contrast agent one uses is partly based on personal preferences. No comparative studies have been conducted comparing the advantages or disadvantages of all three agents directly against each other. (orig.)

  5. Onychomycosis: Clinical findings, etiological agents and evaluation of laboratory methods

    Directory of Open Access Journals (Sweden)

    Dubljanin Eleonora

    2014-01-01

    Full Text Available The aim of this study was to identify the etiological agents in patients with suspected onychomycosis, and to carry out comparative testing of individual or combinations of tests: direct microscopy with KOH and Blankophor (BP, culturing on Sabouraud’s dextrose agar (SDA, diluted Sabouraud’s dextrose agar (D-SDA and dermatophyte test medium (DTM. From 70 nail samples (65 toenails, 5 fingernails, 46 (60.5% had at least one of five positive tests. Isolation was possible in 41, while in 5 samples the presence of fungi was observed by KOH and/or BP. Dermatophytes were most frequently isolated (80.5% where Trichophyton rubrum was predominant. Candida spp. was isolated in 9.8%, Aspergillus spp. 4.9%, Alternaria spp. 2.4% and Fusarium spp. 2.4%. Application of BP as an individual test was the most sensitive method. The combination of BP with DTM or D-SDA provides the best sensitivity and allows the identification of fungi to the species/genus level.

  6. In vitro contractile effects of agents used in the clinical management of postpartum haemorrhage.

    Science.gov (United States)

    Morrison, John J; Crosby, David A; Crankshaw, Denis J

    2016-10-15

    Uterine atony is a major cause of postpartum haemorrhage and maternal mortality. However, the comparative pharmacology of agents used to treat this condition is poorly understood. This study evaluates, using human pregnant myometrium in vitro, a range of contractile parameters for agents used in the clinical treatment of atonic postpartum haemorrhage. The effects of oxytocin, carbetocin, ergometrine, carboprost, syntometrine and misoprostol were investigated in 146 myometrial strips from 19 donors. The potency and maximal response values were obtained, and compared, using both maximal amplitude and mean contractile force as indices of contraction. Single, EC50 concentrations of the agents were administered and both force and contraction peak parameters were compared during a 15-min exposure. Differences were considered significant when Poxytocin and carbetocin being the most potent. The most important difference between the agents was in their ability to increase the mean contractile force, with oxytocin superior to all agents except syntometrine. In single dose experiments, mean contractile force was the parameter that separated the agents. In this respect, oxytocin was not statistically different from carboprost or syntometrine, but was superior to all other agents. These findings support a clear role for oxytocin as the first line agent for treatment of postpartum haemorrhage and raise doubts about the potential clinical usefulness of misoprostol. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Hematotoxicity response in rats by the novel copper-based anticancer agent: casiopeina II

    International Nuclear Information System (INIS)

    Vizcaya-Ruiz, A. de; Rivero-Mueller, A.; Ruiz-Ramirez, L.; Howarth, J.A.; Dobrota, M.

    2003-01-01

    The in vivo toxicity of the novel copper-based anticancer agent, casiopeina II (Cu(4,7-dimethyl-1,10-phenanthroline)(glycine)NO 3 ) (CII), was investigated. Casiopeinas are a family of copper-coordinated complexes that have shown promising anticancer activity. The major toxic effect attributed to a single i.v. administration of CII (5 mg/kg dose) in the rat was an hemolytic anemia (reduced hemoglobin concentration (HB), red blood cell (RBC) count and packed cell volume (PCV) accompanied by a marked neutrophilic leukocytosis) 12 h and 5 days after administration, attributed to a direct erythrocyte damage. Increased reticulocyte levels and presence of normoblasts in peripheral blood 5 days post-administration indicated an effective erythropoietic response with recovery at 15 days. Increase in spleen weight and the morphological evidence of congestion of the red pulp (RP) with erythrocytes (E) resulting in a higher ratio of red to white pulp (WP) was consistent with increased uptake of damaged erythrocytes by the reticuloendothelial system observed by histopathology and electron microscopy. Extramedullary hemopoiesis was markedly increased at 5 days giving further evidence of a regenerative erythropoietic response that had an effective recovery by 15 days. Morphological changes in spleen cellularity were consistent with hematotoxicity, mainly a reduction of the red pulp/white pulp ratio, increase in erythrocyte content at 12 h, and an infiltration of nucleated cells in the red pulp at 5 days, with a tendency towards recovery 15 days after administration. The erythrocyte damage is attributed to generation of free radicals and oxidative damage on the membrane and within cells resulting from the reduction of Cu(II) and the probable dissociation of the CII complex

  8. Enhancement effects of reducing agents on the degradation of tetrachloroethene in the Fe(II)/Fe(III) catalyzed percarbonate system

    International Nuclear Information System (INIS)

    Miao, Zhouwei; Gu, Xiaogang; Lu, Shuguang; Brusseau, Mark L.; Yan, Ni; Qiu, Zhaofu; Sui, Qian

    2015-01-01

    Highlights: • PCE degradation by reducing-agent modified Fe-catalyzed percarbonate was studied. • The addition of reducing agents significantly increased PCE degradation. • Hydroxylamine hydrochloride showed the best effect on enhancing PCE degradation. • The primary PCE degradation mechanism was oxidation by hydroxyl radical. • O_2·"− participated in the degradation of PCE in reducing-agent modified system. - Abstract: In this study, the effects of reducing agents on the degradation of tetrachloroethene (PCE) were investigated in the Fe(II)/Fe(III) catalyzed sodium percarbonate (SPC) system. The addition of reducing agents, including hydroxylamine hydrochloride, sodium sulfite, ascorbic acid and sodium ascorbate, accelerated the Fe(III)/Fe(II) redox cycle, leading to a relatively steady Fe(II) concentration and higher production of free radicals. This, in turn, resulted in enhanced PCE oxidation by SPC, with almost complete PCE removal obtained for appropriate Fe and SPC concentrations. The chemical probe tests, using nitrobenzene and carbon tetrachloride, demonstrated that HO· was the predominant radical in the system and that O_2·"− played a minor role, which was further confirmed by the results of electron spin resonance measurements. PCE degradation decreased significantly with the addition of isopropanol, a HO· scavenger, supporting the hypothesis that HO· was primarily responsible for PCE degradation. It is noteworthy that Cl"− release was slightly delayed in the first 20 min, indicating that intermediate products were produced. However, these intermediates were further degraded, resulting in the complete conversion of PCE to CO_2. In conclusion, the use of reducing agents to enhance Fe(II)/Fe(III) catalyzed SPC oxidation appears to be a promising approach for the rapid degradation of organic contaminants in groundwater.

  9. Enhancement effects of reducing agents on the degradation of tetrachloroethene in the Fe(II)/Fe(III) catalyzed percarbonate system

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Zhouwei [State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, Shanghai 200237 (China); Soil, Water and Environmental Science Department, School of Earth and Environmental Sciences, The University of Arizona, 429 Shantz Building, Tucson, AZ 85721 (United States); Gu, Xiaogang [State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, Shanghai 200237 (China); Lu, Shuguang, E-mail: lvshuguang@ecust.edu.cn [State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, Shanghai 200237 (China); Brusseau, Mark L. [Soil, Water and Environmental Science Department, School of Earth and Environmental Sciences, The University of Arizona, 429 Shantz Building, Tucson, AZ 85721 (United States); Yan, Ni [Hydrology and Water Resources Department, School of Earth and Environmental Sciences, University of Arizona, 429 Shantz Building, Tucson, AZ 85721 (United States); Qiu, Zhaofu; Sui, Qian [State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, Shanghai 200237 (China)

    2015-12-30

    Highlights: • PCE degradation by reducing-agent modified Fe-catalyzed percarbonate was studied. • The addition of reducing agents significantly increased PCE degradation. • Hydroxylamine hydrochloride showed the best effect on enhancing PCE degradation. • The primary PCE degradation mechanism was oxidation by hydroxyl radical. • O{sub 2}·{sup −} participated in the degradation of PCE in reducing-agent modified system. - Abstract: In this study, the effects of reducing agents on the degradation of tetrachloroethene (PCE) were investigated in the Fe(II)/Fe(III) catalyzed sodium percarbonate (SPC) system. The addition of reducing agents, including hydroxylamine hydrochloride, sodium sulfite, ascorbic acid and sodium ascorbate, accelerated the Fe(III)/Fe(II) redox cycle, leading to a relatively steady Fe(II) concentration and higher production of free radicals. This, in turn, resulted in enhanced PCE oxidation by SPC, with almost complete PCE removal obtained for appropriate Fe and SPC concentrations. The chemical probe tests, using nitrobenzene and carbon tetrachloride, demonstrated that HO· was the predominant radical in the system and that O{sub 2}·{sup −} played a minor role, which was further confirmed by the results of electron spin resonance measurements. PCE degradation decreased significantly with the addition of isopropanol, a HO· scavenger, supporting the hypothesis that HO· was primarily responsible for PCE degradation. It is noteworthy that Cl{sup −} release was slightly delayed in the first 20 min, indicating that intermediate products were produced. However, these intermediates were further degraded, resulting in the complete conversion of PCE to CO{sub 2}. In conclusion, the use of reducing agents to enhance Fe(II)/Fe(III) catalyzed SPC oxidation appears to be a promising approach for the rapid degradation of organic contaminants in groundwater.

  10. PERICARDITIS: ETIOLOGY, CLASSIFICATION, CLINIC, DIAGNOSTICS, TREATMENT. PART II

    Directory of Open Access Journals (Sweden)

    A.B. Sugak

    2009-01-01

    Full Text Available Pericarditis maybe caused by different agents: viruses, bacteria, tuberculosis, and it may be autoimmune. All these types of diseases have similar clinical signs, but differ by prevalence, prognosis and medical tactics. Due to achievements of radial methods of visualization, molecular biology, and immunology, we have an opportunity to provide early specific diagnostics and etiological treatment of inflammatory diseases of pericardium. The second part of lecture presents main principles of differential diagnostics of specific types of pericarditis, gives characteristics of several often accruing types of disease, and describes treatment and tactics of management of patients with pericarditis.Key words: children, pericarditis.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(3:76-81

  11. The potential of SGLT2 inhibitors in phase II clinical development for treating type 2 diabetes.

    Science.gov (United States)

    Pafili, K; Maltezos, E; Papanas, N

    2016-10-01

    There is now an abundance of anti-diabetic agents. However, only few patients achieve glycemic targets. Moreover, current glucose-lowering agents mainly depend upon insulin secretion or function. Sodium glucose co-transporter type 2 (SGLT2) inhibitors present a novel glucose-lowering therapy, inducing glycosuria in an insulin-independent fashion. In this review, the authors discuss the key efficacy and safety data from phase II clinical trials in type 2 diabetes mellitus (T2DM) of the main SGLT2 inhibitors approved or currently in development, and provide a rationale for their use in T2DM. Despite the very promising characteristics of this new therapeutic class, a number of issues await consideration. One important question is what to expect from head-to-head comparison data. We also need to know if dual inhibition of SGLT1/SGLT2 is more efficacious in reducing HbA1c and how this therapy affects metabolic and cardiovascular parameters. Additionally, several SGLT2 agents that have not yet come to market have hitherto been evaluated in Asian populations, whereas approved SGLT2 inhibitors have been frequently studied in other populations, including Caucasian subjects. Thus, we need more information on the potential role of ethnicity on their efficacy and safety.

  12. Majewski osteodysplastic primordial dwarfism type II (MOPD II): natural history and clinical findings.

    Science.gov (United States)

    Hall, Judith G; Flora, Christina; Scott, Charles I; Pauli, Richard M; Tanaka, Kimi I

    2004-09-15

    A description of the clinical features of Majewski osteodysplastic primordial dwarfism type II (MOPD II) is presented based on 58 affected individuals (27 from the literature and 31 previously unreported cases). The remarkable features of MOPD II are: severe intrauterine growth retardation (IUGR), severe postnatal growth retardation; relatively proportionate head size at birth which progresses to true and disproportionate microcephaly; progressive disproportion of the short stature secondary to shortening of the distal and middle segments of the limbs; a progressive bony dysplasia with metaphyseal changes in the limbs; epiphyseal delay; progressive loose-jointedness with occasional dislocation or subluxation of the knees, radial heads, and hips; unusual facial features including a prominent nose, eyes which appear prominent in infancy and early childhood, ears which are proportionate, mildly dysplastic and usually missing the lobule; a high squeaky voice; abnormally, small, and often dysplastic or missing dentition; a pleasant, outgoing, sociable personality; and autosomal recessive inheritance. Far-sightedness, scoliosis, unusual pigmentation, and truncal obesity often develop with time. Some individuals seem to have increased susceptibility to infections. A number of affected individuals have developed dilation of the CNS arteries variously described as aneurysms and Moya Moya disease. These vascular changes can be life threatening, even in early years because of rupture, CNS hemorrhage, and strokes. There is variability between affected individuals even within the same family. Copyright 2004 Wiley-Liss, Inc.

  13. Debugging and Event Tracing for Multi-Agent Systems, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Large-scale agent systems have become a key part of in modeling and simulation tools such as NASA's Airspace Concept Evaluation System (ACES), an agent-based...

  14. Phase II drugs under clinical investigation for the treatment of chronic constipation.

    Science.gov (United States)

    Mozaffari, Shilan; Didari, Tina; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2014-11-01

    Chronic constipation (CC) is a common gastrointestinal (GI) motility disorder that significantly impairs the quality of life in affected subjects. As almost half of the patients suffering from CC are not satisfied with currently available medicines, there is a need to develop new molecules with better effectiveness and tolerability. The authors include all experimental and clinical trials (up to Phase II) about new investigational drugs for the treatment of CC. The article identifies nine new agents: mitemcinal, TD-8954, YKP10811, itopride, RM-131, KWA-0711, elobixibat, velusetrag, and naronapride. All nine agents have shown prokinetic effects in different stages of the development. The mechanisms of new developing drugs include: the activation of 5-hydroxytryptamine type-4 (5-HT4), ghrelin and motilin receptors, antagonizing dopamine type-2 (D2) receptors, inhibition of ileal bile acid reabsorption and acetylcholine esterase, as well as water absorption from the GI tract. At this current point in time, new generations of 5-HT4 receptor agonists (velusetrag, noranopride and YKP10811) are hoped to progress, further in the future, due to better efficiency and safety. However, it is not possible to make a concise conclusion at this current time due to a lack of evidence. Further clinical trials with a longer duration and a larger sample size are warranted.

  15. Microcephalic Osteodysplastic Primordial Dwarfism, Type II: a Clinical Review.

    Science.gov (United States)

    Bober, Michael B; Jackson, Andrew P

    2017-04-01

    This review will provide an overview of the microcephalic primordial dwarfism (MPD) class of disorders and provide the reader comprehensive clinical review with suggested care guidelines for patients with microcephalic osteodysplastic primordial dwarfism, type II (MOPDII). Over the last 15 years, significant strides have been made in the diagnosis, natural history, and management of MOPDII. MOPDII is the most common and well described form of MPD. The classic features of the MPD group are severe pre- and postnatal growth retardation, with marked microcephaly. In addition to these features, individuals with MOPDII have characteristic facies, skeletal dysplasia, abnormal dentition, and an increased risk for cerebrovascular disease and insulin resistance. Biallelic loss-of-function mutations in the pericentrin gene cause MOPDII, which is inherited in an autosomal recessive manner.

  16. Bayesian Nonparametric Estimation of Targeted Agent Effects on Biomarker Change to Predict Clinical Outcome

    Science.gov (United States)

    Graziani, Rebecca; Guindani, Michele; Thall, Peter F.

    2015-01-01

    Summary The effect of a targeted agent on a cancer patient's clinical outcome putatively is mediated through the agent's effect on one or more early biological events. This is motivated by pre-clinical experiments with cells or animals that identify such events, represented by binary or quantitative biomarkers. When evaluating targeted agents in humans, central questions are whether the distribution of a targeted biomarker changes following treatment, the nature and magnitude of this change, and whether it is associated with clinical outcome. Major difficulties in estimating these effects are that a biomarker's distribution may be complex, vary substantially between patients, and have complicated relationships with clinical outcomes. We present a probabilistically coherent framework for modeling and estimation in this setting, including a hierarchical Bayesian nonparametric mixture model for biomarkers that we use to define a functional profile of pre-versus-post treatment biomarker distribution change. The functional is similar to the receiver operating characteristic used in diagnostic testing. The hierarchical model yields clusters of individual patient biomarker profile functionals, and we use the profile as a covariate in a regression model for clinical outcome. The methodology is illustrated by analysis of a dataset from a clinical trial in prostate cancer using imatinib to target platelet-derived growth factor, with the clinical aim to improve progression-free survival time. PMID:25319212

  17. A Comparison of Predictive Thermo and Water Solvation Property Prediction Tools and Experimental Data for Selected Traditional Chemical Warfare Agents and Simulants II: COSMO RS and COSMOTherm

    Science.gov (United States)

    2017-04-01

    SELECTED TRADITIONAL CHEMICAL WARFARE AGENTS AND SIMULANTS II: COSMO-RS AND COSMOTHERM ECBC-TR-1454 Jerry B. Cabalo RESEARCH AND TECHNOLOGY...Traditional Chemical Warfare Agents and Simulants II: COSMO-RS and COSMOTherm 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER CB10115...in the ADF 2012 suite of programs for the physico- chemical properties of a set of traditional chemical warfare agents and selected simulants. To

  18. Clinical and radiographic evaluation of Portland cement added to radiopacifying agents in primary molar pulpotomies.

    Science.gov (United States)

    Lourenço Neto, N; Marques, N C T; Fernandes, A P; Hungaro Duarte, M A; Abdo, R C C; Machado, M A A M; Oliveira, T M

    2015-10-01

    This was to evaluate the clinical and radiographic outcomes of Portland cement (PC) added to radiopacifying agents in primary molar pulpotomies. Thirty primary mandibular molars of children aged between 5 and 9 years were randomly assigned to the following groups: PC; PC with iodoform (PC + CHI(3)); PC with zirconium oxide (PC + ZrO(2)) and treated by pulpotomy technique. Clinical and radiographic follow-up assessments were performed at 6, 12 and 24 months. Statistical analysis was performed by Fisher's exact test (P < 0.05). The clinical and radiographic evaluations showed 100 % success rates, and the results showed no statistically significant difference between groups. According to this study, PC added to radiopacifying agents exhibited satisfactory clinical and radiographic results in primary molar pulpotomies.

  19. Newer Clinical Strategies for Combining Interferon and Cytotoxic Agents Against Solid Tumours and Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Scott Wadler

    1994-01-01

    Full Text Available The role of interferons in the treatment of cancer continues to evolve. Despite limited single agent activity against solid tumours, interferons now appear to have an important role as modulators of the activity of a variety of cytotoxic drugs. Clinical benefits have been observed for combinations of interferons and alkylating agents against low grade lymphomas, interferons and dacarbazine against malignant melanoma, and interferons and 5-fluorouracil against gastrointestinal and genitourinary malignancies. Further progress will depend on a grealer understanding of the biology of the interaction.

  20. Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.

    Science.gov (United States)

    Kim, Michelle M; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A; Oronsky, Arnold; Knox, Susan J; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S; Lao, Christopher D

    2016-04-01

    Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. Published by Elsevier Inc.

  1. Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

    International Nuclear Information System (INIS)

    Telang, Sucheta; Gragg, Hana; Clem, Brian F; McMasters, Kelly M; Miller, Donald M; Chesney, Jason; Rasku, Mary Ann; Clem, Amy L; Carter, Karen; Klarer, Alden C; Badger, Wesley R; Milam, Rebecca A; Rai, Shesh N; Pan, Jianmin

    2011-01-01

    We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4 + CD25 HI Foxp3 + regulatory T cells and expanded melanoma-specific CD8 + T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients. In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[ 18 F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging. After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; p value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year. These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma. http://www.clinicaltrials.gov/ct2/show/NCT00299689

  2. Clinical evaluation of Dyslipidemia among type II diabetic patients at Public hospital Penang, Malaysia

    Directory of Open Access Journals (Sweden)

    Zaki Nada F

    2010-11-01

    Full Text Available Abstract Background Global views emphasize the need for early; effective intervention against the atherogenic dyslipidemia associated with type 2 diabetes and metabolic syndrome to reduce the risk of premature cardiovascular diseases. Our aim was to determine the clinical practices and compliance among dyslipidemia with type II diabetes and hypertension in multiracial society. Method(s Study was carried out in out-patient department of General hospital Penang over a period of ten months (Jan - Oct 2008. Study reflects the retrospective data collection covering a period of three years from Jan 2005 - Dec 2007. Universal sampling technique was used to select all the patients' undergone treatment for diabetes type II and dyslipidemia. All the concerned approvals were obtained from Clinical research Committee (CRC. Data was analyzed by using SPSS 15®. Result(s A total of 501 diabetes type 2 patients with dyslipidemia were identified in this study. The demographic data showed that 55.9% (n = 280 were female patients and 44.1% (n = 221 were males. Patients on combination therapy of metformin with other antidiabetic agent were 79%, while 21% were on monotherapy. Lovastatin was received as monotherapy in 83% of study population, while only 17% were on combination with gemfibrozil. Means of FPG and lipid profile were reduced from the initial (2005 to the latest level (2007 significantly (p Conclusion Metformin and lovastatin use among patients of type 2 diabetes and dyslipidemia is significantly improved the clinical outcomes. No significant association of metformin or lovastatin is found against the hypertension. Metformin and calcium channel blocker combination therapy was found to be the best choice in the co-treatment of diabetes and hypertension.

  3. Myocardial Contrast Agents – Safety Considerations and Clinical Efficacy in Stress Echocardiography

    Directory of Open Access Journals (Sweden)

    Maier Anca

    2016-11-01

    Full Text Available Transthoracic echocardiographic examination is known to be a safe, non-invasive and reproducible method, used in every day clinical practice to obtain important information about cardiac structure and function. Unfortunately, a significant proportion of studies have highlighted the considerable technically difficultly in producing diagnostic images due to a poor acoustic window and more than 33% of patients undergoing stress echocardiography have suboptimal echocardiographic images. All these limitations have led to the use of contrast agents to improve the quality of standard ultrasound examination to provide a better delineation of left ventricle endocardial borders or to obtain information that cannot be achieved by using standard echocardiography, such as assessing myocardial microcirculation and therefore perfusion. This paper sought to review the clinical efficacy and safety of ultrasound contrast agents focusing on stress echocardiography.

  4. Autonomous Collaborative Agents for Onboard Multi-Sensor Re-Targeting, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In our Phase I effort we developed a prototype software-agent based framework to provide for autonomous re-targeting of sensors hosted on satellites in polar orbits,...

  5. Removal of Hg(II) from aqueous solution using sodium humate as heavy metal capturing agent.

    Science.gov (United States)

    Wang, Shixiang; Liu, Yong; Fan, Qin; Zhou, Anlan; Fan, Lu; Mu, Yulan

    2016-12-01

    An environmental friendly and economic natural biopolymer-sodium humate (HA-Na) was used to capture Hg(II) from aqueous solutions, and the trapped Hg(II) (HA-Na-Hg) was then removed by aluminium coagulation. The best Hg(II) capturing performance (90.60%) was observed under the following conditions: initial pH of 7.0, coagulation pH of 6.0, HA-Na dosage of 5.0 g L -1 , Al 2 (SO 4 ) 3 .18H 2 O dosage of 4.0 g L -1 , initial Hg(II) concentration of 50 mg L -1 and capturing time of 30 min. The HA-Na compositions with the molecular weight beyond 70 kDa showed the most intense affinity toward Hg(II). The results showed that the reaction equilibrium was achieved within 10 min (pH 7.0), and could be well fitted by the pseudo-second-order kinetics model. The capturing process could be well described by the Langmuir isotherm model and the maximum capturing capacity of Hg(II) was high up to 9.80 mg g -1 at 298 K (pH 7.0). The Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis showed that the redox reaction between Hg(II) and HA-Na and the coordination reaction of carboxyl and hydroxy groups of HA-Na with Hg(II) were responsible for Hg(II) removal. The successive regeneration experiment showed that the capturing efficiency of humates for Hg(II) was maintained at about 51% after five capture-regeneration recycles.

  6. ESGAR consensus statement on liver MR imaging and clinical use of liver-specific contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Neri, E.; Boraschi, P.; Bartolozzi, C. [University of Pisa, Department of Diagnostic and Interventional Radiology, Pisa (Italy); Bali, M.A.; Matos, C. [Hopital Erasme, MRI Clinics, Department of Radiology, Bruxelles (Belgium); Ba-Ssalamah, A. [The General Hospital of the Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Brancatelli, G. [University of Palermo, Department of Radiology, Palermo (Italy); Alves, F.C. [University Hospital of Coimbra, Medical Imaging Department and Faculty of Medicine, Coimbra (Portugal); Grazioli, L. [Spedali Civili di Brescia, Department of Radiology, Brescia (Italy); Helmberger, T. [Academic Teaching Hospital of the Technical University, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Klinikum Bogenhausen, Munich (Germany); Lee, J.M. [Seoul National University College of Medicine, Division of Abdominal Imaging, Department of Radiology, Seoul (Korea, Republic of); Manfredi, R. [University of Verona, Department of Radiology, Verona (Italy); Marti-Bonmati, L. [Hospital Universitario y Politecnico La Fe, Area Clinica de Imagen Medica, Valencia (Spain); Merkle, E.M. [Universitaetsspital Basel, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland); Op De Beeck, B. [Antwerp University Hospital, Department of Radiology, Edegem (Belgium); Schima, W. [KH Goettlicher Heiland, Krankenhaus der Barmherzigen Schwestern and Sankt Josef-Krankenhaus, Department of Diagnostic and Interventional Radiology, Vienna (Austria); Skehan, S. [St Vincent' s University Hospital, Department of Radiology, Dublin (Ireland); Vilgrain, V. [Assistance Publique-Hopitaux de Paris, APHP, Hopital Beaujon, Radiology Department, Clichy, Paris (France); Zech, C. [Universitaetsspital Basel, Abteilungsleiter Interventionelle Radiologie, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland)

    2016-04-15

    To develop a consensus and provide updated recommendations on liver MR imaging and the clinical use of liver-specific contrast agents. The European Society of Gastrointestinal and Abdominal Radiology (ESGAR) formed a multinational European panel of experts, selected on the basis of a literature review and their leadership in the field of liver MR imaging. A modified Delphi process was adopted to draft a list of statements. Descriptive and Cronbach's statistics were used to rate levels of agreement and internal reliability of the consensus. Three Delphi rounds were conducted and 76 statements composed on MR technique (n = 17), clinical application of liver-specific contrast agents in benign, focal liver lesions (n = 7), malignant liver lesions in non-cirrhotic (n = 9) and in cirrhotic patients (n = 18), diffuse and vascular liver diseases (n = 12), and bile ducts (n = 13). The overall mean score of agreement was 4.84 (SD ±0.17). Full consensus was reached in 22 % of all statements in all working groups, with no full consensus reached on diffuse and vascular diseases. The consensus provided updated recommendations on the methodology, and clinical indications, of MRI with liver specific contrast agents in the study of liver diseases. (orig.)

  7. A New Bis(aquated) High Relaxivity Mn(II) Complex as an Alternative to Gd(III)-Based MRI Contrast Agent.

    Science.gov (United States)

    Phukan, Bedika; Mukherjee, Chandan; Goswami, Upashi; Sarmah, Amrit; Mukherjee, Subhajit; Sahoo, Suban K; Moi, Sankar Ch

    2018-03-05

    Disclosed here are a piperazine, a pyridine, and two carboxylate groups containing pentadentate ligand H 2 pmpa and its corresponding water-soluble Mn(II) complex (1). DFT-based structural optimization implied that the complex had pentagonal bipyramidal geometry where the axial positions were occupied by two water molecules, and the equatorial plane was constituted by the ligand ON 3 O donor set. Thus, a bis(aquated) disc-like Mn(II) complex has been synthesized. The complex showed higher stability compared with Mn(II)-EDTA complex [log K MnL = 14.29(3)] and showed a very high r 1 relaxivity value of 5.88 mM -1 s -1 at 1.41 T, 25 °C, and pH = 7.4. The relaxivity value remained almost unaffected by the pH of the medium in the range of 6-10. Although the presence of 200 equiv of fluoride and bicarbonate anions did not affect the relaxivity value appreciably, an increase in the value was noticed in the presence of phosphate anion due to slow tumbling of the complex. Cell viability measurements, as well as phantom MR images using clinical MRI imager, consolidated the possible candidature of complex 1 as a positive contrast agent.

  8. Direct synthesis of magnetite nanoparticles from iron(II) carboxymethylcellulose and their performance as NMR contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Gomes da Silva, Delmarcio; Hiroshi Toma, Sergio; Menegatti de Melo, Fernando [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil); Carvalho, Larissa Vieira C.; Magalhães, Alvicler; Sabadini, Edvaldo [Instituto de Química, Universidade Estadual de Campinas – UNICAMP, Campinas, SP (Brazil); Domingues dos Santos, Antônio [Instituto de Física, Universidade de São Paulo, São Paulo, SP (Brazil); Araki, Koiti [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil); Toma, Henrique E., E-mail: henetoma@iq.usp.br [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil)

    2016-01-01

    Iron(II) carboxymethylcellulose (CMC) has been successfully employed in the synthesis of hydrophylic magnetite nanoparticles stabilized with a biopolymer coating, aiming applications in NMR imaging. The new method encompasses a convenient one-step synthetic procedure, allowing a good size control and yielding particles of about 10 nm (core size). In addition to the biocompatibility, the nanoparticles have promoted a drastic reduction in the transverse relaxation time (T{sub 2}) of the water protons. The relaxivity rates have been investigated as a function of the nanoparticles concentration, showing a better performance in relation to the common NMR contrast agents available in the market. - Highlights: • Stable, hydrophylic magnetic nanoparticles have been obtained. • Direct use of iron(II) carboxymethylcellulose improves the synthesis. • The magnetic nanoparticles exhibit high spin–spin relaxivity. • The particles promote dark contrast by decreasing the T{sub 2} relaxation time.

  9. Minimal agent based model for financial markets II. Statistical properties of the linear and multiplicative dynamics

    Science.gov (United States)

    Alfi, V.; Cristelli, M.; Pietronero, L.; Zaccaria, A.

    2009-02-01

    We present a detailed study of the statistical properties of the Agent Based Model introduced in paper I [Eur. Phys. J. B, DOI: 10.1140/epjb/e2009-00028-4] and of its generalization to the multiplicative dynamics. The aim of the model is to consider the minimal elements for the understanding of the origin of the stylized facts and their self-organization. The key elements are fundamentalist agents, chartist agents, herding dynamics and price behavior. The first two elements correspond to the competition between stability and instability tendencies in the market. The herding behavior governs the possibility of the agents to change strategy and it is a crucial element of this class of models. We consider a linear approximation for the price dynamics which permits a simple interpretation of the model dynamics and, for many properties, it is possible to derive analytical results. The generalized non linear dynamics results to be extremely more sensible to the parameter space and much more difficult to analyze and control. The main results for the nature and self-organization of the stylized facts are, however, very similar in the two cases. The main peculiarity of the non linear dynamics is an enhancement of the fluctuations and a more marked evidence of the stylized facts. We will also discuss some modifications of the model to introduce more realistic elements with respect to the real markets.

  10. Indirect complexometric determination of mercury(II) using potassium bromide as selective masking agent

    International Nuclear Information System (INIS)

    Sreekumar, N.V.; Nazareth, R.A.; Narayana, B.; Hegde, P.; Manjunatha, B.R.

    2002-01-01

    A complexometric method for the determination of mercury in presence of other metal ions based on the selective masking ability of potassium bromide towards mercury is described. Mercury(II) present in a given sample solution is first complexed with a known excess of EDTA and the surplus EDTA is titrated against zinc sulfate solution at pH 5-6 using xylenol orange as the indicator. A known excess of 10 % solution of potassium bromide is then added and the EDTA released from Hg-EDTA complex is titrated against standard zinc sulfate solution. Reproducible and accurate results are obtained for 8 mg to 250 mg of mercury(II) with a relative error ±0.28 % and standard deviations /leg 0.5 mg. The interference of various ions is studied. This method was applied to the determination of mercury(II) in its alloys. (author)

  11. EcoBot-II: An artificial agent with a natural metabolism

    Directory of Open Access Journals (Sweden)

    Chris Melhuish

    2008-11-01

    Full Text Available In this paper we report the development of the robot EcoBot-II, which exhibits a primitive form of artificial symbiosis. Microbial Fuel Cells (MFCs were used as the onboard energy supply, which consisted of bacterial cultures from sewage sludge and employed oxygen from free air for oxidation at the cathode. EcoBot-II was able to perform sensing, information processing, communication and actuation when fed (amongst other substrates with flies. This is the first robot in the world, to utilise unrefined substrate, oxygen from free air and exhibit four different types of behaviour.

  12. PEG conjugates in clinical development or use as anticancer agents: an overview.

    Science.gov (United States)

    Pasut, Gianfranco; Veronese, Francesco M

    2009-11-12

    During the almost forty years of PEGylation, several antitumour agents, either proteins, peptides or low molecular weight drugs, have been considered for polymer conjugation but only few entered clinical phase studies. The results from the first clinical trials have shared and improved the knowledge on biodistribution, clearance, mechanism of action and stability of a polymer conjugate in vivo. This has helped to design conjugates with improved features. So far, most of the PEG conjugates comprise of a protein, which in the native form has serious shortcomings that limit the full exploitation of its therapeutic action. The main issues can be short in vivo half-life, instability towards degrading enzymes or immunogenicity. PEGylation proved to be effective in shielding sensitive sites at the protein surface, such as antigenic epitopes and enzymatic degradable sequences, as well as in prolonging the drug half-life by decreasing the kidney clearance. In this review PEG conjugates of proteins or low molecular weight drugs, in clinical development or use as anticancer agents, will be taken into consideration. In the case of PEG-protein derivatives the most represented are depleting enzymes, which act by degrading amino acids essential for cancer cells. Interestingly, PEGylated conjugates have been also considered as adjuvant therapy in many standard anticancer protocols, in this regard the case of PEG-G-CSF and PEG-interferons will be presented.

  13. Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents

    Directory of Open Access Journals (Sweden)

    Petrillo Richard L

    2010-02-01

    Full Text Available Abstract Histone deacetylases (HDACs can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently, the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by FDA for treating cutaneous T-cell lymphoma (CTCL for patients with progressive, persistent, or recurrent disease on or following two systemic therapies. Other inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275, valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combination with other anti-tumor drugs in CTCL and other malignancies. At least 80 clinical trials are underway, testing more than eleven different HDAC inhibitory agents including both hematological and solid malignancies. This review focuses on recent development in clinical trials testing HDAC inhibitors as anti-tumor agents.

  14. Complexation of buffer constituents with neutral complexation agents: part II. Practical impact in capillary zone electrophoresis.

    Science.gov (United States)

    Beneš, Martin; Riesová, Martina; Svobodová, Jana; Tesařová, Eva; Dubský, Pavel; Gaš, Bohuslav

    2013-09-17

    This article elucidates the practical impact of the complexation of buffer constituents with complexation agents on electrophoretic results, namely, complexation constant determination, system peak development, and proper separation of analytes. Several common buffers, which were selected based on the pH study in Part I of this paper series (Riesová, M.; Svobodová, J.; Tošner, Z.; Beneš, M.; Tesařová, E.; Gaš, B. Anal. Chem., 2013, DOI: 10.1021/ac4013804); e.g., CHES, MES, MOPS, Tricine were used to demonstrate behavior of such complex separation systems. We show that the value of a complexation constant determined in the interacting buffers environment depends not only on the analyte and complexation agent but it is also substantially affected by the type and concentration of buffer constituents. As a result, the complexation parameters determined in the interacting buffers cannot be regarded as thermodynamic ones and may provide misleading information about the strength of complexation of the compound of interest. We also demonstrate that the development of system peaks in interacting buffer systems significantly differs from the behavior known for noncomplexing systems, as the mobility of system peaks depends on the concentration and type of neutral complexation agent. Finally, we show that the use of interacting buffers can totally ruin the results of electrophoretic separation because the buffer properties change as the consequence of the buffer constituents' complexation. As a general conclusion, the interaction of buffer constituents with the complexation agent should always be considered in any method development procedures.

  15. Ruthenium (II) complexes of thiosemicarbazone: Synthesis, biosensor applications and evaluation as antimicrobial agents

    Energy Technology Data Exchange (ETDEWEB)

    Yildirim, Hatice [Dokuz Eylul University, The Graduate School of Natural and Applied Sciences, Department of Chemistry, 35160 Buca, Izmir (Turkey); Guler, Emine [Ege University, Faculty of Science, Department of Biochemistry, 35100 Bornova, Izmir (Turkey); Yavuz, Murat, E-mail: myavuz@dicle.edu.tr [Ege University, Faculty of Science, Department of Biochemistry, 35100 Bornova, Izmir (Turkey); Dicle University, Faculty of Science, Department of Chemistry, 21280 Diyarbakir (Turkey); Ozturk, Nurdan; Kose Yaman, Pelin [Dokuz Eylul University, The Graduate School of Natural and Applied Sciences, Department of Chemistry, 35160 Buca, Izmir (Turkey); Subasi, Elif; Sahin, Elif [Dokuz Eylul University, Faculty of Science, Department of Chemistry, 35160 Buca, Izmir (Turkey); Timur, Suna [Ege University, Faculty of Science, Department of Biochemistry, 35100 Bornova, Izmir (Turkey); Ege University, Institute on Drug Abuse, Toxicology and Pharmaceutical Science (BATI), 35100 Bornova, Izmir (Turkey)

    2014-11-01

    A conformationally rigid half-sandwich organoruthenium (II) complex [(η{sup 6}-p-cymene)RuClTSC{sup N–S}]Cl, (1) and carbonyl complex [Ru(CO)Cl(PPh{sub 3}){sub 2}TSC{sup N–S}] (2) have been synthesized from the reaction of [{(η"6-p-cymene)RuCl}{sub 2}(μ-Cl){sub 2}] and [Ru(H)(Cl)(CO)(PPh{sub 3}){sub 3}] with thiophene-2-carboxaldehyde thiosemicarbazon (TSC) respectively and both novel ruthenium (II) complexes have been characterized by elemental analysis, FT-IR and NMR spectroscopy. The peripheral TSC in the complexes acts as an electrochemical coupling unit providing the ability to carry out electrochemical deposition (ED) and to form an electro-deposited film on a graphite electrode surface. The biosensing applicability of complexes 1 and 2 was investigated by using glucose oxidase (GOx) as a model enzyme. Electrochemical measurements at − 0.9 V versus Ag/AgCl electrode by following the ED Ru(II) reduction/oxidation due to from the enzyme activity, in the presence of glucose substrate. The designed biosensor showed a very good linearity for 0.01–0.5 mM glucose. The in vitro antimicrobial activities of complexes 1 and 2 were also investigated against nine bacterial strains and one fungus by the disc diffusion test method. No activity was observed against the Gram-negative strains and fungus, whereas complex 1 showed moderate antibacterial activities against Gram-positive bacterial strains. - Highlights: • Novel Ru (II) thiosemicarbazone complexes were synthesized and characterized. • Electrochemical depositions were performed. • Rigid half-sandwich Ru (II) complex showed enhanced antibacterial activity.

  16. Ruthenium (II) complexes of thiosemicarbazone: Synthesis, biosensor applications and evaluation as antimicrobial agents

    International Nuclear Information System (INIS)

    Yildirim, Hatice; Guler, Emine; Yavuz, Murat; Ozturk, Nurdan; Kose Yaman, Pelin; Subasi, Elif; Sahin, Elif; Timur, Suna

    2014-01-01

    A conformationally rigid half-sandwich organoruthenium (II) complex [(η 6 -p-cymene)RuClTSC N–S ]Cl, (1) and carbonyl complex [Ru(CO)Cl(PPh 3 ) 2 TSC N–S ] (2) have been synthesized from the reaction of [{(η 6 -p-cymene)RuCl} 2 (μ-Cl) 2 ] and [Ru(H)(Cl)(CO)(PPh 3 ) 3 ] with thiophene-2-carboxaldehyde thiosemicarbazon (TSC) respectively and both novel ruthenium (II) complexes have been characterized by elemental analysis, FT-IR and NMR spectroscopy. The peripheral TSC in the complexes acts as an electrochemical coupling unit providing the ability to carry out electrochemical deposition (ED) and to form an electro-deposited film on a graphite electrode surface. The biosensing applicability of complexes 1 and 2 was investigated by using glucose oxidase (GOx) as a model enzyme. Electrochemical measurements at − 0.9 V versus Ag/AgCl electrode by following the ED Ru(II) reduction/oxidation due to from the enzyme activity, in the presence of glucose substrate. The designed biosensor showed a very good linearity for 0.01–0.5 mM glucose. The in vitro antimicrobial activities of complexes 1 and 2 were also investigated against nine bacterial strains and one fungus by the disc diffusion test method. No activity was observed against the Gram-negative strains and fungus, whereas complex 1 showed moderate antibacterial activities against Gram-positive bacterial strains. - Highlights: • Novel Ru (II) thiosemicarbazone complexes were synthesized and characterized. • Electrochemical depositions were performed. • Rigid half-sandwich Ru (II) complex showed enhanced antibacterial activity

  17. The function of Sn(II)-apatite as a Tc immobilizing agent

    Energy Technology Data Exchange (ETDEWEB)

    Asmussen, R. Matthew, E-mail: matthew.asmussen@pnnl.gov [Energy and Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA, 99352 (United States); Neeway, James J.; Lawter, Amanda R.; Levitskaia, Tatiana G. [Energy and Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA, 99352 (United States); Lukens, Wayne W. [Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720 (United States); Qafoku, Nikolla P. [Energy and Environment Directorate, Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA, 99352 (United States)

    2016-11-15

    At the U.S. Department of Energy Hanford Site, Tc-99 is a component of low-activity waste (LAW) fractions of the nuclear tank waste and removal of Tc from LAW streams would greatly benefit the site remediation process. In this study, we investigated the removal of Tc(VII), as pertechnetate, from deionized water (DIW) and a LAW simulant through batch sorption testing and solid phase characterization using tin (II) apatite (Sn-A) and SnCl{sub 2}. Sn-A showed higher levels of Tc removal from both DIW and LAW simulant. Scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/XEDS) and X-ray absorption spectroscopy (XAS) of reacted Sn-A in DIW showed that TcO4- is reduced to Tc(IV) on the Sn-A surface. The performance of Sn-A in the LAW simulant was lowered due to a combined effect of the high alkalinity, which lead to an increased dissolution of Sn from the Sn-A, and a preference for the reduction of Cr(VI). - Highlights: • Sn(II)-Apatite shows high proficiency in removing Tc(VII) from neutral solutions. • The removal of the Tc(VII) by Sn(II)-apatite is done via reduction to Tc(IV)O{sub 2} × H{sub 2}O. • In LAW Sn(II)-apatite is less efficient in removing Tc(VII). • Interference in LAW due to a preference for the reduction of Cr(VI) and the high pH. • Sn(II)-apatite can remove Tc(VII) from LAW effectively through increasing material added.

  18. The Removal of Cu (II) from Aqueous Solution using Sodium Borohydride as a Reducing Agent

    Science.gov (United States)

    Sithole, N. T.; Ntuli, F.; Mashifana, T.

    2018-03-01

    The removal and recovery of metals from wastewater has been a subject of significant importance due the negative impact these toxic metals have on human health and the environment as a result of water and soil pollution. Increased use of the metals and chemicals in the process industries has resulted in generation of large quantity of effluents that contains high level of toxic metals and other pollutants. The objective of this work was to recover of Cu in its elemental form as metallic powder from aqueous solution using NaBH4 as a reducing agent. Reductive precipitation was achieved in a batch reactor at 65°C using Cu powder as a seeding material. This study also investigated the effect of concentration of sodium borohydride (NaBH4) as a reducing agent. The amount of NaBH4 was varied based on mole ratios which are 1:1, 1:0.25 and 1:0.1 to recover Cu from synthetic wastewater. The results obtained showed that sodium borohydride is an effective reducing agent to recover Cu from wastewater. The optimum concentration of NaBH4 that gives the best results the 1:1 molar ratio with over 99% Cu removal.

  19. ORAL HYPOGLYCAEMIC AGENTS IN THE MANAGEMENT OF TYPE II DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Durgaprasad M.

    2016-06-01

    Full Text Available OBJECTIVES Diabetes is fast gaining the status of a potential epidemic globally. The number of people with diabetes has risen from 108 million in 1980 to 422 million in 2014, the rise seen more rapidly in developing and under developed countries. Type 2 Diabetes Mellitus (T2DM being the most common type, accounting for an estimated 85-95% of all diabetes cases. Diabetes remains a major cause of blindness, renal failure, and cardiovascular events including heart attacks, stroke and limb amputations. 1 Being an heterogeneous disorder, many adults with T2DM have difficulty controlling their blood sugar levels and associated complications as most of available antidiabetic agents aim to achieve only normoglycaemia and relieve diabetes symptoms, such as polydipsia, polyuria, weight loss, ketoacidosis while the longterm goals to prevent the development of or slow the progression of longterm complications of the disease is often unaddressed, therefore, there remains, a significant unmet demand for new agents that will help diabetic patients achieve treatment targets without increasing the risk for weight gain or hypoglycaemia. Among the new classes of oral agents, SGLT-2 inhibitors and mTOT insulin sensitisers appear to hold some good promise. However, recent articles published describing its adverse effect profile of SGLT-2 inhibitors had put a question mark on its utility. In this article, we have reviewed the plethora of available OHAs along with the newer OHAs for managing T2DM optimally.

  20. Detecting comorbid Axis-II status among inpatients using the MMPI-2 Restructured Clinical Scales

    NARCIS (Netherlands)

    Kamphuis, J.H.; Arbisi, P.A.; Ben-Porath, Y.S.; McNulty, J.L.

    2008-01-01

    This study examined the differential diagnostic utility of the MMPI-2 Restructured Clinical Scales (RCS) and Clinical Scales (CS) in detecting a complex multivariate clinical phenomenon: that is, comorbid Axis-II status in two matched samples of inpatients. Psychiatric inpatients diagnosed with

  1. Introduction to economic modeling for clinical rheumatologists: application to biologic agents in rheumatoid arthritis.

    Science.gov (United States)

    Marra, Carlo A; Bansback, Nick; Anis, Aslam H; Shojania, Kamran

    2011-03-01

    Rheumatoid arthritis (RA) is a chronic, debilitating inflammatory, progressive musculoskeletal disease that affects 0.5-1.0% of the adult population in Western countries. The joint destruction and progressive functional disability associated with uncontrolled RA result in tremendous impacts on health-related quality of life, ability to work, and mortality. In addition, the treatment of the disease and associated complications exact a substantial economic burden to the patients, their families, and society. In the last decade, several biological agents (biologics) have been approved for use in RA, revolutionizing treatment. These biologics, which target cytokines such as tumor necrosis factor or lymphocytes such as B or T cells, reduce functional disability and substantially slow the progression of joint damage. However, because these agents typically cost ten to 100 times more than existing available older drug therapies, there has been worldwide concern regarding their impact on healthcare budgets. As such, there has been increased attention towards economic evaluation as a means to determine whether, and in which subgroup of patients, these newer, more expensive agents confer appropriate value for their additional cost. Indeed, evaluations have guided coverage decisions for both private and public health insurance agencies such as the National Institute for Health and Clinical Excellence in the UK. The use of economic evaluations to determine value for money for these agents has attracted both debate and controversy. Some of the controversy is related to the appropriateness of the structure of, and assumptions underlying, the decision models employed to estimate the long-term costs and benefits of these agents over existing therapies. To fully appreciate the debate, one must first understand the basic principles of economic evaluation and the necessity for using decision models to evaluate cost effectiveness. To understand the basic principles of economic

  2. Pre-Clinical Testing of Real-Time PCR Assays for Diarrheal Disease Agents of Genera Escherichia and Shigella

    Science.gov (United States)

    2014-05-16

    FOR DIARRHEAL DISEASE AGENTS OF GENERA ESCHERICHIA AND SHIGELLA May 16, 2014 Reporting Period: October 1, 2010 to September 30, 2013...10-2010 - 30-09-2013 PRE-CLINICAL TESTING OF REAL-TIME PCR ASSAYS FOR DIARRHEAL DISEASE AGENTS OF GENERA ESCHERICHIA AND SHIGELLA ...Texas (MOA 2007 - 2013. Agreement No.: DODI 4000.19; AFI 25-201). Pre-clinical test results qualify ETEC and Shigella real-time PCR assays as lead

  3. Copper(II)-bis(thiosemicarbazonato) complexes as anti-chlamydial agents.

    Science.gov (United States)

    Marsh, James W; Djoko, Karrera Y; McEwan, Alastair G; Huston, Wilhelmina M

    2017-09-29

    Lipophilic copper (Cu)-containing complexes have shown promising antibacterial activity against a range of bacterial pathogens. To examine the susceptibility of the intracellular human pathogen Chlamydia trachomatis to copper complexes containing bis(thiosemicarbazone) ligands [Cu(btsc)], we tested the in vitro effect of CuII-diacetyl- and CuII-glyoxal-bis[N(4)-methylthiosemicarbazonato] (Cu(atsm) and Cu(gtsm), respectively) on C. trachomatis. Cu(atsm) and to a greater extent, Cu(gtsm), prevented the formation of infectious chlamydial progeny. Impacts on host cell viability and respiration were also observed in addition to the Chlamydia impacts. This work suggests that copper-based complexes may represent a new lead approach for future development of new therapeutics against chlamydial infections, although host cell impacts need to be fully explored. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. MAJEWSKI OSTEODYSPLASTIC PRIMORDIAL DWARFISM TYPE II: CLINICAL FINDINGS AND DENTAL MANAGEMENT OF A CHILD PATIENT

    OpenAIRE

    Terlemez, Arslan; Altunsoy, Mustafa; Çelebi, Hakkı

    2015-01-01

    Majewski osteodysplastic primordial dwarfism type II (MOPD II) is an unusual autosomal recessive inherited form of primordial dwarfism, which is characterized by a small head diameter at birth, but which also progresses to severe microcephaly, progressive bony dysplasia, and characteristic facies and personality. This report presents a case of a five-year-old girl with MOPD II syndrome. The patient was referred to our clinic with the complaint of severe tooth pain at the left mandibular prima...

  5. EVIDENCE-BASED MEDICINE – II. CLINICAL USE AND CRITICS

    Directory of Open Access Journals (Sweden)

    Angela Čuk

    2004-01-01

    Full Text Available Background. Evidence-based medicine employs systematic searching, evaluation and use of current research findings as the basis for clinical decision-making. However, there are some problems and uncertainties hindering introduction and spreading of the use of the method in clinical practice. Physicians often have no time for literature searching and for use of the method in practice. For certain questions in clinical practice there are no answers in medical literature. Most of the evidences in medical literature are only available in English. Introduction of the method is hampered also by the fact that clinical decision-making is complex and does not allow procedures prescribed in advance. Rigidity and universality of decisions resulting from the evidence may appear impersonal and may affect the relationship between the physician and the patient. Trends towards evidence based medicine are followed also by big multinational pharmaceutical corporations. They carry out large and expensive clinical trials using the results for promotional purposes. In this way, they get the competitive advantage and influence the objectivity of physicians’ clinical decision-making.Conclusions. With introduction of evidence based medicine into clinical practice physicians acquire new information and use a new form of continuing education by following new developments in their field. This way, new findings from medical literature get into clinical practice faster and more efficiently. In addition, physicians get more professional satisfaction and quality in clinical practice is higher.

  6. Treatment outcomes regarding the addition of targeted agents in the therapeutic portfolio for stage II-III rectal cancer undergoing neoadjuvant chemoradiation.

    Science.gov (United States)

    Liang, Jin-Tung; Chen, Tzu-Chun; Huang, John; Jeng, Yung-Ming; Cheng, Jason Chia-Hsien

    2017-11-24

    To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT). A retrospective study was performed in 124 consecutive patients with clinically T 3 N 0-2 M 0 -staged rectal cancer incorporating targeted agents in CCRT. Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, panalysis within bevacizumab+FOLFOX-treated patients with either wild-type (n=36) or mutant (n=40) K-ras status indicated K-ras status did not significantly influence the treatment outcomes. The addition of bevacizumab instead of cetuximab to FOLFOX in the neoadjuvant settings for T 3 N 0-2 M 0 -staged rectal cancer could induce a promising rate of pathologic complete response and lesser hepatotoxicity.

  7. Rates of nickel(II) capture from complexes with NTA, EDDA, and related tetradentate chelating agents by the hexadentate chelating agents EDTA and CDTA: Evidence of a "semijunctive" ligand exchange pathway

    Science.gov (United States)

    Boland, Nathan E.; Stone, Alan T.

    2017-09-01

    Many siderophores and metallophores produced by soil organisms, as well as anthropogenic chelating agent soil amendments, rely upon amine and carboxylate Lewis base groups for metal ion binding. UV-visible spectra of metal ion-chelating agent complexes are often similar and, as a consequence, whole-sample absorbance measurements are an unreliable means of monitoring the progress of exchange reactions. In the present work, we employ capillary electrophoresis to physically separate Ni(II)-tetradentate chelating agent complexes (NiL) from Ni(II)-hexadentate chelating agent complexes (NiY) prior to UV detection, such that progress of the reaction NiL + Y → NiY + L can be conveniently monitored. Rates of ligand exchange for Ni(II) are lower than for other +II transition metal ions. Ni(II) speciation in environmental media is often under kinetic rather than equilibrium control. Nitrilotriacetic acid (NTA), with three carboxylate groups all tethered to a central amine Lewis base group, ethylenediamine-N,N‧-diacetic acid (EDDA), with carboxylate-amine-amine-carboxylate groups arranged linearly, plus four structurally related compounds, are used as tetradentate chelating agents. Ethylenediaminetetraacetic acid (EDTA) and the structurally more rigid analog trans-cyclohexaneethylenediaminetetraacetic acid (CDTA) are used as hexadentate chelating agents. Effects of pH and reactant concentration are explored. Ni(II) capture by EDTA was consistently more than an order of magnitude faster than capture by CDTA, and too fast to quantify using our capillary electrophoresis-based technique. Using NiNTA as a reactant, Ni(II) capture by CDTA is independent of CDTA concentration and greatly enhanced by a proton-catalyzed pathway at low pH. Using NiEDDA as reactant, Ni(II) capture by CDTA is first order with respect to CDTA concentration, and the contribution from the proton-catalyzed pathway diminished by CDTA protonation. While the convention is to assign either a disjunctive

  8. Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II): A Randomized Clinical Trial.

    Science.gov (United States)

    Prajna, N Venkatesh; Krishnan, Tiruvengada; Rajaraman, Revathi; Patel, Sushila; Srinivasan, Muthiah; Das, Manoranjan; Ray, Kathryn J; O'Brien, Kieran S; Oldenburg, Catherine E; McLeod, Stephen D; Zegans, Michael E; Porco, Travis C; Acharya, Nisha R; Lietman, Thomas M; Rose-Nussbaumer, Jennifer

    2016-12-01

    To compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. The Mycotic Ulcer Treatment Trial II (MUTT II), a multicenter, double-masked, placebo-controlled, randomized clinical trial, was conducted in India and Nepal, with 2133 individuals screened for inclusion. Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 (logMAR 1.3) or worse were randomized to receive oral voriconazole vs oral placebo; all participants received topical antifungal eyedrops. The study was conducted from May 24, 2010, to November 23, 2015. All trial end points were analyzed on an intent-to-treat basis. Study participants were randomized to receive oral voriconazole vs oral placebo; a voriconazole loading dose of 400 mg was administered twice daily for 24 hours, followed by a maintenance dose of 200 mg twice daily for 20 days, with dosing altered to weight based during the trial. All participants received topical voriconazole, 1%, and natamycin, 5%. The primary outcome of the trial was rate of corneal perforation or the need for therapeutic penetrating keratoplasty (TPK) within 3 months. Secondary outcomes included microbiologic cure at 6 days, rate of re-epithelialization, best-corrected visual acuity and infiltrate and/or scar size at 3 weeks and 3 months, and complication rates associated with voriconazole use. A total of 2133 patients in India and Nepal with smear-positive ulcers were screened; of the 787 who were eligible, 240 (30.5%) were enrolled. Of the 119 patients (49.6%) in the oral voriconazole treatment group, 65 were male (54.6%), and the median age was 54 years (interquartile range, 42-62 years). Overall, no difference in the rate of corneal perforation or the need for TPK was determined for oral voriconazole vs placebo (hazard ratio, 0.82; 95% CI, 0.57-1.18; P = .29). In prespecified subgroup analyses comparing treatment effects among organism subgroups, there was some

  9. Majewski osteodysplastic primordial dwarfism type II (MOPD II) complicated by stroke: clinical report and review of cerebral vascular anomalies.

    Science.gov (United States)

    Brancati, Francesco; Castori, Marco; Mingarelli, Rita; Dallapiccola, Bruno

    2005-12-15

    We report on a 2 9/12-year-old boy with disproportionate short stature, microcephaly, subtle craniofacial dysmorphisms, and generalized skeletal dysplasia, who developed a left hemiparesis. Brain neuroimaging disclosed a complex cerebral vascular anomaly (CVA) with stenosis of the right anterior cerebral artery and telangiectatic collateral vessels supplying the cerebral cortex, consistent with moyamoya disease. Based on clinical and skeletal features, a diagnosis of Majewski osteodysplastic primordial dwarfism type II (MOPD II) was established. Review of 16 published patients with CVA affected by either Seckel syndrome or MOPD II suggested that CVA is preferentially associated to the latter subtype affecting about 1/4 of the patients. 2005 Wiley-Liss, Inc.

  10. Effect of the tether on the Mg(II), Ca(II), Cu(II) and Fe(III) stability constants and pM values of chelating agents related to EDDHA.

    Science.gov (United States)

    Sierra, Miguel A; Gómez-Gallego, Mar; Alcázar, Roberto; Lucena, Juan J; Yunta, Felipe; García-Marco, Sonia

    2004-11-07

    The effect of the length and the structure of the tether on the chelating ability of EDDHA-like chelates have not been established. In this work, PDDHA (propylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid), BDDHA (butylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid) and XDDHA (p-xylylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid) have been obtained and their chemical behaviour has been studied and compared with that of EDDHA following our methodology. The purity of the chelating agents, and their protonation, Ca(II), Mg(II), Fe(III) and Cu(II) stability constants and pM values have been determined. The stability constants and pM values indicate that EDDHA forms the most stable chelates followed by PDDHA. However, the differences among the pFe values are small when a nutrient solution is used, and in these conditions the XDDHA/Fe(III) chelate is the most stable. The results obtained in this work indicate that all the chelating agents studied can be used as iron chlorosis correctors and they can be applied to soil/plant systems.

  11. Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (II

    Directory of Open Access Journals (Sweden)

    Rongshi Li

    2013-08-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA continues to be a major problem, causing severe and intractable infections worldwide. MRSA is resistant to all beta-lactam antibiotics, and alternative treatments are limited. A very limited number of new antibiotics have been discovered over the last half-century, novel agents for the treatment of MRSA infections are urgently needed. Marinopyrrole A was reported to show antibiotic activity against MRSA in 2008. After we reported the first total synthesis of (±-marinopyrrole A, we designed and synthesized a series of marinopyrrole derivatives. Our structure activity relationship (SAR studies of these novel derivatives against a panel of Gram-positive pathogens in antibacterial assays have revealed that a para-trifluoromethyl analog (33 of marinopyrrole A is ≥63-, 8-, and 4-fold more potent than vancomycin against methicillin-resistant Staphylococcus epidermidis (MRSE, methicillin-susceptible Staphylococcus aureus (MSSA and MRSA, respectively. The results provide valuable information in the search for new-generation antibiotics.

  12. Potential Clinical Implications of the Urotensin II Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Emilie Kane

    2011-07-01

    Full Text Available Urotensin-II (UII, which binds to its receptor UT, plays an important role in the heart, kidneys, pancreas, adrenal gland and CNS. In the vasculature, it acts as a potent endothelium-independent vasoconstrictor and endothelium-dependent vasodilator. In disease states, this constriction-dilation equilibrium is disrupted. There is an upregulation of the UII system in heart disease, metabolic syndrome and kidney failure. The increase in UII release and UT expression suggest that UII system may be implicated in the pathology and pathogenesis of these diseases by causing an increase in ACAT-1 activity leading to SMC proliferation and foam cell infiltration, insulin resistance (DMII, as well as inflammation, high blood pressure and plaque formation. Recently, UT antagonists such as SB-611812, palosuran, and most recently a piperazino-isoindolinone based antagonist have been developed in the hope of better understanding the UII system and treating its associated diseases.

  13. CLINICAL RISK INDEX FOR BABIES (CRIB) II SCORE AS A ...

    African Journals Online (AJOL)

    2011-01-01

    Jan 1, 2011 ... Clinical Research, Kenya Medical Research Institute, P. O. Box ... specificity of 75.3%, and a predictive value of 77.7% compared to 72.5, 71.2, and 71.8% ... with worst prognosis in level 3 and 4. ... Social Sciences (SPSS).

  14. Waardenburg syndrome: clinical differentiation between types I and II.

    Science.gov (United States)

    Pardono, Eliete; van Bever, Yolande; van den Ende, Jenneke; Havrenne, Poti C; Iughetti, Paula; Maestrelli, Sylvia R P; Costa F, Orozimbo; Richieri-Costa, Antonio; Frota-Pessoa, Oswaldo; Otto, Paulo A

    2003-03-15

    Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the

  15. Etiologic Agents and Diseases Found Associated with Clinical Aspergillosis in Falcons

    Directory of Open Access Journals (Sweden)

    Walter Tarello

    2011-01-01

    Full Text Available The aim of this study was to describe parasitological, microbiological, and pathological findings associated with the isolation of Aspergillus species in 94 clinically diseased captive falcons from Dubai. Concomitant agents and/or diseases were identified in 64 cases, causing either single (=36 or multiple coinfections (=28. Diagnoses found more often in association with aspergillosis were chronic fatigue and immune dysfunction syndrome (CFIDS (=29, Caryospora sp. (=16, Serratospiculum seurati infestation (=14, cestodiasis (=6, bumblefoot (=5, trematodosis due to Strigea falconispalumbi (=5, trichomoniasis (=4, Babesia shortti (=4, Mannheimia (Pastorella haemolytica (=4, interstitial hepatitis (=4, Escherichia coli (=3, and Clostridium perfringens enterotoxemia (=2. Compared with a control group of 2000 diseased falcons without evidence of aspergillosis, the prevalence of Babesia shortti, CFIDS, Mannheimia (Pastorella haemolytica, Escherichia coli, and falcon herpes virus infection was conspicuously higher in association with aspergillosis. These entities may be considered suitable candidates as predisposing factors for the mycosis.

  16. CLINICAL CASE OF RUSSIAN THROMBOLYTIC AGENT FORTELYZIN® USE IN PATIENTS WITH ACUTE CORONARY ARTERY DISEASE

    Directory of Open Access Journals (Sweden)

    K. A. Kireev

    2015-01-01

    Full Text Available One of the three clinical examples of hospital thrombolysis using Russian thrombolytic agent recombinant protein comprising an amino acid sequence of staphylokinase is described. The trial was held in Chelyabinsk Regional Vascular Centre of specialized medical care for patients with acute coronary syndromes. Each of the three patients had similar reasons for systemic intravenous thrombolysis: hospitalization with ST-segment elevation myocardial infarction, unavailability of coronary interventions due to the X-ray operating room occupancy, high need for the reperfusion therapy in the setting of significant acute myocardial ischemia. In all the cases the pharmacologic reperfusion with recombinant protein comprising an amino acid sequence of staphylokinase was successful, hereafter percutaneous coronary interventions were performed. There were no complications registered.

  17. Accessing the public MIMIC-II intensive care relational database for clinical research.

    Science.gov (United States)

    Scott, Daniel J; Lee, Joon; Silva, Ikaro; Park, Shinhyuk; Moody, George B; Celi, Leo A; Mark, Roger G

    2013-01-10

    The Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) database is a free, public resource for intensive care research. The database was officially released in 2006, and has attracted a growing number of researchers in academia and industry. We present the two major software tools that facilitate accessing the relational database: the web-based QueryBuilder and a downloadable virtual machine (VM) image. QueryBuilder and the MIMIC-II VM have been developed successfully and are freely available to MIMIC-II users. Simple example SQL queries and the resulting data are presented. Clinical studies pertaining to acute kidney injury and prediction of fluid requirements in the intensive care unit are shown as typical examples of research performed with MIMIC-II. In addition, MIMIC-II has also provided data for annual PhysioNet/Computing in Cardiology Challenges, including the 2012 Challenge "Predicting mortality of ICU Patients". QueryBuilder is a web-based tool that provides easy access to MIMIC-II. For more computationally intensive queries, one can locally install a complete copy of MIMIC-II in a VM. Both publicly available tools provide the MIMIC-II research community with convenient querying interfaces and complement the value of the MIMIC-II relational database.

  18. Pharmacokinetic and in vivo evaluation of a self-assembled gadolinium(III)-iron(II) contrast agent with high relaxivity.

    Science.gov (United States)

    Parac-Vogt, Tatjana N; Vander Elst, Luce; Kimpe, Kristof; Laurent, Sophie; Burtéa, Carmen; Chen, Feng; Van Deun, Rik; Ni, Yicheng; Muller, Robert N; Binnemans, Koen

    2006-01-01

    A high-molecular weight tetrametallic supramolecular complex [(Ln-DTPA-phen)3Fe]- (Ln = Gd, Eu, La) has been obtained upon self-assembly around one iron(II) ion of three 1,10-phenantroline-based molecules substituted in 5'-position with the polyaminocarboxylate diethylenetriamine-N,N,N',N',N'-pentaacetate, DTPA-phen(4-). The ICP-MS measurements indicated that the lanthanide:iron ratio is 3:1. Photoluminescence spectra of [Eu-DTPA-phen](-) and of [(Eu-DTPA-phen)3Fe]- are nearly identical, implying that the first coordination sphere of the lanthanide(III) ion has not been changed upon coordination of phenantroline unit to iron(II) ion. NMRD measurements revealed that at 20 MHz and 310 K the relaxivity of the [(Gd-DTPA-phen)3Fe]- is equal to 9.5 +/- 0.3 s(-1) mM(-1) of Gd (28.5 s(-1) per millimole per liter of complex) which is significantly higher than that for Gd-DTPA (3.9 s(-1) mM(-1)). The pharmacokinetic parameters of [(Gd-DTPA-phen)3Fe]- in rats indicate that the elimination of [(Gd-DTPA-phen)3Fe]- is significantly slower than that of Gd-DTPA and is correlated with a reduced volume of distribution. The low volume of distribution and the longer elimination time (T(e1/2)) suggest that the agent is confined to the blood compartment, so it could have an important potential as a blood pool contrast agent. The biodistribution profile of [(Gd-DTPA-phen)3Fe]- 2 h after injection indicates significantly higher concentrations of [(Gd-DTPA-phen)3Fe]- as compared with Gd-DTPA in kidney, liver, lungs, heart and spleen. The images obtained on rats by MR angiography show the enhancement of the abdominal blood vessels. The signal intensity reaches a maximum of 55% at 7 min post-contrast and remains around 25% after 90 min. MRI-histomorphological correlation studies of [Gd-DTPA-phen]- and [(Gd-DTPA-phen)3Fe]- showed that both agents displayed potent contrast enhancement in organs including the liver. The necrosis avidity tests indicated that, in contrast to the [Gd

  19. A study on etiologic agents and clinical manifestations of dermatophytosis in Yazd, Iran

    Science.gov (United States)

    Rashidian, S; Falahati, M; Kordbacheh, P; Mahmoudi, M; Safara, M; Sadeghi Tafti, H; Mahmoudi, S; Zaini, F

    2015-01-01

    Background and Purpose: Dermatophytosis is one of the most common infections of skin, hair, and nails, caused by a group of keratinophilic fungi known as dermatophytes. Species identification of these fungi is of great significance from epidemiological and therapeutic points of view. The objective of the present study was to investigate dermatophytosis and its causative agents in patients, referring to the Central Mycology Laboratory of Yazd University of Medical Sciences, Yazd, Iran. Materials and Methods: In total, 139 clinically suspected cases of dermatophytosis were examined during 12 months from February 2014 to February 2015. Skin scrapings were assessed through direct microscopic examinations and culture studies. Dermatophyte isolates were identified based on colony morphology on potato dextrose agar and dermatophyte test medium, nutritional requirements, urease and hair perforation tests, and microscopic characteristics on slide cultures. Results: Dermatophytosis was mycologically confirmed in 26 (18.70%) out of 139 cases. Although there was a statistically insignificant difference between male and female subjects, men were dominantly affected. Infection was significantly common in the age group of ≤ 29 years (P<0.043). The most common clinical manifestation of dermatophytosis was tinea corporis (69.2%), followed by tinea cruris (15.4%), tinea manuum (11.5%), and tinea pedis (3.8%). Trichophyton mentagrophytes complex was the main etiologic agent (38.5%), followed by T. rubrum (23%), T. violaceum (15.5%), T. verrucosum (11.5%), Microsporum canis (7.7%), and Epidermophyton floccosum (3.8%). Conclusion: In comparison with previous research, epidemiology of dermatophytosis has changed in Yazd over the past decades. Therefore, periodical investigations on the epidemiological aspects of this infection are required for efficient control and prevention of this cutaneous dermatophytic disease. PMID:28681000

  20. Clinical Features and Antimicrobial Resistance of Bacterial Agents of Ventilator-Associated Tracheobronchitis in Hamedan, Iran

    Directory of Open Access Journals (Sweden)

    Seyyed Hamid Hashemi

    2017-09-01

    Full Text Available Objectives: Ventilator-associated tracheobronchitis (VAT is a common cause of mortality and morbidity in patients admitted to intensive care units (ICUs. This study was conducted to evaluate the clinical course, etiology, and antimicrobial resistance of bacterial agents of VAT in ICUs in Hamedan, Iran. Methods: During a 12-month period, all patients with VAT in a medical and a surgical ICU were included. The criteria for the diagnosis of VAT were fever, mucus production, a positive culture of tracheal secretions, and the absence of lung infiltration. Clinical course, including changes in temperature and tracheal secretions, and outcomes were followed. The endotracheal aspirates were cultured on blood agar and chocolate agar, and antimicrobial susceptibility testing of isolates were performed using the disk diffusion method. Results: Of the 1 070 ICU patients, 69 (6.4% were diagnosed with VAT. The mean interval between the patient’s intubation and the onset of symptoms was 4.7±8.5 days. The mean duration of response to treatment was 4.9±4.7 days. A total of 23 patients (33.3% progressed to ventilator-associated pneumonia (VAP, and 38 patients (55.0% died. The most prevalent bacterial isolates included Acinetobacter baumannii (24.6%, Pseudomonas aeruginosa (20.2%, and Enterobacter(13.0%. P. aeruginosa and Enterobacter were the most prevalent bacteria in surgical ICU, and A. baumannii and K. pneumoniae were the most common in the medical ICU. All A. baumannii and Citrobacter species were multidrug-resistant (MDR. MDR pathogens were more prevalent in medical ICU compared to surgical ICU (p < 0.001. Conclusions: VAT increases the rates of progression to VAP, the need for tracheostomy, and the incidence of mortality in ICUs. Most bacterial agents of VAT are MDR. Preventive policies for VAP, including the use of ventilator care bundle, and appropriate empirical antibiotic therapy for VAT may reduce the incidence of VAP.

  1. [Prescribed drug use for bipolar disorder type I and II in clinical practice].

    Science.gov (United States)

    Persson, Charlotte; Kardell, Mathias; Karanti, Alina; Isgren, Anniella; Annerbrink, Kristina; Landen, Mikael

    2017-01-10

    Prescribed drug use for bipolar disorder type I and II in clinical practice Practice guidelines based on available evidence and clinical consensus are available for the treatment of bipolar disorder. We surveyed to which extent those guidelines are implemented in clinical practice in Sweden. We analysed pharmacological treatment in patients with bipolar disorder in 2015 using the national quality register for bipolar disorder (BipoläR). We compared bipolar disorder type I (BDI) with type bipolar disorder type II (BDII). The vast majority of patients were prescribed a mood stabilizer either as monotherapy or as a part of combination therapy (BDI 87%, BDII 83%, pbipolar disorder.

  2. Harnessing the potential clinical use of medicinal plants as anti-diabetic agents

    Directory of Open Access Journals (Sweden)

    Campbell-Tofte JI

    2012-08-01

    Full Text Available Joan IA Campbell-Tofte,1 Per Mølgaard,2 Kaj Winther11Department of Clinical Biochemistry, Frederiksberg University Hospital, Frederiksberg, Denmark; 2Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, DenmarkAbstract: Diabetes is a metabolic disorder arising from complex interactions between multiple genetic and/or environmental factors. The characteristic high blood sugar levels result from either lack of the hormone insulin (type 1 diabetes, T1D, or because body tissues do not respond to the hormone (type 2 diabetes, T2D. T1D patients currently need exogenous insulin for life, while for T2D patients who do not respond to diet and exercise regimes, oral anti-diabetic drugs (OADs and sometimes insulin are administered to help keep their blood glucose as normal as possible. As neither the administration of insulin nor OADs is curative, many patients develop tissue degenerative processes that result in life-threatening diabetes comorbidities. Several surveys of medicinal plants used as anti-diabetic agents amongst different peoples have been published. Some of this interest is driven by the ongoing diabetes pandemic coupled with the inadequacies associated with the current state of-the-art care and management of the syndrome. However, there is a huge cleft between traditional medicine and modern (Western medicine, with the latter understandably demanding meaningful and scientific validation of anecdotal evidence for acceptance of the former. The main problems for clinical evaluation of medicinal plants with promising anti-diabetic properties reside both with the complexity of components of the plant materials and with the lack of full understanding of the diabetes disease etiology. This review is therefore focused on why research activities involving an integration of Systems Biology-based technologies of pharmacogenomics, metabolomics, and bioinformatics with standard clinical data

  3. Keeping pace with ACE: are ACE inhibitors and angiotensin II type 1 receptor antagonists potential doping agents?

    Science.gov (United States)

    Wang, Pei; Fedoruk, Matthew N; Rupert, Jim L

    2008-01-01

    activity or block the action of angiotensin II, the question is relevant to the study of ergogenic agents and to the efforts to rid sports of 'doping'. This article discusses the possibility that ACE inhibitors and ARBs, by virtue of their effects on ACE or angiotensin II function, respectively, have performance-enhancing capabilities; it also reviews the data on the effects of these medications on VO2max, muscle composition and endurance capacity in patient and non-patient populations. We conclude that, while the direct evidence supporting the hypothesis that ACE-related medications are potential doping agents is not compelling, there are insufficient data on young, athletic populations to exclude the possibility, and there is ample, albeit indirect, support from genetic studies to suggest that they should be. Unfortunately, given the history of drug experimentation in athletes and the rapid appropriation of therapeutic agents into the doping arsenal, this indirect evidence, coupled with the availability of ACE-inhibiting and ACE-receptor blocking medications may be sufficiently tempting to unscrupulous competitors looking for a shortcut to the finish line.

  4. Effectively simultaneous naked-eye detection of Cu(II), Pb(II), Al(III) and Fe(III) using cyanidin extracted from red cabbage as chelating agent

    Science.gov (United States)

    Khaodee, Warangkhana; Aeungmaitrepirom, Wanlapa; Tuntulani, Thawatchai

    Simultaneous determination of Cu(II), Pb(II), Al(III) and Fe(III) using cyanidin as a chelating agent was investigated in terms of both quantitative and qualitative detections. Cyanidin was extracted and purified from red cabbage which is a local plant in Thailand. The selectivity of this method was examined by regulating the pH of cyanidin solution operated together with masking agents. It was found that Cu(II), Pb(II), Al(III) and Fe(III) simultaneously responded with the color change at pH 7, pH 6, pH 5 and pH 4, respectively. KF, DMG and the mixture of KF and DMG were used as masking agents for the determination of Fe(III), Al(III) and Pb(II), respectively. Results from naked-eye detection were evaluated by comparing with those of inductively coupled plasma (ICP), and there was no significant difference noticed. Cyanidin using as a multianalyte reagent could be employed for simultaneous determination of Cu(II), Pb(II), Al(III) and Fe(III) at the lowest concentration at 50, 80, 50 and 200 μM, respectively, by slightly varying pHs. Moreover, the proposed method could be potentially applied for real water samples with simplicity, rapidity, low cost and environmental safety.

  5. Ulnar-sided wrist pain. II. Clinical imaging and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Atsuya; Souza, Felipe [Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Vezeridis, Peter S.; Blazar, Philip [Brigham and Women' s Hospital, Department of Orthopaedic Surgery, Boston, MA (United States); Yoshioka, Hiroshi [Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); University of California-Irvine, Department of Radiological Sciences, Irvine, CA (United States); UC Irvine Medical Center, Department of Radiological Sciences, Orange, CA (United States)

    2010-09-15

    Pain at the ulnar aspect of the wrist is a diagnostic challenge for hand surgeons and radiologists due to the small and complex anatomical structures involved. In this article, imaging modalities including radiography, arthrography, ultrasound (US), computed tomography (CT), CT arthrography, magnetic resonance (MR) imaging, and MR arthrography are compared with regard to differential diagnosis. Clinical imaging findings are reviewed for a more comprehensive understanding of this disorder. Treatments for the common diseases that cause the ulnar-sided wrist pain including extensor carpi ulnaris (ECU) tendonitis, flexor carpi ulnaris (FCU) tendonitis, pisotriquetral arthritis, triangular fibrocartilage complex (TFCC) lesions, ulnar impaction, lunotriquetral (LT) instability, and distal radioulnar joint (DRUJ) instability are reviewed. (orig.)

  6. Forensic psychiatric nursing: skills and competencies: II clinical aspects.

    Science.gov (United States)

    Mason, T; Coyle, D; Lovell, A

    2008-03-01

    This study reports on research undertaken to identify the skills and competencies of forensic psychiatric nurses working in secure psychiatric services in the UK. The rationale for this research is the lack of clarity in the role definition of nurses working in these environments and the specific content that may underscore the curriculum for training forensic nurses. Over 3300 questionnaires were distributed to forensic psychiatric nurses, non-forensic psychiatric nurses and other disciplines and information obtained on (1) the perceived clinical problems that give forensic nurses the most difficulty; (2) the skills best suited to overcome those problems; and (3) the priority aspects of clinical nursing care that needs to be developed. A 35% response rate was obtained with 1019 forensic psychiatric nurses, 110 non-forensic psychiatric nurses and 43 other disciplines. The results highlighted a 'top ten' list of main problems with possible solutions and main areas for development. The conclusions drawn include a focus on skills and competencies regarding the management of personality disorders and the management of violence and aggression.

  7. Treatment of geographic atrophy with subconjunctival sirolimus: results of a phase I/II clinical trial.

    Science.gov (United States)

    Wong, Wai T; Dresner, Samuel; Forooghian, Farzin; Glaser, Tanya; Doss, Lauren; Zhou, Mei; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A; Ferris, Frederick L; Chew, Emily Y

    2013-04-26

    To investigate the safety and effects of subconjunctival sirolimus, an mTOR inhibitor and immunosuppressive agent, for the treatment of geographic atrophy (GA). The study was a single-center, open-label phase II trial, enrolling 11 participants with bilateral GA; eight participants completed 24 months of follow-up. Sirolimus (440 μg) was administered every 3 months as a subconjunctival injection in only one randomly assigned eye in each participant for 24 months. Fellow eyes served as untreated controls. The primary efficacy outcome measure was the change in the total GA area at 24 months. Secondary outcomes included changes in visual acuity, macular sensitivity, central retinal thickness, and total drusen area. The study drug was well tolerated with few symptoms and related adverse events. Study treatment in study eyes was not associated with structural or functional benefits relative to the control fellow eyes. At month 24, mean GA area increased by 54.5% and 39.7% in study and fellow eyes, respectively (P = 0.41), whereas mean visual acuity decreased by 21.0 letters and 3.0 letters in study and fellow eyes, respectively (P = 0.03). Substantial differences in mean changes in drusen area, central retinal thickness, and macular sensitivity were not detected for all analysis time points up to 24 months. Repeated subconjunctival sirolimus was well-tolerated in patients with GA, although no positive anatomic or functional effects were identified. Subconjunctival sirolimus may not be beneficial in the prevention of GA progression, and may potentially be associated with effects detrimental to visual acuity. (ClinicalTrials.gov number, NCT00766649.).

  8. [Polyetheretherketone (PEEK). Part II: application in clinical practice].

    Science.gov (United States)

    Pokorný, D; Fulín, P; Slouf, M; Jahoda, D; Landor, I; Sosna, A

    2010-01-01

    Polyetheretherketone (PEEK) is one of the up-to-date organic polymer thermoplastics with applications in orthopaedics and trauma medicine. This study presents a detailed analysis of its tests and applications in clinical medicine. A wide range of PEEK modifications and composites are commercially available, e.g., PEEK-Classix, PEEK-Optima, Endolign and Motis. They differ in their physical properties, which makes them suitable for different applications. Other forms, so-called PEEK bioactive composites, contain beta-tricalcium phosphate and hydroxyapatite. Research in this field is also concerned with the surface finish of this polymer thermoplastic and involves macroporous titanium and hydroxyapatite layers, or treatment with laser for an exactly defined surface structure. The clinical applications of PEEK and its composites include, in addition to components for spinal surgery, osteosynthesis plates, screws, intramedullary nails or external fixators, which are implants still at the stage of prototypes. In this review, attention is paid to the use of PEEK thermoplastics for joint replacement. Mid-term studies involving hundreds of patients have shown that, for instance, the VerSys Epoch Fullcoat Hip System (Zimmer) has a markedly lower stress-shielding effect. Carbon fibre-reinforced (CFR-PEEK) composites are used to make articulating components for total hip replacement. Their convenient properties allow for production of much thinner liners and an enlargement of the femoral head diameter, thus reducing the wear of joint implants. CFR-PEEK composites are particularly effective for hip resurfacing in which the Mitch PCR (Stryker) acetabular component has been used with good results. The MOTIS polymer acetabular cup (Invibio Ltd.) is another example. Further PEEK applications include the construction of finger-joint prostheses (Mathys AG), suture anchors (Stryker) and various kinds of augmentations (Medin). Based on the information obtained, the authors suggest

  9. Uncommon and Neglected Venezuelan Viral Diseases: Etiologic Agents, Physiopathological, Clinical and Epidemiological Characteristics

    Directory of Open Access Journals (Sweden)

    Juan C. Gabaldon-Figueira

    2015-10-01

    Full Text Available Abstract (english Viral infectious diseases are common in Venezuela, influenza, dengue, yellow fever, HIV infection, viral Hepatitis, chikungunya fever and many others represent public health problems in the country and therefore, have been well documented. However, other rarer and even unique or lethal viral illnesses present in Venezuela are usually poorly understood or even unknown. This review described Venezuelan Hemorrhagic Fever, Venezuelan Equine Encephalitis, Hantavirus Infections and Mayaro fever, named as neglected diseases, emphasizing the etiologic agents and their most relevant pathogenic mechanisms, clinical and epidemiological characteristics. Although there is not an official report about the re-emergence of these diseases, falling living standards and unsanitary conditions, together with limited accessibility to hygiene products and medical supplies, put us on alert about the re-emergence of these neglected diseases. Resumen (español Las enfermedades infecciosas virales son comunes en Venezuela, influenza, dengue, fiebre amarilla, infección por VIH, hepatitis viral, fiebre chikungunya y muchas otras representan problemas de salud pública en el país y por lo tanto, han sido bien documentadas. Sin embargo, otras enfermedades virales más raras e incluso únicas y letales presentes en Venezuela son generalmente poco estudiadas y hasta desconocidas. Esta revisión describe alguna de estas enfermedades olvidadas tales como la fiebre hemorrágica venezolana, la encefalitis equina venezolana, las infecciones por hantavirus y la fiebre de Mayaro, haciendo hincapié en los agentes etiológicos y en sus mecanismos patogénicos más relevantes, características clínicas y epidemiológicas. Aunque no hay informes oficiales sobre el resurgimiento de estas enfermedades, la caída de los niveles de vida y las condiciones insalubres, junto con el acceso limitado a los productos de higiene y suministros médicos, debe alertar sobre el

  10. Preparation of a Cobalt(II) Cage: An Undergraduate Laboratory Experiment That Produces a ParaSHIFT Agent for Magnetic Resonance Spectroscopy

    Science.gov (United States)

    Burns, Patrick J.; Tsitovich, Pavel B.; Morrow, Janet R.

    2016-01-01

    Laboratory experiments that demonstrate the effect of paramagnetic complexes on chemical shifts and relaxation times of protons are a useful way to introduce magnetic resonance spectroscopy (MRS) probes or magnetic resonance imaging (MRI) contrast agents. In this undergraduate inorganic chemistry experiment, a paramagnetic Co(II) cage complex is…

  11. Omega-3 fatty acids in schizophrenia Part II: Clinical applications

    Directory of Open Access Journals (Sweden)

    Róg Joanna

    2016-12-01

    Full Text Available Ω-3 unsaturated fatty acids are compounds belonging to the group of essential fatty acids (EFAs. The history of the discovery of EFAs dates back to the 1930s of the twentieth century, however, growing interest in ω-3 EFAs in the context of mental health has been observed since the year 2000. In view of their multidirectional action, these compounds are a promising form of adjunctive therapy of many illnesses, including psychiatric disorders. The present article aims to review the literature on the clinical applicability of ω-3 EFAs in treating schizophrenia. We present the results of preclinical studies in this area and the mechanisms of ω-3 EFAs action discussed by the authors. The randomized controlled trials (RCTs evaluating the possibility of using ω-3 EFAs in schizophrenia are characterized in detail. The results of the tests are not clear, which may result from the methodological diversity of interventions made. Ω-3 EFAs seem to be a promising form of adjunctive therapy of schizophrenia. Further research is needed, which will allow for defining groups of patients in which intervention will bring the expected results.

  12. Ocular toxoplasmosis II: clinical features, pathology and management

    Science.gov (United States)

    Butler, Nicholas J; Furtado, João M; Winthrop, Kevin L; Smith, Justine R

    2014-01-01

    The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis. PMID:22712598

  13. Emerging medical informatics with case-based reasoning for aiding clinical decision in multi-agent system.

    Science.gov (United States)

    Shen, Ying; Colloc, Joël; Jacquet-Andrieu, Armelle; Lei, Kai

    2015-08-01

    This research aims to depict the methodological steps and tools about the combined operation of case-based reasoning (CBR) and multi-agent system (MAS) to expose the ontological application in the field of clinical decision support. The multi-agent architecture works for the consideration of the whole cycle of clinical decision-making adaptable to many medical aspects such as the diagnosis, prognosis, treatment, therapeutic monitoring of gastric cancer. In the multi-agent architecture, the ontological agent type employs the domain knowledge to ease the extraction of similar clinical cases and provide treatment suggestions to patients and physicians. Ontological agent is used for the extension of domain hierarchy and the interpretation of input requests. Case-based reasoning memorizes and restores experience data for solving similar problems, with the help of matching approach and defined interfaces of ontologies. A typical case is developed to illustrate the implementation of the knowledge acquisition and restitution of medical experts. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.

    Science.gov (United States)

    da Cruz, Lyndon; Dorn, Jessy D; Humayun, Mark S; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E; Hafezi, Farhad; Safran, Avinoam B; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V; de Juan, Eugene; Duncan, Jacque L; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C; Ho, Allen C; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V; Arditi, Aries; Greenberg, Robert J

    2016-10-01

    The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. Thirty participants in 10 centers in the United States and Europe. The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  15. A pancreas imaging agent-131I-HIPDM: the animal experiment and preliminary clinical application

    International Nuclear Information System (INIS)

    Shao Hesheng

    1988-01-01

    131 I-HIPDM has been used clinically for studying regional cerebral perfusion. The [ 131 I] HIPDM was prepared in a kit. The labelling yields were consistently more than 95%, as analyzed by the TLC-Silica gel. The labelled compound is stable in vitro and in vivo. S D Strain rats (170-220 g) and mice (18-22 g) were used. The pancreatic uptake of [ 131 I] HIPDM is rather slow in mice and rats. At 8 hr after iv, the pancreas activity and the pancreas to liver (P/L) ratio are highest in mice and rats. The effect of carrier loading dose from 0.010 to 6.0 mg/kg on blodistribution in mice has been studied. The liver uptake was increased by adding carrier HIPDM. The result indicates that administration between 0.010 and 0.05 mg/kg carrier dose is most suitable for the pancreas imaging. Gamma camera imaging of dog at 6 hr after iv with 300 μCi [ 131 I] HIPMD, 0.05 mg/kg body weight showed clear pancreas image. The P/L ratio of the dog is 0.40. Preliminary clinical tests were satisfactory. Using 1 to 1.5 mCi of [ 131 I] HIPDM, 0.05 mg/kg, the pancreas imaging was operated in 4 cases of volunteers and pancreas cyst respectively with the good diagnostic quality. The authors are of the opinion that this pancreas imaging agent may have potential value for routine use

  16. PRESCRIBING OF ANTIHYPERTENSIVE AGENTS IN PUBLIC PRIMARY CARE CLINICS – IS IT IN ACCORDANCE WITH CURRENT EVIDENCE?

    Directory of Open Access Journals (Sweden)

    SAJARI J

    2010-01-01

    Full Text Available Background: Large population surveys in Malaysia have consistently shown minimal improvement of blood pressure control rates over the last 10 years. Poor adherence to antihypertensive medication has been recognized as a major reason for poor control of hypertension. This study aimed to describe the prescribing pattern of antihypertensive agents in 2 public primary care clinics and assess its appropriateness in relation to current evidence and guidelines. Methods: A cross-sectional survey to describe the prescribing pattern of antihypertensive agents was carried out in 2 publicprimary care clinics in Selangor from May to June 2009. Hypertensive patients on pharmacological treatment for ≥1 year who attended the clinics within the study period of 7 weeks were selected. Appropriate use of antihypertensive agents was defined based on current evidence and the recommendations by the Malaysian Clinical Practice Guidelines (CPG on the Management of Hypertension, 2008. Data were obtained from patients’ medical records and were analysed using the SPSS software version 16.0. Results: A total of 400 hypertensive patients on treatment were included. Mean age was 59.5 years (SD ±10.9, range 28 to91 years, of which 52.8% were females and 47.2% were males. With regards to pharmacotherapy, 45.7% were on monotherapy,43.3% were on 2 agents and 11.0% were on ≥3 agents. Target blood pressure of <140/90mmHg was achieved in 51.4% of patients on monotherapy, and 33.2% of patients on combination of ≥2 agents. The commonest monotherapy agents being prescribed were β-blockers (atenolol or propranolol, followed by the short-acting calcium channel blocker (nifedipine. The commonest combination of 2-drug therapy prescribed was β-blockers and short-acting calcium channel blocker. Conclusion: This study shows that the prescribing pattern of antihypertensive agents in the 2 primary care clinics was not in accordance with current evidence and guidelines.

  17. Cerebral near infrared spectroscopy oximetry in extremely preterm infants : Phase II randomised clinical trial

    NARCIS (Netherlands)

    Hyttel-Sorensen, Simon; Pellicer, Adelina; Alderliesten, Thomas; Austin, Topun; Van Bel, Frank; Benders, Manon; Claris, Olivier; Dempsey, Eugene; Franz, Axel R.; Fumagalli, Monica; Gluud, Christian; Grevstad, Berit; Hagmann, Cornelia; Lemmers, Petra; Van Oeveren, Wim; Pichler, Gerhard; Plomgaard, Anne Mette; Riera, Joan; Sanchez, Laura; Winkel, Per; Wolf, Martin; Greisen, Gorm

    2015-01-01

    Objective: To determine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants monitored by cerebral near infrared spectroscopy (NIRS) oximetry. Design: Phase II randomised, single blinded, parallel clinical trial. Setting Eight tertiary neonatal intensive care units in

  18. Zinc-sensitive MRI contrast agent detects differential release of Zn(II) ions from the healthy vs. malignant mouse prostate.

    Science.gov (United States)

    Clavijo Jordan, M Veronica; Lo, Su-Tang; Chen, Shiuhwei; Preihs, Christian; Chirayil, Sara; Zhang, Shanrong; Kapur, Payal; Li, Wen-Hong; De Leon-Rodriguez, Luis M; Lubag, Angelo J M; Rofsky, Neil M; Sherry, A Dean

    2016-09-13

    Many secretory tissues release Zn(II) ions along with other molecules in response to external stimuli. Here we demonstrate that secretion of Zn(II) ions from normal, healthy prostate tissue is stimulated by glucose in fasted mice and that release of Zn(II) can be monitored by MRI. An ∼50% increase in water proton signal enhancement is observed in T1-weighted images of the healthy mouse prostate after infusion of a Gd-based Zn(II) sensor and an i.p. bolus of glucose. Release of Zn(II) from intracellular stores was validated in human epithelial prostate cells in vitro and in surgically exposed prostate tissue in vivo using a Zn(II)-sensitive fluorescent probe known to bind to the extracellular surface of cells. Given the known differences in intracellular Zn(II) stores in healthy versus malignant prostate tissues, the Zn(II) sensor was then evaluated in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model in vivo. The agent proved successful in detecting small malignant lesions as early as 11 wk of age, making this noninvasive MR imaging method potentially useful for identifying prostate cancer in situations where it may be difficult to detect using current multiparametric MRI protocols.

  19. The clinical pharmacology of alkylating agents in high-dose chemotherapy

    NARCIS (Netherlands)

    Huitema, A. D.; Smits, K. D.; Mathôt, R. A.; Schellens, J. H.; Rodenhuis, S.; Beijnen, J. H.

    2000-01-01

    Alkylating agents are widely used in high-dose chemotherapy regimens in combination with hematological support. Knowledge about the pharmacokinetics and pharmacodynamics of these agents administered in high doses is critical for the safe and efficient use of these regimens. The aim of this review is

  20. Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

    Science.gov (United States)

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Novel Antitumor Platinum(II) Conjugates Containing the Nonsteroidal Anti-inflammatory Agent Diclofenac: Synthesis and Dual Mechanisms of Antiproliferative Effects.

    Science.gov (United States)

    Intini, Francesco Paolo; Zajac, Juraj; Novohradsky, Vojtech; Saltarella, Teresa; Pacifico, Concetta; Brabec, Viktor; Natile, Giovanni; Kasparkova, Jana

    2017-02-06

    One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines. One of these compounds, compound 3, in which DCF molecules are coordinated to Pt(II) through their carboxylic group, is more potent than parental conventional Pt(II) drug cisplatin, free DCF and the congeners of 3 in which DCF ligands are conjugated to Pt(II) via a diamine. The potency of 3 is due to several factors including enhanced internalization that correlates with enhanced DNA binding and cytotoxicity. Mechanistic studies show that 3 combines multiple effects. After its accumulation in cells, it releases Pt(II) drug capable of binding/damaging DNA and DCF ligands, which affect distribution of cells in individual phases of the cell cycle, inhibit glycolysis and lactate transport, collapse mitochondrial membrane potential, and suppress the cellular properties characteristic of metastatic progression.

  2. Five-year safety and performance results from the Argus II Retinal Prosthesis System clinical trial

    Science.gov (United States)

    da Cruz, Lyndon; Dorn, Jessy D.; Humayun, Mark S.; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E.; Hafezi, Farhad; Safran, Avinoam B.; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V.; de Juan, Eugene; Duncan, Jacque L.; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C.; Ho, Allen C.; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V.; Arditi, Aries; Greenberg, Robert J.

    2016-01-01

    Purpose The Argus® II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) was developed to restore some vision to patients blind from retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception due to end-stage RP. Design The study is a prospective, multicenter, single-arm, clinical trial. Within-patient controls included the non-implanted fellow eye and patients' native residual vision compared to their vision when using the System. Subjects There were 30 subjects in 10 centers in the U.S. and Europe. Methods The worse-seeing eye of blind patients was implanted with the Argus II System. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by three computer-based, objective tests. Secondary measures included functional vision performance on objectively-scored real-world tasks. Results Twenty-four out of 30 patients remained implanted with functioning Argus II Systems at 5 years post-implant. Only one additional serious adverse event was experienced since the 3-year time point. Patients performed significantly better with the System ON than OFF on all visual function tests and functional vision tasks. Conclusions The five-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. PMID:27453256

  3. [How to assess clinical practice guidelines with AGREE II: The example of neonatal jaundice].

    Science.gov (United States)

    Renesme, L; Bedu, A; Tourneux, P; Truffert, P

    2016-03-01

    Neonatal jaundice is a very frequent condition that occurs in approximately 50-70% of term or near-term (>35 GA) babies in the 1st week of life. In some cases, a high bilirubin blood level can lead to kernicterus. There is no consensus for the management of neonatal jaundice and few countries have published national clinical practice guidelines for the management of neonatal jaundice. The aim of this study was to assess the quality of these guidelines. We conducted a systematic review of the literature for national clinical practice guidelines for the management of neonatal jaundice in term or near-term babies. Four independent reviewers assessed the quality of each guideline using the AGREE II evaluation. For each of the clinical practice guidelines, the management modalities were analyzed (screening, treatment, follow-up, etc.). Seven national clinical practice guidelines were found (South Africa, USA AAP, UK NICE, Canada, Norway, Switzerland, and Israel). The AGREE II score showed widespread variation regarding the quality of these national guidelines. There was no major difference between the guidelines concerning the clinical management of these babies. The NICE guideline is the most valuable guideline regarding the AGREE II score. NICE showed that, despite a strong and rigorous methodology, there is no evidenced-based recommended code of practice (RCP). Comparing RCPs, we found no major differences. The NICE guideline showed the best quality. The AGREE II instrument should be used as a framework when developing clinical practice guidelines to improve the quality of the future guideline. In France, a national guideline is needed for a more standardized management of neonatal jaundice. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Studies of the labelling of human serum albumin with 99mTc using Sn(II) tartrate and Sn(II)Cl2 as reducing agents

    International Nuclear Information System (INIS)

    El-Kolaly, M.T.; El-Asrag, H.A.; El-Wetery, A.S.; El-Mohty, A.A.

    1990-01-01

    A comparative study has been carried out on the effect of Sn(II) tartrate and Sn(II)Cl 2 on the labelling efficiency and tissue distribution of 99m Tc-human serum albumin. The effect of reductant content, reaction time (incubation time), albumin content, pH, and ascorbic acid on the efficiency of labelling and the tissue distribution of the labelled albumin has been investigated. The percentage of labelling was determined by paper and thin layer radiochromatography. Ascorbic acid shows no effect on either labelling efficiency or tissue distribution of 99m Tc-HSA prepared by Sn(II) tartrate or Sn(II)Cl 2 . (author)

  5. [New intensifying screens in clinical radiology. II. Examinations in clinical practice].

    Science.gov (United States)

    Freyschmidt, J; Saure, D; Hagemann, G

    1976-09-01

    A clinically applicable procedure for testing new intensifying rare earth screens, as well as the special Siemens' screen is described. The results are related to universal screens. The film-screen combination alpha 4XD (gadolinium oxysulphide with normal, green sensitive film) results in a reduction of radiation dose to half with detail comparable with universal screens. The Siemens' special screen has similar advantages. Screens with a higher intensification factor and reduction of the mAs to one sixth results in loss of detail. This does not necessarily reduce their clinical use if they are used for appropriate purposes. The results of this clinically orientated technique agreed well with physically objective methods using lead grids. The advantages of the new screens are discussed in terms of their practical application.

  6. Scientific and industrial challenges of developing nanoparticle-based theranostics and multiple-modality contrast agents for clinical application

    Science.gov (United States)

    Wáng, Yì Xiáng J.; Idée, Jean-Marc; Corot, Claire

    2015-10-01

    Designing of theranostics and dual or multi-modality contrast agents are currently two of the hottest topics in biotechnology and biomaterials science. However, for single entity theranostics, a right ratio of their diagnostic component and their therapeutic component may not always be realized in a composite suitable for clinical application. For dual/multiple modality molecular imaging agents, after in vivo administration, there is an optimal time window for imaging, when an agent is imaged by one modality, the pharmacokinetics of this agent may not allow imaging by another modality. Due to reticuloendothelial system clearance, efficient in vivo delivery of nanoparticles to the lesion site is sometimes difficult. The toxicity of these entities also remains poorly understood. While the medical need of theranostics is admitted, the business model remains to be established. There is an urgent need for a global and internationally harmonized re-evaluation of the approval and marketing processes of theranostics. However, a reasonable expectation exists that, in the near future, the current obstacles will be removed, thus allowing the wide use of these very promising agents.

  7. Reproducing a Prospective Clinical Study as a Computational Retrospective Study in MIMIC-II.

    Science.gov (United States)

    Kury, Fabrício S P; Huser, Vojtech; Cimino, James J

    2015-01-01

    In this paper we sought to reproduce, as a computational retrospective study in an EHR database (MIMIC-II), a recent large prospective clinical study: the 2013 publication, by the Japanese Association for Acute Medicine (JAAM), about disseminated intravascular coagulation, in the journal Critical Care (PMID: 23787004). We designed in SQL and Java a set of electronic phenotypes that reproduced the study's data sampling, and used R to perform the same statistical inference procedures. All produced source code is available online at https://github.com/fabkury/paamia2015. Our program identified 2,257 eligible patients in MIMIC-II, and the results remarkably agreed with the prospective study. A minority of the needed data elements was not found in MIMIC-II, and statistically significant inferences were possible in the majority of the cases.

  8. Susceptibility of three clinical isolates of Actinomodura madurae to α-pinene, the bioactive agent of Pinus pinaster turpentine oil

    Directory of Open Access Journals (Sweden)

    Stojković D.

    2008-01-01

    Full Text Available In vitro susceptibility of the turpentine oil obtained from Pinus pinaster oleoresin was evaluated against three Sudanese clinical isolates of Actinomadura madurae, which is the main causative agent of actinomycetoma. The minimum inhibitory concentrations (MICs of the oil ranged from 100.3 to 124.8 μL/mL, and the minimum microbicidal concentrations (MMCs were between 100.3 and 150.0 μL/mL. α-Pinene exhibited prominent bioactivity with MICs ranging between 3.3 and 5.0 μL/mL, while its MMC was 10.0 μL/mL against the same clinical isolates. Pinus pinaster turpentine oil and α-pinene might be useful agents in the treatment of mycetoma caused by A. madurae.

  9. Majewski osteodysplastic primordial dwarfism type II: clinical findings and dental management of a child patient.

    Science.gov (United States)

    Terlemez, Arslan; Altunsoy, Mustafa; Celebi, Hakki

    2015-01-01

    Majewski osteodysplastic primordial dwarfism type II (MOPD II) is an unusual autosomal recessive inherited form of primordial dwarfism, which is characterized by a small head diameter at birth, but which also progresses to severe microcephaly, progressive bony dysplasia, and characteristic facies and personality. This report presents a case of a five-year-old girl with MOPD II syndrome. The patient was referred to our clinic with the complaint of severe tooth pain at the left mandibular primary molar teeth. Clinical examination revealed that most of the primary teeth had been decayed and all primary teeth were hypoplastic. Patient's history revealed delayed development in the primary dentition and radiographic examination showed rootless primary molar teeth and short-rooted incisors. The treatment was not possible due to the lack of root of the left mandibular primary molars; so the teeth were extracted. Thorough and timely dental evaluation is crucial for the prevention of dental problems and the maintenance of oral health in patients with MOPD II syndrome is of utmost importance.

  10. MAJEWSKI OSTEODYSPLASTIC PRIMORDIAL DWARFISM TYPE II: CLINICAL FINDINGS AND DENTAL MANAGEMENT OF A CHILD PATIENT

    Directory of Open Access Journals (Sweden)

    Arslan Terlemez

    2015-01-01

    Full Text Available Majewski osteodysplastic primordial dwarfism type II (MOPD II is an unusual autosomal recessive inherited form of primordial dwarfism, which is characterized by a small head diameter at birth, but which also progresses to severe microcephaly, progressive bony dysplasia, and characteristic facies and personality. This report presents a case of a five-year-old girl with MOPD II syndrome. The patient was referred to our clinic with the complaint of severe tooth pain at the left mandibular primary molar teeth. Clinical examination revealed that most of the primary teeth had been decayed and all primary teeth were hypoplastic. Patient’s history revealed delayed development in the primary dentition and radiographic examination showed rootless primary molar teeth and short-rooted incisors. The treatment was not possible due to the lack of root of the left mandibular primary molars; so the teeth were extracted. Thorough and timely dental evaluation is crucial for the prevention of dental problems and the maintenance of oral health in patients with MOPD II syndrome is of utmost importance.

  11. Acute and subchronic toxicity of the antitumor agent rhodium (II citrate in Balb/c mice after intraperitoneal administration

    Directory of Open Access Journals (Sweden)

    Marcella L.B. Carneiro

    2015-01-01

    Full Text Available This study aimed to investigate potential acute and subchronic toxicity of rhodium (II citrate in female Balb/c mice after intraperitoneal injections. In the acute test, independent groups received five doses; the highest dose (107.5 mg/kg was equivalent to 33 times that used in our previous reports. The other doses were chosen as proportions of the highest, being 80.7 (75%, 53.8 (50%, 26.9 (25% or 13.8 mg/kg (12.5%. Animals were monitored over 38 days and no severe signs of toxicity were observed, according to mortality, monitoring of adverse symptoms, hematological, biochemical and genotoxic parameters. We conclude that the median lethal dose (LD50 could be greater than 107.5 mg/kg. In the subchronic test, five doses of Rh2Cit (80, 60, 40, 20 or 10 mg/kg were evaluated and injections were conducted on alternate days, totaling five applications per animal. Paclitaxel (57.5 mg/kg and saline solution were controls. Clinical observations, histopathology of liver, lung and kidneys and effects on hematological, biochemistry and genotoxic records indicated that Rh2Cit induced no severe toxic effects, even at an accumulated dose up to 400 mg/kg.We suggest Rh2Cit has great potential as an antitumor drug without presenting acute and subchronic toxicity.

  12. Clinical effect of Cystenosine on leukocytopenia at the time of therapy with radiation and antineoplastic agents

    International Nuclear Information System (INIS)

    Sato, Kazuhide; Usui, Ryu; Inoue, Hiroshi; Mihashi, Norio; Niibe, Hideo.

    1977-01-01

    Out of 62 cases, 25 cases received only radiotherapy, 11 cases received both radiotherapy and antineoplastic agents, and 26 cases received only antineoplastic agents. Total dose of x-ray ranges from 3000 to 6200 rad in 18 of 36 cases of the former two groups, and 2600 to 6260 rad of 60 Co dose were irradiated to 18 cases of the rest. This agent was administered 9 tablets per a day (one tablet contains 200 mg of inosine and 20 mg of cystine) for 19 to 142 days. Its effects on leukocytopenia showed marked effectiveness in 9 out of 25 cases treated with only radiation, effectiveness in 8 cases, and ineffectiveness in 3 cases. Its effective rate was 72.8%. The effective rate was 65.4% in the cases treated with only antineoplastic agents, and was 67.7% in all cases. A certain relationship between dose and the effective rate was not recognized. Radiation sickness, such as loss of appetite general fatigue and mausea, decreased gradually by using this agent. Side effect was not recognized particularly. (Kanao. N.)

  13. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development.

    Science.gov (United States)

    Smelick, Gillian S; Heffron, Timothy P; Chu, Laura; Dean, Brian; West, David A; Duvall, Scott L; Lum, Bert L; Budha, Nageshwar; Holden, Scott N; Benet, Leslie Z; Frymoyer, Adam; Dresser, Mark J; Ware, Joseph A

    2013-11-04

    Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered

  14. Clinical application of a triombrin in urology, a new Soviet radiographic contrast agent

    International Nuclear Information System (INIS)

    Perel'man, V.M.

    1980-01-01

    A water-soluble radiographic contrast agent triombrin which is a methylglucosamine sodium salt mixture of diatrizoate was studied. The analysis is based on the observation of 175 patients subjected to 186 tests, mainly excretory urography with the double dose of the contrast agent. The correlation between the quality of the picture obtained and the individual features of the patients has been established. Assessment of urograms obtained with the use of hypaque, urografin, verografin, urotrast and triombrin has revealed results similar to those with triombrin. Allergic reactions and complications have been noted in 23 (14%) of 164 patients after excretory and infusion urography. Satisfactory contrast and a good tolerance of the agent allowed recommending triombrin for wide use in medical practice

  15. Issues in the assessment of personality disorder and substance abuse using the Millon Clinical Multiaxial Inventory (MCMI-II).

    Science.gov (United States)

    Flynn, P M; McCann, J T; Fairbank, J A

    1995-05-01

    Substance abuse treatment clients often present other severe mental health problems that affect treatment outcomes. Hence, screening and assessment for psychological distress and personality disorder are an important part of effective treatment, discharge, and aftercare planning. The Millon Clinical Multiaxial Inventory-II (MCMI-II) frequently is used for this purpose. In this paper, several issues of concern to MCMI-II users are addressed. These include the extent to which MCMI-II scales correspond to DSM-III-R disorders; overdiagnosis of disorders using the MCMI-II; accuracy of MCMI-II diagnostic cut-off scores; and the clinical utility of MCMI-II diagnostic algorithms. Approaches to addressing these issues are offered.

  16. Synthesis, structural characterization, and pro-apoptotic activity of 1-indanone thiosemicarbazone platinum(II) and palladium(II) complexes: potential as antileukemic agents.

    Science.gov (United States)

    Gómez, Natalia; Santos, Diego; Vázquez, Ramiro; Suescun, Leopoldo; Mombrú, Alvaro; Vermeulen, Monica; Finkielsztein, Liliana; Shayo, Carina; Moglioni, Albertina; Gambino, Dinorah; Davio, Carlos

    2011-08-01

    In the search for alternative chemotherapeutic strategies against leukemia, various 1-indanone thiosemicarbazones, as well as eight novel platinum(II) and palladium(II) complexes, with the formula [MCl₂(HL)] and [M(HL)(L)]Cl, derived from two 1-indanone thiosemicarbazones were synthesized and tested for antiproliferative activity against the human leukemia U937 cell line. The crystal structure of [Pt(HL1)(L1)]Cl·2MeOH, where L1=1-indanone thiosemicarbazone, was solved by X-ray diffraction. Free thiosemicarbazone ligands showed no antiproliferative effect, but the corresponding platinum(II) and palladium(II) complexes inhibited cell proliferation and induced apoptosis. Platinum(II) complexes also displayed selective apoptotic activity in U937 cells but not in peripheral blood monocytes or the human hepatocellular carcinoma HepG2 cell line used to screen for potential hepatotoxicity. Present findings show that, in U937 cells, 1-indanone thiosemicarbazones coordinated to palladium(II) were more cytotoxic than those complexed with platinum(II), although the latter were found to be more selective for leukemic cells suggesting that they are promising compounds with potential therapeutic application against hematological malignancies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Amphetamines and pH-shift agents for brain imaging: Basic research and clinical results

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Winkler, C.

    1986-01-01

    This book contains 18 selections. Some of the titles are: Labelling of amphetamines with /sup 123/I: Receptors for amphetamines; New amphetamine derivatives; Potential new approaches for the development of brain imaging agents for single-photon applications; and IM SPECT with the pinhole collimator.

  18. Radiographic scanning agent

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    A stable radiographic scanning agent on a sup(99m)Tc basis has been developed. The substance contains a pertechnetate reduction agent, tin(II)-chloride, chromium(II)-chloride, or iron(II)-sulphate, as well as an organospecific carrier and ascorbic acid or a pharmacologically admissible salt or ester of ascorbic acid. (VJ) [de

  19. Clinical efficacy of terlipressin in treatment of type II hepatorenal syndrome

    Directory of Open Access Journals (Sweden)

    DING Xiaohong

    2015-05-01

    Full Text Available ObjectiveTo investigate the clinical efficacy of domestic terlipressin in the treatment of type II hepatorenal syndrome (HRS-II. MethodsA total of 25 HRS-II patients admitted to our hospital from November 2011 to June 2014 were recruited into the treatment group, and 28 HRS-II patients treated with dopamine before 2011 were recruited into the control group. Patients in the treatment group were randomly divided into two subgroups: one subgroup (n=12 was given terlipressin once every 8 h, and the other subgroup (n=13 was given terlipressin once every 12 h. Both groups received albumin (Alb infusion to expand the blood volume before treatment with terlipressin or dopamine, and the course of treatment was 7 days. The improvement in clinical symptoms, levels of blood urea nitrogen (BUN, serum creatinine and electrolytes, urine volume, changes in liver function, and ascites disappearance in the two groups before and after treatment were compared. Comparison of categorical data between the two groups was made by χ2 test, and comparison of continuous data was made by t test. ResultsPatients in the control group showed no obvious symptom relief, but those in the treatment group had varying degrees of improvement in clinical symptoms. Neither group had significant changes in liver function and serum sodium level after treatment. The treatment group had significantly more patients whose ascites volume had decreased from large to medium than the control group (χ2=5.705, P<0.05. There was a slight but not significant decrease in the levels of BUN and serum creatinine in the control group after treatment with dopamine (all P>0.05, whereas the urine volume showed significant difference after the treatment (t=15.534, P<0.01. The treatment group showed significant differences in the levels of BUN and serum creatinine and urine volume after terlipressin treatment (t=11.535, 9.941, and 19.685, respectively; all P<0.01, and significant differences in

  20. Clinical aspects of percutaneous poisoning by the chemical warfare agent VX: effects of application site and decontamination.

    Science.gov (United States)

    Hamilton, Murray G; Hill, Ira; Conley, John; Sawyer, Thomas W; Caneva, Duane C; Lundy, Paul M

    2004-11-01

    O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) is an extremely toxic organophosphate nerve agent that has been weaponized and stockpiled in a number of different countries, and it has been used in recent terrorist events. It differs from other well-known organophosphate nerve agents in that its primary use is as a contact poison rather than as an inhalation hazard. For this reason, we examined the effects of application site and skin decontamination on VX toxicity in anesthetized domestic swine after topical application. VX applied to the surface of the ear rapidly resulted in signs of toxicity consistent with the development of cholinergic crisis, including apnea and death. VX on the epigastrium resulted in a marked delayed development of toxic signs, reduced toxicity, and reduction in the rate of cholinesterase depression compared with animals exposed on the ear. Skin decontamination (15 minutes post-VX on the ear) arrested the development of clinical signs and prevented further cholinesterase inhibition and death. These results confirm earlier work that demonstrates the importance of exposure site on the resultant toxicity of this agent and they also show that decontamination postexposure has the potential to be an integral and extremely important component of medical countermeasures against this agent.

  1. Failsafe automation of Phase II clinical trial interim monitoring for stopping rules.

    Science.gov (United States)

    Day, Roger S

    2010-02-01

    In Phase II clinical trials in cancer, preventing the treatment of patients on a study when current data demonstrate that the treatment is insufficiently active or too toxic has obvious benefits, both in protecting patients and in reducing sponsor costs. Considerable efforts have gone into experimental designs for Phase II clinical trials with flexible sample size, usually implemented by early stopping rules. The intended benefits will not ensue, however, if the design is not followed. Despite the best intentions, failures can occur for many reasons. The main goal is to develop an automated system for interim monitoring, as a backup system supplementing the protocol team, to ensure that patients are protected. A secondary goal is to stimulate timely recording of patient assessments. We developed key concepts and performance needs, then designed, implemented, and deployed a software solution embedded in the clinical trials database system. The system has been in place since October 2007. One clinical trial tripped the automated monitor, resulting in e-mails that initiated statistician/investigator review in timely fashion. Several essential contributing activities still require human intervention, institutional policy decisions, and institutional commitment of resources. We believe that implementing the concepts presented here will provide greater assurance that interim monitoring plans are followed and that patients are protected from inadequate response or excessive toxicity. This approach may also facilitate wider acceptance and quicker implementation of new interim monitoring algorithms.

  2. Clinical features and outcomes of plasma cell leukemia: a single-institution experience in the era of novel agents

    Directory of Open Access Journals (Sweden)

    Giampaolo Talamo

    2012-08-01

    Full Text Available Plasma cell leukemia (PCL is a rare hematologic malignancy with aggressive clinical and biologic features. Data regarding its prognosis with the use of the novel agents, i.e., the immunomodulatory drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, are limited. We retrospectively reviewed clinical outcomes, response to therapy, and survival of 17 patients seen at the Penn State Hershey Cancer Institute since the availability of novel agents (2006-2011. Twelve patients had primary PCL (pPCL, and 5 second- ary PCL (sPCL. PCL was associated with aggressive clinicobiological features, such as high-risk cytogenetics, elevated serum beta-2-microglobulin and lactate dehydrogenase, International Staging System stage III, and rapid relapse after therapy. With the use of thalidomide, lenalidomide, and bortezomib in 53%, 53%, and 88% patients, respectively, median overall survival (OS was 18 months in the whole group (95% confidence interval, 11-21 months, and 21 and 4 months in pPCL and sPCL, respectively (P=0.015. OS was inferior to that of 313 consecutive patients with multiple myeloma (MM treated in the same period, even when compared with a subset of 47 MM with high-risk cytogenetics. Although our data are limited by the small sample size, we conclude that novel agents may modestly improve survival in patients with PCL, when compared to historical controls. Novel therapies do not seem to overcome the negative prognosis of PCL as compared with MM.

  3. Clinical features and outcomes of plasma cell leukemia: a single-institution experience in the era of novel agents.

    Science.gov (United States)

    Talamo, Giampaolo; Dolloff, Nathan G; Sharma, Kamal; Zhu, Junjia; Malysz, Jozef

    2012-06-26

    Plasma cell leukemia (PCL) is a rare hematologic malignancy with aggressive clinical and biologic features. Data regarding its prognosis with the use of the novel agents, i.e., the immunomodulatory drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, are limited. We retrospectively reviewed clinical outcomes, response to therapy, and survival of 17 patients seen at the Penn State Hershey Cancer Institute since the availability of novel agents (2006-2011). Twelve patients had primary PCL (pPCL), and 5 secondary PCL (sPCL). PCL was associated with aggressive clinicobiological features, such as high-risk cytogenetics, elevated serum beta-2-microglobulin and lactate dehydrogenase, International Staging System stage III, and rapid relapse after therapy. With the use of thalidomide, lenalidomide, and bortezomib in 53%, 53%, and 88% patients, respectively, median overall survival (OS) was 18 months in the whole group (95% confidence interval, 11-21 months), and 21 and 4 months in pPCL and sPCL, respectively (P=0.015). OS was inferior to that of 313 consecutive patients with multiple myeloma (MM) treated in the same period, even when compared with a subset of 47 MM with high-risk cytogenetics. Although our data are limited by the small sample size, we conclude that novel agents may modestly improve survival in patients with PCL, when compared to historical controls. Novel therapies do not seem to overcome the negative prognosis of PCL as compared with MM.

  4. Differences in clinical presentation between bipolar I and II disorders in the early stages of bipolar disorder: A naturalistic study.

    Science.gov (United States)

    Vinberg, Maj; Mikkelsen, Rie Lambaek; Kirkegaard, Thomas; Christensen, Ellen Margrethe; Kessing, Lars Vedel

    2017-01-15

    In a naturalistic clinical study of patients in the early stages of bipolar disorders the aim was to assess differences between patients with bipolar I (BD I) and bipolar II (BD II) disorders on clinical characteristics including affective symptoms, subjective cognitive complaints, functional level, the presence of comorbid personality disorders and coping strategies. Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Disorders. Clinical symptoms were rated with the Young Mania Rating Scale and the Hamilton Depression Rating Scale, and functional status using the Functional Assessment Short Test. Cognitive complaints were assessed using the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, the presence of comorbid personality disorders using the Standardized Assessment of Personality - Abbreviated Scale and coping style using the Coping Inventory for Stressful Situations. In total, 344 patients were included (BD I (n=163) and BD II (n=181). Patients with BD II presented with significantly more depressive symptoms, more cognitive complaints, lower overall functioning, and a higher prevalence of comorbid personality disorders. Finally, they exhibited a trend towards using less adaptive coping styles. It cannot be omitted that some patients may have progressed from BD II to BD I. Most measures were based on patient self report. Overall, BD II was associated with a higher disease burden. Clinically, it is important to differentiate BD II from BD I and research wise, there is a need for tailoring and testing specific interventions towards BD II. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Impregnation of chelating agent 3,3-bis-N,N bis-(carboxymethylaminomethyl-o-cresolsulfonephthalein in biopolymer chitosan: adsorption equilibrium of Cu(II in aqueous medium

    Directory of Open Access Journals (Sweden)

    Luciano Vitali

    2006-06-01

    Full Text Available The aim of this study was to impregnate the chelating agent 3,3-bis-N,N,bis-(carboxymethylaminomethyl-o-cresolsulfonephthalein in chitosan and to investigate the adsorption of Cu(II ions. The chemical modification was confirmed by FTIR spectrometry, thermogravimetric analysis (TGA and energy dispersive x-ray spectroscopy (EDX. The adsorption studies were carried out with Cu(II ions in a batch process and were shown to be dependent on pH. The adsorption kinetics was tested using three models: pseudo first-order, pseudo second order and intraparticle diffusion. The experimental kinetics data were best fitted with the pseudo second-order model (R² = 0.999, which provided a rate constant, k2, of 1.21 x 10-3 g mg-1 min-1. The adsorption rate depended on the concentration of Cu(II ions on the adsorbent surface and on the quantity of Cu(II ions adsorbed at equilibrium. The Langmuir isotherm model provided the best fit for the equilibrium data in the concentration range investigated, with the maximum adsorption capacity being 81.0 mg of Cu(II per gram of adsorbent, as obtained from the linear equation of the isotherm. Desorption tests revealed that around 90% of the adsorbed metal was removed, using EDTA solution as the eluent. This result suggests that the polymeric matrix can be reused.

  6. Using AGREE II to Evaluate the Quality of Traditional Medicine Clinical Practice Guidelines in China.

    Science.gov (United States)

    Deng, Wei; Li, Le; Wang, Zixia; Chang, Xiaonan; Li, Rui; Fang, Ziye; Wei, Dang; Yao, Liang; Wang, Xiaoqin; Wang, Qi; An, Guanghui

    2016-03-15

    To evaluate/assess the quality of the Clinical Practice Guidelines (CPGs) of traditional medicine in China. We systematically searched the literature databases WanFang Data, VIP, CNKI and CBM for studies published between 1978 and 2012 to identify and select CPGs of traditional medicine. We used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument to evaluate these guidelines. A total of 75 guidelines were included, of which 46 guidelines (62%) were on Traditional Chinese Medicine, 19 (25%) on Chinese Integrated Medicine, and 10 (13%) on Uyghur Medicine. Most traditional medicine CPGs published in domestic journals scored medicine. In each domain of AGREE II, traditional Medicine CPGs performed clearly better than international CPGs. The same trend was seen in guidelines of Modern Medicine. An increasing amount of CPGs are being published, but their quality is low. Referring to the key points of international guidelines development, supervision through AGREE II, cooperating with international groups and exploring the strategy of guideline development could improve the quality of CPGs on traditional medicine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Clinical Results of Flexor Tendon Repair in Zone II Using a six Strand Double Loop Technique.

    Science.gov (United States)

    Savvidou, Christiana; Tsai, Tsu-Min

    2015-06-01

    The purpose of this study is to report the clinical results after repair of flexor tendon zone II injuries utilizing a 6-strand double-loop technique and early post-operative active rehabilitation. We retrospectively reviewed 22 patients involving 51 cases with zone II flexor tendon repair using a six strand double loop technique from September 1996 to December 2012. Most common mechanism of injuries was sharp lacerations (86.5 %). Tendon injuries occurred equally in manual and non-manual workers and were work-related in 33 % of the cases. The Strickland score for active range of motion (ROM) postoperatively was excellent and good in the majority of the cases (81 %). The rupture rate was 1.9 %. The six strand double loop technique for Zone II flexor tendon repair leads to good and excellent motion in the majority of patients and low re- rupture rate. It is clinically effective and allows for early postoperative active rehabilitation.

  8. Two-year clinical evaluation of IPS Empress II ceramic onlays/inlays.

    Science.gov (United States)

    Tagtekin, D A; Ozyöney, G; Yanikoglu, F

    2009-01-01

    The stronger the ceramic material, the longer the restoration stays in the mouth. The current study evaluated the two-year clinical performance of a strong ceramic system, IPS Empress II, with increased strength on onlay/inlay restorations of molars. Teeth from 35 patients, including three premolars and 32 molars, were prepared for 28 onlay and seven inlay restorations with IPS Empress II ceramics. The restorations were cemented with a highly viscous, dual-curing luting composite cement (Bifix) and evaluated by two examiners using USPHS criteria at baseline (one week following insertion), six months, one year and two years. The baseline scores and recalls were assessed by Wilcoxon signed rank test. Statistically significant marginal discoloration at the Bravo level was found at the 12- and 24-month recalls (p=0.046). One debonding was statistically insignificant. No changes were observed with respect to anamnesis, such as any symptom from the TMJ or masticatory muscles. No restorations were replaced due to hypersensitivity or were missing at the two-year evaluation. Any wear on the restoration, antagonist tooth or any changes of proximal contacts were not observed. IPS Empress II Ceramics were found to be appropriate as onlay/inlay restorations for clinical use under the conditions of the current study.

  9. Evaluation of three topical anaesthetic agents against pain : A clinical study

    Directory of Open Access Journals (Sweden)

    Nayak R

    2006-01-01

    Full Text Available AIM : To compare pain responses of children during local anaesthetic infiltration at bilateral buccal sites prepared with topical application of EMLA 5% cream, benzocaine 18% gel or lignocaine 5% ointment and also to find out the rapidity of onset of action of these agents. METHODS : 60 healthy children aged 6 to 12 years old, received bilateral buccal infiltration following application of topical anaesthetic agents applied in a double blind design. Pain responses were compared based on subject self report using visual analogue scale (VAS and operator assessment using Sound -Eye -Motor (SEM scale. RESULTS : Benzocaine gel had the rapidest onset of action. EMLA 5% cream proved to be superior in pain reduction compared to benzocaine and lignocaine. Taste acceptance was better with benzocaine gel. Further studies are required for EMLA cream with an improved formulation more suitable for mucosal application before its routine use in dentistry.

  10. [Clinical significance of drug resistance-associated mutations in treatment of hepatitis C with direct-acting antiviral agents].

    Science.gov (United States)

    Li, Z; Chen, Z W; Ren, H; Hu, P

    2017-03-20

    Direct-acting antiviral agents (DAAs) achieve a high sustained virologic response rate in the treatment of chronic hepatitis C virus infection. However, drug resistance-associated mutations play an important role in treatment failure and have attracted more and more attention. This article elaborates on the clinical significance of drug resistance-associated mutations from the aspects of their definition, association with genotype, known drug resistance-associated mutations and their prevalence rates, the impact of drug resistance-associated mutations on treatment naive and treatment-experienced patients, and the role of clinical detection, in order to provide a reference for clinical regimens with DAAs and help to achieve higher sustained virologic response rates.

  11. Multislice CT cholangiography without biliary contrast agent: technique and initial clinical results in the assessment of patients with biliary obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Zandrino, F.; Benzi, L.; Ferretti, M.L.; Ferrando, R.; Reggiani, G.; Musante, F. [Department of Radiology, Azienda Ospedaliera ' ' SS Antonio e Biagio e C. Arrigo' ' , Alessandria (Italy)

    2002-05-01

    Our objective was to describe our technique for multislice CT cholangiography without cholangiographic contrast agent, and to present our preliminary clinical results. Thirty-seven patients with suspected biliary obstruction were studied. A multislice CT unit was used with the following technical parameters: 2.5-mm collimation; 7.5-mm/s table speed; pitch 6; 0.8-s rotation time; 300 mA; 120 kVp; 18- to 24-s scan time; scan volume ranging from the hepatic dome to below the pancreatic head; 70-s delay after injection of 150 ml of iodinated contrast agent at 4 ml/s. No biliary contrast material was given; oral iodinated contrast agent was administered to opacify bowel loops. Axial, multiplanar reformatted, and minimum intensity projection images were evaluated. The CT findings were compared with the gold standard techniques: endoscopic retrograde cholangiography (ERCP) in 30 patients, percutaneous transhepatic cholangiography in 5, and intraoperative cholangiography in 2. In 5 patients with ampullary lesions biopsy was made during ERCP, 9 underwent surgery, and 11 US-guided fine-needle aspiration. Bile ducts appeared hypodense within the surrounding enhanced structures. Regarding the site of obstruction, agreement between multislice CT and conventional cholangiography was observed in all cases. One patient presented negative findings on both CT and ERCP. In 31 of 36 (86%) patients, multislice CT cholangiography without cholangiographic contrast agent correctly assessed the cause of bile duct obstruction. Multislice CT cholangiography without cholangiographic contrast agent seems to be a promising diagnostic tool in the assessment of patients with bile duct obstruction. (orig.)

  12. Multislice CT cholangiography without biliary contrast agent: technique and initial clinical results in the assessment of patients with biliary obstruction

    International Nuclear Information System (INIS)

    Zandrino, F.; Benzi, L.; Ferretti, M.L.; Ferrando, R.; Reggiani, G.; Musante, F.

    2002-01-01

    Our objective was to describe our technique for multislice CT cholangiography without cholangiographic contrast agent, and to present our preliminary clinical results. Thirty-seven patients with suspected biliary obstruction were studied. A multislice CT unit was used with the following technical parameters: 2.5-mm collimation; 7.5-mm/s table speed; pitch 6; 0.8-s rotation time; 300 mA; 120 kVp; 18- to 24-s scan time; scan volume ranging from the hepatic dome to below the pancreatic head; 70-s delay after injection of 150 ml of iodinated contrast agent at 4 ml/s. No biliary contrast material was given; oral iodinated contrast agent was administered to opacify bowel loops. Axial, multiplanar reformatted, and minimum intensity projection images were evaluated. The CT findings were compared with the gold standard techniques: endoscopic retrograde cholangiography (ERCP) in 30 patients, percutaneous transhepatic cholangiography in 5, and intraoperative cholangiography in 2. In 5 patients with ampullary lesions biopsy was made during ERCP, 9 underwent surgery, and 11 US-guided fine-needle aspiration. Bile ducts appeared hypodense within the surrounding enhanced structures. Regarding the site of obstruction, agreement between multislice CT and conventional cholangiography was observed in all cases. One patient presented negative findings on both CT and ERCP. In 31 of 36 (86%) patients, multislice CT cholangiography without cholangiographic contrast agent correctly assessed the cause of bile duct obstruction. Multislice CT cholangiography without cholangiographic contrast agent seems to be a promising diagnostic tool in the assessment of patients with bile duct obstruction. (orig.)

  13. Clinical and Radiological Findings of Autosomal Dominant Osteopetrosis Type II: A Case Report

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    Priyanka Kant

    2013-01-01

    Full Text Available Osteopetrosis is a rare inherited genetic disease characterized by sclerosis of the skeleton caused by the absence or malfunction of osteoclasts. Three distinct forms of the disease have been recognized, autosomal dominant osteopetrosis being the most common. Autosomal dominant osteopetrosis exhibits a heterogeneous trait with milder symptoms, often at later childhood or adulthood. The aim of this case report is to present the clinical and radiographic features of a 35-year-old female patient with autosomal dominant osteopetrosis type II who exhibited features of chronic generalised periodontitis, and the radiographs revealed generalised osteosclerosis and hallmark radiographic features of ADO type II, that is, “bone-within-bone appearance” and “Erlenmeyer-flask deformity.”

  14. [Alkylating agents].

    Science.gov (United States)

    Pourquier, Philippe

    2011-11-01

    With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

  15. Dendritic chelating agents. 1. Cu(II) binding to ethylene diamine core poly (amidoamine) denderimers in aqueous solutions

    International Nuclear Information System (INIS)

    Diallo, Mamadou S.; Christie, Simone; Swaminathan, Pirabalini; Balogh, Lajos; Shi, XIANGYANG; Um, Wooyong; Papelis, Charalambos; Goddard, William A.; Johnson, J. H.

    2004-01-01

    The overall results of the proton and metal ion binding measurements suggest that the uptake of Cu(II) by EDA core PAMAM dendrimers involves both the dendrimer tertiary amine and terminal groups. However, the extents of protonation of these groups control the ability of the dentrimers to bind Cu(II). Analysis of the EXAFS spectra suggests that Cu(II) forms octahedral complexes involving the tertiary amine groups of Gx-NH2 EDA core PAMAM dendrimers at pH 7.0. The central Cu(II) metal ion of each of these complexes appears to be coordinated to 2-4 dendrimer tertiary amine groups located in the equatorial plane and 2 axial water molecules. Finally, we combine the results of our experiments with literature data to formulate and evaluate a phenomenological model of Cu(II) uptake by Gx-NH2 PAMAM dendrimers in aqueous solutions. At low metal ion-dendrimer loadings, the model provides a good fit of the measured extent of binding of Cu(II) in aqueous solutions of G4-NH2 PAMAM dendrimers at pH 7.0

  16. Pre-clinical evaluation of a nanoparticle-based blood-pool contrast agent for MR imaging of the placenta.

    Science.gov (United States)

    Ghaghada, Ketan B; Starosolski, Zbigniew A; Bhayana, Saakshi; Stupin, Igor; Patel, Chandreshkumar V; Bhavane, Rohan C; Gao, Haijun; Bednov, Andrey; Yallampalli, Chandrasekhar; Belfort, Michael; George, Verghese; Annapragada, Ananth V

    2017-09-01

    Non-invasive 3D imaging that enables clear visualization of placental margins is of interest in the accurate diagnosis of placental pathologies. This study investigated if contrast-enhanced MRI performed using a liposomal gadolinium blood-pool contrast agent (liposomal-Gd) enables clear visualization of the placental margins and the placental-myometrial interface (retroplacental space). Non-contrast MRI and contrast-enhanced MRI using a clinically approved conventional contrast agent were used as comparators. Studies were performed in pregnant rats under an approved protocol. MRI was performed at 1T using a permanent magnet small animal scanner. Pre-contrast and post-liposomal-Gd contrast images were acquired using T1-weighted and T2-weighted sequences. Dynamic Contrast enhanced MRI (DCE-MRI) was performed using gadoterate meglumine (Gd-DOTA, Dotarem ® ). Visualization of the retroplacental clear space, a marker of normal placentation, was judged by a trained radiologist. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated for both single and averaged acquisitions. Images were reviewed by a radiologist and scored for the visualization of placental features. Contrast-enhanced CT (CE-CT) imaging using a liposomal CT agent was performed for confirmation of the MR findings. Transplacental transport of liposomal-Gd was evaluated by post-mortem elemental analysis of tissues. Ex-vivo studies in perfused human placentae from normal, GDM, and IUGR pregnancies evaluated the transport of liposomal agent across the human placental barrier. Post-contrast T1w images acquired with liposomal-Gd demonstrated significantly higher SNR (p = 0.0002) in the placenta compared to pre-contrast images (28.0 ± 4.7 vs. 6.9 ± 1.8). No significant differences (p = 0.39) were noted between SNR in pre-contrast and post-contrast liposomal-Gd images of the amniotic fluid, indicating absence of transplacental passage of the agent. The placental margins were

  17. Differences in clinical presentation between bipolar I and II disorders in the early stages of bipolar disorder

    DEFF Research Database (Denmark)

    Vinberg, Maj; Mikkelsen, Rie Lambaek; Kirkegaard, Thomas

    2017-01-01

    Aim In a naturalistic clinical study of patients in the early stages of bipolar disorders the aim was to assess differences between patients with bipolar I (BD I) and bipolar II (BD II) disorders on clinical characteristics including affective symptoms, subjective cognitive complaints, functional...... level, the presence of comorbid personality disorders and coping strategies. Methods Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Disorders. Clinical symptoms were rated with the Young Mania Rating Scale and the Hamilton Depression Rating Scale, and functional status using...... Inventory for Stressful Situations. Results In total, 344 patients were included (BD I (n=163) and BD II (n=181). Patients with BD II presented with significantly more depressive symptoms, more cognitive complaints, lower overall functioning, and a higher prevalence of comorbid personality disorders...

  18. Effects of some chelating agents on the uptake and distribution of 54Mn(II) in the brown trout (Salmo trutta)

    International Nuclear Information System (INIS)

    Rouleau, C.; Tjaelve, H.; Pelletier, E.; Gottofrey, J.

    1994-01-01

    The effects of humic acids, which are natural metal-complexing compounds, and potassium ethylxanthate, sodium diethyldithiophosphate, sodium dimethyldithicarbamate, which are sulphur-containing man-made chelating agents, on the uptake and tissue distribution of 54 Mn(II) were studied in brown trout (Salmo trutta). Fish were exposed for 7 days to 0.1 μg Mn(II)x. -2 as NmCl 2 (l μCia 54 Mnxl -1 ) with or without chelat agents. Examination of the partition of Mn between octanol and a Tris-HCl buffer in the presence of these compounds was also performed. Humic acids had only small effects on Mn uptake and distribution in trout, probably because of the low stability of Mn-humate complexes. Partition of Mn in the presence of potassium ethylxanthate, sodium diethyldithiophosphate, sodium dimethyldithiocarbamate, and sodium diethyldithiocarbamate between octanol and Tris-HCl buffer showed formation of lipophilic complex with the latter two compounds, but not with the former. However, these four chelating agents all decreased Mn uptake in the trout by 40-45%. These substances also changed the distribution of Mn within the fish, with a higher proportion of the metal being present in some visceral organs and a smaller proportion being localized in some non-parenchymateous tissues, such as skin, fins and bones. The mechanisms underlying these effects are not known. however, the interaction of chelating agents with the Mn, although weak, may have partially withdrawn the metal from the uptake process inthe gills. The redistribution of Mn in the fish may be due to the binding of the metal to complexing compounds which have reached the intestinal lumen. Previous studies with other metals have shown increased or unchanged metal levels in tissues of fish at exposure together with potasium ethylxanthate, sodium diethyldithiophosphate, sodium dimethyldithiocarbamate, and sodium diethyldithiocarbamate, but decreased metal levels have not been observed before. (au) (37 refs.)

  19. CHARACTERIZATION OF SORBENT PRODUCED THROUGH IMMOBILIZATION OF HUMIC ACID ON CHITOSAN USING GLUTARALDEHYDE AS CROSS-LINKING AGENT AND Pb(II ION AS ACTIVE SITE PROTECTOR

    Directory of Open Access Journals (Sweden)

    Uripto Trisno Santoso

    2010-12-01

    Full Text Available Sorbent produced through immobilization of humic acid (HA on chitosan using glutaraldehyde as cross-linking agent and Pb(II ions as active site protector has been characterized. Active sorption site of HA was protected by reacting HA with Pb(II ion, and the protected-HA was then activated by glutaraldehyde, crosslinked onto chitosan, and deprotected by 0.1 M disodium ethylenediamine tetra-acetic acid (Na2EDTA. The protected-crosslinking method enhanced the content of immobilized-HA and its chemical stability. Based on the FTIR spectra, crosslinking of HA on chitosan probably occurred through a chemical reaction. The sorption capacity of sorbent still remains unchanged after the second regeneration, but some of HA start to be soluble. The latter shows that cross-linking reaction between HA and chitosan is through formation an unstable product. The effectiveness of sorbent regeneration can also be identified by the XRD pattern.

  20. Current methods of the analysis of immunosuppressive agents in clinical materials: A review.

    Science.gov (United States)

    Mika, Adriana; Stepnowski, Piotr

    2016-08-05

    More than 100000 solid organ transplantations are performed every year worldwide. Calcineurin (cyclosporine A, tacrolimus), serine/threonine kinase (sirolimus, everolimus) and inosine monophosphate dehydrogenase inhibitor (mycophenolate mofetil), are the most common drugs used as immunosuppressive agents after solid organ transplantation. Immunosuppressive therapy, although necessary after transplantation, is associated with many adverse consequences, including the formation of secondary metabolites of drugs and the induction of their side effects. Calcineurin inhibitors are associated with nephrotoxicity, cardiotoxicity and neurotoxicity; moreover, they increase the risk of many diseases after transplantation. The review presents a study of the movement of drugs in the body, including the processes of absorption, distribution, localisation in tissues, biotransformation and excretion, and also their accompanying side effects. Therefore, there is a necessity to monitor immunosuppressants, especially because these drugs are characterised by narrow therapeutic ranges. Their incorrect concentrations in a patient's blood could result in transplant rejection or in the accumulation of toxic effects. Immunosuppressive pharmaceuticals are macrolide lactones, peptides, and high molecular weight molecules that can be metabolised to several metabolites. Therefore the two main analytical methods used for their determination are high performance liquid chromatography with various detection methods and immunoassay methods. Despite the rapid development of new analytical methods of analysing immunosuppressive agents, the application of the latest generation of detectors and increasing sensitivity of such methods, there is still a great demand for the development of highly selective, sensitive, specific, rapid and relatively simple methods of immunosuppressive drugs analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Magnetic resonance imaging using paramagnetic contrast agents in the clinical evaluation of myocardial infarction. Chapter 15

    International Nuclear Information System (INIS)

    Dijkman, P.R.M. van; Wall, E.E. van der

    1992-01-01

    MRI is noninvasive and specific method for production of high resolution tomographic images in blocks of 3D information. Apart from scintigraphic techniques and computed tomography for evaluation of myocardial ischemia and infarcts, MRI has emerged as a new diagnostic technique to study the extent of anatomical and functional abnormalities in patients with coronary artery disease. Conventional noncontrast MRI can identify acute-infarcted myocardial areas, although the difficulty in identifying myocardial ischemia and infarct with noncontrast MRI suggests a potential role for contrast enhanced MRI. Use of the paramagnetic contrast agent gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) improves depiction of infarcted myocardium on T1-weighted spin -echo MR images that are obtained soon after acute myocardial infarction. This is of particular interest for the estimation of myocardial infarct size. Furthermore, ultrafast subsecond imaging, in combination with Gd-DTPA, offers the potential to analyze cardiac first pass and myocardial perfusion. The development of nontoxic paramagnetic contrast agents which are selectively taken up by viable myocardium would be helpful in assessing the presence of ischemic/infarcted myocardium salvage by MRI following reperfusion. (author). 58 refs., 6 figs

  2. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents.

    Science.gov (United States)

    Esteller, M; Garcia-Foncillas, J; Andion, E; Goodman, S N; Hidalgo, O F; Vanaclocha, V; Baylin, S B; Herman, J G

    2000-11-09

    The DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents. MGMT activity is controlled by a promoter; methylation of the promoter silences the gene in cancer, and the cells no longer produce MGMT. We examined gliomas to determine whether methylation of the MGMT promoter is related to the responsiveness of the tumor to alkylating agents. We analyzed the MGMT promoter in tumor DNA by a methylation-specific polymerase-chain-reaction assay. The gliomas were obtained from patients who had been treated with carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, or BCNU). The molecular data were correlated with the clinical outcome. The MGMT promoter was methylated in gliomas from 19 of 47 patients (40 percent). This finding was associated with regression of the tumor and prolonged overall and disease-free survival. It was an independent and stronger prognostic factor than age, stage, tumor grade, or performance status. Methylation of the MGMT promoter in gliomas is a useful predictor of the responsiveness of the tumors to alkylating agents.

  3. EFFECTIVITY OF TWO BLEACHING AGENT OF 10% CARBAMIDE PEROXIDE WITH AND WITHOUT POTASSIUM NITRATE-FLUORIDE (CLINICAL STUDY

    Directory of Open Access Journals (Sweden)

    Ayus Lusiyanti

    2015-06-01

    Full Text Available Tooth bleaching has become a popular treatment for esthetic improvement in dentistry. There are several 10% carbamide peroxide bleaching agents that are available in Indonesia which contained potassium nitrate-fluoride or without potassium nitrate-fluoride. However, there was no clinical report about these products in Indonesia. This study was conducted to compare the effectiveness of two bleaching and sensitivity of tooth and gingiva. Sixty-four participants were divided into 2 groups. The first group was treated with bleaching agent that contained potassium nitrate-fluoride (Opalescence PF, Ultradent. Bleaching treatment was done for 6-8 hours per night over a 2 week-period. Evaluations were performed at the baseline and at 3, 7, 14 day afterwards. Color change was measured using a value-ordered Vita classic shade guide; tooth and gingival sensitivity were examine using Electric Pulp Tester, Gingival Index and patient log. The results showed that there were no statistical differences in degree of color change between the two products. The mean color change after 2 weeks was 7-8 tabs lighter than baseline. Also there was no statistical difference in tooth and gingival sensitivity between the products. It can be concluded that 10% carbamide peroxide containing potassium nitrate-fluoride has the same effectiveness compared to other agent without potassium nitrate-fluoride for tooth color change and tooth and gingival sensitivity.

  4. MODELING OF THE HEAT PUMP STATION CONTROLABLE LOOP OF AN INTERMEDIATE HEAT-TRANSFER AGENT (Part II

    Directory of Open Access Journals (Sweden)

    Sit M.L.

    2011-08-01

    Full Text Available It is studied the model of the heat pump station controllable loop of an intermediate heat-transfer agent for the use in wineries. There are demonstrated transients after the disturbing action of the temperature on the input of cooling jacket of the fermentation stirred tank. There are compared different control laws of the object.

  5. Continuity Between DSM-5 Section II and III Personality Disorders in a Dutch Clinical Sample.

    Science.gov (United States)

    Orbons, Irene M J; Rossi, Gina; Verheul, Roel; Schoutrop, Mirjam J A; Derksen, Jan L L; Segal, Daniel L; van Alphen, Sebastiaan P J

    2018-05-14

    The goal of this study was to evaluate the continuity across the Section II personality disorders (PDs) and the proposed Section III model of PDs in the Diagnostic and Statistical Manual of Mental Disorders (5th ed. [DSM-5]; American Psychiatric Association, 2013a ). More specifically, we analyzed association between the DSM-5 Section III pathological trait facets and Section II PDs among 110 Dutch adults (M age = 35.8 years, range = 19-60 years) receiving mental health care. We administered the Structured Clinical Interview for DSM-IV Axis II Disorders to all participants. Participants also completed the self-report Personality Inventory for DSM-5 (PID-5) as a measure of pathological trait facets. The distributions underlying the dependent variable were modeled as criterion counts, using negative binomial regression. The results provided some support for the validity of the PID-5 and the DSM-5 Section III Alternative Model, although analyses did not show a perfect match. Both at the trait level and the domain level, analyses showed mixed evidence of significant relationships between the PID-5 trait facets and domains with the traditional DSM-IV PDs.

  6. Physical activity in type II Diabetes Mellitus, an effective therapeutic element: review of the clinical impact

    Directory of Open Access Journals (Sweden)

    Pedro Iván Arias-Vázquez

    2015-07-01

    Full Text Available A review was conducted in databases (PubMed, PEDro of type studies clinical trial, cohort study, systematic reviews, meta-analysis and clinical practice guidelines based on evidence they have studied the benefits of physical activity in the prevention , treatment and decreased risk of complications and death in patients with Type II Diabetes Mellitus. Realization regular physical activity is associated with a decreased risk of developing Diabetes Mellitus; likewise was associated with decrease in glycated hemoglobin percentage A1C values. Diabetic patients undergoing high levels of physical activity had decreased risk of complications and death from cardiovascular disease and all causes. At present the scientific evidence on the impact of physical activity in the prevention and treatment of Diabetes Mellitus is solid, so it must be emphasized promoting physical activity as a fundamental part of the therapeutic regimens for this disease.

  7. Proposed quality control guidelines for National Committee for Clinical Laboratory Standards Susceptibility Tests using the veterinary antimicrobial agent tiamulin.

    Science.gov (United States)

    Pfaller, M A; Jones, R N; Walter, D H

    2001-01-01

    Quality control guidelines for standardized antimicrobial susceptibility test methods are critical for the continuing accuracy of these clinical tests. In this report, quality control limits were proposed for the veterinary antimicrobial agent tiamulin with minimum inhibitory concentration (MIC) ranges of three or four log(2) dilution steps in two different medium formulations. Disk diffusion zone diameter ranges were proposed for tiamulin tested against Actinobacillus pleuropneumoniae ATCC 27090 (12-18 mm) and Staphylococcus aureus ATCC 25923 (25-32 mm). The data from eight participating laboratories produced 100% of results within proposed MIC limits (8-32 microg/mL), and 95.8-97.0% of zones were found within suggested zone diameter QC guidelines. These proposed QC ranges should be validated by in-use results from veterinary clinical laboratories.

  8. [Verrucous pastern dermatitis syndrome in heavy draught horses. Part II: Clinical findings].

    Science.gov (United States)

    Geburek, F; Deegen, E; Hewicker-Trautwein, M; Ohnesorge, B

    2005-07-01

    In the present field study the skin of the feet of 37 heavy draught horses of different breeds showing verrucous pastern dermatitis was examined clinically. Included were the degree of severity of the disease and the prevalence of anatomically normal structures associated with the skin: fetlock tufts of hair ("feathering"), ergots, chestnuts, bulges in the pastern region, cannon circumference. Each horse was examined for Chorioptes sp. skin mites. Information was also collected on the development of the skin alterations and housing conditions and feeding. These individual data were correlated with the clinical degree of severity of verrucous pastern dermatitis, which was evaluated using a numerical code (scoring system). In addition, punch biopsies were taken from the diseased skin of the feet and from healthy skin of the neck for comparative patho-histological examination (see Part III). Verrucous pastern dermatitis is a chronic disease which can be divided into four groups: scaling (group I), hyperkeratotic and hyperplastic plaque-like lesions (group II), tuberous skin masses (group III), and verrucous skin lesions with rugged surfaces (group IV). No correlation was found between the clinical degree of severity of the skin lesions and sex, breed, amount of work, use of stallions for breeding, grooming condition of the hair, white markings in the foot region, or Chorioptes sp. infestation. In regard to feeding it was found that the amount of maize and oats fed had some influence on the clinical degree of severity. Statistical analysis revealed a significant correlation between the clinical degree of severity and the age, the grooming condition of the hooves, and the mean cannon circumference. The prevalence of fetlock tufts of hair, chestnuts, ergots, and anatomically normal bulges in the pastern region also increased significantly with the clinical degree of severity. Furthermore the study revealed that the clinical degree of severity depended on the hygienic

  9. Closure of the patent ductus arteriosus with the Amplatzer Duct Occluder II: a clinical experience.

    Science.gov (United States)

    Karagöz, Tevfik; Akin, Alper; Ertuğrul, Ilker; Aykan, Hayrettin Hakan; Alehan, Dursun; Ozer, Sema; Ozkutlu, Süheyla

    2012-12-01

    The aim of our study was to share our clinical experience on cases with patent ductus arteriosus treated with the Amplatzer Duct Occluder II. Between 2008 and 2012, 26 of 31 patients with patent ductus arteriosus underwent successful transcatheter closure of patent ductus arteriosus using the Amplatzer Duct Occluder II. Mean age was 3.3 years and mean weight was 15.7 kilograms. The presence of a residual shunt, left pulmonary artery or aortic obstruction was explored by administering contrast material during the procedure. The patients were discharged 24 hours after the procedure. The procedure was successful in 26 of 31 patients and failed in five patients. According to the Krichenko classification, 26 patients had type A, one patient had type B and 4 patients had type C ductus. The mean narrowest ductus diameter was 3.2 mm and the mean ductus length was 6.7 mm. Complete angiographic occlusion occurred immediately after the procedure in 22 out of 26 patients in whom the ductus was closed successfully with the Amplatzer Duct Occluder II. Complete occlusion was achieved in the remaining patients with residual shunt one month after the procedure. The procedure was preceded by closure with an Amplatzer Duct Occluder I in two patients and an Amplatzer Vascular Plug I in one patient. Amplatzer Duct Occluder II is highly effective in transcatheter closure of patent ductus arteriosus. We think that an alternative closure device and alternative techniques can be attempted in patients with type C ductus. The success rate could increase with accumulating experience.

  10. Genetic and structural study of DNA-directed RNA polymerase II of Trypanosoma brucei, towards the designing of novel antiparasitic agents

    Directory of Open Access Journals (Sweden)

    Louis Papageorgiou

    2017-03-01

    Full Text Available Trypanosoma brucei brucei (TBB belongs to the unicellular parasitic protozoa organisms, specifically to the Trypanosoma genus of the Trypanosomatidae class. A variety of different vertebrate species can be infected by TBB, including humans and animals. Under particular conditions, the TBB can be hosted by wild and domestic animals; therefore, an important reservoir of infection always remains available to transmit through tsetse flies. Although the TBB parasite is one of the leading causes of death in the most underdeveloped countries, to date there is neither vaccination available nor any drug against TBB infection. The subunit RPB1 of the TBB DNA-directed RNA polymerase II (DdRpII constitutes an ideal target for the design of novel inhibitors, since it is instrumental role is vital for the parasite’s survival, proliferation, and transmission. A major goal of the described study is to provide insights for novel anti-TBB agents via a state-of-the-art drug discovery approach of the TBB DdRpII RPB1. In an attempt to understand the function and action mechanisms of this parasite enzyme related to its molecular structure, an in-depth evolutionary study has been conducted in parallel to the in silico molecular designing of the 3D enzyme model, based on state-of-the-art comparative modelling and molecular dynamics techniques. Based on the evolutionary studies results nine new invariant, first-time reported, highly conserved regions have been identified within the DdRpII family enzymes. Consequently, those patches have been examined both at the sequence and structural level and have been evaluated in regard to their pharmacological targeting appropriateness. Finally, the pharmacophore elucidation study enabled us to virtually in silico screen hundreds of compounds and evaluate their interaction capabilities with the enzyme. It was found that a series of chlorine-rich set of compounds were the optimal inhibitors for the TBB DdRpII RPB1 enzyme. All

  11. A phase 2 clinical study of 99mTc-MAG3 injectable, a dynamic renal imaging agent

    International Nuclear Information System (INIS)

    Torizuka, Kanji; Yamamoto, Kazutaka; Nishibuchi, Shigeo; Ishibashi, Akira; Ikekubo, Katsuji.

    1993-01-01

    A phase 2 clinical study of 99m Tc-mercapto acetyl glycylglycylglycine ( 99m Tc-MAG3) injectable, a new dynamic renal imaging agent, was performed in 110 patients with renal and/or urinary disorders to evaluate the safety, efficacy and optimal dose of this agent. Neither adverse reactions nor abnormal laboratory findings due to intravenous administration of 99m Tc-MAG3 were observed. The investigators evaluated the clinical efficacy of 99m Tc-MAG3 was to be effective in 96 of 97 cases. Among the doses of 92.5 MBq, 370 MBq and 555 MBq, the dose of 92.5 MBq was not large enough to provide adequate-quality blood flow images or reliable information for evaluation of the renal blood flow. It was concluded that the optimal dose range of 99m Tc-MAG3 was 185-555 MBq with 370 MBq as the standard dose. Also, we summarize that 555 MBq is especially recommendable when detailed blood flow information is required. These results indicate that 99m Tc-MAG3 injectable is useful for the diagnosis of renal and urinary disorders. (author)

  12. Clinical effects of Angelica dahurica dressing on patients with I-II phase pressure sores.

    Science.gov (United States)

    Gong, Fen; Niu, Junzhi; Pei, Xing

    2016-11-02

    Angelica dahurica is a well-known traditional Chinese Medicine (TCM), while little information is available about its effects on pressure sores. We aimed to investigate the clinical effect of Angelica dahurica on patients with I-II phase pressure sores, as well as the underlying mechanism. Patients (n = 98) with phase I and phase II pressure sores were enrolled and randomly assigned to control and treated groups. In addition to holistic nursing, patients in the control group received compound clotrimazole cream, while patients in the treated group received continuous 4 weeks of external application of Angelica dahurica dressing. Therapeutic effect was recorded, along with the levels of interleukin-8 (IL-8), epidermal growth factor (EGF), transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF). Besides, HaCaT cells were cultured with different concentrations of Angelica dahurica, and then cell viability, clone formation numbers, cell cycle, and levels of cyclin D1 and cyclin-dependent kinase (CDK) 2 were determined. The total effective rate in the treated group was significantly higher than in the control group. Levels of IL-8, EGF, TGF-β, and VEGF were statistically increased by Angelica dahurica. In addition, the cell viability and clone formation numbers were significantly upregulated by Angelica dahurica in a dose-dependent manner. Also, the percentage of cells in G0/G1 phase, and levels of cyclin D1 and CDK2 were significantly elevated. Our results suggest that Angelica dahurica may provide an effective clinical treatment for I-II phase pressure sores.

  13. Methodology of phase II clinical trials in metastatic elderly breast cancer: a literature review.

    Science.gov (United States)

    Cabarrou, B; Mourey, L; Dalenc, F; Balardy, L; Kanoun, D; Roché, H; Boher, J M; Rougé-Bugat, M E; Filleron, Thomas

    2017-08-01

    As the incidence of invasive breast cancer will increase with age, the number of elderly patients with a diagnosis metastatic breast cancer will also rise. But the use of cytotoxic drugs in elderly metastatic breast cancer patients is not systematic and is dreaded by medical oncologists. The need for prospective oncologic data from this population seems increasingly obvious. The main objective of this review is to investigate design and characteristics of phase II trials that assess activity and feasibility of chemotherapies in elderly advanced/metastatic breast cancer patients. An electronic search in PUBMED allowed us to retrieve articles published in English language on phase II trials in elderly metastatic breast cancer between January 2002 and May 2016. Sixteen publications were finally included in this review. The primary endpoint was a simple, a composite, and a co-primary endpoints in 11, three, and two studies, respectively. Efficacy was the primary objective in 15 studies: simple (n = 10), composite (n = 3), co-primary endpoints (n = 2). Composite or co-primary endpoints combined efficacy and toxicity. Thirteen studies used multistage designs. Only five studies evaluated the feasibility, i.e., to jointly assess efficacy and tolerance to treatment (toxicity, quality of life, etc) as primary endpoint. Development of elderly specific phase III clinical trials might be challenging, it therefore seems essential to conduct phase II clinical trials evaluating jointly efficacy and toxicity in a well-defined geriatric population. Use of multistage designs that take into account heterogeneity would allow to identify a subpopulation at interim analysis and to reduce the number of patients exposed to an inefficient or a toxic treatment regimen. It is crucial to evaluate new therapies (targeted therapies, immunotherapies) using adequate methodologies (Study design, endpoint).

  14. Indirect complexometric determination of mercury(II in synthetic alloys and complexes using ethanethiol as a selective masking agent

    Directory of Open Access Journals (Sweden)

    J. KARTHIKEYAN

    2006-03-01

    Full Text Available Acomplexometric method for the determination of mercury(II in presence of other metal ions, based on the selective masking action of ethanethiol towards mercury(II is described. Mercury(II present in a given sample solution is first complexed with an excess of EDTAand the unreacted EDTAis titrated against zinc sulphate solution at pH 5–6 (hexamine buffer using xylenol orange as the indicator. An excess of a 0.3 % solution of ethanethiol is then added to displace EDTA from the Hg(II–EDTA complex. The released EDTAis titrated with a standard zinc sulphate solution. Reproducible and accurate results are obtained for 4–85 mg of mercury(II with a relative error of less than ± 0.46 % and coefficient of variation of not more than 0.47 %. The effects of the presence of various ions were studied. The method can be used for the analysis of mercury in its synthetic alloy mixtures and also in complexes.

  15. Mitocans as anti-cancer agents targeting mitochondria: lessons from studies with vitamin E analogues, inhibitors of complex II

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Dyason, J.C.; Freeman, R.; Dong, L.F.; Procházka, L.; Wang, X. F.; Scheffler, I.; Ralph, S.J.

    2007-01-01

    Roč. 39, č. 1 (2007), s. 65-72 ISSN 0145-479X Institutional research plan: CEZ:AV0Z50520701; CEZ:AV0Z50520514 Keywords : mitocans * mitochondria * complex II Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.634, year: 2007

  16. SU-E-QI-21: Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Stereotactic Synchrotron Radiotherapy Clinical Trials

    Energy Technology Data Exchange (ETDEWEB)

    Obeid, L; Esteve, F; Adam, J [Grenoble Institut des Neurosciences, La Tronche, Isere (France); Tessier, A; Balosso, J [Centre Hospitalier Universitaire, La Tronche, Isere (France)

    2014-06-15

    Purpose: Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. In the present study, the reproducibility of iodine concentrations between the CT planning scan day (Day 0) and the treatment day (Day 10) was assessed in order to predict dose errors. Methods: For each of days 0 and 10, three patients received a biphasic intravenous injection of iodinated contrast agent (40 ml, 4 ml/s, followed by 160 ml, 0.5 ml/s) in order to ensure stable intra-tumoral amounts of iodine during the treatment. Two volumetric CT scans (before and after iodine injection) and a multi-slice dynamic CT of the brain were performed using conventional radiotherapy CT (Day 0) or quantitative synchrotron radiation CT (Day 10). A 3D rigid registration was processed between images. The absolute and relative differences of absolute iodine concentrations and their corresponding dose errors were evaluated in the GTV and PTV used for treatment planning. Results: The differences in iodine concentrations remained within the standard deviation limits. The 3D absolute differences followed a normal distribution centered at zero mg/ml with a variance (∼1 mg/ml) which is related to the image noise. Conclusion: The results suggest that dose errors depend only on the image noise. This study shows that stable amounts of iodine are achievable in brain metastasis for SSRT treatment in a 10 days interval.

  17. Growth/differentiation factor-5: a candidate therapeutic agent for periodontal regeneration? A review of pre-clinical data.

    Science.gov (United States)

    Moore, Yolanda R; Dickinson, Douglas P; Wikesjö, Ulf M E

    2010-03-01

    Therapeutic concepts involving the application of matrix, growth and differentiation factors have been advocated in support of periodontal wound healing/regeneration. Growth/differentiation factor-5 (GDF-5), a member of the bone morphogenetic protein family, represents one such factor. The purpose of this review is to provide a background of the therapeutic effects of GDF-5 expressed in various musculoskeletal settings using small and large animal platforms. A comprehensive literature search was conducted to identify all reports in the English language evaluating GDF-5 using the PubMed and Google search engines, and a manual search of the reference lists from the electronically retrieved reports. Two reviewers independently screened the titles and abstracts from a total of 69 reports, 22 of which were identified as pre-clinical (in vivo) evaluations of GDF-5. The full-length article of the 22 pre-clinical reports was then reviewed. Various applications including cranial and craniofacial bone formation, spine fusion, long bone fracture healing, cartilage, and tendon/ligament repair using a variety of small and large animal platforms evaluating GDF-5 as a therapeutic agent were identified. A majority of studies, using biomechanical, radiographic, and histological analysis, demonstrated significant dose-dependent effects of GDF-5. These include increased/enhanced local bone formation, fracture healing/repair, and cartilage and tendon/ligament formation. GDF-5 frequently was shown to accelerate wound maturation. Several studies demonstrated GDF-5 to be a realistic alternative to autograft bone. Studies using pre-clinical models and human histology suggest GDF-5 may also increase/enhance periodontal wound healing/regeneration. GDF-5 appears a promising therapeutic agent for periodontal wound healing/regeneration as GDF-5 supports/accelerates bone and tendon/ligament formation in several musculoskeletal settings including periodontal tissues.

  18. Curcumin as a clinically-promising anti-cancer agent: pharmacokinetics and drug interactions.

    Science.gov (United States)

    Adiwidjaja, Jeffry; McLachlan, Andrew J; Boddy, Alan V

    2017-09-01

    Curcumin has been extensively studied for its anti-cancer properties. While a diverse array of in vitro and preclinical research support the prospect of curcumin use as an anti-cancer therapeutic, most human studies have failed to meet the intended clinical expectation. Poor systemic availability of orally-administered curcumin may account for this disparity. Areas covered: This descriptive review aims to concisely summarise available clinical studies investigating curcumin pharmacokinetics when administered in different formulations. A critical analysis of pharmacokinetic- and pharmacodynamic-based interactions of curcumin with concomitantly administered drugs is also provided. Expert opinion: The encouraging clinical results of curcumin administration are currently limited to people with colorectal cancer, given that sufficient curcumin concentrations persist in colonic mucosa. Higher parent curcumin systemic exposure, which can be achieved by several newer formulations, has important implications for optimal treatment of cancers other than those in gastrointestinal tract. Curcumin-drug pharmacokinetic interactions are also almost exclusively in the enterocytes, owing to extensive first pass metabolism and poor curcumin bioavailability. Greater scope of these interactions, i.e. modulation of the systemic elimination of co-administered drugs, may be expected from more-bioavailable curcumin formulations. Further studies are still warranted, especially with newer formulations to support the inclusion of curcumin in cancer therapy regimens.

  19. Genotyping of the MTL loci and susceptibility to two antifungal agents of Candida glabrata clinical isolates

    Directory of Open Access Journals (Sweden)

    María Teresa Lavaniegos-Sobrino

    2009-08-01

    Full Text Available The opportunistic fungal pathogen Candida glabrata is the second most common isolate from bloodstream infections worldwide and is naturally less susceptible to the antifungal drug fluconazole than other Candida species. C. glabrata is a haploid yeast that contains three mating-type like loci (MTL, although no sexual cycle has been described. Strains containing both types of mating information at the MTL1 locus are found in clinical isolates, but it is thought that strains containing type a information are more common. Here we investigated if a particular combination of mating type information at each MTLlocus is more prevalent in clinical isolates from hospitalized patients in Mexico and if there is a correlation between mating information and resistance to fluconazole and 5-fluorocytosine. We found that while both types of information at MTL1 are equally represented in a collection of 64 clinical isolates, the vast majority of isolates contain a-type information at MTL2 and α-type at MTL3. We also found no correlation of the particular combination of mating type information at the three MTL loci and resistance to fluconazole.

  20. The Value of the SYNTAX Score II in Predicting Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation.

    Science.gov (United States)

    Ryan, Nicola; Nombela-Franco, Luis; Jiménez-Quevedo, Pilar; Biagioni, Corina; Salinas, Pablo; Aldazábal, Andrés; Cerrato, Enrico; Gonzalo, Nieves; Del Trigo, María; Núñez-Gil, Iván; Fernández-Ortiz, Antonio; Macaya, Carlos; Escaned, Javier

    2017-11-27

    The predictive value of the SYNTAX score (SS) for clinical outcomes after transcatheter aortic valve implantation (TAVI) is very limited and could potentially be improved by the combination of anatomic and clinical variables, the SS-II. We aimed to evaluate the value of the SS-II in predicting outcomes in patients undergoing TAVI. A total of 402 patients with severe symptomatic aortic stenosis undergoing transfemoral TAVI were included. Preprocedural TAVI angiograms were reviewed and the SS-I and SS-II were calculated using the SS algorithms. Patients were stratified in 3 groups according to SS-II tertiles. The coprimary endpoints were all-cause death and major adverse cardiovascular events (MACE), a composite of all-cause death, cerebrovascular event, or myocardial infarction at 1 year. Increased SS-II was associated with higher 30-day mortality (P=.036) and major bleeding (P=.015). The 1-year risk of death and MACE was higher among patients in the 3rd SS-II tertile (HR, 2.60; P=.002 and HR, 2.66; P<.001) and was similar among patients in the 2nd tertile (HR, 1.27; P=.507 and HR, 1.05; P=.895) compared with patients in the 1st tertile. The highest SS-II tertile was an independent predictor of long-term mortality (P=.046) and MACE (P=.001). The SS-II seems more suited to predict clinical outcomes in patients undergoing TAVI than the SS-I. Increased SS-II was associated with poorer clinical outcomes at 1 and 4 years post-TAVI, independently of the presence of coronary artery disease. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  1. Agent-Based Modelling of the Evolution of the Russian Party System Based on Pareto and Hotelling Distributions. Part II

    Directory of Open Access Journals (Sweden)

    Владимир Геннадьевич Иванов

    2015-12-01

    Full Text Available The given article presents research of the evolution of the Russian party system. The chosen methodology is based on the heuristic potential of agent-based modelling. The author analyzes various scenarios of parties’ competition (applying Pareto distribution in connection with recent increase of the number of political parties. In addition, the author predicts the level of ideological diversity of the parties’ platforms (applying the principles of Hotelling distribution in order to evaluate their potential competitiveness in the struggle for voters.

  2. Increasing referral of at-risk travelers to travel health clinics: evaluation of a health promotion intervention targeted to travel agents.

    Science.gov (United States)

    MacDougall, L A; Gyorkos, T W; Leffondré, K; Abrahamowicz, M; Tessier, D; Ward, B J; MacLean, J D

    2001-01-01

    Increases in travel-related illness require new partnerships to ensure travelers are prepared for health risks abroad. The travel agent is one such partner and efforts to encourage travel agents to refer at-risk travelers to travel health clinics may help in reducing travel-attributable morbidity. A health promotion intervention encouraging travel agents to refer at-risk travelers to travel health clinics was evaluated. Information on the knowledge, attitudes, and behaviors of travel agents before and after the intervention was compared using two self-administered questionnaires. The Wilcoxon signed rank test was used to compare the mean difference in overall scores to evaluate the overall impact of the intervention and also subscores for each of the behavioral construct groupings (attitudes, barriers, intent, and subjective norms). Multiple regression techniques were used to evaluate which travel agent characteristics were independently associated with a stronger effect of the intervention. A small improvement in travel agents overall attitudes and beliefs (p =.03) was found, in particular their intention to refer (p =.01). Sixty-five percent of travel agents self-reported an increase in referral behavior; owners or managers of the agency were significantly more likely to do so than other travel agents (OR = 7.25; 95% CI: 1.64 32.06). Older travel agents, those that worked longer hours and those with some past referral experience, had significantly higher post-intervention scores. Travel agents can be willing partners in referral, and agencies should be encouraged to develop specific referral policies. Future research may be directed toward investigating the role of health education in certification curricula, the effectiveness of different types of health promotion interventions, including Internet-facilitated interventions, and the direct impact that such interventions would have on travelers attending travel health clinics.

  3. Advances in hepatitis E - II: Epidemiology, clinical manifestations, treatment and prevention.

    Science.gov (United States)

    Goel, Amit; Aggarwal, Rakesh

    2016-09-01

    Infection with hepatitis E virus (HEV) is the commonest cause of acute hepatitis worldwide. This infection, with fecal-oral transmission, was previously thought to be limited to humans residing in developing countries with poor sanitation, spreading via contaminated drinking water. In recent years, our understanding of epidemiology and clinical spectrum of this infection have changed markedly. This article reviews the epidemiology, including routes of transmission, and clinical manifestations of HEV infection around the world. In addition, recent findings on transmission-associated HEV infection, extrahepatic manifestations of hepatitis E and chronic infection with HEV, and treatment and prevention of this infection are discussed. Expert commentary: HEV infection has two distinct epidemiologic forms and clinical patterns of disease: (i) acute epidemic or sporadic hepatitis caused by fecal-oral (usually water-borne) transmission of genotype 1 and 2 HEV from a human reservoir in areas with poor hygiene and frequent water contamination, and (ii) infrequent sporadic hepatitis E caused by zoonotic infection, possibly from an animal source through ingestion of undercooked animal meal, of genotype 3 or 4 virus. In disease-endemic areas, pregnant women are at a particular risk of serious disease and high mortality. In less-endemic areas, chronic infection with HEV among immunosuppressed persons is observed. HEV can also be transmitted through Transfusion of blood and blood products. Ribivirin treatment is effective in chronic hepatitis E. Two efficacious vaccines have been tried in humans; one of these has received marketing approval in its country of origin.

  4. Enterobacter and Klebsiella species isolated from fresh vegetables marketed in Valencia (Spain) and their clinically relevant resistances to chemotherapeutic agents.

    Science.gov (United States)

    Falomir, María Pilar; Rico, Hortensia; Gozalbo, Daniel

    2013-12-01

    Occurrence of antibiotic-resistant pathogenic or commensal enterobacteria in marketed agricultural foodstuffs may contribute to their incorporation into the food chain and constitutes an additional food safety concern. In this work, we have determined the clinically relevant resistances to 11 common chemotherapeutic agents in Enterobacter and Klebsiella isolates from fresh vegetables from various sources (supermarkets and greengrocers' shops in Valencia, Spain). A total of 96 isolates were obtained from 160 vegetables analyzed (50% positive samples): 68 Enterobacter isolates (59 E. cloacae, two E. aerogenes, two E. cancerogenus, one E. gergoviae, and four E. sakazakii, currently Cronobacter spp.), and 28 Klebsiella isolates (19 K. oxytoca and 9 K. pneumoniae). Only seven isolates were susceptible to all agents tested, and no resistances to ceftazidime, ciprofloxacin, gentamicin, and chloramphenicol were detected. Most isolates were resistant to amoxicillin/clavulanic acid (74 [58 Enterobacter and 16 Klebsiella]) or to ampicillin (80 [55/25]). Other resistances were less frequent: nitrofurantoin (13 isolates [12/1]), tetracycline (6 [5/1]), co-trimoxazole (3 [3/0]), cefotaxime (1 [1/0]), and streptomycin (2 [1/1]). Multiresistant isolates to two (56 [41/15]), three (10 E. cloacae isolates), four (one E. cloacae and one K. pneumoniae isolate), and five (two E. cloacae isolates) chemotherapeutic agents were also detected. The presence of potential pathogens points to marketed fresh produce, which often is eaten raw, as a risk factor for consumer health. In addition, these results support the usefulness of these bacterial species as indicators of the spreading of antibiotic resistances into the environment, particularly in the food chain, and suggest their role as carriers of resistance determinants from farms to consumers, which may constitute an additional "silent" food safety concern. Therefore, there is a need to improve the hygienic quality of marketed fresh

  5. Timing and modality of the sclerosing agents binding to the human proteins: laboratory analysis and clinical evidences

    Directory of Open Access Journals (Sweden)

    Lorenzo Tessari

    2014-07-01

    Full Text Available Sclerosing agents (SA are blood inactivated. Nevertheless, investigations concerning the interaction among SA and blood components have never been deeply investigated. Aim of the study is to precisely identify SA blood ligands, to determine their binding time and to highlight the clinical consequences. Thirty-one blood samples were collected from chronic venous disease patients and tested by capillary and agarose gel (AGE electrophoresis before and after adding polidocanol (POL and sodiumtetradecylsulphate (STS. The two different types of electrophoresis allowed an evaluation of the blood proteins binding with the sclerosing agents, with a reaction time lower than 8 seconds for the AGE. Subsequently six patients underwent foam sclerotherapy and then were subdivided in group A (4 patients and B (2 patients. In group A blood sample was obtained from the ipsilateral brachial vein immediately before (T0 and repeated 1, 3, 5, and 10 minutes after injection of STS 3% injection into the GSV. In group B, the same procedure was performed with the same timing from the ipsilateral femoral vein. Free STS (fSTS and total proteinbound STS (bSTS were measured. POL mainly binds to β-globulins (11%, while STS to albumin and α-globulins (62.6% and 30.7% on the protidogram, respectively. Both in the brachial and in the femoral vein, the average fSTS was always 0. STS binds to albumin (62.6% and α-globulins (30.7%, while POL is bound mainly by the b-globulins (11%. The present paper demonstrates how the vast majority of the sclerosing agent is bound to the blood proteins, suggesting the need to look for possible sclerotherapy complications factors also in the used gas and/or in the subsequent cathabolites release.

  6. A clinical trial of Empress II porcelain inlays luted to vital teeth with a dual-curing adhesive system and a self-curing resin cement.

    Science.gov (United States)

    Fabianelli, Andrea; Goracci, Cecilia; Bertelli, Egidio; Davidson, Carel L; Ferrari, Marco

    2006-12-01

    The aim of the study was to clinically evaluate Empress II inlays cemented with a dual-curing bonding agent and a self-curing luting system. Forty patients were selected to receive one Empress II inlay. Empress II is a heat-pressed glass ceramic containing lithium disilicate and lithium orthophosphate crystals, purported to provide higher stress resistance and improved strength. The restorations were placed between March and May 2000. Recalls were performed after 6, 12, 24, and 36 months. At the 3-year recall, 7 patients were lost to follow-up. Inlays were evaluated for postoperative sensitivity, marginal integrity, marginal leakage, color stability, surface staining, retention, and surface crazing (microcracks). At the 3-year recall, all the restorations were in place and only one showed postoperative sensitivity (at the first recall, 1 week after placement). Only 3 inlays showed slight marginal staining, and 4 inlays showed gaps, with little surface staining or microcracks. No inlay debonded or fractured during theobservation period. All the evaluated inlays were in place and acceptable.

  7. Picrorhiza kurroa (Kutaki Royle ex Benth as a hepatoprotective agent--experimental & clinical studies.

    Directory of Open Access Journals (Sweden)

    Vaidya A

    1996-10-01

    Full Text Available Picrorhiza kurroa (Pk, a known hepatoprotective plant, was studied in experimental and clinical situtations. The standardization of active principles--Picroside 1 and 2 was done with High Performance Liquid Chromatography. Picroside 1 ranged from 2.72 to 2.88 mg/capsule and picroside 2 from 5.50 to 6.00 mg/capsule. In the galactosamine-induced liver injury in rats, Pk at a dose of 200 mg/kg p.o. showed a significant reduction (p < 0.05 in liver lipid content, GOT and GPT. In a randomised, double-blind placebo controlled trial in patients diagnosed to have acute viral hepatitis (HBsAg negative, Pk root powder 375 mg three times a day was given for 2 weeks (n = 15 or a matching placebo (n = 18 was given. Difference in values of bilirubin, SGOT and SGPT was significant between placebo and Pk groups. The time in days required for total serum bilirubin to drop to average value of 2.5 mg% was 75.9 days in placebo as against 27.44 days in Pk group. The present study has shown a biological plausability of efficacy of Pk as supported by clinical trial in viral hepatitis, hepatoprotection in animal model and an approach for standardizing extracts based on picroside content.

  8. Preparation of the 99mTc-dextran lymphoscin tigraphic agent and its preliminary clinical application

    International Nuclear Information System (INIS)

    Lu Weiyue; You Dejian; Ma Yuanming; He Guangren; Zhang Wei; Tu Zhipei; Jin Bixia

    1991-01-01

    Dextran-70 was treated by gradient sedimentation, and that with a mean molecular weight of 105000 which was optimal for lymphatic system imaging rabbits was selected. Sn-Dextran kit was produced containing the above-mentioned dextran. Sn-Dextran kits can be stored at 4 deg C for 8 months. Its efficiency of labelling is more than 95%. The biodistribution, pharmacokinetics studies and lymphoscintigraphy in rabbits for 99m Tc-dextran showed: (1) high radioactivity in the popliteal nodes and very low redioactivity in other nontarget organs except kidneys through which it was excreted; (2) 99m Tc-dextran accumulated markedly and rapidly in lymphatic system. The lymph channels and nodes were well visualized in scintigrams; (3) 99m Tc-dextran cleared rapidly from the injection site. Radioactivity of 95% of the injected dose disappearing after 6.5h. Toxicity tests indicated that: 99m Tc-dextran is a drug of low toxicity and safe. Preliminary clinical applications of 99m Tc-dextran in 100 cases provided satisfactory results. The process of imaging usually took less than 1h after injection, and no side-effects occurred in any patient. In most cases, the results corresponded basically with the clinical diagnosis. Hence, 99m Tc-dextran is an ideal radiopharmaceutical that can be used for the visualization of the lymphatic system. It is recomminded for routine use in clincal practice

  9. Clinical and genetic investigation of families with type II Waardenburg syndrome.

    Science.gov (United States)

    Chen, Yong; Yang, Fuwei; Zheng, Hexin; Zhou, Jianda; Zhu, Ganghua; Hu, Peng; Wu, Weijing

    2016-03-01

    The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia‑associated transcription factor (MITF), sex‑determining region Y‑box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease‑causing mutation in pedigree 1. However, there are novel disease‑causing genes in Waardenburg syndrome type II, which require further research.

  10. Clinical effects of fixed functional Herbst appliance in the treatment of class II/1 malocclusion

    Directory of Open Access Journals (Sweden)

    Nedeljković Nenad

    2009-01-01

    Full Text Available Introduction. Sagittal mandible deficiency is the most common cause of skeletal Class II malocclusion. Treatment objective is to stimulate sagittal mandible growth. Fixed functional Herbst appliance use is beneficial for shortening the time required for treatment and does not depend on patient compliance. Case outline. A 13-year-old girl was referred to the Clinic of Orthodontics, School of Dentistry in Belgrade following previous unsuccessful treatment of her skeletal Class II malocclusion using an activator. The patient's poor cooperation had led to failure of the treatment. Patient was subjected to the Herbst treatment for 6 months followed by fixed appliance for another 8 months. Lateral cephalograms before and after the treatment was performed. The remodelation of condylar and fossal articulation was assessed by superimposition of pre- and post-treatment temporomandibular joint tomograms. The promotion of oral hygiene and fluoride use was performed because orthodontic treatment carries a high caries risk and risk for periodontal disease. Skeletal and dental changes were observed after treatment (correction [Max+Mand]: molar relation 7 mm, overjet 8 mm, skeletal relation 5 mm, molars 2 mm, incisors 3 mm. Combination of Herbst and fixed appliances was effective in the treatment of dental and skeletal irregularities for a short period of time. Conclusion . In the retention period, 14 months after treatment, occlusal stability exists. Follow-up care in oral prevention is based on regular recalls at the dental office and supervision at home by the parents.

  11. Bolus and continuous infusion mitoxantrone in newly diagnosed adult acute lymphoblastic leukemia: results of two consecutive phase II clinical studies.

    Science.gov (United States)

    Koc, Y; Akpek, G; Kansu, E; Kars, A; Tekuzman, G; Baltali, E; Güler, N; Barista, I; Güllü, I; Ozisik, Y; Firat, D

    1998-01-01

    Two consecutive phase II clinical studies were designed to evaluate the efficacy and safety of bolus and continuous infusion (CI) mitoxantrone (MTZ) in 39 patients with newly diagnosed acute lymphocytic leukemia (ALL). MTZ was used as part of the classical ALL induction regimen. Twenty patients were treated with bolus MTZ (10 mg/m2 for 3 days) combined with vincristine and prednisone. The same regimen was given to a second set of 19 patients, except that MTZ was administered as a 24-hr CI. Both groups received bimonthly intensifications with vincristine and prednisone for 3 years, along with oral maintenance therapy. Patients in the CI-MTZ study arm received additional MTZ on the first day of intensification cycles. Seventeen patients (85%) in the bolus arm and 15 patients (79%) in the CI arm achieved complete remission (CR). Median disease-free survivals (DFS) in the bolus and CI groups were 11 and 15 months after median follow-ups of 16 (3.5-96) and 13 (2.3-32) months, respectively. At 2.5 years, DFS rates were 29.4% and 34.4% in the bolus and CI groups (p > 0.05). There were no significant differences between two groups in rates of early death, degree of organ toxicity, or duration of neutropenia and thrombocytopenia. Significant cardiac toxicity was not observed in either group. Bolus or CI administration of MTZ was equally effective and was well tolerated. Neither the mode of administration nor increasing the dose intensity of MTZ by incorporating intensification cycles reduced relapse rates. Development of new antileukemia agents and novel treatment approaches are still needed to improve the high relapse rates in adult ALL once a complete response is achieved.

  12. Effect of low zinc intake and oral contraceptive agents on nitrogen utilization and clinical findings in young women.

    Science.gov (United States)

    Hess, F M; King, J C; Margen, S

    1977-12-01

    In a previous paper we reported that serum, urine and fecal zinc levels fell markedly in women taking a combination oral contraceptive agent (+OCA) and in women with normal menstrual cycles (-OCA) when they consumed a low-zinc diet (less than 0.2 mg/day) for 35 days. We evaluated other biochemical and clinical data in order to determine if depletion of accessible body zinc and/or physiologic adjustment to conserve body zinc stores had occurred. Neither low zinc intake nor oral contraceptive use appeared to influence nitrogen balance or body weight. Use of contraceptive drugs appeared to influence the response of blood parameters to zinc depletion. Serum transferrin and cholesterol declined significantly in the -OCA group, whereas alkaline phosphatase and gamma-globulin changed significantly in both groups. Clinical problems developed in all the subjects with serum zinc levels below 50 microgram/dl during the study; three of the six with serum zinc levels above 50 microgram/dl also complained of clinical symptoms. The results suggest that zinc deficiency through depletion of accessible body zinc stores developed during the 35-day study.

  13. Levels and clinical significance of serum IGF-II in patients with five kinds of malignant tumors

    International Nuclear Information System (INIS)

    Qi Falian; Xu Jun; Du Xiumin; Ke Bingkun; Yang Daoli

    2002-01-01

    Objective: To study the levels and clinical significance of serum IGF-II in patients with malignant tumor. Methods: Levels of serum IGF-II were detected in patients with gastric cancer, lung cancer, liver cancer, ovarian carcinoma and endometrial carcinoma by radioimmunoassay, levels in patients with hepatic cirrhosis, uterine myoma and normal controls were also determined for comparison. Results: The levels of serum IGF-II in patients with gastric cancer, lung cancer and liver cancer were significantly higher than those in normal controls (p 0.05). Conclusion: The determination of serum IGF-II has no clinical significance in patients with endometrial carcinoma, ovarian carcinoma and uterine myoma but it could be useful to judge the severity and evaluate the prognosis in patients with gastric cancer, lung cancer, liver cancer and cirrhosis

  14. Application of ICHD-II Criteria in a Headache Clinic of China

    Science.gov (United States)

    Dong, Zhao; Di, Hai; Dai, Wei; Liang, Jingyao; Pan, Meiyan; Zhang, Mingjie; Zhou, Zhibin; Li, Zheng; Liu, Ruozhuo; Yu, Shengyuan

    2012-01-01

    Background China has the huge map and the largest population in the world. Previous studies on the prevalence and classification of headaches were conducted based on the general population, however, similar studies among the Chinese outpatient population are scarce. This study aimed to analyze the characteristics of 1843 headache patients enrolled in a North China headache clinic of the General Hospital for Chinese People's Liberation Army from October 2011 to May 2012, with the International Classification of Headache Disorders, 2nd Edition (ICHD-II). Methods and Results Personal interviews were carried out and a detailed questionnaire was used to collect medical records including age, sex and headache characteristics. Patients came from 28 regions of China with the median age of 40.9 (9–80) years and the female/male ratio of 1.67/1. The primary headaches (78.4%) were classified as the following: migraine (39.1%), tension-type headache (32.5%), trigeminal autonomic cephalalgias (5.3%) and other primary headache (1.5%). Among the rest patients, 12.9% were secondary headaches, 5.9% were cranial neuralgias and 2.5% were unspecified or not elsewhere classified. Fourteen point nine percent (275/1843) were given an additional diagnosis of chronic daily headache, including medication-overuse headache (MOH, 49.5%), chronic tension-type headache (CTTH, 32.7%) and chronic migraine (CM, 13.5%). The visual analogue scale (VAS) score of TTH with MOH was significantly higher than that of CTTH (6.8±2.0 vs 5.6±2.0, Pheadache clinic outpatients in a tertiary hospital of North China that migraine is the most common diagnosis. Furthermore, most headaches in this patient population can be classified using ICHD-II criteria. PMID:23239993

  15. Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II Pancreatic Adenocarcinoma.

    Science.gov (United States)

    Swords, Douglas S; Mulvihill, Sean J; Skarda, David E; Finlayson, Samuel R G; Stoddard, Gregory J; Ott, Mark J; Firpo, Matthew A; Scaife, Courtney L

    2017-07-11

    To (1) evaluate rates of surgery for clinical stage I-II pancreatic ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery, (3) quantify the degree to which patient- and hospital-level factors explain differences in hospital surgery rates, and (4) evaluate the association between adjusted hospital-specific surgery rates and overall survival (OS) of patients treated at different hospitals. Curative-intent surgery for potentially resectable PDAC is underutilized in the United States. Retrospective cohort study of patients ≤85 years with clinical stage I-II PDAC in the 2004 to 2014 National Cancer Database. Mixed effects multivariable models were used to characterize hospital-level variation across quintiles of hospital surgery rates. Multivariable Cox proportional hazards models were used to estimate the effect of adjusted hospital surgery rates on OS. Of 58,553 patients without contraindications or refusal of surgery, 63.8% underwent surgery, and the rate decreased from 2299/3528 (65.2%) in 2004 to 4412/7092 (62.2%) in 2014 (P < 0.001). Adjusted hospital rates of surgery varied 6-fold (11.4%-70.9%). Patients treated at hospitals with higher rates of surgery had better unadjusted OS (median OS 10.2, 13.3, 14.2, 16.5, and 18.4 months in quintiles 1-5, respectively, P < 0.001, log-rank). Treatment at hospitals in lower surgery rate quintiles 1-3 was independently associated with mortality [Hazard ratio (HR) 1.10 (1.01, 1.21), HR 1.08 (1.02, 1.15), and HR 1.09 (1.04, 1.14) for quintiles 1-3, respectively, compared with quintile 5] after adjusting for patient factors, hospital type, and hospital volume. Quality improvement efforts are needed to help hospitals with low rates of surgery ensure that their patients have access to appropriate surgery.

  16. Durable clinical activity of single-agent bevacizumab in a nonagenarian patient with metastatic alveolar soft part sarcoma.

    Science.gov (United States)

    Mir, Olivier; Boudou-Rouquette, Pascaline; Larousserie, Frédérique; Blanchet, Benoit; Babinet, Antoine; Anract, Philippe; Goldwasser, François

    2012-08-01

    Alveolar soft part sarcoma is a rare malignancy usually considered resistant to conventional chemotherapy, but recent data suggest that the multikinase inhibitors sunitinib and cediranib could be active in this setting. A 90-year-old lady with alveolar soft part sarcoma of the leg and lung metastases was started on sunitinib 37.5 mg daily. The treatment was poorly tolerated with grade 3 hypertension and grade 3 thrombocytopenia, which persisted after dose reduction to 25 mg daily. The patient was subsequently started on bevacizumab 10 mg/kg every 2 weeks, resulting in a marked improvement in pain and a partial response on lung metastases for 16 months and ongoing. Agents targeting the vascular endothelial growth factor-signalling pathway seem to exert clinically relevant and prolonged activity against alveolar soft part sarcoma and deserve further evaluation in the treatment of this rare soft tissue sarcoma.

  17. Clinical Profile and Response to Chemotherapeutic Agents in Non-specific Urethritis

    Directory of Open Access Journals (Sweden)

    R K Pandhi

    1984-01-01

    Full Text Available The epidemiological and clinical profile of 159 patients having non-specific iiretbritis is repoed. The majority (67.39o of patients were unm and most (70.4% of the we m re in the age group of 21-30 years. The incubation period in the majority (69.2% of patients was 1-4 weeks. Almost all the (98.1% patients complained of dysuria but urethral discharge was seen only in 48.4% of patients. Out of tetracycline′s doxycline, erythromycin and cotrimoxazole tried in this study, tetracycline′s in the dosage of 2 gm/day for 3 weeks was found to give the best (90.5%′cure rate.

  18. Type II autosomal dominant osteopetrosis (Albers-Schönberg disease): clinical and radiological manifestations in 42 patients.

    Science.gov (United States)

    Bénichou, O D; Laredo, J D; de Vernejoul, M C

    2000-01-01

    Type II autosomal dominant osteopetrosis (ADO II, Albers-Schonberg disease) is a genetic condition characterized by generalized osteosclerosis predominating in some skeletal sites such as the spine and pelvis. ADO II is rare, and most available clinical descriptions are based on small numbers of patients. We report the clinical and radiological manifestations in 42 ADO II patients. To our knowledge, this is the largest series reported so far. Our inclusion criterion was presence on radiographs of the spine of vertebral endplate thickening, producing the classic sandwich vertebra appearance. We found various patterns of sandwich vertebra, of which we provide a description to assist physicians in diagnosing ADO II. The classic bone-within-bone appearance was present in most but not all skeletal sites. The radiological penetrance of the disease was high (90%) and increased after 20 years of age. As many as 81% of our patients experienced clinical manifestations. Fractures were common (78% of patients) and healed slowly. Hip osteoarthritis developed in 27% of patients and required arthroplasty in 9 of the 16 affected hips. Nonmandibular osteomyelitis occurred in 4 cases (11%). Twenty-four percent of patients had thoracic or lumbar scoliosis. Orthopedic surgery was performed in 52.8% of patients, of whom half had at least three surgical procedures for internal fracture fixation, arthroplasty, limb deformity correction, or treatment of surgical complications. There was a high rate of surgical complications including nonunion, infection, prosthesis loosening, and intraoperative fractures. Nearly two-thirds of patients (64%) had stomatologic manifestations, including mandibular osteomyelitis in 4 patients (11%). Cranial nerve involvement responsible for hearing loss, bilateral optic atrophy, and/or facial palsy was present in 14 patients but was clearly attributable to ADO II in only 6 cases (16%). This large series sheds new light on several aspects of ADO II, most

  19. Postoperative vaginal cuff irradiation using high dose rate remote afterloading: a Phase II clinical protocol

    International Nuclear Information System (INIS)

    Noyes, William R.; Bastin, Kenneth; Edwards, Scott A.; Buchler, Dolores A.; Stitt, Judith A.; Thomadsen, Bruce R.; Fowler, Jack F.; Kinsella, Timothy J.

    1995-01-01

    Purpose: In September 1989, a postoperative Phase II high dose rate (HDR) brachytherapy protocol was started for International Federation of Gynecology and Obstetrics (FIGO) Stage I endometrial adenocarcinoma. This review reports the overall survival, local control, and complication rates for the initial 63 patients treated in this Phase II study. Methods and Materials: High dose rate brachytherapy was delivered using an Iridium-192 HDR remote afterloader. Sixty-three patients were entered into the Phase II protocol, each receiving two vaginal cuff treatments 1 week apart (range 4-12 days) with vaginal ovoids (diameter 2.0-3.0 cm). No patient received adjuvant external beam radiation. A dose of 32.4 Gy in two fractions was prescribed to the ovoid surface in 63 patients. The first three patients treated at our institution received 15, 16.2, and 29 Gy, respectively, to determine acute effects. Results: At a median follow-up of 1.6 years (range 0.75-4.3 years) no patient has developed a vaginal cuff recurrence. One regional recurrence (1.6%) occurred at 1.2 years at the pelvic side wall. This patient is alive and without evidence of disease 7 months after completion of salvage irradiation, which resulted in the only vaginal stenosis (1.6%). Fourteen patients (22%) experienced vaginal apex fibrosis by physical exam, which was clinically symptomatic in four patients. Two patients reported stress incontinence; however, these symptoms were noted prior to their HDR therapy. One patient died 2.4 years after HDR therapy due to cardiovascular disease without evidence of cancer at autopsy. Conclusion: Preliminary results of our phase II HDR vaginal cuff protocol for postoperative FIGO Stage IA, Grade 3 or Stage IB, Grade 1-2 patients demonstrate that 32.4 Gy in two fractions is well tolerated by the vaginal cuff mucosa. Local control appears comparable to our prior experience and others with low dose rate (LDR) brachytherapy. Additional patient accrual and further follow

  20. Mixed-state bipolar I and II depression: time to remission and clinical characteristics.

    Science.gov (United States)

    Shim, In Hee; Woo, Young Sup; Jun, Tae-Youn; Bahk, Won-Myong

    2014-01-01

    We compared the time to achieve remission and the clinical characteristics of patients with bipolar depressive mixed state and those with bipolar depressive non-mixed state. The subjects (N=131) were inpatients diagnosed between 2006 and 2012 with bipolar I or II disorder, depression and were classified into the following three groups: "pure depressive state" (PD, n=70), "sub-threshold mixed state" (SMX, n=38), and "depressive mixed state" (DMX, n=23). Diagnosis of a DMX was in accordance with Benazzi's definition: three or more manic symptoms in a depressive episode. The subjects' charts were retrospectively reviewed to ascertain the time to achieve remission from the index episode and to identify other factors, such as demographic and clinical characteristics, specific manic symptoms, and pharmacological treatment, that may have contributed to remission. The time to achieve remission was significantly longer in the DMX (p=0.022) and SMX (p=0.035) groups than in the PD group. Adjustment for covariates using a Cox proportional hazards model did not change these results. Clinically, subjects with a DMX were more likely to have manic symptoms in the index episode, especially inflated self-esteem and psychomotor agitation than those in the PD. We investigated only inpatients and therefore could not comment on outpatients. These findings showed that sub-syndromal manic symptoms in bipolar depression had different clinical characteristics and a more severe illness course, including a longer time to achieve remission, than did a pure depressive state. © 2013 Elsevier B.V. All rights reserved.

  1. [The external patello-tibial transfixation (EPTT). Part II: Clinical application and results].

    Science.gov (United States)

    Ishaque, B; Gotzen, L; Ziring, E; Petermann, J

    1999-07-01

    In part I of the paper the biomechanical and technical background of the EPTT using the MPT fixator and the indications for this procedure have been described. In part II we report about the clinical application of the EPTT in 67 patients with a wide spectrum of repairs and reconstructions of the extensor mechanism. 48 patients had fresh injuries, 18 of them with severe concomitant knee lesions and 19 patients had neglected rsp. unsuccessfully operated injuries. There were 4 deep infections, two of them related to the MPT fixator. In the patients with uneventful healing the fixator remained in place for 7.3 weeks in average. The clinical, isokinetic and radiological results were reviewed in 17 patients with an average follow-up time of 37.3 months. There were 5 patients with partial patellectomy and tendon reattachment because of lower patella pole comminution and 12 patients with tendon reattachment ruptured at the inferior patella pole or suture repair in midsubstance rupture. The clinical results according to the IKDC score were rated in 3 patients as normal, in 10 patients as nearly normal and in 4 patients as abnormal. This rating was highly dependend on the subjective judgement by the patients who considered their operated knees not as normal as the contralateral knees. From our clinical experiences and results we can derive that the EPTT enables the surgical management of extensor mechanism disruptions with a minimum of internal fixation material and provides a safe protection of the repairs and reconstructions during the healing period. The EPTT allows immediate unrestricted functional rehabilitation and early walking without crutches. Thus the EPTT represents an effective alternative to the patello-tibial cerclage with a wire or synthetic ligaments.

  2. Report on NCI symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. II. Cellular and animal models

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1984-01-01

    The point at which the common final pathway for induction of cancer by chemical carcinogens and ionizing radiation has not been identified. Although common molecular targets are suggested by recent findings about the role of oncogenes, the mechanism by which the deposition of radiation energy and the formation of adducts or other DNA lesions induced by chemicals affects the changes in the relevant targets may be quite different. The damage to DNA that plays no part in the transformation events, but that influences the stability of the genome, and therefore, the probability of subsequent changes that influence tumorigenesis may be more readily induced by some agents than others. Similarly, the degree of cytotoxic effects that disrupt tissue integrity and increase the probability of expression of initiated cells may be dependent on the type of carcinogen. Also, evidence was presented that repair of the initial lesions could be demonstrated after exposure to low-LET radiation but not after exposure to chemical carcinogens

  3. Report on NCI symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. II. Cellular and animal models

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1984-01-01

    The point at which the common final pathway for induction of cancer by chemical carcinogens and ionizing radiation has not been identified. Although common molecular targets are suggested by recent findings about the role of oncogenes, the mechanism by which the deposition of radiation energy and the formation of adducts or other DNA lesions induced by chemicals affects the changes in the relevant targets may be quite different. The damage to DNA that plays no part in the transformation events, but that influences the stability of the genome, and therefore, the probability of subsequent changes that influence tumorigenesis may be more readily induced by some agents than others. Similarly, the degree of cytotoxic effects that disrupt tissue integrity and increase the probability of expression of initiated cells may be dependent on the type of carcinogen. Also, evidence was presented that repair of the initial lesions could be demonstrated after exposure to low-LET radiation but not after exposure to chemical carcinogens.

  4. American tertiary clinic-referred bipolar II disorder versus bipolar I disorder associated with hastened depressive recurrence.

    Science.gov (United States)

    Dell'Osso, Bernardo; Shah, Saloni; Do, Dennis; Yuen, Laura D; Hooshmand, Farnaz; Wang, Po W; Miller, Shefali; Ketter, Terence A

    2017-12-01

    Bipolar disorder (BD) is a chronic, frequently comorbid condition characterized by high rates of mood episode recurrence and suicidality. Little is known about prospective longitudinal characterization of BD type II (BD II) versus type I (BD I) in relation to time to depressive recurrence and recovery from major depressive episode. We therefore assessed times to depressive recurrence/recovery in tertiary clinic-referred BD II versus I patients. Outpatients referred to Stanford BD Clinic during 2000-2011 were assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and with Clinical Monitoring Form during up to 2 years of naturalistic treatment. Prevalence and clinical correlates of bipolar subtype in recovered (euthymic ≥8 weeks) and depressed patients were assessed. Kaplan-Meier analyses assessed the relationships between bipolar subtype and longitudinal depressive severity, and Cox proportional hazard analyses assessed the potential mediators. BD II versus BD I was less common among 105 recovered (39.0 vs. 61.0%, p = 0.03) and more common among 153 depressed (61.4 vs. 38.6%, p = 0.006) patients. Among recovered patients, BD II was associated with 6/25 (24.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics and hastened depressive recurrence (p = 0.015). Among depressed patients, BD II was associated with 8/25 (33.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics, but only non-significantly associated with delayed depressive recovery. BD II versus BD I was significantly associated with current depression and hastened depressive recurrence, but only non-significantly associated with delayed depressive recovery. Research on bipolar subtype relationships with depressive recurrence/recovery is warranted to enhance clinical management of BD patients.

  5. Divergences between clinical and research methods for assessing personality disorders: implications for research and the evolution of axis II.

    Science.gov (United States)

    Westen, D

    1997-07-01

    The purpose of this study was to examine the extent to which instruments for assessing axis II diverge from clinical diagnostic processes. Subjects in the first study were 52 clinicians with experience in assessment and treatment of patients with personality disorders, who were surveyed about the methods they use in clinical practice to make diagnoses and other aspects of the diagnostic process. A second study replicated the major findings with a random national sample of 1,901 experienced psychiatrists and psychologists. Whereas current instruments rely primarily on direct questions derived from DSM-IV, clinicians of every theoretical persuasion found direct questions useful for assessing axis I disorders but only marginally so for axis II. They made axis II diagnoses, instead, by listening to patients describe interpersonal interactions and observing their behavior with the interviewer. In contrast to findings with current research instruments, most patients with personality disorders in clinical practice receive only one axis II diagnosis, and if they receive more than one, one is considered primary. Clinicians reported treating a substantial number of patients for enduring personality patterns that current axis II instruments do not assess, many of which meet neither axis I nor axis II criteria, notably problems with relatedness, work, self-esteem, and chronic subclinical depressive traits. Measurements of axis II were constructed by using a model derived from axis I instruments that diverges from clinical diagnostic procedures in a way that may be problematic for the assessment of personality disorders and the development of a more clinically and empirically sound taxonomy.

  6. Preclinical and Clinical Assessment of Cannabinoids as Anti-Cancer Agents

    Directory of Open Access Journals (Sweden)

    Daniel A. Ladin

    2016-10-01

    Full Text Available Cancer is the second leading cause of death in the United States with 1.7 million new cases estimated to be diagnosed in 2016. This disease remains a formidable clinical challenge and represents a substantial financial burden to the US health care system. Therefore, research and development of novel therapeutics for the treatment of cancer is of high priority. Cannabinoids and their derivatives have been utilized for their medicinal and therapeutic properties throughout history. Cannabinoid activity is regulated through the endocannabinoid system, which is comprised of cannabinoid receptors, transporters, and enzymes involved in cannabinoid synthesis and breakdown. More recently, cannabinoids have gained special attention for their role in cancer development and reduction. However, many studies investigated these roles using in vitro models which may not adequately mimic tumor growth and metastasis. As such, this article aims to review study results which evaluated effects of cannabinoids from plant, synthetic and endogenous origins on cancer development in preclinical models and to examine the current standing of cannabinoids currently being tested in human cancer patients.

  7. In vitro susceptibility of Candida albicans clinical isolates to eight antifungal agents in Ouagadougou (Burkina Faso).

    Science.gov (United States)

    Zida, A; Yacouba, A; Bamba, S; Sangare, I; Sawadogo, M; Guiguemde, T; Kone, S; Traore, L K; Ouedraogo-Traore, R; Guiguemde, R T

    2017-12-01

    In recent years, the infection Candida albicans infection worldwide has risen, and the incidence of resistance to traditional antifungal therapies is also increasing. The aim of this study was to evaluate in vitro susceptibility of C. albicans clinical isolates to eight antifungal agents in Ouagadougou. A cross-sectional study was conducted from January 2013 to December 2015 at Yalgado Ouédraogo University Teaching Hospital. Two hundred seven strains have been isolated from 347 symptomatic patients received in different clinical services. Samples were cultured on Sabouraud Dextrose Agar supplemented with Cloramphenicol. Isolates were diagnosed as C. albicans using germ tube test, chlamydospore formation on Corn Meal Agar, and Api-Candida test (Biomérieux). Antifungal susceptibility testing was performed by disk diffusion method and isolates classified as susceptible, susceptible dose-dependent and resistant. Three hundred forty-seven (347) patients are included in this study. Two hundred and six (206) out of 347 collected samples (59.36%) were found positive for C. albicans. The strains were mostly isolated from vulvovaginal (49%) and oral infections (40.3%). The highest resistance rates of azoles were obtained with fluconazole (66.5%), itraconazole (52.3%) and ketoconazole (22.9%) when all clinical isolates were included. The resistance rates of fluconazole, itraconazole and ketoconazole remain highest for vulvovaginal and oral isolates. The rate of resistance to the polyene amphotericin B was 32.0% for all clinical isolates and was 56.4% for vulvovaginal strains. Resistance rate to nystatin was 6.3% for all clinical isolates. Cross-resistance analysis with data of all clinical strains revealed that the incidence of resistance to ketoconazole and itraconazole in fluconazole-resistant isolates was significantly higher than recorded for fluconazole-susceptible isolates. In vitro C. albicans antifungal susceptibility test in this study showed relatively high

  8. [Clinical Practice Guidelines for Management of Schizophrenia: Evaluation Using AGREE II].

    Science.gov (United States)

    de la Hoz Bradford, Ana María; Ávila, Mauricio J; Bohórquez Peñaranda, Adriana Patricia; García Valencia, Jenny; Arenas Borrero, Álvaro Enrique; Vélez Traslaviña, Ángela; Jaramillo González, Luis Eduardo; Gómez-Restrepo, Carlos

    2014-01-01

    Colombia is developing multiple national practice guidelines from a range of diseases. Clinical practice guidelines represent a very useful tool to be able to take decision over a patient care that is widely available for the clinician. In psychiatry there are a good number of international clinical guidelines for the treatment of schizophrenia nevertheless there is no article that evaluate them scientifically In the settings of developing a Colombian schizophrenia practice guideline, a systematic search was performed in multiple databases and the results were then evaluated by two trained persons. We present the results globally and by domains. We found 164 matches for possible guidelines. After screening 7 guidelines were evaluated with the AGREE II instrument. Globally and by the different domains, the National Institute for Health and Care Excellence (NICE) was the guideline that got the best score. From the guidelines that were reviewed, 4 were from Europe and only 2 were from Latin America. None of the guidelines used GRADE methodology for the recommendations. The diversity of the schizophrenia treatment guidelines does not allow an easy adoption of the recommendation by a psychiatrist in Colombia. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  9. Ru(II)-polypyridyl surface functionalised gold nanoparticles as DNA targeting supramolecular structures and luminescent cellular imaging agents.

    Science.gov (United States)

    Martínez-Calvo, Miguel; Orange, Kim N; Elmes, Robert B P; la Cour Poulsen, Bjørn; Williams, D Clive; Gunnlaugsson, Thorfinnur

    2016-01-07

    The development of Ru(II) functionalized gold nanoparticles 1–3·AuNP is described. These systems were found to be mono-disperse with a hydrodynamic radius of ca. 15 nm in water but gave rise to the formation of higher order structures in buffered solution. The interaction of 1–3·AuNP with DNA was also studied by spectroscopic and microscopic methods and suggested the formation of large self-assembly structures in solution. The uptake of 1–3·AuNP by cancer cells was studied using both confocal fluorescence as well as transmission electron microscopy (TEM), with the aim of investigating their potential as tools for cellular biology. These systems displaying a non-toxic profile with favourable photophysical properties may have application across various biological fields including diagnostics and therapeutics.

  10. Major adverse cardiovascular event reduction with GLP-1 and SGLT2 agents: evidence and clinical potential

    Science.gov (United States)

    Røder, Michael E.

    2017-01-01

    Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes. However, these drugs seem to have other effects such as weight reduction, low risk of hypoglycemia, and blood pressure reduction. Emerging evidence suggests pleiotropic effects, which potentially could be important in reducing cardiovascular risk. Prompted by regulatory authorities demanding cardiovascular outcome trials (CVOTs) assessing the cardiovascular safety of new antihyperglycemic drug candidates, many CVOTs are ongoing and a few of these are finalized. Somewhat surprising recent CVOTs in both drug classes have shown promising data on cardiovascular morbidity and mortality in patients with a very high risk of cardiovascular events. It is uncertain whether this is a class effect of the two drug classes, and it is yet unproven whether long-term cardiovascular benefits of these drugs can be extrapolated to populations at lower risk of cardiovascular disease. The aim of the present review is to give an overview of our current knowledge of the GLP-1RA and SGLT2-i classes, with specific focus on mechanisms of action, effects on cardiovascular risk factors and cardiovascular morbidity and mortality from the CVOTs presently available. The clinical potential of these data is discussed. PMID:29344329

  11. Identification of Agents Active against Methicillin-Resistant Staphylococcus aureus USA300 from a Clinical Compound Library

    Directory of Open Access Journals (Sweden)

    Hongxia Niu

    2017-09-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA poses a significant threat for effective treatment of several difficult-to-treat infections in humans. To identify potential new treatment options for MRSA infections, we screened a clinical compound library consisting of 1524 compounds using a growth inhibition assay in 96-well plates. We identified 34 agents which are either bacteriostatic or bactericidal against log-phase clinical MRSA strain USA300. Among them, 9 candidates (thonzonium, cetylpyridinium, trilocarban, benzododecinium, bithionol, brilliant green, chlorquinaldol, methylbenzethonium and green violet are known antiseptics, 11 candidates are known antibiotics currently recommended for the treatment of MRSA. We identified 9 new drug candidates, 5 of which (thiostrepton, carbomycin, spiramycin, clofazimine and chloroxine are antibiotics used for treating other infections than S. aureus infections; 4 of which (quinaldine blue, closantel, dithiazanine iodide and pyrvinium pamoate are drugs used for treating parasitic diseases or cancer. We ranked these new drug candidates according to their MICs against the MRSA strain USA300. Our findings may have implications for more effective treatment of MRSA infections.

  12. Clinical and radiographic comparison of platelet-rich fibrin and mineral trioxide aggregate as pulpotomy agents in primary molars

    Directory of Open Access Journals (Sweden)

    Surendra Patidar

    2017-01-01

    Full Text Available Aim: This study aimed to evaluate and compare the Platelet-rich fibrin (PRF and Mineral trioxide aggregate (MTA as a pulpotomy agent in primary molars. Material and Methods: In this study, 50 primary molars from 50 healthy children aged 5–9 years requiring pulpotomy were randomly allocated into two groups. In PRF group, after coronal pulp removal and hemostasis, remaining pulp tissue was covered with PRF preparation. In the MTA group, the pulp stumps were covered with MTA (Pro Root MTA-Root Canal Repair Material, Dentsply International Inc. paste obtained by mixing MTA powder with sterile water at a 3:1 powder to water ratio. All teeth were restored with reinforced zinc oxide eugenol base and glass – ionomer cement. Stainless steel crowns were given in both groups 24 h after treatment. Clinical evaluation was undertaken at 1, 3, and 6 months intervals whereas radiographic evaluation of the treated teeth was carried out at the interval of 6 months. Results: By the end of 6 months, the overall success rate was 90% in PRF group and 92% in MTA Group. A statistically significant difference was observed between the groups at 6 months of follow-up (P 0.05. Conclusion: Radiographic and clinical outcome in PRF group could suggest it as an acceptable alternative in pulpotomy of primary teeth. PRF holds a promising future in the area of primary tooth vital pulp therapy.

  13. Donepezil improves gait performance in older adults with mild Alzheimer's disease: a phase II clinical trial.

    Science.gov (United States)

    Montero-Odasso, Manuel; Muir-Hunter, Susan W; Oteng-Amoako, Afua; Gopaul, Karen; Islam, Anam; Borrie, Michael; Wells, Jennie; Speechley, Mark

    2015-01-01

    Gait deficits are prevalent in people with dementia and increase their fall risk and future disability. Few treatments exist for gait impairment in Alzheimer's disease (AD) but preliminary studies have shown that cognitive enhancers may improve gait in this population. To determine the efficacy of donepezil, a cognitive enhancer that improves cholinergic activity, on gait in older adults newly diagnosed with AD. Phase II clinical trial in 43 seniors with mild AD who received donepezil. Participants had not previously received treatment with cognitive enhancers. Primary outcome variables were gait velocity (GV) and stride time variability (STV) under single and dual-task conditions measured using an electronic walkway. Secondary outcomes included attention and executive function. After four months of treatment, participants with mild AD improved their GV from 108.4 ± 18.6 to 113.3 ± 19.5 cm/s, p = 0.010; dual-task GV from 80.6 ± 23.0 to 85.3 ± 22.3 cm/s, p = 0.028. Changes in STV were in the expected direction although not statistically significant. Participants also showed improvements in Trail Making Tests A (p = 0.030), B (p = 0.001), and B-A (p = 0.042). Donepezil improved gait in participants with mild AD. The enhancement of dual-task gait suggests the positive changes achieved in executive function as a possible causal mechanism. This study yielded a clinically significant estimate of effect size; as well, the findings are relevant to the feasibility and ethics considerations for the design of a Phase III clinical trial.

  14. Plant-Derived Antimalarial Agents: New Leads and Efficient Phytomedicines. Part II. Non-Alkaloidal Natural Products

    Directory of Open Access Journals (Sweden)

    Alaíde Braga de Oliveira

    2009-08-01

    Full Text Available Malaria is still the most destructive and dangerous parasitic infection in many tropical and subtropical countries. The burden of this disease is getting worse, mainly due to the increasing resistance of Plasmodium falciparum against the widely available antimalarial drugs. There is an urgent need for new, more affordable and accessible antimalarial agents possessing original modes of action. Natural products have played a dominant role in the discovery of leads for the development of drugs to treat human diseases, and this fact anticipates that new antimalarial leads may certainly emerge from tropical plant sources. This present review covers most of the recently-published non-alkaloidal natural compounds from plants with antiplasmodial and antimalarial properties, belonging to the classes of terpenes, limonoids, flavonoids, chromones, xanthones, anthraquinones, miscellaneous and related compounds, besides the majority of papers describing antiplasmodial crude extracts published in the last five years not reviewed before. In addition, some perspectives and remarks on the development of new drugs and phytomedicines for malaria are succinctly discussed.

  15. SU-E-J-35: Clinical Performance Evaluation of a Phase II Proton CT Scanner

    International Nuclear Information System (INIS)

    Mandapaka, A; Ghebremedhin, A; Farley, D; Giacometti, V; Vence, N; Bashkirov, V; Patyal, B; Schulte, R; Plautz, T; Zatserklyaniy, A; Johnson, R; Sadrozinski, H

    2014-01-01

    Purpose: To develop the methodology to evaluate the clinical performance of a Phase II Proton CT scanner Methods: Range errors on the order of 3%-5% constitute a major uncertainty in current charged particle treatment planning based on Hounsfield Unit (HU)-relative stopping power (RSP) calibration curves. Within our proton CT collaboration, we previously developed and built a Phase I proton CT scanner that provided a sensitive area of 9 cm (axial) × 18 cm (in-plane). This scanner served to get initial experience with this new treatment planning tool and to incorporate lessons learned into the next generation design. A Phase II scanner was recently completed and is now undergoing initial performance testing. It will increase the proton acquisition rate and provide a larger detection area of 9 cm x 36 cm. We are now designing a comprehensive evaluation program to test the image quality, imaging dose, and range uncertainty associated with this scanner. The testing will be performed along the lines of AAPM TG 66. Results: In our discussion of the evaluation protocol we identified the following priorities. The image quality of proton CT images, in particular spatial resolution and low-density contrast discrimination, will be evaluated with the Catphan600 phantom. Initial testing showed that the Catphan uniformity phantom did not provide sufficient uniformity; it was thus replaced by a cylindrical water phantom. The imaging dose will be tested with a Catphan dose module, and compared to a typical cone beam CT dose for comparable image quality. Lastly, we developed a dedicated dosimetry range phantom based on the CIRS pediatric head phantom HN715. Conclusion: A formal evaluation of proton CT as a new tool for proton treatment planning is an important task. The availability of the new Phase II proton CT scanner will allow us to perform this task. This research is supported by the National Institute of Biomedical Imaging and Bioengineering of the NIH under award number R01

  16. A clinical evaluation of a bioresorbable membrane and porous hydroxyapatite in the treatment of human molar class II furcations

    Directory of Open Access Journals (Sweden)

    K Gita Malathi

    2013-01-01

    Full Text Available Background: The ultimate goal of periodontal therapy is predictable regeneration of a functional attachment apparatus destroyed as a result of periodontitis. Reconstructive procedures have been used with varying success during the past decades to accomplish this goal. Aim: To evaluate whether the use of porous hydroxyapatite alone or a bioresorbable membrane alone would enhance the clinical results in the treatment of class II furcation defects in human lower molars. Materials and Methods: Fifteen patients with chronic periodontitis, aged between 39 and 49 years, with a pair of similar bilateral class II furcation defects (classification of Hamp et al. in mandibular first molars were selected. A split-mouth design was incorporated and the selected 30 furcation defects were assigned to one of the two treatment groups, i.e., Group I treated with a bioresorbable membrane from bovine-derived collagen guided tissue regeneration membrane and Group II treated using porous hydroxyapatite bone graft material on the contralateral sides. Evaluation of clinical parameters, probing depths and attachment levels, and radiographs was done preoperatively and 6 months postoperatively. Results: Both the groups showed statistically significant mean reduction in probing depths and gain in clinical attachment levels and linear bone fill. Comparison between Group I and Group II showed insignificant difference. Conclusion: Within the limits of this study, both the treatment modalities are beneficial for the treatment of human mandibular class II furcation defects.

  17. Application of ICHD-II criteria in a headache clinic of China.

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    Zhao Dong

    Full Text Available China has the huge map and the largest population in the world. Previous studies on the prevalence and classification of headaches were conducted based on the general population, however, similar studies among the Chinese outpatient population are scarce. This study aimed to analyze the characteristics of 1843 headache patients enrolled in a North China headache clinic of the General Hospital for Chinese People's Liberation Army from October 2011 to May 2012, with the International Classification of Headache Disorders, 2nd Edition (ICHD-II.Personal interviews were carried out and a detailed questionnaire was used to collect medical records including age, sex and headache characteristics. Patients came from 28 regions of China with the median age of 40.9 (9-80 years and the female/male ratio of 1.67/1. The primary headaches (78.4% were classified as the following: migraine (39.1%, tension-type headache (32.5%, trigeminal autonomic cephalalgias (5.3% and other primary headache (1.5%. Among the rest patients, 12.9% were secondary headaches, 5.9% were cranial neuralgias and 2.5% were unspecified or not elsewhere classified. Fourteen point nine percent (275/1843 were given an additional diagnosis of chronic daily headache, including medication-overuse headache (MOH, 49.5%, chronic tension-type headache (CTTH, 32.7% and chronic migraine (CM, 13.5%. The visual analogue scale (VAS score of TTH with MOH was significantly higher than that of CTTH (6.8±2.0 vs 5.6±2.0, P<0.001. The similar result was also observed in VAS score between migraine with MOH and CM (8.0±1.5 vs 7.0±1.5, P = 0.004. The peak age at onset of TTH for male and female were both in the 3(rd decade of life. However, the age distribution at onset of migraine shows an obvious sex difference, i.e. the 2(nd decade for females and the 1(st decade for males.This study revealed the characteristics of the headache clinic outpatients in a tertiary hospital of North China that migraine is

  18. Trans- and cis-2-phenylindole platinum(II) complexes as cytotoxic agents against human breast adenocarcinoma cell lines

    Science.gov (United States)

    Tomé, Maria; López, Concepción; González, Asensio; Ozay, Bahadir; Quirante, Josefina; Font-Bardía, Mercè; Calvet, Teresa; Calvis, Carme; Messeguer, Ramon; Baldomá, Laura; Badía, Josefa

    2013-09-01

    The synthesis and characterization of the new 2-phenylindole derivative: C8H3N-2-C6H5-3NOMe-5OMe (3c) and the trans- and cis-isomers of [Pt(3c)Cl2(DMSO)] complexes (4c and 5c, respectively) are described. The crystal structures of 4c·CH2Cl2 and 5c confirm: (a) the existence of a Pt-Nindole bond, (b) the relative arrangement of the Cl- ligands [trans- (in 4c) or cis- (in 5c)] and (c) the anti-(E) configuration of the oxime. The cytotoxic assessment of C8H3N-2-(C6H4-4‧R1)-3NOMe-5R2 [with R1 = R2 = H (3a); R1 = Cl, R2 = H (3b) and R1 = H, R2 = OMe (3c)] and the geometrical isomers of [Pt(L)Cl2(DMSO)] with L = 3a-3c [trans- (4a-4c) and cis- (5a-5c), respectively] against human breast adenocarcinoma cell lines (MDA-MB231 and MCF-7) is also reported and reveals that all the platinum(II) complexes (except 4a) are more cytotoxic than cisplatin in front of the MCF7 cell line. Electrophoretic DNA migration studies of the synthesized compounds in the absence and in the presence of topoisomerase-I have been performed, in order to get further insights into their mechanism of action.

  19. Clinical performance of a glass ionomer sealant protected with two different resin-based agents over a 2-year follow-up period.

    Science.gov (United States)

    Ulusoy, A T; Tunc, E S; Bayrak, Ş

    2017-03-01

    To evaluate the effects of two different resin coating materials on the clinical performance of a conventional glass ionomer sealant. Permanent first mandibular molars of 60 children aged 6-9 years were sealed with Fuji VII. In each child, G-Coat Plus coating agent was applied to molars on one side and Heliobond coating agent to molars on the opposite side of the mouth. Clinical evaluations were carried out at 1, 6, 12, 18 and 24 months after sealant and coating application. At 1, 6, 12, 18 and 24 months after sealant and coating application, total sealant retention rates were 88%, 40%, 19%, 15% and 9% for molars coated with G-Coat Plus, and 93%, 47%, 17%, 15% and 7% for those coated with Heliobond. The differences between the two coating agents were not statistically significant (p>0.05). No incidence of caries was observed in either group during the two-year evaluation period. Wilcoxon signed rank test was used to compare differences in retention rates and caries incidence by coating agent. Although retention rates of Fuji VII were relatively low and similar for both resin coating agents tested, dental caries were not observed in either group during the 24-month study period. In children with a high risk of caries and partially erupted molars, the use of a glass ionomer sealant with a resin-based coating agent should be encouraged.

  20. Prospective double blind randomized placebo-controlled clinical trial of the pectoral nerves (Pecs) block type II

    NARCIS (Netherlands)

    Versyck, B.; Geffen, G.J. van; Houwe, P. Van

    2017-01-01

    STUDY OBJECTIVE: The aim of this clinical trial was to test the hypothesis whether adding the pectoral nerves (Pecs) block type II to the anesthetic procedure reduces opioid consumption during and after breast surgery. DESIGN: A prospective randomized double blind placebo-controlled study. SETTING:

  1. Phase II Clinical Trial of Robotic Stereotactic Body Radiosurgery for Metastatic Gynecologic Malignancies

    International Nuclear Information System (INIS)

    Kunos, Charles A.; Brindle, James; Waggoner, Steven; Zanotti, Kristine; Resnick, Kimberly; Fusco, Nancy; Adams, Ramon; Debernardo, Robert

    2012-01-01

    Background: Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT) in women with metastatic gynecologic cancers. Methods: A total of 50 patients with recurrent gynecologic cancer who had single or multiple (≤4) metastases underwent robotic-armed Cyberknife SBRT (24Gy/3 daily doses). Toxicities were graded prospectively by common toxicity criteria for adverse events (version 4.0). SBRT target responses were recorded following RECIST criteria (version 1.0). Rates of clinical benefit for SBRT and non-radiosurgical disease relapse were calculated. Disease-free and overall survivals were estimated by the Kaplan–Meier method and the Cox proportional hazards model was used to control for prognostic variables. Findings: SBRT was safely delivered, with 49 (98%) of 50 patients completing three prescribed fractions. The most frequent grade 2 or higher adverse events attributed to SBRT included fatigue (16%), nausea (8%), and diarrhea (4%). One (2%) grade four hyperbilirubinemia occurred. SBRT target response was 96% (48 of 50 patients). A 6-month clinical benefit was recorded in 34 [68% (95% CI, 53.2, 80.1)] patients. No SBRT targeted disease progressed. Non-radiosurgical disease relapse occurred in 31 (62%) patients. Median disease-free survival was 7.8 months (95% CI, 4.0, 11.6). Median overall survival was 20.2 months (95% CI, 10.9, 29.5). Interpretation: SBRT safely controlled metastatic gynecologic cancer targets. Given an observed high rate of non-radiosurgical disease relapse, a phase I trial assessing co-administration of SBRT and cytotoxic chemotherapy is underway. Funding: Case Comprehensive Cancer Center.

  2. Phase II clinical trial of robotic stereotactic body radiosurgery for metastatic gynecologic malignancies

    Directory of Open Access Journals (Sweden)

    Charles eKunos

    2012-12-01

    Full Text Available Background Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT in women with metastatic gynecologic cancers. Methods A total of 50 patients with recurrent gynecologic cancer who had single or multiple (≤4 metastases underwent robotic-armed Cyberknife SBRT (24Gy/3 daily doses. Toxicities were graded prospectively by common toxicity criteria for adverse events (version 4.0. SBRT target responses were recorded following RECIST criteria (version 1.0. Rates of clinical benefit for SBRT and non-radiosurgical disease relapse were calculated. Disease-free and overall survivals were estimated by the Kaplan-Meier method and the Cox proportional hazards model was used to control for prognostic variables.Findings SBRT was safely delivered, with 49 (98% of 50 patients completing three prescribed fractions. The most frequent grade 2 or higher adverse events attributed to SBRT included fatigue (16%, nausea (8% and diarrhea (4%. One (2% grade 4 hyperbilirubinemia occurred. SBRT target response was 96% (48 of 50 patients. A 6-month clinical benefit was recorded in 34 (68% [95% CI, 53.2, 80.1] patients. No SBRT-targeted disease progressed. Non-radiosurgical disease relapse occurred in 31 (62% patients. Median disease-free survival was 7.8 months (95% CI, 4.0, 11.6. Median overall survival was 20.2 months (95% CI, 10.9, 29.5.Interpretation SBRT safely controlled metastatic gynecologic cancer targets. Given an observed high rate of non-radiosurgical disease relapse, a phase I trial assessing co-administration of SBRT and cytotoxic chemotherapy is underway.Funding Case Comprehensive Cancer Center

  3. Phase II Clinical Trial of Robotic Stereotactic Body Radiosurgery for Metastatic Gynecologic Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Kunos, Charles A.; Brindle, James [Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University, School of Medicine, Cleveland, OH (United States); Waggoner, Steven; Zanotti, Kristine; Resnick, Kimberly; Fusco, Nancy; Adams, Ramon; Debernardo, Robert, E-mail: charles.kunos@uhhospitals.org [Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University Hospitals Case Medical Center and Case Western Reserve University, School of Medicine, Cleveland, OH (United States)

    2012-12-05

    Background: Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT) in women with metastatic gynecologic cancers. Methods: A total of 50 patients with recurrent gynecologic cancer who had single or multiple (≤4) metastases underwent robotic-armed Cyberknife SBRT (24Gy/3 daily doses). Toxicities were graded prospectively by common toxicity criteria for adverse events (version 4.0). SBRT target responses were recorded following RECIST criteria (version 1.0). Rates of clinical benefit for SBRT and non-radiosurgical disease relapse were calculated. Disease-free and overall survivals were estimated by the Kaplan–Meier method and the Cox proportional hazards model was used to control for prognostic variables. Findings: SBRT was safely delivered, with 49 (98%) of 50 patients completing three prescribed fractions. The most frequent grade 2 or higher adverse events attributed to SBRT included fatigue (16%), nausea (8%), and diarrhea (4%). One (2%) grade four hyperbilirubinemia occurred. SBRT target response was 96% (48 of 50 patients). A 6-month clinical benefit was recorded in 34 [68% (95% CI, 53.2, 80.1)] patients. No SBRT targeted disease progressed. Non-radiosurgical disease relapse occurred in 31 (62%) patients. Median disease-free survival was 7.8 months (95% CI, 4.0, 11.6). Median overall survival was 20.2 months (95% CI, 10.9, 29.5). Interpretation: SBRT safely controlled metastatic gynecologic cancer targets. Given an observed high rate of non-radiosurgical disease relapse, a phase I trial assessing co-administration of SBRT and cytotoxic chemotherapy is underway. Funding: Case Comprehensive Cancer Center.

  4. The Clinical and Economic Impact of Generic Locking Plate Utilization at a Level II Trauma Center.

    Science.gov (United States)

    Mcphillamy, Austin; Gurnea, Taylor P; Moody, Alastair E; Kurnik, Christopher G; Lu, Minggen

    2016-12-01

    In today's climate of cost containment and fiscal responsibility, generic implant alternatives represent an interesting area of untapped resources. As patents have expired on many commonly used trauma implants, generic alternatives have recently become available from a variety of sources. The purpose of this study was to examine the clinical and economic impact of a cost containment program using high quality, generic orthopaedic locking plates. The implants available for study were anatomically precontoured plates for the clavicle, proximal humerus, distal radius, proximal tibia, distal tibia, and distal fibula. Retrospective review. Level II Trauma center. 828 adult patients with operatively managed clavicle, proximal humerus, distal radius, proximal tibia, tibial pilon, and ankle fractures. Operative treatment with conventional or generic implants. The 414 patients treated with generic implants were compared with 414 patients treated with conventional implants. There were no significant differences in age, sex, presence of diabetes, smoking history or fracture type between the generic and conventional groups. No difference in operative time, estimated blood loss or intraoperative complication rate was observed. No increase in postoperative infection rate, hardware failure, hardware loosening, malunion, nonunion or need for hardware removal was noted. Overall, our hospital realized a 56% reduction in implant costs, an average savings of $1197 per case, and a total savings of $458,080 for the study period. Use of generic orthopaedic implants has been successful at our institution, providing equivalent clinical outcomes while significantly reducing implant expenditures. Based on our data, the use of generic implants has the potential to markedly reduce operative costs as long as quality products are used. Therapeutic Level III.

  5. Comparative clinical characteristics of depression in bipolar affective disorders types I and II

    Directory of Open Access Journals (Sweden)

    N. A. Tyuvina

    2016-01-01

    Full Text Available Objective: to investigate the clinical features of depression within bipolar affective disorders types I and II (BADI and BADII.Patients and methods. An examination was made in 100 depressive patients, including 25 with BADI, 37 with BADII, and 38 with recurrent depressive disorder (RDD (a comparison group. The patients' status was evaluated in accordance with the ICD-10 and DSM-V affective disorder criteria, by using a specially developed questionnaire.Results. BAD-related depression has features distinguishing it from RDD: sexual preference (men; an earlier age of disease onset; a shorter duration, but a higher frequency of exacerbations; a greater tendency for the continuum; a more marked decrease in social and family adaptation; development in people with predominantly hyperthymic premorbid; more frequently a family history of affective disorders, schizophrenia, and alcoholism; high comorbidity with metabolic diseases and psychoactive substance abuse; worse health more commonly in autumn and winter; a predominant anxious affect and an obviously decreasing interest in the structure of depression; a higher incidence of atypical sleep, appetite, and weight disorders; high suicidal activity; higher motor retardation (in BADI; relatively small involvement of somatic complaints in BAD I and frequent panic attacks in BADII.Conclusion. Knowledge of the specific features of BAD-related depression will be able to make a more accurate differential diagnosis and to perform more effective treatment in these patients.

  6. Clinical significance of nuclide renal dynamic imaging and urine microalbumin inspection of type II diabetic patients

    International Nuclear Information System (INIS)

    Wang Ying; Jin Yaoge; Shi Xueying; Gao Yong

    2011-01-01

    To investigate clinical value of glomerular filtration rate (GFR) and urine microalbumin in early diagnosis of diabetic nephropathy, GFR in 60 patients with type II diabetes mellitus and a control group of 20 were determined using 99 Tc m DTPA renal dynamic imaging and urine microalbumin. The following results were obtained.Among the 60 patients with diabetes, 5 patients had increased GFRs of, 142.0±13.6 mg/min, which was 35% higher than that of controls and differed significantly from the control (P<0.01); 20 patients had GFRs of 102.2±10.2 mg/min, which differed little from the control; and 35 patients had declined GFRs of 57.2±18.0 mg/min, which was 54.3% lowered than the control and differed significantly from the control (P<0.01). The urine microalbumin in diabetes patients was significantly higher than the control. In conclusion, the GFR is a good index of the early kidney injury in diabetic patients. The combined detection of GFR and urine microalbumin can improve the early diagnosis of diabetic nephropathy, and may help to monitor the treatment response and assess prognosis. (authors)

  7. Clinical practice guidelines for treatment of acne vulgaris: a critical appraisal using the AGREE II instrument.

    Science.gov (United States)

    Sanclemente, Gloria; Acosta, Jorge-Luis; Tamayo, Maria-Eulalia; Bonfill, Xavier; Alonso-Coello, Pablo

    2014-04-01

    A significant number of clinical practice guidelines (CPGs) about the treatment of acne vulgaris in adolescents and adults have been published worldwide. However, little is known about the quality of CPGs in this field. The aim of this study was to appraise the methodological quality of published acne vulgaris CPGs. We performed a systematic review of published CPGs on acne vulgaris therapy from July 2002 to July 2012. Three reviewers independently assessed each CPG using the AGREE II instrument. A standardized score was calculated for each of the six domains. Our search strategy identified 103 citations but just six met our inclusion criteria. Agreement among reviewers was very good: 0.981. The domains that scored better were: "scope and purpose" and "clarity and presentation". Those that scored worse were "stakeholder involvement", "rigor of development", and "applicability". The European and the Malaysian CPGs were the only recommended with no further modifications. In addition, the Mexican, Colombian and the United States guidelines were recommended with provisos, with lower scores regarding stakeholder involvement, rigor of development and applicability. Only two guidelines clearly reported outcome measures for evaluating efficacy or included quality of life outcomes. CPGs varied regarding the consideration of light/laser therapy or consideration of complementary/alternative medicines. None of them included cost considerations of drugs such as systemic isotretinoin. In conclusion, published acne vulgaris CPGs for acne therapy vary in quality with a clear need to improve their methodological rigor. This could be achieved with the adherence to current CPGs development standards.

  8. Clinical Evaluation of applying a hydrophobic and a hydrophilic bonding agent on the retention and durability of fissure sealant therapy

    Directory of Open Access Journals (Sweden)

    Mostafa GHandi

    2016-03-01

    Full Text Available Background and Aims: As in fissure sealant therapy the tooth surface is mostly enamel, the use of an enamel bonding agent (hydrophobic bonding agent may be more cost effective than that of newer generations of bonding (hydrophilic bonding agents. The aim of this study was to compare the retention and durability of fissure sealant therapy when applying an enamel bonding agent, a dentin bonding agent and no bonding agent during 4 years. Materials and Methods: This study was done on the first permanent molars of the upper and lower jaws of 24 students of the first grade of a primary school (6-7 years old. On 36 teeth, a dentin bonding agent (Excite was applied under the fissure sealant and on 36 teeth an enamel bonding agent (Margin bond was applied under the fissure sealant. Then, 24 teeth were selected from these two groups and were compared with a group (including 24 teeth with no bonding agent under the fissure sealant (as control group. All the fissures of the teeth were evaluated annually for 4 years to find out the presence or absence of fissure sealant substance. Data were analyzed using Wilcoxon test. Results: From the statistical analysis, there was no significant difference in retention and durability of the fissure sealant substance comparing the group with dentin bonding agent (Excite and the group with enamel bonding agent (Margin bond. Also, using a bonding agent made no significant difference (P>0.05. Conclusion: According to the results of this study, using a bonding agent made no improvement in the retention and durability of fissure sealant substance.

  9. [Susceptibility surveillance of clinical isolates to fluoroquinolone antimicrobial agents from 2003 to 2008: post-marketing study of prulifloxacin].

    Science.gov (United States)

    Kawai, Shin; Yoshida, Atsushi; Okazaki, Mitsuhiro; Tsujihara, Yoshito; Inuzuka, Kazuhisa; Takeuchi, Kazuhide; Yamashita, Naoko; Onodera, Makoto; Hiraishi, Toru; Ida, Takashi; Maebashi, Kazunori

    2010-06-01

    Yearly changes in the susceptibility of clinical isolates to ulifloxacin (UFX) and other fluoroquinolones were examined through surveys over 3 periods. In the first survey, 534 strains derived from 19 species were collected from clinical specimens during 6 months from December 2003 to May 2004. In the same way, 805 strains were collected from December 2005 to May 2006 in the second survey, and 863 strains were from December 2007 to May 2008 in the third survey. Over these 3 study periods, the susceptibilities of fluoroquinolones against methicillin-susceptible Staphylococcus aureus and Escherichia coli were decreased. The isolation frequency of levofloxacin-nonsusceptible strain was increased from 0% to 11.8% and from 14.6% to 20.8%, respectively. MIC90s of UFX against these pathogens were also increased, but its MIC90 for E. coli was 2 to 4 times lower than that of levofloxacin. On the other hand, the susceptibility of strains of Klebsiella pneumoniae to UFX was increased. Among the fluoroquinolones tested, UFX showed the most potent activity against Pseudomonas aeruginosa, and no changes in the MIC90s occurred during the surveillance. Although one strain of Streptococcus pneumoniae isolated in the third study period showed levofloxacin-resistance (MIC, 8 microg/mL), there were nearly no changes in the MIC90s of any agents tested including UFX against S. pneumoniae during the surveillance. As for other bacterial species, a tendency to increase in resistance to UFX was not observed. The activity of UFX against Salmonella spp. and Shigella spp. was superior/equal to those of fluoroquinolones tested.

  10. Mycoplasma genitalium Compared to Chlamydia, Gonorrhea and Trichomonas as an Etiologic Agent of Urethritis in Men Attending STD Clinics

    Science.gov (United States)

    Gaydos, Charlotte; Maldeis, Nancy E.; Hardick, Andrew; Hardick, Justin; Quinn, Thomas C.

    2009-01-01

    Objectives This purpose of this study was to investigate prevalence of M. genitalium C. trachomatis, N. gonorrhoeae, and T. vaginalis in men, frequency of coinfections, and relationships among organisms with urethritis in men. Methods This was a cross-sectional study of 290 men (age range 19-34 yr) attending Baltimore City STD Clinics. M. genitalium, C. trachomatis, N. gonorrhoeae, and T. vaginalis, during 2004 were detected using nucleic acid amplification tests (NAATs). (N = 153 with urethritis and 137 without urethritis). Demographic characteristics and risk factors were ascertained. Results The overall prevalences of infection with C. trachomatis, N. gonorrhoeae, T. vaginalis, and M. genitalium, were 20.3%, 12.8%, 3.4%, and 15.2% respectively. Prevalences in men with urethritis were 32.7%, 24.2%, 5.2%, and 22.2% for C. trachomatis, N. gonorrhoeae, T. vaginalis, and M. genitalium, respectively. Percentages of coinfections were high. All men with N. gonorrhoeae had urethritis. C. trachomatis and M. genitalium were found to be significantly associated with urethritis in univariate analysis and in multiple logistic regression analysis. Conclusion The association of M. genitalium with urethritis in this study provides confirmation of the importance of screening men for M. genitalium as a cause of non-gonococcal urethritis and supports treatment considerations for urethritis for agents other than gonococci and chlamydia. Short Summary Men attending STD clinics were found to have high prevalences of M. genitalium (MG), C. trachomatis (CT), and N. gonorrhoeae (NG); moderate prevalence of T. vaginalis. MG was associated with urethritis in addition to NG and CT. PMID:19383597

  11. Determining the agent factors related with time management of responsible doctors and nurses in clinics at Ankara University hospitals.

    Science.gov (United States)

    Acuner, Ahmet Munir; Nilgun, Sarp; Cifteli, F Gulay

    2006-01-01

    This research has been planned and conducted as a descriptive scanning model field study in order to determine the agent factors related with time management of doctors and nurses in positions of responsibility at Ankara University hospitals. As data collection instruments; the "Personal Information Form" which has been developed to determine the socio-demographical characteristics of the research group, the questionnaire of "Determining the Time Management Attitudes and Behaviour of Managers, Time Management Opportunities of the Managers, Prodcutive Working Times of the Managers and the Factors Causing Them to Lose Time", developed by Erdem has been used. It has been determined that the time management attitudes and behaviour of doctors, nurses and nurse assistants responsible for clinics are all different. It was found that nurse assistants graduated from pre-undergraduate or high schools are the least conscious of time management. In particular, nurse assistants of 36 years old and over with 21 years of work experience and 11 years of management experience show little awareness of time management. The time losing factors of the research group were found to be unnecessary visitors, lack of materials and the excessive amount of time spent on obtaining the necessary equipment.

  12. Mycoplasma genitalium compared to chlamydia, gonorrhoea and trichomonas as an aetiological agent of urethritis in men attending STD clinics.

    Science.gov (United States)

    Gaydos, C; Maldeis, N E; Hardick, A; Hardick, J; Quinn, T C

    2009-10-01

    To investigate prevalence of Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in men, frequency of co-infections, and association of organisms with urethritis in men. This was a cross-sectional study of 290 men (age range 19-34 years) attending Baltimore City STD clinics. M genitalium, C trachomatis, N gonorrhoeae and T vaginalis, during 2004 were detected using nucleic acid amplification tests (NAATs) (153 with urethritis and 137 without urethritis). Demographic characteristics and risk factors were ascertained. The overall prevalences of infection with C trachomatis, N gonorrhoeae, T vaginalis and M genitalium were 20.3%, 12.8%, 3.4% and 15.2%, respectively. Prevalences in men with urethritis were 32.7%, 24.2%, 5.2% and 22.2% for C trachomatis, N gonorrhoeae, T vaginalis and M genitalium, respectively. Percentages of co-infections were high. All men with N gonorrhoeae had urethritis. C trachomatis and M genitalium were found to be significantly associated with urethritis in univariate analysis and in multiple logistic regression analysis. The association of M genitalium with urethritis in this study provides confirmation of the importance of screening men for M genitalium as a cause of non-gonococcal urethritis and supports treatment considerations for urethritis for agents other than gonococci and chlamydia.

  13. Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update.

    Science.gov (United States)

    Bautista, Francisco; Fioravantti, Victoria; de Rojas, Teresa; Carceller, Fernando; Madero, Luis; Lassaletta, Alvaro; Moreno, Lucas

    2017-11-01

    Survival rates for patients with medulloblastoma have improved in the last decades but for those who relapse outcome is dismal and new approaches are needed. Emerging drugs have been tested in the last two decades within the context of phase I/II trials. In parallel, advances in genetic profiling have permitted to identify key molecular alterations for which new strategies are being developed. We performed a systematic review focused on the design and outcome of early-phase trials evaluating new agents in patients with relapsed medulloblastoma. PubMed, clinicaltrials.gov, and references from selected studies were screened to identify phase I/II studies with reported results between 2000 and 2015 including patients with medulloblastoma aged <18 years. A total of 718 studies were reviewed and 78 satisfied eligibility criteria. Of those, 69% were phase I; 31% phase II. Half evaluated conventional chemotherapeutics and 35% targeted agents. Overall, 662 patients with medulloblastoma/primitive neuroectodermal tumors were included. The study designs and the response assessments were heterogeneous, limiting the comparisons among trials and the correct identification of active drugs. Median (range) objective response rate (ORR) for patients with medulloblastoma in phase I/II studies was 0% (0-100) and 6.5% (0-50), respectively. Temozolomide containing regimens had a median ORR of 16.5% (0-100). Smoothened inhibitors trials had a median ORR of 8% (3-8). Novel drugs have shown limited activity against relapsed medulloblastoma. Temozolomide might serve as backbone for new combinations. Novel and more homogenous trial designs might facilitate the development of new drugs. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  14. Comparative Analysis between preoperative Radiotherapy and postoperative Radiotherapy in Clinical Stage I and II Endometrial Carcinoma

    International Nuclear Information System (INIS)

    Keum, Ki Chang; Lee, Chang Geol; Chung, Eun Ji; Lee, Sang Wook; Kim, Woo Cheol; Chang, Sei Kyung; Oh, Young Taek; Suh, Chang Ok; Kim, Gwi Eon

    1995-01-01

    Purpose : To obtain the optical treatment method in patients with endometrial carcinoma(clinical stage FIGO I, II) by comparative analysis between preoperative radiotherapy(pre-op R) and postoperative radiotherapy(post-op RT). Materials and Methods : A retrospective review of 62 endometrial carcinoma patients referred to the Yonsei Cancer Center for radiotherapy between 1985 and 1991 was undertaken. Of 62 patients, 19 patients(Stage I; 12 patients, Stage II; 7 patients) received pre-op RT before TAH(Total Abdominal Hysterectomy) and BSO(Bilateral Salphingoophorectomy) (Group 1) and 43 patients( Stage 1; 32 patients, Stage 2; 11 patients) received post-op RT after TAH and BSO (Group 2). Pre-op irradiation was given 4-6 weeks prior to surgery and post-op RT was administered on 4-5 weeks following surgery. All patients exept 1 patient(Group2; ICR alone) received external irradiation. Seventy percent(13/19) of pre-op RT group and 54 percent(23/42) of post-op RT group received external pelvic irradiation and intracavitary radiation therapy(ICR). External radiation dose was 39.6-55Gy(median 45Gy) in 5-6 week through opposed AP/PA fields or 4-field box technique treating daily, five days per week, 180cGy per fraction. ICR doses were prescribed to point A(20-39.6 Gy, median 39Gy) in Group 1 and 0.5cm depth from vaginal surface (18-30 Gy, median 21Gy) in Group2. Results : The overall 5 year survival rate was 95%. No survival difference between pre-op and post-op RT group.(89.3% vs 97.7%, p>0.1) There was no survival difference by stage, grade and histology between two groups. The survival rate was not affected by presence of residual tumor of surgical specimen after pre-op RT in Group 1(p>0.1), but affected by presence of lymph node metastasis in post-op RT group(p<0.5). The complication rate of pre-op RT group was higher than post-op RT.(16% vs 5%) Conclusion : Post-op radiotherapy offers the advantages of accurate surgical-pathological staging and low complication rate

  15. Overall survival patterns in patients with multiple myeloma in the era of novel agents and the role of initial clinical presentation and comorbidities: A population-based study

    NARCIS (Netherlands)

    Oortgiesen, Berdien; Van Roon, Eric N.; Joosten, Peter; Kibbelaar, Robby; Storm, Huib; Hovenga, Sjoerd; Van Rees, Bas P.; Woolthuis, Gerhard; Veeger, Nic J. G. M.; Hoogendoorn, Mels

    2014-01-01

    Introduction Clinical trials have shown improved response rates, progression-free survival and overall survival (OS) in patients with multiple myeloma (MM) when using the novel agents thalidomide, lenalidomide and bortezomib. However, outcome data provided by population-based registries, reflecting

  16. Phase 2 clinical study of 123I-IBF, a dopamine D2 receptor imaging agent, to evaluate clinical efficacy and safety in Parkinson's disease and Parkinson syndromes

    International Nuclear Information System (INIS)

    Torizuka, Kanji; Mizuno, Yoshikuni; Kubo, Atsushi

    1999-01-01

    A Phase 2 multicenter trial of 123 I-IBF, (S)-5-iodo-7-N-[(1-ethyl-2-pyrrolidinyl)methyl] carboxamido-2,3-dihydrobenzofuran, was conducted to evaluate its clinical efficacy and safety in 158 patients with Parkinson's disease (PD) or Parkinson syndromes (PS). SPECT data were acquired at two hours (2H-SPECT), after intravenous injection of 123 I-IBF (167 MBq). Additional SPECT scan at three hours (3H-SPECT) and dynamic SPECT scan at most until one hour were performed when possible. No severe side effects due to 123 I-IBF injection were observed. The sensitivity, specificity and accuracy for discriminating PS from PD using the striatal specific binding count-to-frontal cortex count ratio (St/Fc-1) in 3H-SPECT were 72.7%, 81.0% and 78.1% in 64 clinically definite cases (i.e., typical cases), respectively. The putamen-to-caudate ratios were significantly lower in striatonigral degeneration compared with those in PD. The contralateral-to-ipsilateral ratios against the symptomatic side of tremor and/or rigidity in the patients with PD (Hoehn and Yahr I) were significantly higher than the left-to-right ratios in the normal controls. St/Fc-1 in 3H-SPECT was significantly lower in the patients showing a poor response to levodopa than in those showing a good response. The dopamine D 2 receptor binding potential (k 3 /k 4 ), obtained by dynamic SPECT based on compartment model analysis, correlated well with the striatal specific binding count-to-occipital cortex count ratio. These results suggest that 123 I-IBF is a promising agent for differential diagnosis and pathophysiological evaluation of PD and PS. (author)

  17. Usher syndrome clinical types I and II: could ocular symptoms and signs differentiate between the two types?

    Science.gov (United States)

    Tsilou, Ekaterini T; Rubin, Benjamin I; Caruso, Rafael C; Reed, George F; Pikus, Anita; Hejtmancik, James F; Iwata, Fumino; Redman, Joy B; Kaiser-Kupfer, Muriel I

    2002-04-01

    Usher syndrome types I and II are clinical syndromes with substantial genetic and clinical heterogeneity. We undertook the current study in order to identify ocular symptoms and signs that could differentiate between the two types. Sixty-seven patients with Usher syndrome were evaluated. Based on audiologic and vestibular findings, patients were classified as either Usher type I or II. The severity of the ocular signs and symptoms present in each type were compared. Visual acuity, visual field area, electroretinographic amplitude, incidence of cataract and macular lesions were not significantly different between Usher types I and II. However, the ages when night blindness was perceived and retinitis pigmentosa was diagnosed differed significantly between the two types. There seems to be some overlap between types I and II of Usher syndrome in regard to the ophthalmologic findings. However, night blindness appears earlier in Usher type I (although the difference in age of appearance appears to be less dramatic than previously assumed). Molecular elucidation of Usher syndrome may serve as a key to understanding these differences and, perhaps, provide a better tool for use in clinical diagnosis, prognosis and genetic counseling.

  18. Comparing the Suitability of Autodock, Gold and Glide for the Docking and Predicting the Possible Targets of Ru(II-Based Complexes as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Adebayo A. Adeniyi

    2013-03-01

    Full Text Available In cancer chemotherapy, metal-based complexes have been recognized as the most promising means of inhibiting cancer growth due to the successful application of cis-platin and its derivatives above many of the existing organic anticancer agents. The limitations in their rational design can be traced to the complexity of the mechanism of their operations, lack of proper knowledge of their targets and lack of force fields in docking packages to appropriately define the metal centre of the organometallic complexes. In this paper, some of the promising anticancer complexes of Ru(II such as the rapta-based complexes formulated as [Ru(η6-p-cymeneL2(pta] and those with unusual ligands are considered. CatB and kinases which have been experimentally confirmed as possible targets of the complexes are also predicted by the three methods as one of the most targeted receptors while TopII and HDAC7 are predicted by two and one of the methods as best targets. The interesting features of the binding of the complexes show that some of the complexes preferentially target specific macromolecules than the others, which is an indication of their specificity and possibility of their therapeutic combination without severe side effects that may come from competition for the same target. Also, introduction of unusual ligands is found to significantly improve the activities of most of the complexes studied. Strong correlations are observed for the predicted binding sites and the orientation of the complexes within the binding site by the three methods of docking. However there are disparities in the ranking of the complexes by the three method of docking, especially that of Glide.

  19. Nimotuzumab combined with radiotherapy for esophageal cancer: preliminary study of a Phase II clinical trial

    Directory of Open Access Journals (Sweden)

    Liang J

    2013-11-01

    Full Text Available Jun Liang,1 Mingyan E,2 Gang Wu,3 Lujun Zhao,4 Xia Li,5 Xia Xiu,6 Ning Li,1 Bo Chen,1 Zhouguang Hui,1 Jima Lv,1 Hui Fang,1 Yu Tang,1 Nan Bi,1 Wenqing Wang,1 Yirui Zhai,1 Tao Li,1 Dongfu Chen,1 Shuangmei Zou,7 Ning Lu,7 Rolando Perez-Rodríguez,8 Junqi Zheng,9 Luhua Wang11Department of Radiotherapy, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China; 2Department of Radiotherapy, Cancer Hospital of Harbin Medical University, Harbin, People's Republic of China; 3Department of Radiotherapy, Tongji Cancer Center Hospital, Wuhan, People's Republic of China; 4Department of Radiotherapy, Cancer Hospital of Tianjin Medical University, Tianjin, People's Republic of China; 5Department of Radiotherapy, LiaoNing Province Cancer Hospital, Shenyang, People's Republic of China; 6Department of Radiotherapy, Beijing Hospital, Beijing, People's Republic of China; 7Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China; 8Center of Molecular Immunology, Havana, Cuba; 9School of Medicine, Tongji University, Shanghai, People's Republic of ChinaObjective: To determine the safety and therapeutic effects of nimotuzumab (h-R3 combined with radiotherapy in esophageal cancer.Methods: This Phase II clinical trial involved 42 patients with stage II (inoperable or refused surgery to stage IV (supraclavicular lymph node metastasis only esophageal cancers treated between November 2008 and July 2010. All patients had squamous cell carcinomas, and all received three-dimensional conformal radiotherapy and 200 mg nimotuzumab per week during radiotherapy.Results: There were 9, 25, and 8 patients with stage II, III and IV disease, respectively. All except two patients received 50–70 Gy radiation; 37 patients (88.1% received more than five nimotuzumab doses. Grade III toxicities (21.4% of all adverse events included esophagitis and gastrointestinal, dermatological and hematological

  20. The clinical-familial correlates and naturalistic outcome of panic-disorder-agoraphobia with and without lifetime bipolar II comorbidity

    Directory of Open Access Journals (Sweden)

    Toni Cristina

    2008-11-01

    Full Text Available Abstract Background Much of the literature on panic disorder (PD-bipolar disorder (BP cormorbidity concerns BP-I. This literature emphasizes the difficulties encountered in pharmacologic treatment and outcome when such comorbidity is present. The present report explores these issues with respect to BP-II. Methods The sample comprised 326 outpatients (aged 34.5 ± 11.5 years old; 222 females with Diagnostic and Statistical Manual of Mental Disorders 3rd edn, revised (DSM-III-R PD-agoraphobia; among them 52 subjects (16% were affected by lifetime comorbidity with BP-II. Patients were evaluated by means of the Structured Clinical Interview for DSM-IV (SCID, the Panic-Agoraphobia Interview, and the Longitudinal Interview Follow-up Examination (Life-Up and treated according to routine clinical practice at the University of Pisa, Italy, for a period of 3 years. Clinical and course features were compared between subjects with and without BP-II. All patients received the clinicians' choice of antidepressants and, in the case of the subsample with BP-II, mood stabilizers (for example, valproate, lithium were among the mainstays of treatment. Results In comparison to patients without bipolar comorbidity, those with BP-II showed a significantly greater frequency of social phobia, obsessive-compulsive disorder, alcohol-related disorders, and separation anxiety during childhood and adolescence. Regarding family history, a significantly greater frequency of PD and mood disorders was present among the BP-II. No significant differences were observed in the long-term course of PD or agoraphobic symptoms under pharmacological treatment or the likelihood of spontaneous pharmacological treatment interruptions. Conclusion Although the severity and outcome of panic-agoraphobic symptomatology appear to be similar in patients with and without lifetime bipolar comorbidity, the higher number of concomitant disorders in our PD patients with BP-II does indicate a greater

  1. Parents as Agents of Change (PAC in pediatric weight management: The protocol for the PAC randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Ball Geoff D C

    2012-08-01

    Full Text Available Abstract Background There is an urgent need to develop and evaluate weight management interventions to address childhood obesity. Recent research suggests that interventions designed for parents exclusively, which have been named parents as agents of change (PAC approaches, have yielded positive outcomes for managing pediatric obesity. To date, no research has combined a PAC intervention approach with cognitive behavioural therapy (CBT to examine whether these combined elements enhance intervention effectiveness. This paper describes the protocol our team is using to examine two PAC-based interventions for pediatric weight management. We hypothesize that children with obesity whose parents complete a CBT-based PAC intervention will achieve greater reductions in adiposity and improvements in cardiometabolic risk factors, lifestyle behaviours, and psychosocial outcomes than children whose parents complete a psycho-education-based PAC intervention (PEP. Methods/Design This study is a pragmatic, two-armed, parallel, single-blinded, superiority, randomized clinical trial. The primary objective is to examine the differential effects of a CBT-based PAC vs PEP-based PAC intervention on children’s BMI z-score (primary outcome. Secondary objectives are to assess intervention-mediated changes in cardiometabolic, lifestyle, and psychosocial variables in children and parents. Both interventions are similar in frequency of contact, session duration, group facilitation, lifestyle behaviour goals, and educational content. However, the interventions differ insofar as the CBT-based intervention incorporates theory-based concepts to help parents link their thoughts, feelings, and behaviours; these cognitive activities are enabled by group leaders who possess formal training in CBT. Mothers and fathers of children (8–12 years of age; BMI ≥85th percentile are eligible to participate if they are proficient in English (written and spoken and agree for at least

  2. Ultrasensitive detection of pepsinogen I and pepsinogen II by a time-resolved fluoroimmunoassay and its preliminary clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Huang Biao [Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province 214063 (China) and Southern Yangzi University, Wuxi, Jiangsu Province 214036 (China)]. E-mail: huangbiao78@hotmail.com; Xiao Hualong [Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province 214063 (China); Zhang Xiangrui [Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province 214063 (China); Zhu, Lan [Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province 214063 (China); Liu Haiyan [Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province 214063 (China); Jin Jian [Southern Yangzi University, Wuxi, Jiangsu Province 214036 (China)

    2006-06-30

    .8 {+-} 7.4 for the PG I/PG II ratio. The normal ranges of Serum PG I levels for healthy volunteers were 58.2-266.6 {mu}g L{sup -1}, and those of serum PG II levels were less than 25.3 {mu}g L{sup -1}. The availability of a highly sensitive, reliable, and convenient PG-TRFIA method for quantifying PG will allow investigations into the possible diagnostic value of this analysis in various clinical conditions, including gastric carcinoma, duodenal ulcer, gastric ulcer and gastritis. The sensitivity and reproducibility of the assay were satisfactory for clinical applications.

  3. Polypharmacy as a Risk Factor for Clinically Relevant Sarcopenia: Results From the Berlin Aging Study II.

    Science.gov (United States)

    König, Maximilian; Spira, Dominik; Demuth, Ilja; Steinhagen-Thiessen, Elisabeth; Norman, Kristina

    2017-12-12

    Sarcopenia affects more than 10% of older adults. Next to age-associated physiologic changes, diseases like diabetes or inflammatory, neurological, malignant and endocrine disorders may contribute to the development of sarcopenia. Likewise, polypharmacy, i.e., multiple drug use, is common among older adults. Although the two conditions frequently co-occur, the association of polypharmacy with sarcopenia has not yet been examined. We investigated the association of polypharmacy and sarcopenia in a large cohort of community-dwelling older adults (60-84 years). Thousand five hundred and two participants from the Berlin Aging Study II were included. Polypharmacy was defined as concurrent use of 5 or more drugs (prescription and nonprescription). Body composition was assessed with dual-energy X-ray absorptiometry, and appendicular lean mass (ALM) was calculated as sum of the four limbs' lean mass. Sarcopenia was defined as low ALM-to-body mass index (BMI)-ratio using validated sex-specific cutoffs. Mean age was 68.7 ± 3.7 years, 50.7% were female. The median (interquartile range) number of drugs was 2 (1-4); 21.1% of subjects reported regular use of ≥5 drugs. Subjects with polypharmacy were more often sarcopenic according to the applied ALM/BMI-cutoffs (16.3% vs 6.9%, p sarcopenia (odds ratio = 2.24, 95% confidence interval [CI] = 1.33-3.75). Polypharmacy is associated with clinically relevant sarcopenia, as assessed by a low ALM/BMI. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Phase-II Clinical Validation of a Powered Exoskeleton for the Treatment of Elbow Spasticity.

    Science.gov (United States)

    Crea, Simona; Cempini, Marco; Mazzoleni, Stefano; Carrozza, Maria Chiara; Posteraro, Federico; Vitiello, Nicola

    2017-01-01

    Introduction: Spasticity is a typical motor disorder in patients affected by stroke. Typically post-stroke rehabilitation consists of repetition of mobilization exercises on impaired limbs, aimed to reduce muscle hypertonia and mitigate spastic reflexes. It is currently strongly debated if the treatment's effectiveness improves with the timeliness of its adoption; in particular, starting intensive rehabilitation as close as possible to the stroke event may counteract the growth and postpone the onset of spasticity. In this paper we present a phase-II clinical validation of a robotic exoskeleton in treating subacute post-stroke patients. Methods: Seventeen post-stroke patients participated in 10 daily rehabilitation sessions using the NEUROExos Elbow Module exoskeleton, each one lasting 45 min: the exercises consisted of isokinetic passive mobilization of the elbow, with torque threshold to detect excessive user's resistance to the movement. We investigated the safety by reporting possible adverse events, such as mechanical, electrical or software failures of the device or injuries or pain experienced by the patient. As regards the efficacy , the Modified Ashworth Scale, was identified as primary outcome measure and the NEEM metrics describing elbow joint resistance to passive extension (i.e., maximum extension torque and zero-torque angle) as secondary outcomes. Results: During the entire duration of the treatments no failures or adverse events for the patients were reported. No statistically significant differences were found in the Modified Ashworth Scale scores, between pre-treatment and post-treatment and between post-treatment and follow-up sessions, indicating the absence of spasticity increase throughout (14 days) and after (3-4 months follow-up) the treatment. Exoskeleton metrics confirmed the absence of significant difference in between pre- and post-treatment data, whereas intra-session data highlighted significant differences in the secondary outcomes

  5. Phase-II Clinical Validation of a Powered Exoskeleton for the Treatment of Elbow Spasticity

    Directory of Open Access Journals (Sweden)

    Simona Crea

    2017-05-01

    Full Text Available Introduction: Spasticity is a typical motor disorder in patients affected by stroke. Typically post-stroke rehabilitation consists of repetition of mobilization exercises on impaired limbs, aimed to reduce muscle hypertonia and mitigate spastic reflexes. It is currently strongly debated if the treatment's effectiveness improves with the timeliness of its adoption; in particular, starting intensive rehabilitation as close as possible to the stroke event may counteract the growth and postpone the onset of spasticity. In this paper we present a phase-II clinical validation of a robotic exoskeleton in treating subacute post-stroke patients.Methods: Seventeen post-stroke patients participated in 10 daily rehabilitation sessions using the NEUROExos Elbow Module exoskeleton, each one lasting 45 min: the exercises consisted of isokinetic passive mobilization of the elbow, with torque threshold to detect excessive user's resistance to the movement. We investigated the safety by reporting possible adverse events, such as mechanical, electrical or software failures of the device or injuries or pain experienced by the patient. As regards the efficacy, the Modified Ashworth Scale, was identified as primary outcome measure and the NEEM metrics describing elbow joint resistance to passive extension (i.e., maximum extension torque and zero-torque angle as secondary outcomes.Results: During the entire duration of the treatments no failures or adverse events for the patients were reported. No statistically significant differences were found in the Modified Ashworth Scale scores, between pre-treatment and post-treatment and between post-treatment and follow-up sessions, indicating the absence of spasticity increase throughout (14 days and after (3–4 months follow-up the treatment. Exoskeleton metrics confirmed the absence of significant difference in between pre- and post-treatment data, whereas intra-session data highlighted significant differences in the

  6. Intraoperative boron neutron capture therapy for malignant gliomas. First clinical results of Tsukuba phase I/II trial using JAERI mixed thermal-epithermal beam

    International Nuclear Information System (INIS)

    Matsumura, A.; Yamamoto, T.; Shibata, Y.

    2000-01-01

    Since October 1999, a clinical trial of intraoperative boron neutron capture therapy (IOBNCT) is in progress at JRR-4 (Japan Research Reactor-4) in Japan Atomic Energy Research Institute (JAERI) using mixed thermal-epithermal beam (thermal neutron beam I: TNB-I). Compared to pure thermal beam (thermal neutron beam II: TNB-II), TNB-I has an improved neutron delivery into the deep region than TNB-II. The clinical protocol and the preliminary results will be discussed. (author)

  7. The evaluation of tetrabutylamonium bis(4-ethylphenylsulphonyldithiocarbimate)zincate(II) (ZNIBU) efficiency as a reclaiming agent for styrene-butadiene rubber (SBR)

    International Nuclear Information System (INIS)

    Moreno, Pedro H.H.; Visconte, Leila L.Y.; Pacheco, Elen B.A.V.; Tavares, Eder C.

    2015-01-01

    In recent years, the production of rubber waste has been reported as a serious environmental problem. The chemical structure of rubbers (crosslinked, insoluble and infusible polymers) makes its reprocessing very difficult, unlike thermoplastics. The most common methods to treat rubber waste are of thermal, mechanical and chemical nature, wherein the chemical methods the purpose is to regenerate the rubber. Early studies with tetrabutylamonium bis(4-methylphenylsulphonyldithiocarbimate)zincate(II) (ZNIBU) point to its ability as an accelerator in the rubber curing process. In this work, this zinc complex was evaluated as a chemical regeneration agent. ZNIBU was synthesized and characterized by Nuclear Magnetic Resonance ("1"3C NMR) and Fourier Transform Infrared Spectroscopy (FTIR). The mixture of virgin SBR with vulcanization ingredients was performed in a two-roll mill, and the composition was then vulcanized and molded on a hydraulic press. The synthesized ZNIBU was then mixed with the vulcanized rubber and devulcanization was observed. Finally, the devulcanized elastomeric composition was revulcanized. The revulcanization of SBR regenerated with ZNIBU led to the formation of a rubber with maximum torque near the maximum torque of the virgin vulcanized rubber. After adjusting the optimal conditions of regeneration, mechanical tests will be carried out (tensile strength, tear strength and hardness) for the specimens of both vulcanized and revulcanized rubbers in order to compare their mechanical properties. (author)

  8. [Biological agents].

    Science.gov (United States)

    Amano, Koichi

    2009-03-01

    There are two types of biological agents for the treatment of rheumatoid arthritis (RA); monoclonal antibodies and recombinant proteins. Among the latter, etanercept, a recombinant fusion protein of soluble TNF receptor and IgG was approved in 2005 in Japan. The post-marketing surveillance of 13,894 RA patients revealed the efficacy and safety profiles of etanercept in the Japanese population, as well as overseas studies. Abatacept, a recombinant fusion protein of CTLA4 and IgG, is another biological agent for RA. Two clinical trials disclosed the efficacy of abatacept for difficult-to-treat patients: the AIM for MTX-resistant cases and the ATTAIN for patients who are resistant to anti-TNF. The ATTEST trial suggested abatacept might have more acceptable safety profile than infliximab. These biologics are also promising for the treatment of RA for not only relieving clinical symptoms and signs but retarding structural damage.

  9. Clinical, immunological and genetic features in eleven Algerian patients with major histocompatibility complex class II expression deficiency

    Directory of Open Access Journals (Sweden)

    Djidjik Réda

    2012-08-01

    Full Text Available Abstract Presenting processed antigens to CD4+ lymphocytes during the immune response involves major histocompatibility complex class II molecules. MHC class II genes transcription is regulated by four transcription factors: CIITA, RFXANK, RFX5 and RFXAP. Defects in these factors result in major histocompatibility complex class II expression deficiency, a primary combined immunodeficiency frequent in North Africa. Autosomal recessive mutations in the RFXANK gene have been reported as being the principal defect found in North African patients with this disorder. In this paper, we describe clinical, immunological and genetic features of 11 unrelated Algerian patients whose monocytes display a total absence of MHC class II molecules. They shared mainly the same clinical picture which included protracted diarrhoea and respiratory tract recurrent infections. Genetic analysis revealed that 9 of the 11 patients had the same RFXANK founder mutation, a 26 bp deletion (named I5E6-25_I5E6+1, also known as 752delG26. Immunological and genetic findings in our series may facilitate genetic counselling implementation for Algerian consanguineous families. Further studies need to be conducted to determine 752delG26 heterozygous mutation frequency in Algerian population.

  10. In vitro activity of econazole in comparison with three common antifungal agents against clinical Candida strains isolated from superficial infections

    Directory of Open Access Journals (Sweden)

    Mahdi Abastabar

    2015-03-01

    Conclusion: The present study demonstrated that for Candida albicans isolates, miconazole and econazole had the best effect, but in non-albicans Candida species, itraconazole and miconazole displayed more activity than other antifungal agents.

  11. Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India

    Directory of Open Access Journals (Sweden)

    Jahnavi Aluri

    2018-02-01

    Full Text Available Major histocompatibility complex (MHC class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT is the only curative therapy available for treating these patients. This is the first report from India wherein we describe the clinical, immunological, and molecular findings in five patients with MHC class II deficiency. Our patients presented with recurrent lower respiratory tract infection as the most common clinical presentation within their first year of life and had a complete absence of human leukocyte antigen-antigen D-related (HLA-DR expression on B cells and monocytes. Molecular characterization revealed novel mutations in RFAXP, RFX5, and CIITA genes. Despite genetic heterogeneity, these patients were clinically indistinguishable. Two patients underwent HSCT but had a poor survival outcome. Detectable level of T cell receptor excision circles (TRECs were measured in our patients, highlighting that this form of PID may be missed by TREC-based newborn screening program for severe combined immunodeficiency.

  12. Distinguishing bipolar II depression from major depressive disorder with comorbid borderline personality disorder: demographic, clinical, and family history differences.

    Science.gov (United States)

    Zimmerman, Mark; Martinez, Jennifer H; Morgan, Theresa A; Young, Diane; Chelminski, Iwona; Dalrymple, Kristy

    2013-09-01

    Because of the potential treatment implications, it is clinically important to distinguish between bipolar II depression and major depressive disorder with comorbid borderline personality disorder. The high frequency of diagnostic co-occurrence and resemblance of phenomenological features has led some authors to suggest that borderline personality disorder is part of the bipolar spectrum. Few studies have directly compared patients with bipolar disorder and borderline personality disorder. In the present study from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we compared these 2 groups of patients on demographic, clinical, and family history variables. From December 1995 to May 2012, 3,600 psychiatric patients presenting to the outpatient practice at Rhode Island Hospital (Providence, Rhode Island) were evaluated with semistructured diagnostic interviews for DSM-IV Axis I and Axis II disorders. The focus of the present study is the 206 patients with DSM-IV major depressive disorder and borderline personality disorder (MDD-BPD) and 62 patients with DSM-IV bipolar II depression without borderline personality disorder. The patients with MDD-BPD were significantly more often diagnosed with posttraumatic stress disorder (P depression had a significantly higher morbid risk for bipolar disorder in their first-degree relatives than the MDD-BPD patients (P depression and major depressive disorder with comorbid borderline personality disorder differed on a number of clinical and family history variables, thereby supporting the validity of this distinction. © Copyright 2013 Physicians Postgraduate Press, Inc.

  13. Early loading of plalatal implants (ortho-type II a prospective multicenter randomized controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Gedrange Tomasz

    2007-09-01

    Full Text Available Abstract Background In orthodontic treatment, anchorage control is a fundamental aspect. Usually conventional mechanism for orthodontic anchorage control can be either extraoral or intraoral that is headgear or intermaxillary elastics. Their use are combined with various side effects such as tipping of occlusal plane or undesirable movements of teeth. Especially in cases, where key-teeth are missing, conventional anchorage defined as tooth-borne anchorage will meet limitations. Therefore, the use of endosseous implants for anchorage purposes are increasingly used to achieve positional stability and maximum anchorage. Methods/Design The intended study is designed as a prospective, multicenter randomized controlled trial (RCT, comparing and contrasting the effect of early loading of palatal implant therapy versus implant loading after 12 weeks post implantation using the new ortho-implant type II anchor system device (Orthosystem Straumann, Basel, Switzerland. 124 participants, mainly adult males or females, whose diagnoses require temporary stationary implant-based anchorage treatment will be randomized 1:1 to one of two treatment groups: group 1 will receive a loading of implant standard therapy after a healing period of 12 week (gold standard, whereas group 2 will receive an early loading of orthodontic implants within 1 week after implant insertion. Participants will be at least followed for 12 months after implant placement. The primary endpoint is to investigate the behavior of early loaded palatal implants in order to find out if shorter healing periods might be justified to accelerate active orthodontic treatment. Secondary outcomes will focus e.g. on achievement of orthodontic treatment goals and quantity of direct implant-bone interface of removed bone specimens. As tertiary objective, a histologic and microtomography evaluation of all retrieved implants will be performed to obtain data on the performance of the SLA surface in human bone

  14. Development of a PET Prostate-Specific Membrane Antigen Imaging Agent: Preclinical Translation for Future Clinical Application

    Science.gov (United States)

    2017-10-01

    are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by...phase 0) application to the FDA by the end of the funding period. The small molecule imaging agents under study home to prostate specific membrane...funding period. The small molecule imaging agents under study home to prostate specific membrane antigen (PSMA) that is prevalent on a majority of

  15. Evaluation of image quality and radiation dose using gold nanoparticles and other clinical contrast agents in dual-energy Computed Tomography (CT): CT abdomen phantom

    Science.gov (United States)

    Zukhi, J.; Yusob, D.; Tajuddin, A. A.; Vuanghao, L.; Zainon, R.

    2017-05-01

    The aim of this study was to evaluate the image quality and radiation dose using commercial gold nanoparticles and clinical contrast agents in dual-energy Computed Tomography (CT). Five polymethyl methacrylate (PMMA) tubes were used in this study, where four tubes were filled with different contrast agents (barium, iodine, gadolinium, and gold nanoparticles). The fifth tube was filled with water. Two optically stimulated luminescence dosimeters (OSLD) were placed in each tube to measure the radiation dose. The tubes were placed in a fabricated adult abdominal phantom of 32 cm in diameter using PMMA. The phantom was scanned using a DECT at low energy (80 kV) and high energy (140 kV) with different pitches (0.6 mm and 1.0 mm) and different slice thickness (3.0 mm and 5.0 mm). The tube current was applied automatically using automatic exposure control (AEC) and tube current modulation recommended by the manufacturer (CARE Dose 4D, Siemens, Germany). The contrast-to-noise ratio (CNR) of each contrast agent was analyzed using Weasis software. Gold nanoparticles has highest atomic number (Z = 79) than barium (Z = 56), iodine (Z = 53) and gadolinium (Z = 64). The CNR value of each contrast agent increases when the slice thickness increases. The radiation dose obtained from this study decreases when the pitch increases. The optimal imaging parameters for gold nanoparticles and other clinical contrast agents is obtained at pitch value of 1.0 mm and slice thickness of 5.0 mm. Low noise and low radiation dose obtained at these imaging parameters. The optimal imaging parameters obtained in this study can be applied in multiple contrast agents imaging.

  16. Evaluation of image quality and radiation dose using gold nanoparticles and other clinical contrast agents in dual-energy Computed Tomography (CT): CT abdomen phantom

    International Nuclear Information System (INIS)

    Zukhi, J; Yusob, D; Vuanghao, L; Zainon, R; Tajuddin, A A

    2017-01-01

    The aim of this study was to evaluate the image quality and radiation dose using commercial gold nanoparticles and clinical contrast agents in dual-energy Computed Tomography (CT). Five polymethyl methacrylate (PMMA) tubes were used in this study, where four tubes were filled with different contrast agents (barium, iodine, gadolinium, and gold nanoparticles). The fifth tube was filled with water. Two optically stimulated luminescence dosimeters (OSLD) were placed in each tube to measure the radiation dose. The tubes were placed in a fabricated adult abdominal phantom of 32 cm in diameter using PMMA. The phantom was scanned using a DECT at low energy (80 kV) and high energy (140 kV) with different pitches (0.6 mm and 1.0 mm) and different slice thickness (3.0 mm and 5.0 mm). The tube current was applied automatically using automatic exposure control (AEC) and tube current modulation recommended by the manufacturer (CARE Dose 4D, Siemens, Germany). The contrast-to-noise ratio (CNR) of each contrast agent was analyzed using Weasis software. Gold nanoparticles has highest atomic number (Z = 79) than barium (Z = 56), iodine (Z = 53) and gadolinium (Z = 64). The CNR value of each contrast agent increases when the slice thickness increases. The radiation dose obtained from this study decreases when the pitch increases. The optimal imaging parameters for gold nanoparticles and other clinical contrast agents is obtained at pitch value of 1.0 mm and slice thickness of 5.0 mm. Low noise and low radiation dose obtained at these imaging parameters. The optimal imaging parameters obtained in this study can be applied in multiple contrast agents imaging. (paper)

  17. Feedback in Clinical Education, Part II: Approved Clinical Instructor and Student Perceptions of and Influences on Feedback

    Science.gov (United States)

    Nottingham, Sara; Henning, Jolene

    2014-01-01

    Context: Approved Clinical Instructors (ACIs; now known as preceptors) are expected to provide feedback to athletic training students (ATSs) during clinical education experiences. Researchers in other fields have found that clinical instructors and students often have different perceptions of actual and ideal feedback and that several factors may influence the feedback exchanges between instructors and students. However, understanding of these issues in athletic training education is minimal. Objective: To investigate the current characteristics and perceptions of and the influences on feedback exchanges between ATSs and ACIs. Design: Qualitative study. Setting: One entry-level master's degree program accredited by the Commission on Accreditation of Athletic Training Education. Patients or Other Participants: Four ACIs and 4 second-year ATSs. Data Collection and Analysis: Individual, semistructured interviews were conducted with participants and integrated with field notes and observations for analysis. We used the constant comparative approach to inductively analyze data and develop codes and categories. Member checking, triangulation, and peer debriefing were used to promote trustworthiness of the study. Results: Participants described that feedback plays an important role in clinical education and has several purposes related to improving performance. The ACIs and ATSs also discussed several preferred characteristics of feedback. Participants identified 4 main influences on their feedback exchanges, including the ACI, the ATS, personalities, and the learning environment. Conclusions: The ACIs and ATSs had similar perceptions of ideal feedback in addition to the actual feedback that was provided during their clinical education experiences. Most of the preferences for feedback were aligned with recommendations in the literature, suggesting that existing research findings are applicable to athletic training clinical education. Several factors influenced the

  18. Clinical application of intravascular administration of non-ionic, low osmolar contrast agent, Ioversol (Optiray 320) and its side effects comparison with Meglumine Iothalamate (Conray 60)

    International Nuclear Information System (INIS)

    Hong, Hyun Sook; Kim, Dae Ho; Lee, Hae Kyung; Chung, Moo Chan; Choi, Deuk Lin; Kwon, Kuy Hyang; Kim, Ki Jung

    1990-01-01

    Ioversol, the non-ionic, low osmolar contrast agent has been well characterized chemically and in terms of basic toxicity testing. Ioversol has a fomula similar to that of other nonionic agent. We review the results of intravascular use of this contrast agent, compared ionic contrast media(Meglumine Iothalamate (Conray 60)). Each study was assessed for imaging quality,and patients were monitored vital signs, changes of hematology and blood chemistry and urinalysis before and after contrast administration and were observed for occurrence of side effects. A small number of side effects were reported but no clinically significant sequelae in Ioversol group and much less vital sign changes compared with Conray group. There were no significant changes in vital signs related to the use of Ioversol, and no significant alterations in the renal function parameter or other blood chemistry and hematology measurement were encountered in both contrast media. In most cases, the image qualities were good. In conclusion, Ioversol is safe, well tolerated and efficious for use in intravascular contrast agent, and less vital sign changes and side effect than ionic Meglumine Iothalamte, and Ioversol is likely to provide a useful and acceptable alternative to other low osmolar and nonionic contrast agents

  19. The clinical application of ultrasonography-guided percutaneous transhepatic injection of iodized oil containing chemotherapeutic agent for the treatment of hilar lymphatic metastasis

    International Nuclear Information System (INIS)

    Zhao Guangsheng; Zhang Yuewei; Yang Xiaohong; Li Chuang; Zhao Mu; Wang Wenqing; Wang Ruoyu

    2010-01-01

    Objective: To discuss the technique and the clinical effect of ultrasonography-guided percutaneous transhepatic injection of iodized oil containing chemotherapeutic agent for the treatment of hepatic hilar lymphatic metastasis. Methods: Under ultrasonographic guidance,percutaneous transhepatic injection of iodized oil containing chemotherapeutic agent, so-called chemo-ablation, into the diseased lymph nodes was performed in thirteen patients with hepatic hilar lymphatic metastasis. The therapeutic results were evaluated based on the post-operative imaging examinations as well as the alleviation of the clinical symptoms. Results: Percutaneous transhepatic injection of iodized oil containing chemotherapeutic agent into the diseased lymph nodes was successfully carried out in all thirteen patients. After the procedure,the patients were followed up for a mean period of 13.5 months. The therapeutic effectiveness was 100%, while the regression rate of the lesions was 76.9%. No operation-related complications occurred. Conclusion: Percutaneous transhepatic injection of iodized oil containing chemotherapeutic agent into the diseased lymph nodes under ultrasonographic guidance is an effective and safe treatment for hepatic hilar lymphatic metastasis with reliable effectiveness. (authors)

  20. In vitro evaluation of the cyto-genotoxic potential of Ruthenium(II) SCAR complexes: a promising class of antituberculosis agents.

    Science.gov (United States)

    De Grandis, Rone Aparecido; Resende, Flávia Aparecida; da Silva, Monize Martins; Pavan, Fernando Rogério; Batista, Alzir Azevedo; Varanda, Eliana Aparecida

    2016-03-01

    Tuberculosis is a top infectious disease killer worldwide, caused by the bacteria Mycobacterium tuberculosis. Increasing incidences of multiple drug-resistance (MDR) strains are emerging as one of the major public health threats. However, the drugs in use are still incapable of controlling the appalling upsurge of MDR. In recent years a marked number of research groups have devoted their attention toward the development of specific and cost-effective antimicrobial agents against targeted MDR-Tuberculosis. In previous studies, ruthenium(II) complexes (SCAR) have shown a promising activity against MDR-Tuberculosis although few studies have indeed considered ruthenium toxicity. Therefore, within the preclinical requirements, we have sought to determine the cyto-genotoxicity of three SCAR complexes in this present study. The treatment with the SCARs induced a concentration-dependent decrease in cell viability in CHO-K1 and HepG2 cells. Based on the clonogenic survival, SCAR 5 was found to be more cytotoxic while SCAR 6 exhibited selectivity action on tumor cells. Although SCAR 4 and 5 did not indicate any mutagenic activity as evidenced by the Ames and Cytokinesis block micronucleus cytome assays, the complex SCAR 6 was found to engender a frameshift mutation detected by Salmonella typhimurium in the presence of S9. Similarly, we observed a chromosomal damage in HepG2 cells with significant increases of micronuclei and nucleoplasmic bridges. These data indicate that SCAR 4 and 5 complexes did not show genotoxicity in our models while SCAR 6 was considered mutagenic. This study presented a comprehensive genotoxic evaluation of SCAR complexes were shown to be genotoxic in vitro. All in all, further studies are required to fully elucidate how the properties can affect human health. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. The Spider Venom Peptide Lycosin-II Has Potent Antimicrobial Activity against Clinically Isolated Bacteria

    Directory of Open Access Journals (Sweden)

    Yongjun Wang

    2016-04-01

    Full Text Available Antimicrobial peptides have been accepted as excellent candidates for developing novel antibiotics against drug-resistant bacteria. Recent studies indicate that spider venoms are the source for the identification of novel antimicrobial peptides. In the present study, we isolated and characterized an antibacterial peptide named lycosin-II from the venom of the spider Lycosa singoriensis. It contains 21 amino acid residue lacking cysteine residues and forms a typical linear amphipathic and cationic α-helical conformation. Lycosin-II displays potent bacteriostatic effect on the tested drug-resistant bacterial strains isolated from hospital patients, including multidrug-resistant A. baumannii, which has presented a huge challenge for the infection therapy. The inhibitory ability of lycosin-II might derive from its binding to cell membrane, because Mg2+ could compete with the binding sites to reduce the bacteriostatic potency of lycosin-II. Our data suggest that lycosin-II might be a lead in the development of novel antibiotics for curing drug-resistant bacterial infections.

  2. Clinical significance of determination of changes of serum IGF-II, CRP levels after treatment in pediatric patients with broncho-pneumonia

    International Nuclear Information System (INIS)

    Chen Chuanbin

    2006-01-01

    Objective: To investigate the changes of serum insulin-like growth factor-II (IGF-II), CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II levels were measured with RIA and serum CRP levels with immune method both before and after treatment in 33 pediatric patients with bronchopneumonia and 35 controls. Results: Before treatment the serum levels of IGF-II, CRP were significantly higher in the patients than those in controls (P 0.05). Conclusion: Determination of serum IGF-II, CRP levels is clinically useful in the management of pediatric patients with bronchopneumonia. (authors)

  3. Comparative clinical evaluation of removable partial dentures made of two different materials in Kennedy Applegate class II partially edentulous situation.

    Science.gov (United States)

    Hundal, Maninder; Madan, Rajesh

    2015-12-01

    Cast Chromium Cobalt alloy has been the material of choice for fabricating Removable Partial Dentures (RPDs) but has certain drawbacks. Newer materials like the flexible Nylon based Super Polyamide have been introduced to overcome these drawbacks. The present study has compared the above two materials for nine clinical parameters. The study was carried out on 30 patients presenting with a Kennedy Applegate class II partially edentulous situation who were divided into two equal groups and clinically assessed. Statistically significant results were obtained in favor of flexible RPDs, in the parameters of 'aesthetics' and 'overall patient satisfaction'. Both groups showed more or less similar values for 'frequency of fracture of the prosthesis during usage' with the incidence being slightly higher for patients wearing the cast RPDs. The clinical parameters of 'oral soft tissue tolerance', 'gingival health', 'periodontal health' and 'adaptability in areas with undercut' were statistically at par for all the 30 patients thus suggesting the comparable biocompatibility of the two materials. The highlight of this study was the relative ease in fabrication of the flexible RPDs as compared to the cast RPDs. Based on the favorable clinical results of this study, it can be summarized that the flexible RPDs is a viable alternative to cast RPDs in Kennedy Applegate class II partially edentulous situation in the short term.

  4. Multicenter Study in Taiwan of the In Vitro Activities of Nemonoxacin, Tigecycline, Doripenem, and Other Antimicrobial Agents against Clinical Isolates of Various Nocardia Species▿

    Science.gov (United States)

    Lai, Chih-Cheng; Liu, Wei-Lun; Ko, Wen-Chien; Chen, Yen-Hsu; Tan, Hon-Ren; Huang, Yu-Tsung; Hsueh, Po-Ren

    2011-01-01

    The aim of this study was to assess the in vitro activities of nemonoxacin (a novel nonfluorinated quinolone), doripenem, tigecycline, and 16 other antimicrobial agents against Nocardia species. The MICs of the 19 agents against 151 clinical isolates of Nocardia species were determined by the broth microdilution method. The isolates were identified to the species level using 16S rRNA gene sequencing analysis. The results showed that N. brasiliensis (n = 60; 40%) was the most common species, followed by N. cyriacigeorgica (n = 24; 16%), N. farcinica (n = 12; 8%), N. beijingensis (n = 9), N. otitidiscaviarum (n = 8), N. nova (n = 8), N. asiatica (n = 7), N. puris (n = 6), N. flavorosea (n = 5), N. abscessus (n = 3), N. carnea (2), and one each of N. alba, N. asteroides complex, N. rhamnosiphila, N. elegans, N. jinanensis, N. takedensis, and N. transvalensis. The MIC90s of the tested quinolones against the N. brasiliensis isolates were in the order nemonoxacin = gemifloxacin Nocardia isolates. Among the four tested carbapenems, imipenem had the lowest MIC90s. All of the clinical isolates of N. beijingensis, N. otitidiscaviarum, N. nova, and N. puris and more than half of the N. brasiliensis and N. cyriacigeorgica isolates were resistant to at least one antimicrobial agent. The results of this in vitro study suggest that nemonoxacin, linezolid, and tigecycline are promising treatment options for nocardiosis. Further investigation of their clinical role is warranted. PMID:21343461

  5. Multicenter study in Taiwan of the in vitro activities of nemonoxacin, tigecycline, doripenem, and other antimicrobial agents against clinical isolates of various Nocardia species.

    Science.gov (United States)

    Lai, Chih-Cheng; Liu, Wei-Lun; Ko, Wen-Chien; Chen, Yen-Hsu; Tan, Hon-Ren; Huang, Yu-Tsung; Hsueh, Po-Ren

    2011-05-01

    The aim of this study was to assess the in vitro activities of nemonoxacin (a novel nonfluorinated quinolone), doripenem, tigecycline, and 16 other antimicrobial agents against Nocardia species. The MICs of the 19 agents against 151 clinical isolates of Nocardia species were determined by the broth microdilution method. The isolates were identified to the species level using 16S rRNA gene sequencing analysis. The results showed that N. brasiliensis (n=60; 40%) was the most common species, followed by N. cyriacigeorgica (n=24; 16%), N. farcinica (n=12; 8%), N. beijingensis (n=9), N. otitidiscaviarum (n=8), N. nova (n=8), N. asiatica (n=7), N. puris (n=6), N. flavorosea (n=5), N. abscessus (n=3), N. carnea (2), and one each of N. alba, N. asteroides complex, N. rhamnosiphila, N. elegans, N. jinanensis, N. takedensis, and N. transvalensis. The MIC90s of the tested quinolones against the N. brasiliensis isolates were in the order nemonoxacin=gemifloxacinNocardia isolates. Among the four tested carbapenems, imipenem had the lowest MIC90s. All of the clinical isolates of N. beijingensis, N. otitidiscaviarum, N. nova, and N. puris and more than half of the N. brasiliensis and N. cyriacigeorgica isolates were resistant to at least one antimicrobial agent. The results of this in vitro study suggest that nemonoxacin, linezolid, and tigecycline are promising treatment options for nocardiosis. Further investigation of their clinical role is warranted.

  6. Use of Rome II criteria in childhood defecation disorders: Applicability in clinical and research practice

    NARCIS (Netherlands)

    Voskuijl, Wieger P.; Heijmans, Jarom; Heijmans, Hugo S. A.; Taminiau, Jan A. J. M.; Benninga, Marc A.

    2004-01-01

    Objectives To evaluate the prevalence of pediatric functional gastrointestinal disorders with the use of the Rome II criteria and to compare these data with the classic Iowa criteria. Study design Patients recorded defecation and encopresis frequency. A standard history was taken and a physical

  7. Evaluation of plitidepsin in patients with primary myelofibrosis and post polycythemia vera/essential thrombocythemia myelofibrosis: results of preclinical studies and a phase II clinical trial

    International Nuclear Information System (INIS)

    Pardanani, A; Tefferi, A; Guglielmelli, P; Bogani, C; Bartalucci, N; Rodríguez, J; Extremera, S; Pérez, I; Alfaro, V; Vannucchi, A M

    2015-01-01

    Previous data established that plitidepsin, a cyclic depsipeptide, exerted activity in a mouse model of myelofibrosis (MF). New preclinical experiments reported herein found that low nanomolar plitidepsin concentrations potently inhibited the proliferation of JAK2V617F-mutated cell lines and reduced colony formation by CD34+ cells of individuals with MF, at least in part through modulation of p27 levels. Cells of MF patients had significantly reduced p27 content, that were modestly increased upon plitidepsin exposure. On these premise, an exploratory phase II trial evaluated plitidepsin 5 mg/m 2 3-h intravenous infusion administered on days 1 and 15 every 4 weeks (q4wk). Response rate (RR) according to the International Working Group for Myelofibrosis Research and Treatment consensus criteria was 9.1% (95% CI, 0.2–41.3%) in 11 evaluable patients during the first trial stage. The single responder achieved a red cell transfusion independence and stable disease was reported in nine additional patients (81.8%). Eight patients underwent a short-lasting improvement of splenomegaly. In conclusion, plitidepsin 5 mg/m 2 3-h infusion q4wk was well tolerated but had a modest activity in patients with primary, post-polycythaemia vera or post-essential thrombocythaemia MF. Therefore, this trial was prematurely terminated and we concluded that further clinical trials with plitidepsin as single agent in MF are not warranted

  8. Digital PCR quantification of MGMT methylation refines prediction of clinical benefit from alkylating agents in glioblastoma and metastatic colorectal cancer

    NARCIS (Netherlands)

    Barault, L.; Amatu, A.; Bleeker, F. E.; Moutinho, C.; Falcomatà, C.; Fiano, V.; Cassingena, A.; Siravegna, G.; Milione, M.; Cassoni, P.; de Braud, F.; Rudà, R.; Soffietti, R.; Venesio, T.; Bardelli, A.; Wesseling, P.; de Witt Hamer, P.; Pietrantonio, F.; Siena, S.; Esteller, M.; Sartore-Bianchi, A.; Di Nicolantonio, F.

    2015-01-01

    O(6)-methyl-guanine-methyl-transferase (MGMT) silencing by promoter methylation may identify cancer patients responding to the alkylating agents dacarbazine or temozolomide. We evaluated the prognostic and predictive value of MGMT methylation testing both in tumor and cell-free circulating DNA

  9. Digital PCR quantification of MGMT methylation refines prediction of clinical benefit from alkylating agents in glioblastoma and metastatic colorectal cancer

    NARCIS (Netherlands)

    Barault, L.; Amatu, A.; Bleeker, F. E.; Moutinho, C.; Falcomatà, C.; Fiano, V.; Cassingena, A.; Siravegna, G.; Milione, M.; Cassoni, P.; de Braud, F.; Rudà, R.; Soffietti, R.; Venesio, T.; Bardelli, A.; Wesseling, P.; de Witt Hamer, P.; Pietrantonio, F.; Siena, S.; Esteller, M.; Sartore-Bianchi, A.; di Nicolantonio, Federica

    2015-01-01

    Background: O6-methyl-guanine-methyl-transferase (MGMT) silencing by promoter methylation may identify cancer patients responding to the alkylating agents dacarbazine or temozolomide. Patients and methods: We evaluated the prognostic and predictive value of MGMT methylation testing both in tumor and

  10. Cyclo-oxygenase-2 inhibitors or nonselective NSAIDs plus gastroprotective agents: What to prescribe in daily clinical practice?

    NARCIS (Netherlands)

    G.M.C. Masclee (Gwen); V.E. Valkhoff (Vera); E.M. van Soest; R. Schade (René); G. Mazzaglia (Giampiero); M. Molokhia (Mariam); G. Trifiro (Gianluca); J.L. Goldstein; S. Hernández-Díaz (Sonia); E.J. Kuipers (Ernst); M.C.J.M. Sturkenboom (Miriam)

    2013-01-01

    textabstractBackground Two strategies for prevention of upper gastrointestinal (UGI) events for nonselective nonsteroidal anti-inflammatory drug (nsNSAID) users are replacement of the nsNSAID by a cyclo-oxygenase-2-selective inhibitor (coxib) or co-prescription of a gastroprotective agent (GPA). Aim

  11. Fundamental study of DSA images using gadolinium contrast agent

    International Nuclear Information System (INIS)

    Nagashima, Hiroyuki; Shiraishi, Akihisa; Igarashi, Hitoshi; Sakamoto, Hajime; Sano, Yoshitomo

    2002-01-01

    Most contrast agents used in digital subtraction angiography (DSA) are non-ionic iodinated contrast agents, which can cause severe side effects in patients with contraindications for iodine or allergic reactions to iodine. Therefore, DSA examinations using carbon dioxide gas or examinations done by magnetic resonance imaging (MRI) and ultrasound (US) were carried out in these patients. However, none of these examinations provided mages as clear as those of DSA with an iodinated contrast agent. We experienced DSA examination using a gadolinium contrast agent in a patient contraindicated for iodine. The patient had undergone MRI examination with a gadolinium contrast agent previously without side effects. The characteristics of gadolinium and the iodinated contrast agent were compared, and the DSA images obtained clinically using these media were also evaluated. The signal-to-noise (SN) ratio of the gadolinium contrast agent was the highest at tube voltages of 70 to 80 kilovolts and improved slightly when the image intensifier (I.I.) entrance dose was greater than 300 μR (77.4 nC/kg). The dilution ratios of five iodinated contrast agents showed the same S/N value as the undiluted gadolinium contrast agent. Clinically, the images obtained showed a slight decrease in contrast but provided the data necessary to make a diagnosis and made it possible to obtain interventional radiology (IVR) without any side effects. DSA examinations using a gadolinium contrast agent have some benefit with low risk and are thought to be useful for patients contraindicated for iodine. (author)

  12. Fibromyalgia in the adult Danish population: II. A study of clinical features

    DEFF Research Database (Denmark)

    Prescott, E; Jacobsen, S; Kjøller, M

    1993-01-01

    Clinical characteristics of fibromyalgia have so far been based mainly on patients identified in rheumatologic settings. This paper offers the clinical findings in fibromyalgia based on a national health interview survey, in which 123 persons fulfilled preset criteria for widespread pain. Clinical......, headache, difficulty in stair-climbing, and poorer self-evaluated health with more tender points was found. Contrary to that which was expected, fibromyalgia subjects did not suffer from sleep disturbances, irritable bowels or morning stiffness. Our findings indicate that clinical characteristics...... of fibromyalgia in the general population may differ from those found in rheumatological settings....

  13. Clinical significance of determination of serum insulin-like growth factor II levels in patients with chronic obstructive pulmonary diseases (COPD)

    International Nuclear Information System (INIS)

    Wu Changming

    2006-01-01

    Objective: To explore the clinical significance of the changes of serum insulinlike growth factor II (IGF-II) levels in patients with chronic obstruive pulmonary diseases (COPD). Methods: The serum IGF-II levels was determined with radioimmunoassay in 60 patients with COPD and 30 controls. Results: The serum IGF-II levels in patients with COPD were significantly higher than those in controls (0.65 ± 0.22μg/L vs 0.51±0.18μg/L, P<0.01). There were no significant differences among the levels in patients of different stages (stages I, II, III). Levels of IGF-II were significantly higher in patients succumbed to the dis- ease than those in patients recoverd (P<0.05). Conclusion: Serum IGF-II levels were significantly increased in patients with COPD, especially in those succumbed. (authors)

  14. Short-interval test-retest interrater reliability of the Dutch version of the structured clinical interview for DSM-IV personality disorders (SCID-II)

    NARCIS (Netherlands)

    Weertman, A; ArntZ, A; Dreessen, L; van Velzen, C; Vertommen, S

    2003-01-01

    This study examined the short-interval test-retest reliability of the Structured Clinical Interview (SCID-II: First, Spitzer, Gibbon, & Williams, 1995) for DSM-IV personality disorders (PDs). The SCID-II was administered to 69 in- and outpatients on two occasions separated by 1 to 6 weeks. The

  15. Metabolic and clinical effects of Ramadan fasting in patients with type II diabetes

    International Nuclear Information System (INIS)

    Yarahmadi, S.; Larijani, B.; Bastanhagh, M.H.; Pajouhi, M.; Bardar, J. R.; Zahedi, F.; Zendehdel, K.; Akrami, S.M.

    2003-01-01

    Objective: To evaluate the effects of fasting on anthropometric indices and carbohydrate and lipid metabolism in patients with type II diabetes. Results: Daily cholesterol intake increased in all subjects (p 0.01). Blood pressure, fasting blood glucose and serum fructosamine did not change during the study. Plasma insulin (p < 0.05), C-peptide (p < 0.01) and insulin resistance (p < 0.01) decreased only in men. Total and LDL cholesterol increased significantly in all subjects during the study. Conclusion: Ramadan fasting does not alter carbohydrate metabolism or tissue insulin sensitivity in patients with type II diabetes given appropriate dietary education and rescheduling of oral hypoglycaemic medication. Lipid profile is unfavorably altered due to changes in both diet and biochemical response to starvation. (author)

  16. Hip protectors: recommendations for conducting clinical trials--an international consensus statement (part II)

    DEFF Research Database (Denmark)

    Cameron, I D; Robinovitch, S; Birge, S

    2010-01-01

    While hip protectors are effective in some clinical trials, many, including all in community settings, have been unable to demonstrate effectiveness. This is due partly to differences in the design and analysis. The aim of this report is to develop recommendations for subsequent clinical research....

  17. Clinical and psychopathological features associated with treatment-emergent mania in bipolar-II depressed outpatients exposed to antidepressants.

    Science.gov (United States)

    Fornaro, Michele; Anastasia, Annalisa; Monaco, Francesco; Novello, Stefano; Fusco, Andrea; Iasevoli, Felice; De Berardis, Domenico; Veronese, Nicola; Solmi, Marco; de Bartolomeis, Andrea

    2018-07-01

    Treatment-emergent affective switch (TEAS), including treatment-emergent mania (TEM), carry significant burden in the clinical management of bipolar depression, whereas the use of antidepressants raises both efficacy, safety and tolerability concerns. The present study assesses the prevalence and clinical correlates of TEM in selected sample of Bipolar Disorder (BD) Type-II (BD-II) acute depression outpatients. Post-hoc analysis of the clinical and psychopathological features associated with TEM among 91 BD-II depressed outpatients exposed to antidepressants. Second-generation antipsychotics (SGA) (p = .005), lithium (≤ .001), cyclothymic/irritable/hyperthymic temperaments (p = ≤ .001; p = .001; p = .003, respectively), rapid-cycling (p = .005) and depressive mixed features (p = .003) differed between TEM + cases vs. TEM - controls. Upon multinomial logistic regression, the accounted psychopathological features correctly classified as much as 88.6% of TEM + cases (35/91 overall sample, or 38.46% of the sample), yet not statistically significantly [Exp(B) = .032; p = ns]. Specifically, lithium [B = - 2.385; p = .001], SGAs [B = - 2.354; p = .002] predicted lower rates of TEM + in contrast to the number of lifetime previous psychiatric hospitalizations [B = 2.380; p = .002], whereas mixed features did not [B = 1.267; p = ns]. Post-hoc analysis. Lack of systematic pharmacological history record; chance of recall bias and Berkson's biases. Permissive operational criterion for TEM. Relatively small sample size. Cyclothymic temperament and mixed depression discriminated TEM + between TEM - cases, although only lithium and the SGAs reliably predicted TEM +/- grouping. Larger-sampled/powered longitudinal replication studies are warranted to allow firm conclusions on the matter, ideally contributing to the identification of clear-cut sub-phenotypes of BD towards patient-tailored-pharmacotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Therapeutic songwriting in music therapy, Part II: Comparing the literature with practice across diverse clinical populations

    DEFF Research Database (Denmark)

    Baker, Felicity; Wigram, Tony; Stott, Dave

    2009-01-01

      A growing body of literature on therapeutic songwriting with diverse clinical populations indicates that clinicians employ a wide range of approaches. The purpose of this research was to establish trends in the clinical practice of songwriting as implemented across a range of clinical populations....... Responses to a 21-question on-line survey were obtained from 419 professional music therapists practicing in 29 countries which focused on approaches to songwriting within their practice with a single clinical population. Results suggest that in general, the literature provides good representation for what...... is occurring in clinical practice. Generally, songs were composed with individual clients in single sessions, with lyrics created prior to the music. Clinicians had a significant role in creating the music with improvised and pre-determined musical structures being equally employed.  Chi-square or comparable...

  19. Functionalized Magnetic Resonance Contrast Agent Selectively Binds to Glycoprotein IIb/IIIa on Activated Human Platelets under Flow Conditions and Is Detectable at Clinically Relevant Field Strengths

    Directory of Open Access Journals (Sweden)

    Constantin von zur Mühlen

    2008-03-01

    Full Text Available Recent progress in molecular magnetic resonance imaging (MRI provides the opportunity to image cells and cellular receptors using microparticles of iron oxide (MPIOs. However, imaging targets on vessel walls remains challenging owing to the quantity of contrast agents delivered to areas of interest under shear stress conditions. We evaluated ex vivo binding characteristics of a functional MRI contrast agent to ligand-induced binding sites (LIBSs on activated glycoprotein IIb/IIIa receptors of human platelets, which were lining rupture-prone atherosclerotic plaques and could therefore facilitate detection of platelet-mediated pathology in atherothrombotic disease. MPIOs were conjugated to anti-LIBS single-chain antibodies (LIBS-MPIO or control antibodies (control MPIO. Ex vivo binding to human platelet-rich clots in a dose-dependent manner was confirmed on a 3 T clinical MRI scanner and by histology (p < .05 for LIBS-MPIO vs control MPIO. By using a flow chamber setup, significant binding of LIBS-MPIO to a platelet matrix was observed under venous and arterial flow conditions, but not for control MPIO (p < .001. A newly generated MRI contrast agent detects activated human platelets at clinically relevant magnetic field strengths and binds to platelets under venous and arterial flow conditions, conveying high payloads of contrast to specific molecular targets. This may provide the opportunity to identify vulnerable, rupture-prone atherosclerotic plaques via noninvasive MRI.

  20. Clinical value of MRI liver-specific contrast agents: a tailored examination for a confident non-invasive diagnosis of focal liver lesions

    International Nuclear Information System (INIS)

    Ba-Ssalamah, Ahmed; Uffmann, Martin; Bastati, Nina; Herold, Christian; Schima, Wolfgang; Saini, Sanjai

    2009-01-01

    Screening of the liver for hepatic lesion detection and characterization is usually performed with either ultrasound or CT. However, both techniques are suboptimal for liver lesion characterization and magnetic resonance (MR) imaging has emerged as the preferred radiological investigation. In addition to unenhanced MR imaging techniques, contrast-enhanced MR imaging can demonstrate tissue-specific physiological information, thereby facilitating liver lesion characterization. Currently, the classes of contrast agents available for MR imaging of the liver include non-tissue-specific extracellular gadolinium chelates and tissue-specific hepatobiliary or reticuloendothelial agents. In this review, we describe the MR features of the more common focal hepatic lesions, as well as appropriate imaging protocols. A special emphasis is placed on the clinical use of non-specific and liver-specific contrast agents for differentiation of focal liver lesions. This may aid in the accurate diagnostic workup of patients in order to avoid invasive procedures, such as biopsy, for lesion characterization. A diagnostic strategy that considers the clinical situation is also presented. (orig.)

  1. A Phase II Clinical Trial Evaluating the Preventive Effectiveness of Lactobacillus Vaginal Suppositories in Patients with Recurrent Cystitis.

    Science.gov (United States)

    Wada, Koichiro; Uehara, Shinya; Ishii, Ayano; Sadahira, Takuya; Yamamoto, Masumi; Mitsuhata, Ritsuko; Takamoto, Atsushi; Araki, Motoo; Kobayashi, Yasuyuki; Watanabe, Masami; Watanabe, Toyohiko; Hotta, Katsuyuki; Nasu, Yasutomo

    2016-08-01

    Urinary tract infections (UTIs) are the most common bacterial infections in women, and many patients experience frequent recurrence. The aim of this report is to introduce an on-going prospective phase II clinical trial performed to evaluate the preventive effectiveness of Lactobacillus vaginal suppositories for prevention of recurrent cystitis. Patients enrolled in this study are administered vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus every 2 days or 3 times a week for one year. The primary endpoint is recurrence of cystitis and the secondary endpoints are adverse events. Recruitment began in December 2013 and target sample size is 20 participants.

  2. Radiosensitizing efficacy of iso-metronidazole after intravesical application in bladder cancer. A clinical phase II study

    International Nuclear Information System (INIS)

    Kob, D.; Lilienthal, A.; Bauhardt, H.; Merkle, K.; Schroeder, E.; Schroeder, E.; Hentschel, M.

    1991-01-01

    The radiosensitizing efficacy of iso-Metronidazole, a 4-Nitroimidazole derivative, was evaluated in a prospective clinical phase II study. The results of combined radiotherapy of 25 patients with bladder cancer were compared with those of a control group of 25 patients treated with radiotherapy only. Tumor regression six months after radiotherapy was used as an endpoint. The surgical procedure was performed as double TUR. Evaluating the local tumor control after additional application of iso-Metronidazole a gain factor of 1.2 is obtained. (orig.) [de

  3. Bloqueio do nervo supraescapular: procedimento importante na prática clínica. Parte II Suprascapular nerve block: important procedure in clinical practice. Part II

    Directory of Open Access Journals (Sweden)

    Marcos Rassi Fernandes

    2012-08-01

    Full Text Available O bloqueio do nervo supraescapular é um método de tratamento reprodutível, confiável e extremamente efetivo no controle da dor no ombro. Esse método tem sido amplamente utilizado por profissionais na prática clínica, como reumatologistas, ortopedistas, neurologistas e especialistas em dor, na terapêutica de enfermidades crônicas, como lesão irreparável do manguito rotador, artrite reumatoide, sequelas de AVC e capsulite adesiva, o que justifica a presente revisão (Parte II. O objetivo deste estudo foi descrever as técnicas do procedimento e suas complicações descritas na literatura, já que a primeira parte reportou as indicações clínicas, drogas e volumes utilizados em aplicação única ou múltipla. Apresentamse, detalhadamente, os acessos para a realização do procedimento tanto direto como indireto, anterior e posterior, lateral e medial, e superior e inferior. Diversas são as opções para se realizar o bloqueio do nervo supraescapular. Apesar de raras, as complicações podem ocorrer. Quando bem indicado, este método deve ser considerado.The suprascapular nerve block is a reproducible, reliable, and extremely effective treatment method in shoulder pain control. This method has been widely used by professionals in clinical practice such as rheumatologists, orthopedists, neurologists, and pain specialists in the treatment of chronic diseases such as irreparable rotator cuff injury, rheumatoid arthritis, stroke sequelae, and adhesive capsulitis, which justifies the present review (Part II. The objective of this study was to describe the techniques and complications of the procedure described in the literature, as the first part reported the clinical indications, drugs, and volumes used in single or multiple procedures. We present in details the accesses used in the procedure: direct and indirect, anterior and posterior, lateral and medial, upper and lower. There are several options to perform suprascapular nerve block

  4. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone.

    Science.gov (United States)

    Wiehle, Ronald D; Fontenot, Gregory K; Wike, Jenny; Hsu, Kuang; Nydell, Jennifer; Lipshultz, Larry

    2014-09-01

    To determine the effect of enclomiphene citrate in men with secondary hypogonadism. Phase II clinical trial. Community dwelling men making visits to physician offices. Men with secondary hypogonadism. Oral administration of enclomiphene citrate or 1% topical T gel. Luteinizing hormone, FSH, T, and semen analysis. Treatment with enclomiphene citrate resulted in increased morning serum T, E2, and LH levels similar to those obtained with a topical T gel in men with secondary hypogonadism. Follicle-stimulating hormone and LH were increased with enclomiphene, and sperm counts were conserved. Enclomiphene citrate reverses the two hallmarks of secondary hypogonadism, namely, low serum total T and low or inappropriately normal LH while preserving sperm production. NCT01270841 (ClinicalTrials.gov Identifier NCT01270841). Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe

    DEFF Research Database (Denmark)

    Burbach, G J; Heinzerling, L M; Edenharter, G

    2009-01-01

    BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance was ...... the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing.......BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance...... was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess...

  6. Clinical significance of measurement of changes of serum IGF-II, NO levels after treatment in pediatric patients with bronchial pneumonia

    International Nuclear Information System (INIS)

    Zhao Huajiang

    2005-01-01

    Objective: To study the clinical significance of changes of serum IGF-II and NO levels after treatment in pediatric patients with bronchial pneumonia. Methods: Serum IGF-II (with RIA) and NO (with Biochemical method) levels were measured in 38 pediatric patients with bronchial pneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, in the patients the serum IGF-II, and NO levels were significantly higher than those in controls (P 0.05). Conclusion: Serum IGF-II and NO levels changes could reflect the disease status of the patients as well as the progress of diseases. (authors)

  7. A Phase II/III Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Ginger (Zingiber officinale) for Nausea Caused by Chemotherapy for Cancer: A Currently Accruing URCC CCOP Cancer Control Study.

    Science.gov (United States)

    Hickok, Jane T; Roscoe, Joseph A; Morrow, Gary R; Ryan, Julie L

    2007-09-01

    Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as ondansetron and granistron, up to 70% of patients with cancer receiving highly emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting. Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after chemotherapy administration) and anticipatory nausea (nausea that develops before chemotherapy administration, in anticipation of it) are poorly controlled by currently available antiemetic agents. Scientific studies suggest that ginger (Zingiber officinale) might have beneficial effects on nausea and vomiting associated with motion sickness, surgery, and pregnancy. In 2 small studies of patients with cancer receiving chemotherapy, addition of ginger to standard antiemetic medication further reduced the severity of postchemotherapy nausea. This article describes a phase II/III randomized, dose-finding, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for nausea associated with chemotherapy for cancer. The study is currently being conducted by private practice oncology groups that are funded by the National Cancer Institute's Community Clinical Oncology Program and affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program Research Base.

  8. Evaluation of the quality of the reporting of phase II clinical trials in oncology: A systematic review.

    Science.gov (United States)

    Rivoirard, Romain; Langrand-Escure, Julien; Oriol, Mathieu; Tinquaut, Fabien; Chauvin, Franck; Rancoule, Chloé; Magné, Nicolas; Bourmaud, Aurélie

    2018-05-01

    To describe the current state of knowledge concerning the quality of reporting in phase II clinical trials in oncology and to describe the various methods published allowing this quality evaluation. databases including MEDLINE and COCHRANE were searched. Reviews and meta-analyses analyzing the quality of the reporting of phase II trials in oncology were included. Descriptive analysis of the results was performed. Thirteen publications were retained. Only 2 publications adopted a systematic approach of evaluation of the quality of reporting by overall scores. The Key Methodological Score (KMS), proposed by Grellety et al., gathering 3 items, seemed adapted for such an evaluation. A score of 3/3 was found in 16.1% of the 156 phase II trials analysed by this score. The other reviews used a qualitative analysis to evaluate the reporting, via an analysis of a single criterion, generally the statistical plan of the study. This item was considered as having been correctly reported in less than 50% of the analysed articles. The quality of reporting in phase II trials in oncology is a field that has been investigated very little (13 publications). When it is studied, the estimated level of quality is not satisfactory, whatever the method employed. The use of an overall score of evaluation is a path which should be pursued, in order to get reliable results. It also seems necessary to propose strong recommendations, which would create a consensus for the methodology and the reporting of these studies. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors.

    Science.gov (United States)

    Canning, Peter; Ruan, Qui; Schwerd, Tobias; Hrdinka, Matous; Maki, Jenny L; Saleh, Danish; Suebsuwong, Chalada; Ray, Soumya; Brennan, Paul E; Cuny, Gregory D; Uhlig, Holm H; Gyrd-Hansen, Mads; Degterev, Alexei; Bullock, Alex N

    2015-09-17

    RIPK2 mediates pro-inflammatory signaling from the bacterial sensors NOD1 and NOD2, and is an emerging therapeutic target in autoimmune and inflammatory diseases. We observed that cellular RIPK2 can be potently inhibited by type II inhibitors that displace the kinase activation segment, whereas ATP-competitive type I inhibition was only poorly effective. The most potent RIPK2 inhibitors were the US Food and Drug Administration-approved drugs ponatinib and regorafenib. Their mechanism of action was independent of NOD2 interaction and involved loss of downstream kinase activation as evidenced by lack of RIPK2 autophosphorylation. Notably, these molecules also blocked RIPK2 ubiquitination and, consequently, inflammatory nuclear factor κB signaling. In monocytes, the inhibitors selectively blocked NOD-dependent tumor necrosis factor production without affecting lipopolysaccharide-dependent pathways. We also determined the first crystal structure of RIPK2 bound to ponatinib, and identified an allosteric site for inhibitor development. These results highlight the potential for type II inhibitors to treat indications of RIPK2 activation as well as inflammation-associated cancers. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints.

    Science.gov (United States)

    Zhou, Heng; Lee, J Jack; Yuan, Ying

    2017-09-20

    We propose a flexible Bayesian optimal phase II (BOP2) design that is capable of handling simple (e.g., binary) and complicated (e.g., ordinal, nested, and co-primary) endpoints under a unified framework. We use a Dirichlet-multinomial model to accommodate different types of endpoints. At each interim, the go/no-go decision is made by evaluating a set of posterior probabilities of the events of interest, which is optimized to maximize power or minimize the number of patients under the null hypothesis. Unlike other existing Bayesian designs, the BOP2 design explicitly controls the type I error rate, thereby bridging the gap between Bayesian designs and frequentist designs. In addition, the stopping boundary of the BOP2 design can be enumerated prior to the onset of the trial. These features make the BOP2 design accessible to a wide range of users and regulatory agencies and particularly easy to implement in practice. Simulation studies show that the BOP2 design has favorable operating characteristics with higher power and lower risk of incorrectly terminating the trial than some existing Bayesian phase II designs. The software to implement the BOP2 design is freely available at www.trialdesign.org. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Biological Agents

    Science.gov (United States)

    ... E-Tools Safety and Health Topics / Biological Agents Biological Agents This page requires that javascript be enabled ... 202) 693-2300 if additional assistance is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. ...

  12. The evaluation of tetrabutylamonium bis(4-ethylphenylsulphonyldithiocarbimate)zincate(II) (ZNIBU) efficiency as a reclaiming agent for styrene-butadiene rubber (SBR); Avalicao da eficiencia do bis(4-metilfenilsulfonilditiocarbimato)zincato(II) de tetrabutilamonio (ZNIBU) como agente de regeneracao para borracha de butadieno-estireno (SBR)

    Energy Technology Data Exchange (ETDEWEB)

    Moreno, Pedro H.H.; Visconte, Leila L.Y.; Pacheco, Elen B.A.V., E-mail: pedro_hhm@ima.ufrj.br [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Tavares, Eder C. [Universidade Federal de Itajuba (UNIFEI), Itajuba, MG (Brazil)

    2015-07-01

    In recent years, the production of rubber waste has been reported as a serious environmental problem. The chemical structure of rubbers (crosslinked, insoluble and infusible polymers) makes its reprocessing very difficult, unlike thermoplastics. The most common methods to treat rubber waste are of thermal, mechanical and chemical nature, wherein the chemical methods the purpose is to regenerate the rubber. Early studies with tetrabutylamonium bis(4-methylphenylsulphonyldithiocarbimate)zincate(II) (ZNIBU) point to its ability as an accelerator in the rubber curing process. In this work, this zinc complex was evaluated as a chemical regeneration agent. ZNIBU was synthesized and characterized by Nuclear Magnetic Resonance ({sup 13}C NMR) and Fourier Transform Infrared Spectroscopy (FTIR). The mixture of virgin SBR with vulcanization ingredients was performed in a two-roll mill, and the composition was then vulcanized and molded on a hydraulic press. The synthesized ZNIBU was then mixed with the vulcanized rubber and devulcanization was observed. Finally, the devulcanized elastomeric composition was revulcanized. The revulcanization of SBR regenerated with ZNIBU led to the formation of a rubber with maximum torque near the maximum torque of the virgin vulcanized rubber. After adjusting the optimal conditions of regeneration, mechanical tests will be carried out (tensile strength, tear strength and hardness) for the specimens of both vulcanized and revulcanized rubbers in order to compare their mechanical properties. (author)

  13. A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

    Science.gov (United States)

    Murakami, Naoya; Kato, Shingo; Nakano, Takashi; Uno, Takashi; Yamanaka, Takeharu; Sakurai, Hideyuki; Yoshimura, Ryoichi; Hiratsuka, Junichi; Kuroda, Yuki; Yoshio, Kotaro; Itami, Jun

    2016-08-17

    This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. UMIN000019081 ; Registration date: 2015/9/30.

  14. [Response of Pharmaceutical Companies to the Crisis of Post-Marketing Clinical Trials of Anti-Cancer Agents -- Results of Questionnaires to Pharmaceutical Companies].

    Science.gov (United States)

    Nakajima, Toshifusa

    2016-04-01

    Investigator-oriented post-marketing clinical trials of anti-cancer agents are faced to financial crisis due to drastic decrease in research-funds from pharmaceutical companies caused by a scandal in 2013. In order to assess the balance of research funds between 2012 and 2014, we made queries to 26 companies manufacturing anti-cancer agents, and only 10 of 26 responded to our queries. Decrease in the fund was observed in 5 of 10, no change in 1, increase in 3 and no answer in 1. Companies showed passive attitude to carry out doctor-oriented clinical trials of off-patent drugs or unapproved drugs according to advanced medical care B program, though some companies answered to proceed approved routines of these drugs if clinical trials showed good results. Most companies declined to make comments on the activity of Japan Agency for Medical Research and Development (AMED), but some insisted to produce good corroboration between AMED and pharmaceutical companies in order to improve the quality of trials. Further corroboration must be necessary for this purpose among researchers, governmental administrative organs, pharmaceutical companies, patients' groups, and mass-media.

  15. The periodontal abscess (II). Short-term clinical and microbiological efficacy of 2 systemic antibiotic regimes.

    Science.gov (United States)

    Herrera, D; Roldán, S; O'Connor, A; Sanz, M

    2000-06-01

    The aim of this short-term open parallel longitudinal clinical study was to compare the clinical and microbiological efficacy of 2 different antibiotic regimes in the treatment of acute periodontal abscesses. After patient selection, a clinical examination was carried out recording the following variables: pain, edema, redness, swelling, bleeding on probing, suppuration, tooth mobility, lymphadenopathy, and probing pocket depth. Microbiological samples were taken from the lesion and the patient was randomly assigned to one of two antibiotic regimes: azithromycin or amoxicillin/clavulanate. Clinical variables were recorded, and microbiological samples were taken, at 3-5 days, 10-12 days and 30 days. Additional mechanical treatment (debridement and scaling) was performed in the third visit (10-12 days). Blood and urine samples were collected at baseline and after 10-12 days. Microbiological samples were processed by anaerobic culturing, and isolated periodontal pathogens were tested for antibiotic susceptibility by means of the spiral gradient endpoint methodology. 15 patients took azithromycin, and 14 amoxicillin/clavulanate. Subjective clinical variables demonstrated statistically significant improvements with both antibiotic regimes, which lasted for at least 1 month (pperiodontal abscesses in periodontitis patients.

  16. Amifostine (WR-2721, a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study

    Directory of Open Access Journals (Sweden)

    C.A. De Souza

    2000-07-01

    Full Text Available Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY (7 g/m2, used to mobilize peripheral blood progenitor cells (PBPC and to reduce tumor burden. We enrolled 29 patients, 22 (75.9% affected by aggressive and 7 (24.1% by indolent non-Hodgkin's lymphoma (NHL, who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04. None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively. Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.

  17. Morfeo Study II: Clinical Course and Complications in Patients With Long-Term Disorders of Consciousness.

    Science.gov (United States)

    Romaniello, Caterina; Bertoletti, Erik; Matera, Nunzio; Farinelli, Marina; Pedone, Vincenzo

    2016-06-01

    The life expectancy of patients with disorders of consciousness (DOCs) is ever-increasing, but little is known about their clinical course over late stages. Several issues (premorbid conditions, complications and pressure sores) are to be considered for their effect on clinical outcome, risk of death and recovery of functional performance. Unfortunately, in late stages of long-term rehabilitation, these aspects are still more neglected than in acute and postacute stages. The aim of this study was to investigate the clinical course and the complications of patients in the late stages of DOCs and to explore the relationship between mortality and specific biomarkers. A total of 112 patients, admitted over 10 years in a dedicated ward, were retrospectively studied. Sociodemographic data, preadmission and inpatient clinical features were collected. Disability Rating Scale scores, complications including pressure sores and blood markers were assessed monthly. Data were analyzed through descriptive statistics and correlations using SPSS. Most patients were men older than 50 years with a nontraumatic etiology and a history of hypertension (42.86%). The most common complication was pneumonia (76.79%). No association was found between sex and mortality or between etiology and mortality (P > 0.05). Mortality correlated significantly with sepsis (ρ = 0.253), albumin (ρ = -0.558), hemoglobin (ρ = -0.354) and white blood cells (ρ = 0.243). Only 42% of patients remained unchanged at Disability Rating Scale evaluation. These data confirmed that DOCs are not static conditions and they require ongoing monitoring and assessment of clinical status, level of consciousness and laboratory biomarkers. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  18. Managing a grossly comminuted and infected mandibular fracture using a maxillary extra-oral distractor as stabilizing agent: A clinical case report

    Directory of Open Access Journals (Sweden)

    Ding Ming Chao

    2017-06-01

    Full Text Available Facial fracture management dates as early as Hippocratic era. Comminuted mandibular fractures are one of the challenging clinical condition requiring high surgical expertise to achieve a good functional and esthetic outcome. In presence of infection and other facial fractures managing comminuted mandibular fracture becomes more challenging.Here we present a case of grossly comminuted and infected mandibular fracture with delayed presentation managed by using maxillary distractor as stabilizing agent. Using a maxillary distractor for managing a fractured mandible has been seldom reported in literature. Current case report gives idea to practicing clinician about the possibility of treatment beyond the established principles. Keywords: Mandibular fracture, Maxillary distractor, Infection

  19. Tumor Vessel Development and Expansion in Ewing's Sarcoma: A Review of the Vasculogenesis Process and Clinical Trials with Vascular-Targeting Agents

    Science.gov (United States)

    Stewart, Keri S.; Kleinerman, Eugenie S.

    2011-01-01

    Ewing's sarcoma accounts for a disproportionately high portion of the overall pediatric mortality rate compared to its rare incidence in the pediatric population. Little progress has been made since the introduction of traditional chemotherapies, and understanding the biology of the tumor is critical for developing new therapies. Ewing's sarcomas rely on a functional vascular supply, which is formed by a combination of angiogenesis and vasculogenesis. Recent insights into the molecular regulation of bone marrow (BM) cell participation in vascular development have identified VEGF, SDF-1α, and DLL4 as critical players in the vasculogenesis process. Clinical trials using vascular targeting agents, specifically targeting VEGF or DLL4, are underway. PMID:21785569

  20. The Johns Hopkins RTR Consortium: A Collaborative Approach to Advance Translational Science and Standardize Clinical Monitoring of Restorative Transplantation - Immunomodulation and Tolerance Induction after VCA using Biologic Agent (cTLA4-Ig) and Donor Bone Marrow Cells

    Science.gov (United States)

    2014-10-01

    Standardize Clinical Monitoring of Restorative Transplantation – Immunomodulation and Tolerance Induction after VCA using Biologic Agent (cTLA4-Ig) and...Translational Science and Standardize Clinical Monitoring of Restorative Transplantation – Immunomodulation and Tolerance Induction after VCA using Biologic...wider application. Thus the purpose of this project is to develop novel clinically relevant regimens for immunomodulation and tolerance induction after

  1. Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

    Science.gov (United States)

    Giraldo, N A; Amariles, P; Monsalve, M; Faus, M J

    Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV ® ) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. [Clinical classification and genetic mutation study of two pedigrees with type II Waardenburg syndrome].

    Science.gov (United States)

    Chen, Yong; Yang, Fuwei; Zheng, Hexin; Zhu, Ganghua; Hu, Peng; Wu, Weijing

    2015-12-01

    To explore the molecular etiology of two pedigrees affected with type II Waardenburg syndrome (WS2) and to provide genetic diagnosis and counseling. Blood samples were collected from the proband and his family members. Following extraction of genomic DNA, the coding sequences of PAX3, MITF, SOX10 and SNAI2 genes were amplified with PCR and subjected to DNA sequencing to detect potential mutations. A heterozygous deletional mutation c.649_651delAGA in exon 7 of the MITF gene has been identified in all patients from the first family, while no mutation was found in the other WS2 related genes including PAX3, MITF, SOX10 and SNAI2. The heterozygous deletion mutation c.649_651delAGA in exon 7 of the MITF gene probably underlies the disease in the first family. It is expected that other genes may also underlie WS2.

  3. A clinical compariosn of sup(99m)Tc-DPD and two sup(99m)Tc-MDP agents

    International Nuclear Information System (INIS)

    Vorne, M.; Vaehaetalo, S.; Lantto, T.

    1983-01-01

    Two hundred and fifty-seven patients were studied with bone-seeking radiopharmaceuticals. They were randomly divided into three groups. Two groups were injected with two different sup(99m)Tc-methylene diphosphonates from two manufactures (MDP 1 and MDP 2) and the third group with sup(99m)Tc-dicarboxypropane diphosphonate (DPD). DPD was found to be superior with respect to blood clearance, femur to soft tissue ratio and subjectivly assessed image quality. There seemed to be no marked differences between the bone-seeking agents in the visualisation of pathological foci. The image quality seemed to be better in the MDP 2 group than in the MDP 1 group but they were similar in other respects. The femur to soft tissue ratio decreased with increasing age in the DPD group but not in the MDP groups. With all agents worsening of scan quality with increasing age was noted and the image quality was better with men than with women. When short incubation times of radiopharmaceuticals were used before injection, the bone to soft tissue ratio was lower and the scan quality was poorer than with incubation times longer than 20 min. (orig.)

  4. Digital PCR quantification of MGMT methylation refines prediction of clinical benefit from alkylating agents in glioblastoma and metastatic colorectal cancer.

    Science.gov (United States)

    Barault, L; Amatu, A; Bleeker, F E; Moutinho, C; Falcomatà, C; Fiano, V; Cassingena, A; Siravegna, G; Milione, M; Cassoni, P; De Braud, F; Rudà, R; Soffietti, R; Venesio, T; Bardelli, A; Wesseling, P; de Witt Hamer, P; Pietrantonio, F; Siena, S; Esteller, M; Sartore-Bianchi, A; Di Nicolantonio, F

    2015-09-01

    O(6)-methyl-guanine-methyl-transferase (MGMT) silencing by promoter methylation may identify cancer patients responding to the alkylating agents dacarbazine or temozolomide. We evaluated the prognostic and predictive value of MGMT methylation testing both in tumor and cell-free circulating DNA (cfDNA) from plasma samples using an ultra-sensitive two-step digital PCR technique (methyl-BEAMing). Results were compared with two established techniques, methylation-specific PCR (MSP) and Bs-pyrosequencing. Thresholds for MGMT methylated status for each technique were established in a training set of 98 glioblastoma (GBM) patients. The prognostic and the predictive value of MGMT methylated status was validated in a second cohort of 66 GBM patients treated with temozolomide in which methyl-BEAMing displayed a better specificity than the other techniques. Cutoff values of MGMT methylation specific for metastatic colorectal cancer (mCRC) tissue samples were established in a cohort of 60 patients treated with dacarbazine. In mCRC, both quantitative assays methyl-BEAMing and Bs-pyrosequencing outperformed MSP, providing better prediction of treatment response and improvement in progression-free survival (PFS) (P alkylating agents. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Multicenter analysis of tolerance and clinical safety of the extracellular MR contrast agent gadobenate dimeglumine (MultiHance registered)

    International Nuclear Information System (INIS)

    Herborn, Christoph U.; Jaeger-Booth, I.; Goyen, M.; Lodemann, K.P.; Spinazzi, A.

    2009-01-01

    Purpose: Retrospective analysis of the occurrence of adverse events and the diagnostic efficacy of a paramagnetic contrast agent with weak intermittent protein binding and high relaxivity. Materials end methods: Postmarketing surveillance studies for gadobenate dimeglumine (MultiHance, BRACCO Altana Pharma, Constance) were conducted in Germany between 1998 and 2006 and then retrospectively analyzed. Demographic data, relevant comorbidities, and allergies were recorded. The safety and tolerability of MultiHance were logged on a standardized data sheet. Results: A total of 38568 patients were included in the study. 829 patients (2.1%) had a known intolerance against contrast media. The examined regions included the central nervous system, the liver, and the vascular bed. The injection rate with automated injectors (n = 10456) varied between 1.0 und 3.0 ml/sec in 86.5% of patients. Adverse events totaled 1.2%. 11 patients (0.03%) experienced serious adverse events. The most frequent findings were nausea, vomiting and a feeling of warmth. Conclusion: MultiHance is a safe and very well tolerated contrast agent for magnetic resonance imaging (MRI) with a profile and frequency of adverse events similar to other extracellular MR contrast materials. (orig.)

  6. Bone radioisotope scanning: usefulness in the evaluation and observation of patients with breast cancer in clinical stage II, III, IV

    International Nuclear Information System (INIS)

    Cano P, R.A.

    1995-01-01

    The clinical records of 420 patients with diagnosis of breast cancer well documented by the pathological anatomy in clinical stage II, III and IV were reviewed. In each one of them has been done at least a bone scanning during the diagnosis. In 52 cases carried out sericeous dosages of CA 15-3 and in some cases it was necessary to administer Samarium-153 EDTMP as palliative therapy of bone pain. The presence of secondary gamma-graphic focuses was 0/84 cases (0%) in clinical stage II, 54/265 cases (20%) in III and 41/91 cases (45%) in IV. The one focus appeared in 6.7% of the cases. In 7 of the 52 cases that received sericeous dosages of CA 15-3 were detected secondary osseous lesions, and 5 of them presented a marker elevation. The bone scanning has shown in many cases the presence of getters focuses in singular places of skeleton, urinary excretory system or mammary tissue. The gamma rays from Sm-153 allowed us to get some appropriate basal views post-therapy of the secondary lesions. The results show that the great incidence of secondary lesions in the skeleton occurred in cases of stages III and IV unlike other countries. The serial repetition of the radioisotope scanning. The presence of one focus in the skeleton of a patient with a well-known neoplasia makes us to do a careful evaluation of the focus nature. The presence of tracer accumulation in the kidney, ureter and bladder allows us to infer the pathology of excretory system that is the first evidence of its presence in many cases. (author). 71 refs., 7 figs., 6 tabs

  7. Clinical developments of chemotherapeutic nanomedicines: Polymers and liposomes for delivery of camptothecins and platinum (II) drugs

    KAUST Repository

    Kieler-Ferguson, Heidi M.

    2013-01-17

    For the past 40 years, liposomal and polymeric delivery vehicles have been studied as systems capable of modulating the cytotoxicity of small molecule chemotherapeutics, increasing tumor bearing animal survival times, and improving drug targeting. Although a number of macromolecular-drug conjugates have progressed to clinical trials, tuning drug release to maintain efficacy in conjunction with controlling drug toxicity has prevented the clinical adoption of many vehicles. In this article, we review the motivations for and approaches to polymer and liposomal delivery with regard to camptothecin and cisplatin delivery. WIREs Nanomed Nanobiotechnol 2013, 5:130-138. doi: 10.1002/wnan.1209 For further resources related to this article, please visit the WIREs website. Conflict of interest: Drs Kieler-Ferguson and Fréchet declare no conflicts of interest. Dr Szoka is the founder of a liposome drug delivery company that is not working on any of the compounds mentioned in this article. © 2013 Wiley Periodicals, Inc.

  8. Prolongevity medicine: Antagonic-Stress drug in distress, geriatrics, and related diseases. II. Clinical review--2003.

    Science.gov (United States)

    Riga, S; Riga, D; Schneider, F

    2004-06-01

    Distress and senescence, their reciprocal aggravating-quickening connections, and their related pathologies have a large worldwide impact on healthcare systems in this new millennium. For this reason, Antagonic-Stress (AS)--an advanced integrative therapy, with specific synergistic composition, and patented internationally--represents a significant strategy in health, aging, and longevity. Clinical research with AS proves the drug's efficacy in the management of distress (neurotic, stress-related, and affective disorders; behavioral syndromes associated with physiological disturbances and physical factors; mental and behavioral disorders due to psychoactive substance uses) and psychogeriatrics [organic, including symptomatic, mental disorders (OMD)]. Specific multiaxial psychopathological instruments and psychometric tests in multiple assessments used for gerontopsychiatry demonstrated strong improvements after AS administration in early-moderate stages of Alzheimer or vascular dementia, as well as in other OMD. In addition, comparative clinical studies evinced the superiority of AS (synergistic multitherapy) versus monotherapy [meclofenoxate (MF), piracetam (PA), pyritinol (PT), and nicergoline (NE), respectively]. These comparative clinical trials agreed closely with comparative preclinical research and confirmed AS synergistic homeostatic, adaptogenic, antioxidative, cerebrovascular, neurometabolic, and nootropic actions. Also, the AS protective actions against oxidative stress recommend this orthomolecular therapy in stress, aging, and free radical pathology.

  9. Analysis of a kinetic multi-segment foot model part II: kinetics and clinical implications.

    Science.gov (United States)

    Bruening, Dustin A; Cooney, Kevin M; Buczek, Frank L

    2012-04-01

    Kinematic multi-segment foot models have seen increased use in clinical and research settings, but the addition of kinetics has been limited and hampered by measurement limitations and modeling assumptions. In this second of two companion papers, we complete the presentation and analysis of a three segment kinetic foot model by incorporating kinetic parameters and calculating joint moments and powers. The model was tested on 17 pediatric subjects (ages 7-18 years) during normal gait. Ground reaction forces were measured using two adjacent force platforms, requiring targeted walking and the creation of two sub-models to analyze ankle, midtarsal, and 1st metatarsophalangeal joints. Targeted walking resulted in only minimal kinematic and kinetic differences compared with walking at self selected speeds. Joint moments and powers were calculated and ensemble averages are presented as a normative database for comparison purposes. Ankle joint powers are shown to be overestimated when using a traditional single-segment foot model, as substantial angular velocities are attributed to the mid-tarsal joint. Power transfer is apparent between the 1st metatarsophalangeal and mid-tarsal joints in terminal stance/pre-swing. While the measurement approach presented here is limited to clinical populations with only minimal impairments, some elements of the model can also be incorporated into routine clinical gait analysis. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Preclinical pharmacokinetics, biodistribution, radiation dosimetry and acute toxicity studies required for regulatory approval of a Clinical Trial Application for a Phase I/II clinical trial of 111In-BzDTPA-pertuzumab

    International Nuclear Information System (INIS)

    Lam, Karen; Chan, Conrad; Done, Susan J.; Levine, Mark N.; Reilly, Raymond M.

    2015-01-01

    Introduction: 111 In-BzDTPA-pertuzumab is a novel imaging probe for detecting changes in HER2 expression in breast cancer (BC) caused by treatment with trastuzumab (Herceptin). Our aim was to evaluate the pharmacokinetics, normal tissue biodistribution, radiation dosimetry and acute toxicity of 111 In-BzDTPA-pertuzumab in non-tumor bearing mice in order to obtain regulatory approval to advance this agent to a first-in-humans Phase I/II clinical trial. Methods: Biodistribution and pharmacokinetic studies were performed in non-tumor bearing Balb/c mice injected i.v. with 111 In-BzDTPA-pertuzumab (2.5 MBq; 2 μg). The cumulative number of disintegrations per source organ derived from the biodistribution data was used to predict the radiation absorbed doses in humans using OLINDA/EXM software. Acute toxicity was studied at two weeks post-injection of 111 In-BzDTPA-pertuzumab (1.0 MBq, 20 μg) with comparison to control mice injected with unlabeled BzDTPA-pertuzumab (20 μg) or Sodium Chloride Injection USP. The dose of 111 In-BzDTPA-pertuzumab corresponded to 23-times the human radioactivity dose and 10-times the protein dose on a MBq/kg and mg/kg basis, respectively. Toxicity was assessed by monitoring body mass, complete blood cell count (CBC), hematocrit (Hct), hemoglobin (Hb), serum creatinine (SCr) and alanine aminotransferease (ALT) and by histopathological examination of tissues at necropsy. Results: 111 In-BzDTPA-pertuzumab exhibited a biphasic elimination from the blood with a distribution half-life (t 1/2 α) of 3.8 h and an elimination half-life (t 1/2 β) of 228.2 h. The radiopharmaceutical was distributed mainly in the blood, heart, lungs, liver, kidneys and spleen. The projected whole-body radiation absorbed dose in humans was 0.05 mSv/MBq corresponding to a total of 16.8 mSv for three separate administrations of 111 In-BzDTPA-pertuzumab (111 MBq) planned for the Phase I/II trial. There were slight changes in Hb and SCr levels associated with

  11. Utilization of a selective tumour artery catheterization technique for the intra-arterial delivery of chemotherapeutic agents and radiopharmaceuticals in a combined chemotherapy-radiotherapy clinical research programme

    International Nuclear Information System (INIS)

    Wiley, A.L. Jr.; Wirtanen, G.W.; Holden, J.E.; Polcyn, R.E.

    1977-01-01

    Combined intra-arterial chemotherapeutic agents (principally actinomycin-D) and radiation therapy has been utilized in the treatment of 35 patients with massive unresectable malignancies. The goals may be separated into three distinct categories. An attempt has been made to convert unresectable malignancies to surgical resectability, to provide a definitive therapy for massive tumours in patients who either refuse surgery or are not surgery candidates, and to provide palliation. Twelve of 15 initially unresectable tumours treated with actinomycin-D became surgically resectable (no resection was attempted in the other four because they either developed metastasis during therapy or did not complete the therapy), 4 of 6 massive tumours treated definitively have remained locally controlled from 18 to 108 months, and 7 of 9 patients treated palliatively were significantly benefited by the therapy. Impressive responses were also achieved in several patients treated with intra-arterial 5-fluorouracil and 5-iodo-2'-deoxyuridine. The authors therefore consider combined, concurrent radiation therapy and intra-arterially administered chemotherapeutic agents worthy of further clinical investigation as a means of treating massive malignancies. They also suggest that the best chance of optimizing the therapeutic ratio of such therapy is dependent primarily on a proper understanding of clinical tumour vascularity and of its subsequent effect on drug and oxygen distributions within the radiation treatment volume. Accordingly, tumour vascularity has been clinically evaluated by the use of intra-arterially administered radiopharmaceuticals. Such clinical data, in conjunction with radiobiological data, might in the future be utilized to optimize both low and high LET combined therapy by allowing for correction of the physical isodose for drug and oxygen concentration variations. (author)

  12. A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Hamid Omid

    2011-11-01

    Full Text Available Abstract Background Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab. Methods In this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365, 82 pretreated or treatment-naïve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated. Results Objective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014 and indoleamine 2,3-dioxygenase (p = 0.012, and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs between baseline and 3 weeks after start of treatment (p = 0.005. Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma. Conclusions Baseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with

  13. Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: Clinical Phase I/II trials

    International Nuclear Information System (INIS)

    Chen Zhinan; Mi Li; Xu Jing

    2006-01-01

    Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine ( 131 I) metuximab injection (Licartin), a novel 131 I-labeled HAb18G/CD147-specific monoclonal antibody F(ab') 2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p 131 I) metuximab injection is safe and active for HCC patients

  14. MIDAS: a practical Bayesian design for platform trials with molecularly targeted agents.

    Science.gov (United States)

    Yuan, Ying; Guo, Beibei; Munsell, Mark; Lu, Karen; Jazaeri, Amir

    2016-09-30

    Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time and thus not efficient for this task. We propose a Bayesian phase II platform design, the multi-candidate iterative design with adaptive selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and 'graduate' the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer

    DEFF Research Database (Denmark)

    Buunen, M; Bonjer, H J; Hop, W C J

    2009-01-01

    clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy...... analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal...

  16. A critical appraisal of chronic kidney disease mineral and bone disorders clinical practice guidelines using the AGREE II instrument.

    Science.gov (United States)

    Sekercioglu, Nigar; Al-Khalifah, Reem; Ewusie, Joycelyne Efua; Elias, Rosilene M; Thabane, Lehana; Busse, Jason W; Akhtar-Danesh, Noori; Iorio, Alfonso; Isayama, Tetsuya; Martínez, Juan Pablo Díaz; Florez, Ivan D; Guyatt, Gordon H

    2017-02-01

    Patients with chronic kidney disease mineral and bone disorders (CKD-MBD) suffer high rates of morbidity and mortality, in particular related to bone and cardiovascular outcomes. The management of CKD-MBD remains challenging. The objective of this systematic survey is to critically appraise clinical practice guidelines (CPGs) addressing CKD-MBD. Data sources included MEDLINE, EMBASE, the National Guideline Clearinghouse, Guideline International Network and Turning Research into Practice up to May 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility and subsequently appraised the guidelines using the Advancing Guideline Development, Reporting and Evaluation in Health Care instrument II (AGREE). Sixteen CPGs published from 2003 to 2015 addressing the diagnosis and management of CKD-MBD in adult patients (11 English, two Spanish, one Italian, one Portuguese and one Slovak) proved eligible. The National Institute for Health and Care Excellence guideline performed best with respect to AGREE II criteria; only three other CPGs warranted high scores on all domains. All other guidelines received scores of under 60% on one or more domains. Major discrepancies in recommendations were not, however, present, and we found no association between quality of CPGs which was not associated with resulting recommendations. Most guidelines assessing CKD-MBD suffer from serious shortcomings using AGREE criteria although limitations with respect to AGREE criteria do not necessarily lead to inappropriate recommendations.

  17. Measurement of DSM-5 section II personality disorder constructs using the MMPI-2-RF in clinical and forensic samples.

    Science.gov (United States)

    Anderson, Jaime L; Sellbom, Martin; Pymont, Carly; Smid, Wineke; De Saeger, Hilde; Kamphuis, Jan H

    2015-09-01

    In the current study, we evaluated the associations between the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008) scale scores and the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013) Section II personality disorder (PD) criterion counts in inpatient and forensic psychiatric samples from The Netherlands using structured clinical interviews to operationalize PDs. The inpatient psychiatric sample included 190 male and female patients and the forensic sample included 162 male psychiatric patients. We conducted correlation and count regression analyses to evaluate the utility of relevant MMPI-2-RF scales in predicting PD criterion count scores. Generally, results from these analyses emerged as conceptually expected and provided evidence that MMPI-2-RF scales can be useful in assessing PDs. At the zero-order level, most hypothesized associations between Section II disorders and MMPI-2-RF scales were supported. Similarly, in the regression analyses, a unique set of predictors emerged for each PD that was generally in line with conceptual expectations. Additionally, the results provided general evidence that PDs can be captured by dimensional psychopathology constructs, which has implications for both DSM-5 Section III specifically and the personality psychopathology literature more broadly. (c) 2015 APA, all rights reserved.

  18. Phase I (or phase II) dose-ranging clinical trials: proposal of a two-stage Bayesian design.

    Science.gov (United States)

    Zohar, Sarah; Chevret, Sylvie

    2003-02-01

    We propose a new design for phase I (or phase II) dose-ranging clinical trials aiming at determining a dose of an experimental treatment to satisfy safety (respectively efficacy) requirements, at treating a sufficiently large number of patients to estimate the toxicity (respectively failure) probability of the dose level with a given reliability, and at stopping the trial early if it is likely that no dose is safe (respectively efficacious). A two-stage design was derived from the Continual Reassessment Method (CRM), with implementation of Bayesian criteria to generate stopping rules. A simulation study was conducted to compare the operating characteristics of the proposed two-stage design to those reached by the traditional CRM. Finally, two applications to real data sets are provided.

  19. A clinical follow up of unemployed. II: Sociomedical evaluations as predictors of re-employment.

    Science.gov (United States)

    Claussen, B

    1993-12-01

    To frame and study sociomedical evaluations in clinical work with unemployed people. In a two-year follow up of routine health examinations, three sociomedical evaluations were set up. The first was the direct conclusion of the check-up, based on sickness and possibilities of treatment. The second dealt with work identity, and the last was a diagnostic set of main unemployment problem. The four municipalities of Grenland, Norway. A representative sample aged 16 to 63 who had been registered with the labour market authorities for more than 12 weeks. 21% of the unemployed needed further treatment. 7% were classified as "discouraged", being on their way out of the labour market, while the majority of the study group was healthy job seekers. Work identity seemed to be wage earning for 83%, homemaking for 9%, cultural work for 3%, and being a pensioner for 5%. The main unemployment problem was lack of work for 46% of the examined. Other problems were poor health, being less attractive workers, or having little courage for job search. The evaluations predicted re-employment after two years. They divided the unemployed in groups with from five to seven times difference in re-employment rate. These standardized sociomedical evaluations seen to be useful in clinical work with unemployed people.

  20. Standards for Clinical Trials in Male and Female Sexual Dysfunction: II. Patient-Reported Outcome Measures.

    Science.gov (United States)

    Fisher, William A; Gruenwald, Ilan; Jannini, Emmanuele A; Lev-Sagie, Ahinoam; Lowenstein, Lior; Pyke, Robert E; Reisman, Yakov; Revicki, Dennis A; Rubio-Aurioles, Eusebio

    2016-12-01

    The second article in this series, Standards for Clinical Trials in Male and Female Sexual Dysfunction, focuses on measurement of patient-reported outcomes (PROs). Together with the design of appropriate phase I to phase IV clinical trials, the development, validation, choice, and implementation of valid PRO measurements-the focus of the present article-form the foundation of research on treatments for male and female sexual dysfunctions. PRO measurements are assessments of any aspect of a patient's health status that come directly from the patient (ie, without the interpretation of the patient's responses by a physician or anyone else). PROs are essential for assessing male and female sexual dysfunction and treatment response, including symptom frequency and severity, personal distress, satisfaction, and other measurements of sexual and general health-related quality of life. Although there are some relatively objective measurements of sexual dysfunction (ie, intravaginal ejaculatory latency time, frequency of sexual activity, etc), these measurements do not comprehensively assess the occurrence and extent of sexual dysfunction or treatment on the patient's symptoms, functioning, and well-being. Data generated by a PRO instrument can provide evidence of a treatment benefit from the patient's perspective. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  1. Methodology Series Module 9: Designing Questionnaires and Clinical Record Forms - Part II.

    Science.gov (United States)

    Setia, Maninder Singh

    2017-01-01

    This article is a continuation of the previous module on designing questionnaires and clinical record form in which we have discussed some basic points about designing the questionnaire and clinical record forms. In this section, we will discuss the reliability and validity of questionnaires. The different types of validity are face validity, content validity, criterion validity, and construct validity. The different types of reliability are test-retest reliability, inter-rater reliability, and intra-rater reliability. Some of these parameters are assessed by subject area experts. However, statistical tests should be used for evaluation of other parameters. Once the questionnaire has been designed, the researcher should pilot test the questionnaire. The items in the questionnaire should be changed based on the feedback from the pilot study participants and the researcher's experience. After the basic structure of the questionnaire has been finalized, the researcher should assess the validity and reliability of the questionnaire or the scale. If an existing standard questionnaire is translated in the local language, the researcher should assess the reliability and validity of the translated questionnaire, and these values should be presented in the manuscript. The decision to use a self- or interviewer-administered, paper- or computer-based questionnaire depends on the nature of the questions, literacy levels of the target population, and resources.

  2. Methodology Series Module 9: Designing Questionnaires and Clinical Record Forms – Part II

    Science.gov (United States)

    Setia, Maninder Singh

    2017-01-01

    This article is a continuation of the previous module on designing questionnaires and clinical record form in which we have discussed some basic points about designing the questionnaire and clinical record forms. In this section, we will discuss the reliability and validity of questionnaires. The different types of validity are face validity, content validity, criterion validity, and construct validity. The different types of reliability are test-retest reliability, inter-rater reliability, and intra-rater reliability. Some of these parameters are assessed by subject area experts. However, statistical tests should be used for evaluation of other parameters. Once the questionnaire has been designed, the researcher should pilot test the questionnaire. The items in the questionnaire should be changed based on the feedback from the pilot study participants and the researcher's experience. After the basic structure of the questionnaire has been finalized, the researcher should assess the validity and reliability of the questionnaire or the scale. If an existing standard questionnaire is translated in the local language, the researcher should assess the reliability and validity of the translated questionnaire, and these values should be presented in the manuscript. The decision to use a self- or interviewer-administered, paper- or computer-based questionnaire depends on the nature of the questions, literacy levels of the target population, and resources. PMID:28584367

  3. Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8, TNF-α levels after treatment in children with bronchopneumonia

    International Nuclear Information System (INIS)

    Feng Yue

    2011-01-01

    Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and TNF-α levels after treatment in children with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 and TNF-α levels with RIA were detected both before and after treatment in 33 patients with children bronchopneumonia as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and TNF-α levels were significantly higher in the patients than those in the controls (P 0.05). Conclusions: Serum IGF-II, IL-6, IL-8 and TNF-α could take part in the pathogenesis of children bronchopneumonia in various ways and determination of these levels was clinically important. (authors)

  4. Aminopropyl-modified mesoporous silica SBA-15 as recovery agents of Cu(II)-sulfate solutions: Adsorption efficiency, functional stability and reusability aspects

    International Nuclear Information System (INIS)

    Lombardo, M.V.; Videla, M.; Calvo, A.; Requejo, F.G.; Soler-Illia, G.J.A.A.

    2012-01-01

    Highlights: ► We produce mesoporous amino-silica as Cu(II) adsorbent (1.15–1.75 mmol Cu(II) g −1 ). ► Elemental analysis and XPS demonstrate that amino groups concentrate at the material surface. ► The integrity of the adsorbent through the adsorption, desorption and recycling processes is assessed. ► These materials can be regenerated by exposure to acidic media. ► A careful thermal processing of the material is central to better durability during reprocessing. - Abstract: Hybrid mesoporous materials are potentially useful for metal ion scavenging and retrieval because of their high surface areas, controlled accessibility and tailored functionalization. Some aspects that are linked to the performance of HMM include pore accessibility, stability of the organic functions and reusability. Knowledge of these aspects is critical in the design of adsorption–desorption protocols. In this work we produce and characterize propylamino-substituted large pore silica (SBA-15-N), which is submitted to Cu(II) adsorption from copper sulfate solutions, followed by desorption in acid media and material regeneration. We find that the hybrid material is an efficient adsorbent (1.15–1.75 mmol Cu(II) g −1 ), although a fraction of the organic groups is lost during the adsorption process. An X-ray photoelectron spectroscopy (XPS) study demonstrates that the contents of amino groups are higher in the material surface, leading to different behaviors in Cu(II) complexation along the material. These materials can be regenerated by exposure to acidic media. Thermal processing of the hybrid materials leads to better durability in aqueous solutions during reprocessing, due to enhanced polycondensation of the inorganic framework. Thermally treated samples, once regenerated, are efficient adsorbents in a second step of Cu(II) adsorption. We discuss the materials processing factors involved in the improved adsorption of Cu(II), its quantitative release and reusability of the

  5. CLINICAL PROFILE OF PATTERN OF DYSLIPIDAEMIA AND ISCHAEMIC HEART DISEASE IN TYPE II DIABETES MELLITUS PATIENTS

    Directory of Open Access Journals (Sweden)

    Atul Vijayrao Rajkondawar

    2017-07-01

    Full Text Available BACKGROUND The present research was undertaken to study the pattern of dyslipidaemia and varied clinical manifestations of ischaemic heart disease, its risk factors in type 2 diabetes mellitus patients. Diabetes Mellitus (DM has become major public health problem in India. It is not only increasing in morbidity and mortality, but also decreases the quality of life. Also, disease and its complications are causing heavy economic burden for patients suffering from it.1,2 Diabetes is endemic globally with increasing prevalence in both developing and developed countries. Diabetes is a major cause of mortality, but several studies indicate that it is likely underreported as a cause of death. A recent estimate suggested that diabetes was the fifth leading cause of death worldwide and was responsible for almost 3 million deaths annually (1.7-5.2% of all deaths. MATERIALS AND METHODS A total of 100 patients attending the outpatient department or admitted to medical wards, ICU of tertiary care centre and fulfilling the inclusion criteria were evaluated clinically. A baseline Electrocardiogram (ECG was taken in all cases irrespective of clinical evidence of cardiac involvement. Patients with normal ECG pattern were further evaluated by Treadmill Testing (TMT or stress test for subclinical cardiac involvement. Risk factor evaluation was done in all cases. RESULTS Prevalence of IHD was found to be 41% with a male predominance (1.067:1. Evaluation of risk factors has shown its strong association with IHD. Incidence of IHD was high when low HDL (P 25 had negatively significant association with IHD in type 2 diabetics (P=0.072. Smoking was not statistically associated (P=0.577 and in male alcoholics, IHD had positive association with alcohol (P=0.193. CONCLUSION The current study points out that there exists an increased incidence of ischaemic heart disease in diabetics with few, but not all risk factors contributing to it. Early detection, optimal glycaemic

  6. Clinical significance of determination of changes of serum IGF-II, GM-CSF and TNF-α levels after treatment in children with acute nephritis

    International Nuclear Information System (INIS)

    Xu Xiaoyan; Zhou Hong; Xu Weiqin; Li Xinghua

    2008-01-01

    Objective: To explore the clinical significance of determination of changes of serum IGF-II, GM-CSF and TNF- α levels after treatment in children with acute nephritis. Methods: Serum IGF-II, GM-CSF and TNF-α levels (with RIA) were measured in 31 pediatric patients with acute nephritis and 35 controls. Results: Before treatment, the serum IGF-II, GM-CSF and TNF-α levels in the patients were significantly higher than those in controls (P< O.01). After treatment for 3 months, the serum IGF-II, GM-CSF and TNF-α levels, though markedly corrected, remained significantly higher than those in controls (P<0.05). Conclusion: Determination of changes of serum IGF-II, GM-CSF and TNF-α contents after treatment might be of prognostic importance in pediatric patients with acute nephritis. (authors)

  7. Clinical significance of measurement of changes of serum IGF-II, EGF and CYFRA21-1 levels after chemotherapy in patients with lung cancer

    International Nuclear Information System (INIS)

    Chen Jianlin

    2010-01-01

    Objective: To study the clinical significance of changes of serum IGF-II, EGF and CYFRA21-1 levels after chemotherapy in patients with lung cancer. Methods: Serum IGF-II, EGF (with RIA), and CYFRA21-1 (with ECLIA) levels were determined both before and after chemotherapy in 39 patients with lung cancer as well as once in 35 controls. Results: Before chemotherapy, serum IGF-II, EGF and CYFRA21-1 levels were significantly higher in the patients than those in controls(P<0.01). Six months after chemotherapy, serum IGF-II, EGF and CYFRA21-1 levels dropped markedly, but remained significantly higher than those in controls(P<0.05). Conclusion: The development of lung cancer in patients was closely related to the serum IGF-II, EGF and CYFRA21-1 levels. (authors)

  8. Feline sporotrichosis: associations between clinical-epidemiological profiles and phenotypic-genotypic characteristics of the etiological agents in the Rio de Janeiro epizootic area.

    Science.gov (United States)

    Boechat, Jéssica Sepulveda; Oliveira, Manoel Marques Evangelista; Almeida-Paes, Rodrigo; Gremião, Isabella Dib Ferreira; Machado, Ana Caroline de Sá; Oliveira, Raquel de Vasconcelos Carvalhaes; Figueiredo, Anna Barreto Fernandes; Rabello, Vanessa Brito de Souza; Silva, Karoline Benevides de Lima; Zancopé-Oliveira, Rosely Maria; Schubach, Tânia Maria Pacheco; Pereira, Sandro Antonio

    2018-03-01

    Sporotrichosis is caused by species of the genus Sporothrix. From 1998 to 2015, 4,703 cats were diagnosed at the Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil. Even after the description of the Sporothrix species, the characterisation of feline isolates is not performed routinely. To characterise the clinical isolates from cats at the species level and correlate them with the clinical and epidemiological characteristics of the cats. Forty seven Sporothrix spp. isolates from cats assisted at Fiocruz from 2010 to 2011 were included. Medical records were consulted to obtain the clinical and epidemiological data. The isolates were identified through their morphological and physiological characteristics. T3B polymerase chain reaction (PCR) fingerprinting was used for molecular identification of the species. In phenotypic tests, 34 isolates were characterised as S. brasiliensis, one as S. schenckii and 12 as Sporothrix spp. PCR identified all isolates as S. brasiliensis. S. brasiliensis is the only etiological agent of feline sporotrichosis in Rio de Janeiro to date. None association was found between the isolates and the clinical and epidemiological data. In addition, we strongly recommend the use of molecular techniques for the identification of isolates of Sporothrix spp.

  9. [Pharmacology of local anesthetics and clinical aspects of segmental blocking. II. Spinal anesthesia].

    Science.gov (United States)

    Kozlov, S P; Svetlov, V A; Luk'ianov, M V

    1998-01-01

    Clinical picture of development of segmental blocking after subarachnoidal injection of hyperbaric solutions of 0.75% bupivacaine, 5% ultracaine, and isobaric 0.5% bupivacaine is studied. A total of 152 patients operated on the lower part of the body and the lower limbs were examined under conditions of single, prolonged subarachnoidal, and combined spinal epidural anesthesia. Ultracaine and bupivacaine in different concentrations with different barism provided anesthesia equivalent by the efficacy, depth, and dissemination of sensory block. Segmental blocking with 5% ultracaine was characterized by the shortest latent period (3.14 +/- 0.16 min, p anesthesia in comparison with a single injection, and combined spinal epidural anesthesia shortened the latent period of segmental blocking and ensured intraoperative anesthesia and postoperative analgesia at the expense of the epidural component.

  10. Metabolic and improved organ scan studies. II. Nitrogen-13 labeled compounds used as in-vivo probes for enzyme therapy and as tumor localizing and organ imaging agents

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    A number of 13 N-labeled compounds have been enzymatically synthesized and are being evaluated as tumor and/or organ localizing agents. 13 N-Ammonia, produced after cyclotron generation of 13 N-nitrate and subsequent reduction was used to enzymatically aminate the appropriate substrate to yield 13 N-L-glutamic acid, L-glutamine, L-asparagine, L-valine, L-leucine and L-alanine. The use of 13 N-asparagine as a myocardial scanning agent and as a tumor localizing agent in asparaginase-sensitive tumors is discussed. Two imaging devices were used to study the effectiveness of the compounds as localizing agents. For static whole body distribution studies, a dual-detector high energy gamma ray (HEG) rectilinear scanner, equipped with constant response collimators was employed. The uniformity of response of this system permits quantitative determination of the amount of 13 N activity present in the organ or tumor of interest. The total organ kinetic imaging monitor (TOKIM) gamma camera system was used for dynamic studies covering smaller areas of the subject's body

  11. Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension

    Science.gov (United States)

    Howard, Luke S.G.E.; Watson, Geoffrey M.J.; Wharton, John; Rhodes, Christopher J.; Chan, Kakit; Khengar, Rajeshree; Robbins, Peter A.; Kiely, David G.; Condliffe, Robin; Elliott, Charlie A.; Pepke-Zaba, Joanna; Sheares, Karen; Morrell, Nicholas W.; Davies, Rachel; Ashby, Deborah; Gibbs, J. Simon R.; Wilkins, Martin R.

    2013-01-01

    Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy. PMID:23662181

  12. Construction of McSPECT II - a clinical brain SPECT system

    Energy Technology Data Exchange (ETDEWEB)

    Chang, W.; Jin, Y.; Liu, J. [Rush-Presbyterian-St. Luke`s Medical Center, Chicago, IL (United States)] [and others

    1994-05-01

    Since reported the design concept and system configuration of the McSPECT II last year, we have settled the design details and moved on to the construction phase. The major components being developed in this phase are: detector, collimator, electronics, interfaces, acquisition and processing software, and gantry systems. To provide adequate number of angular sampling (= views), we have increased the number of transverse detector elements to 120 NaI(Tl) bar-detectors in the new cylindrical detector system. These bar-detector are housed in 24 detector modules. Since we have developed a new light-guide and implemented a new 2-step centriod position calculation, the intrinsic performance of the detector modules has been substantially improved. These improvements lead to a simpler position estimation which yields < 4 mm FWHM spatial resolution in the 12 cm axial FOV. The imaging volume is 21 cm (dia.) x 12.8 (axial) cm. The number of collimator units (= rays) is increased to 100 to achieve high linear sampling density (2.3 mm) and sampling resolution ({approximately}5.6 mm). The collimator is still being manufacture. The electronics, acquisition, and processing systems are all in the final phases of debugging through simulated testing. The electronics is divided into 24 independent channels, one for each module. A 10-bit 1.0{mu}s ADC is connected to each of the 72 PMTs. A Pentium based PC performs real-time position calculation in 20 {mu}s/event. After de-randomizing, we expect 50 K/sec count-rate performance with little loss. Linearity and energy corrections are being implemented, in a separate calibration procedure, to yield <0.5 mm non-linearity and {approximately}10% energy resolution at 140 keV. The gantry construction is moving along well but slowly. The large (27.5 cm) aperture and the adjustable orientation of the gantry plane promise easy operation and patient comfort. The system construction should be completed soon to allow imaging studies to be performed.

  13. [Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria].

    Science.gov (United States)

    Igari, Jun; Oguri, Toyoko; Hiramatsu, Nobuyoshi; Akiyama, Kazumitsu; Koyama, Tsuneo

    2003-10-01

    As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, monobactams, and penicillins. Changes in CZOP susceptibility among bacteria were also evaluated with the bacterial resistance ratio calculated from the breakpoint MIC. Twenty-five species (4,154 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Citrobacter freundii, Citrobacter koseri, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Acinetobacter baumannii, Acinetobacter Iwoffii, Burkholderia cepacia, Stenotrophomonas maltophilia, Bacteroides fragilis group, and Prevotella/Porphyromonas. CZOP preserved its antibacterial activity against M. (B.) catarrhalis (MIC90: 4 micrograms/mL) and showed comparable activity to carbapenems against H. influenzae (MIC90: 1 microgram/mL). The antibacterial activity of CZOP against E. coli was preferable (MIC90: 0.125 microgram/mL) and comparable to those of cefpirome (CPR), cefepime (CFPM), and imipenem (IPM). The MIC90 of CZOP against K. pneumoniae and K. oxytoca was 1 and 0.25 microgram/mL, respectively. The MIC90 of CZOP against E. cloacae increased during 6 years (32 to 128 micrograms/mL). The antibacterial activity of CZOP against E. aerogenes was preferable (MIC90: 1 microgram/mL). The antibacterial activities of CZOP against S. marcescens and S. liquefaciens were relatively potent (MIC90: 0.5 and 0.25 microgram/mL) and comparable to those of CPR, CFPM, and carumonam. CZOP preserved comparable antibacterial

  14. Optimizing therapeutic efficacy of chemopreventive agents: A critical review of delivery strategies in oral cancer chemoprevention clinical trials

    OpenAIRE

    Andrew S Holpuch; Kashappa-Goud H Desai; Steven P Schwendeman; Susan R Mallery

    2011-01-01

    Due to its characterized progression from recognized premalignant oral epithelial changes (i.e., oral epithelial dysplasia) to invasive cancer, oral squamous cell carcinoma represents an optimal disease for chemopreventive intervention prior to malignant transformation. The primary goal of oral cancer chemoprevention is to reverse, suppress, or inhibit the progression of premalignant lesions to cancer. Over the last several decades, numerous oral cancer chemoprevention clinical trials have as...

  15. Bifunctional RuII -Complex-Catalysed Tandem C-C Bond Formation: Efficient and Atom Economical Strategy for the Utilisation of Alcohols as Alkylating Agents.

    Science.gov (United States)

    Roy, Bivas Chandra; Chakrabarti, Kaushik; Shee, Sujan; Paul, Subhadeep; Kundu, Sabuj

    2016-12-12

    Catalytic activities of a series of functional bipyridine-based Ru II complexes in β-alkylation of secondary alcohols using primary alcohols were investigated. Bifunctional Ru II complex (3 a) bearing 6,6'-dihydroxy-2,2'-bipyridine (6DHBP) ligand exhibited the highest catalytic activity for this reaction. Using significantly lower catalyst loading (0.1 mol %) dehydrogenative carbon-carbon bond formation between numerous aromatic, aliphatic and heteroatom substituted alcohols were achieved with high selectivity. Notably, for the synthesis of β-alkylated secondary alcohols this protocol is a rare one-pot strategy using a metal-ligand cooperative Ru II system. Remarkably, complex 3 a demonstrated the highest reactivity compared to all the reported transition metal complexes in this reaction. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Micropulse diode laser trabeculoplasty (MDLT: A phase II clinical study with 12 months follow-up

    Directory of Open Access Journals (Sweden)

    Antonio Maria Fea

    2008-06-01

    Full Text Available Antonio Maria Fea, Alex Bosone, Teresa Rolle, Beatrice Brogliatti, Federico Maria GrignoloIstituto di Fisiopatologia Clinica, Clinica Oculistica dell’ Università di Torino, Torino, ItalyObjective: This pilot study evaluates the pressure lowering potential of subthreshold micropulse diode laser trabeculoplasty (MDLT for a clinically meaningful duration in patients with medically uncontrolled open angle glaucoma (OAG.Design: prospective interventional case series.Participants: Thirty-two eyes of 20 consecutive patients with uncontrolled OAG (12 bilateral and 8 unilateral.Methods: Confluent subthreshold laser applications over the inferior 180° of the anterior TM using an 810 nm diode laser in a micropulse operating mode. The intraocular pressure (IOP was measured at baseline and at 1 hour, 1 day, 1 week, 3, 6, 9, and 12 months post-treatment. Flare was measured with a Kowa FM 500 flare-meter at baseline and at 3 hours, 1 day, 1 week, and 12 months post-treatment. After treatment, the patients were maintained on their pre-treatment drug regimen.Main outcome measures: Criteria for treatment response were IOP reduction ≥3 mm Hg and IOP ≤21 mm Hg within the first week after MDLT. Eyes not complying to the above criteria during the follow-up were considered treatment failure. Mean IOP change and percentage of IOP reduction during the follow-up were calculated.Results: One eye was analyzed for bilateral patients. A total of 20 eyes were thus included. Four eyes (20% did not respond to treatment during the first week. One additional eye failed at the 6 month visit. The treatment was successful in 15 eyes (75% at 12 months. The IOP was significantly lower throughout follow-up (p < 0.01. At 12 months, the mean percentage of IOP reduction in the 15 respondent eyes was 22.1% and 12 eyes (60% had IOP reduction higher than 20%. During the first two postoperative days, one eye with pigmentary glaucoma experienced a significant increase of flare

  17. Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer.

    Science.gov (United States)

    Golan, Talia; Sella, Tal; O'Reilly, Eileen M; Katz, Matthew H G; Epelbaum, Ron; Kelsen, David P; Borgida, Ayelet; Maynard, Hannah; Kindler, Hedy; Friedmen, Eitan; Javle, Milind; Gallinger, Steven

    2017-03-14

    BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. A larger multi-centre, case-control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ 2 - and Fisher's exact test, and median DFS/OS using Kaplan-Meier method and log-rank testing. Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34-78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly

  18. The effect of a non-denaturing detergent and a guanidinium-based inactivation agent on the viability of Ebola virus in mock clinical serum samples.

    Science.gov (United States)

    Burton, J E; Easterbrook, L; Pitman, J; Anderson, D; Roddy, S; Bailey, D; Vipond, R; Bruce, C B; Roberts, A D

    2017-12-01

    The 2014 Ebola outbreak in West Africa required the rapid testing of clinical material for the presence of potentially high titre Ebola virus (EBOV). Safe, fast and effective methods for the inactivation of such clinical samples are required so that rapid diagnostic tests including downstream analysis by RT-qPCR or nucleotide sequencing can be carried out. One of the most commonly used guanidinium - based denaturing agents, AVL (Qiagen) has been shown to fully inactivate EBOV once ethanol is added, however this is not compatible with the use of automated nucleic acid extraction systems. Additional inactivation agents need to be identified that can be used in automated systems. A candidate inactivation agent is Triton X-100, a non-denaturing detergent that is frequently used in clinical nucleic acid extraction procedures and has previously been used for inactivation of EBOV. In this study the effect of 0.1% and 1.0% Triton X-100 (final concentration 0.08% and 0.8% respectively) alone and in combination with AVL on the viability of EBOV (10 6 TCID 50 /ml) spiked into commercially available pooled negative human serum was tested. The presence of viable EBOV in the treated samples was assessed by carrying out three serial passages of the samples in Vero E6 cells (37°C, 5% CO 2 , 1 week for each passage). At the end of each passage the cells were observed for evidence of cytopathic effect and samples were taken for rRT-PCR analysis for the presence of EBOV RNA. Before cell culture cytotoxic components of AVL and Triton X-100 were removed from the samples using size exclusion spin column technology or a hydrophobic adsorbent resin. The results of this study showed that EBOV spiked into human serum was not fully inactivated when treated with either 0.1% (v/v) Triton X-100 for 10 mins or 1.0% (v/v) Triton X-100 for 20 mins (final concentrations 0.08% and 0.8% Triton X-100 respectively). AVL alone also did not consistently provide complete inactivation. Samples treated

  19. Antibiotic Prescribing Patterns in Outpatient Emergency Clinics at Queen Rania Al Abdullah II Children's Hospital, Jordan, 2013.

    Science.gov (United States)

    Al-Niemat, Sahar I; Aljbouri, Tareq M; Goussous, Lana S; Efaishat, Rania A; Salah, Rehab K

    2014-07-01

    To investigate antibiotics prescribing patterns in the outpatient pediatric emergency clinic at Queen Rania Al Abdullah II Children's Hospital at Royal Medical Services in Amman, Jordan. The data was collected from the emergency pharmacy over the period of a -five consecutive months. The methodology recommended by the World Health Organization for investigating drug use in a health facility was followed. The study measures the percentage of encounter with a prescribed antibiotic and the percentage share of each antibiotic category. The distribution of diagnostic categories that accounted for all antibiotics being prescribed and the distribution of each antibiotic being prescribed for upper respiratory tract infections (URTIs) were also measured. Antibiotic prescribing was frequent during pediatric visits to the outpatient pediatric emergency clinic resulting in a high percentage of encounters (85%) when compared to appropriate. Emergency physicians continue to frequently prescribe broad spectrum antibiotics which accounted for approximately (60%) of the total prescribed antibiotics and (83%) of prescribed antibiotics for upper respiratory tract infections and macrolides (primarily azithromycin) were the leading class among them. Our results showed high consumption of antibiotics by emergency department pediatricians which highlight the importance for interventions to promote rational and judicious prescribing. An insight into factors influencing antibiotics prescribing patterns by military prescribers is required.

  20. Antibiotic Prescribing Patterns in Outpatient Emergency Clinics at Queen Rania Al Abdullah II Children's Hospital, Jordan, 2013

    Directory of Open Access Journals (Sweden)

    Sahar I. Al-Niemat

    2014-07-01

    Full Text Available Objective: To investigate antibiotics prescribing patterns in the outpatient pediatric emergency clinic at Queen Rania Al Abdullah II Children’s Hospital at Royal Medical Services in Amman, Jordan. Methods: The data was collected from the emergency pharmacy over the period of a -five consecutive months. The methodology recommended by the World Health Organization for investigating drug use in a health facility was followed. The study measures the percentage of encounter with a prescribed antibiotic and the percentage share of each antibiotic category. The distribution of diagnostic categories that accounted for all antibiotics being prescribed and the distribution of each antibiotic being prescribed for upper respiratory tract infections (URTIs were also measured. Results: Antibiotic prescribing was frequent during pediatric visits to the outpatient pediatric emergency clinic resulting in a high percentage of encounters (85% when compared to appropriate. Emergency physicians continue to frequently prescribe broad spectrum antibiotics which accounted for approximately (60% of the total prescribed antibiotics and (83% of prescribed antibiotics for upper respiratory tract infections and macrolides (primarily azithromycin were the leading class among them. Conclusion: Our results showed high consumption of antibiotics by emergency department pediatricians which highlight the importance for interventions to promote rational and judicious prescribing. An insight into factors influencing antibiotics prescribing patterns by military prescribers is required.

  1. Pediatric cancer gone viral. Part II: potential clinical application of oncolytic herpes simplex virus-1 in children

    Directory of Open Access Journals (Sweden)

    Gregory K Friedman

    Full Text Available Oncolytic engineered herpes simplex viruses (HSVs possess many biologic and functional attributes that support their use in clinical trials in children with solid tumors. Tumor cells, in an effort to escape regulatory mechanisms that would impair their growth and progression, have removed many mechanisms that would have protected them from virus infection and eventual virus-mediated destruction. Viruses engineered to exploit this weakness, like mutant HSV, can be safely employed as tumor cell killers, since normal cells retain these antiviral strategies. Many preclinical studies and early phase trials in adults demonstrated that oncolytic HSV can be safely used and are highly effective in killing tumor cells that comprise pediatric malignancies, without generating the toxic side effects of nondiscriminatory chemotherapy or radiation therapy. A variety of engineered viruses have been developed and tested in numerous preclinical models of pediatric cancers and initial trials in patients are underway. In Part II of this review series, we examine the preclinical evidence to support the further advancement of oncolytic HSV in the pediatric population. We discuss clinical advances made to date in this emerging era of oncolytic virotherapy.

  2. Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: A review of the literature.

    Science.gov (United States)

    Janzen, Darren; Delaney, Kathleen A; Shapiro, Elsa G

    2017-06-01

    Sensitive, reliable measurement instruments are critical for the evaluation of disease progression and new treatments that affect the brain in the mucopolysaccharidoses (MPS). MPS I, II, and III have early onset clinical phenotypes that affect the brain during development and result in devastating cognitive decline and ultimately death without treatment. Comparisons of outcomes are hindered by diverse protocols and approaches to assessment including applicability to international trials necessary in rare diseases. We review both cognitive and adaptive measures with the goal of providing evidence to a Delphi panel to come to a consensus about recommendations for clinical trials for various age groups. The results of the consensus panel are reported in an accompanying article. The following data were gathered (from internet resources and from test manuals) for each measure and summarized in the discussion: reliability, validity, date and adequacy of normative data, applicability of the measure's metrics, cross cultural validity including translations and adaptations, feasibility in the MPS population, familiarity to sites, sensitivity to change, and interpretability. If, resulting from this consensus, standard protocols are used for both natural history and treatment studies, patients, their families, and health care providers will benefit from the ability to compare study outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Post-treatment resistance analysis of hepatitis C virus from phase II and III clinical trials of ledipasvir/sofosbuvir.

    Science.gov (United States)

    Wyles, David; Dvory-Sobol, Hadas; Svarovskaia, Evguenia S; Doehle, Brian P; Martin, Ross; Afdhal, Nezam H; Kowdley, Kris V; Lawitz, Eric; Brainard, Diana M; Miller, Michael D; Mo, Hongmei; Gane, Edward J

    2017-04-01

    Ledipasvir/sofosbuvir combination treatment in phase III clinical trials resulted in sustained viral suppression in 94-99% of patients. This study characterized drug resistance in treatment failures, which may help to inform retreatment options. We performed NS5A and NS5B deep sequencing of hepatitis C virus (HCV) from patients infected with genotype (GT) 1 who participated in ledipasvir/sofosbuvir phase II and III clinical trials. Fifty-one of 2144 (2.4%) (42 GT1a and 9 GT1b) treated patients met the criteria for resistance analysis due to virologic failure following the end of treatment. The majority of patients with virologic failure (38 of 51; 74.5%) had detectable ledipasvir-specific resistance-associated substitutions (RASs) at the time of virologic failure (1% deep sequencing cut-off). The percent of patients with NS5A RASs at virologic failure were 37.5%, 66.7%, 94.7% and 100% in patients treated for 6, 8, 12 and 24weeks, respectively. The common substitutions detected at failure were Q30R/H, and/or Y93H/N in GT1a and Y93H in GT1b. At failure, 35.3% (18/51) of virologic failure patients' viruses had two or more NS5A RASs and the majority of patients harbored NS5A RASs conferring a 100-1000-fold (n=10) or >1000-fold (n=23) reduced susceptibility to ledipasvir. One patient in a phase II study with a known ledipasvir RAS at baseline (L31M) developed the S282T sofosbuvir (NS5B) RAS at failure. In GT1 HCV-infected patients treated with ledipasvir/sofosbuvir±ribavirin, virologic failure was rare. Ledipasvir resistance in NS5A was selected or enhanced in most patients with virologic failure, one of whom also developed resistance to sofosbuvir. Clinical studies have shown that combination treatment with ledipasvir/sofosbuvir efficiently cures most patients with genotype 1 hepatitis C infection. For the few patients failing treatment, we show that resistance to ledipasvir was observed in most patients, whereas resistance to sofosbuvir was less common. This has

  4. PREVALENCE OF MEIBOMIAN GLAND DISEASE IN TYPE II DIABETIC PATIENTS & ITS CLINICAL PRESENTATIONS

    Directory of Open Access Journals (Sweden)

    Reshma Pathan

    2015-01-01

    Full Text Available AIMS : To study the prevalence of the meibomian gland disease in typ e 2 diabetic patients and its clinical presentations. SETTING AND DESIGN : A hospital based cross sectional descriptive study of 100 type 2 diabetic patients attending a medical college was conducted. METHODS : Detailed diabetic history was recorded. Assessment of ocular surface i.e. the lid margins , conjunctiva , corneal surface was done via slit lamp biomicroscopy. Meibomian gland disease (MGD severity was assessed by the quality and expressibility of the meibomian secretion. Dry eye tests like schir mer’s test and tear film breakup time were done. STATISTICAL ANALYSIS USED : SPSS statistical software version 17 was used. RESULTS : 56% of the patients out of 100 diabetic patients had MGD. The most common symptom was burning (46.9% , followed by dryness ( 23.5% , 5.6% had conjunctival injection , 7.14% had corneal erosions , 25% had mucus debris , 53.65% had dry eye which was statistically significant (p=0.001 , 56.25% males and 72.2% females had the disease which was not statistically significant. CONCLUSION : The prevalence of Meibomian gland disease in the diabetic population was 56% which is more than the general population prevalence. Apart from other disorders diabetics are also more prone for ocular surface diseases like Meibomian gland disease. MGD is an important pre disposer for severe diseases like Dry eye in this subgroup of patients which can lead to complications like conjunctival keratinisations , corneal erosions and perforations. Careful examination of these patients for ocular surface disease and prompt treatment is required.

  5. Attention deficit hyperactivity disorder characteristics: II. Clinical correlates of irritable mood

    Science.gov (United States)

    Ambrosini, Paul J.; Bennett, David S.; Elia, Josephine

    2012-01-01

    Background This study describes the relationship of irritable mood (IRR) with affective disorders in youths with attention deficit hyperactivity disorder (ADHD). Methods Five hundred ADHD subjects were assessed with the childhood version of the Schedule for Affective Disorder & Schizophrenia. Subjects were in a genetic ADHD protocol and limited to those of Caucasian/European descent. Results The most prevalent concurrent diagnoses were oppositional defiant disorder (ODD) (43.6%), minor depression/dysthymic disorder (MDDD) (18.8%), and generalized anxiety (13.2%)/overanxious disorder (12.4%). IRR subjects (21.0%) compared to the non-IRR (NIRR) group had higher rates of all affective disorders (76.2% vs. 9.6%) and ODD (83.8% vs. 32.9%) but lower rates of hyperactive ADHD (1.9% vs. 8.9%). Among those without comorbidities, 98.3% were NIRR. Logistic regression found IRR mood significantly associated with major depressive disorder (odds ratio [OR]: 33.4), MDDD (OR: 11.2), ODD (OR: 11.6), and combined ADHD (OR: 1.7) but not with anxiety disorders. Among symptoms, it associated IRR mood with a pattern of dysthymic and ODD symptoms but with fewer separation anxiety symptoms. Diagnostic and symptomatic parameters were unaffected by demographic variables. Limitations Potential confounders influencing these results include patient recruitment from only one clinical service; a cohort specific sample effect because some presumed affective disorders and non-Caucasians were excluded; and the young mean age (10.2 years) limiting comorbid patterns. Conclusions The prominence of an MDDD pattern suggests this IRR group is appropriate in the DSM V's proposed chronic depressive disorder, possibly with or without temper dysregulation. A new diagnosis of disruptive mood dysregulation disorder may be unwarranted. PMID:22868057

  6. Cutaneous adverse drug reactions: clinical pattern and causative agents--a 6 year series from Chandigarh, India.

    Directory of Open Access Journals (Sweden)

    Sharma V

    2001-04-01

    Full Text Available AIM: To study the different clinical spectrum of cutaneous adverse drug reactions (ADR and to determine the causative drugs. MATERIALS & METHODS: A prospective, hospital based study was carried out over a period of 6 years recording various cutaneous ADR. RESULTS: A total of 500 patients with cutaneous ADR were enrolled in the study. The most common types of cutaneous ADR patterns were maculopapular rash (34.6%, fixed drug eruption (FDE (30% and urticaria (14%. The drugs most often incriminated for the various cutaneous ADR were antimicrobials (42.6%, anticonvulsants (22.2% and NSAIDs (18%. Anticonvulsants were implicated in 41.6% of maculopapular rashes. Sulfonamides accounted for 43.3% and NSAIDs for 30.7% of FDE. Urticaria was caused mainly by NSAIDs(24.3% and penicillins(20%. Anticonvulsants were responsible for 43.8% of life-threatening toxic epidermal necrolysis and Stevens Johnson syndrome. CONCLUSIONS: The clinical pattern and drugs causing cutaneous ADR are similar to those observed in other countries except for minor variations. Cutaneous ADR patterns and the drugs causing various reactions are changing every year, which may be due to the emergence of newer molecules and changing trends in the use of drugs.

  7. Clinical study of a new therapy for nerve agent poisoning: Ascending dose tolerance study of HI-6 + atropine

    Energy Technology Data Exchange (ETDEWEB)

    Clement, J.G.; Bailey, D.G.; Madill, H.D.; Spence, J.D.

    1993-05-13

    HI-6 was rapidly absorbed from an IM injection site. Maximum HI-6 plasma concentrations of 1.88, 4.96, 8.31 15.0 ug/ml were found 28-36 min after administration and maintained above 4 ug/ml concentration for 0, 39, 112 172.5 min following administration of 62.5, 125, 250 or 500 mg HI-6 + atropine (2 mg), respectively. The calculated half life of HI-6 was 78.2 min following 62.5 mg HI-6 + atropine dose and approximately 64-67 min following 125-500 mg HI-6 + atropine doses. Approximately 50 % of the total dose of HI-6 was eliminated unchanged in the urine. There were significant changes (p < 0.05) in AST, CPK, creatinine and gamma GT following the 500 mg HI-6 + atropine dose but they were not considered to be clinically significant. Urinalysis, hematology and semen analysis over the 24 hr observation period was uneventful. There were no clinically significant changes in heart rate or ECG trace, respiration or blood pressure, visual and mental acuity following HI-6 + atropine.

  8. Waffle production: influence of batter ingredients on sticking of waffles at baking plates-Part II: effect of fat, leavening agent, and water.

    Science.gov (United States)

    Huber, Regina; Schoenlechner, Regine

    2017-05-01

    Fresh egg waffles are continuously baked in tunnel baking ovens in industrial scale. Waffles that partly or fully stick to the baking plates cause significant product loss and increased costs. The aim of this study was, therefore, to investigate the effect of different recipe ingredients on the sticking behavior of waffles. In this second part, ingredients investigated were different leavening agents (sodium acid pyrophosphate, ammonium bicarbonate, magnesium hydroxide carbonate, or monocalcium phosphate), different fat sources (rapeseed oil, cocos fat, butter, or margarine), and different water sources (tap water 12°dH and distilled water). Within the different types of fats, solid fats with high amount of short-chain fatty acids (cocos fat or butter) decreased the number of sticking waffles compared to liquid oils (rapeseed oil). Regarding leavening agents, magnesium hydroxide carbonate and ammonium bicarbonate were superior to sodium acid pyrophosphate or monocalcium phosphate. Between the two water sources, effects were small.

  9. Aminopropyl-modified mesoporous silica SBA-15 as recovery agents of Cu(II)-sulfate solutions: Adsorption efficiency, functional stability and reusability aspects

    Energy Technology Data Exchange (ETDEWEB)

    Lombardo, M.V. [Gerencia Quimica, Centro Atomico Constituyentes, CNEA, Av. General Paz 1499 (B1650KNA), San Martin, Buenos Aires (Argentina); Videla, M. [Rhein Chemie Argentina, Luis Maria Drago 1555 - (B1852LGS) Burzaco, Buenos Aires (Argentina); Calvo, A.; Requejo, F.G. [INIFTA-CONICET, Universidad Nacional de La Plata, CC 16 Sucursal 4 (1900), La Plata (Argentina); Soler-Illia, G.J.A.A., E-mail: gsoler@cnea.gov.ar [Gerencia Quimica, Centro Atomico Constituyentes, CNEA, Av. General Paz 1499 (B1650KNA), San Martin, Buenos Aires (Argentina); DQIAyQF, FCEN, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II (C1428EHA), Buenos Aires (Argentina)

    2012-07-15

    Highlights: Black-Right-Pointing-Pointer We produce mesoporous amino-silica as Cu(II) adsorbent (1.15-1.75 mmol Cu(II) g{sup -1}). Black-Right-Pointing-Pointer Elemental analysis and XPS demonstrate that amino groups concentrate at the material surface. Black-Right-Pointing-Pointer The integrity of the adsorbent through the adsorption, desorption and recycling processes is assessed. Black-Right-Pointing-Pointer These materials can be regenerated by exposure to acidic media. Black-Right-Pointing-Pointer A careful thermal processing of the material is central to better durability during reprocessing. - Abstract: Hybrid mesoporous materials are potentially useful for metal ion scavenging and retrieval because of their high surface areas, controlled accessibility and tailored functionalization. Some aspects that are linked to the performance of HMM include pore accessibility, stability of the organic functions and reusability. Knowledge of these aspects is critical in the design of adsorption-desorption protocols. In this work we produce and characterize propylamino-substituted large pore silica (SBA-15-N), which is submitted to Cu(II) adsorption from copper sulfate solutions, followed by desorption in acid media and material regeneration. We find that the hybrid material is an efficient adsorbent (1.15-1.75 mmol Cu(II) g{sup -1}), although a fraction of the organic groups is lost during the adsorption process. An X-ray photoelectron spectroscopy (XPS) study demonstrates that the contents of amino groups are higher in the material surface, leading to different behaviors in Cu(II) complexation along the material. These materials can be regenerated by exposure to acidic media. Thermal processing of the hybrid materials leads to better durability in aqueous solutions during reprocessing, due to enhanced polycondensation of the inorganic framework. Thermally treated samples, once regenerated, are efficient adsorbents in a second step of Cu(II) adsorption. We discuss the

  10. The Effectiveness of a New Hemostatic Agent (Ankaferd Blood Stopper for the Control of Bleeding following Tooth Extraction in Hemophilia: A Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Hakkı Oğuz Kazancıoğlu

    2013-03-01

    Full Text Available Objective: To assess the hemostatic efficacy of a new local hemostatic agent, Ankaferd Blood Stopper (ABS, for the control of bleeding following tooth extraction in hemophiliacs. Materials and Methods: Simple tooth extractions were performed in 27 hemophilia A patients. In the treatment group (n=17 local hemostasis was achieved via application of ABS to the extraction sockets, whereas in the control group (n=10 local hemostasis was achieved via direct packing with gauze. Results: In all, 57 (21 primary and 36 permanent teeth extractions were performed in 27 hemophilia A patients. There were no significant differences in age or factor VIII level distribution between the 2 groups (p>0.05. The most significant clinical difference between the groups was associated with the use of ABS; those in the treatment group had significantly shorter duration of bleeding (p=0.002. Conclusion: This is the first study to evaluate the efficacy of ABS for the control of bleeding following tooth extraction in hemophiliacs. ABS can be considered an alternative local hemostatic agent for reducing clotting factor concentrates in hemophilia patients.

  11. Antibacterial and synergy of berberines with antibacterial agents against clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA).

    Science.gov (United States)

    Zuo, Guo-Ying; Li, Yang; Han, Jun; Wang, Gen-Chun; Zhang, Yun-Ling; Bian, Zhong-Qi

    2012-08-29

    Antibacterial activity of berberine (Ber) and 8-acetonyl-dihydroberberine (A-Ber) alone and combined uses with antibacterial agents ampicillin (AMP), azithromycin (AZM), cefazolin (CFZ) and levofloxacin (LEV) was studied on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA). Susceptibility to each agent alone was tested using a broth microdilution method and the chequerboard and time-kill tests for the combined evaluations, respectively. The alone MICs/MBCs (μg/mL) ranges were 32-128/64-256 (Ber) and 32-128/128-512 (A-Ber). Significant synergies were observed for the Ber (A-Ber)/AZM and Ber (A-Ber)/LEV combinations against 90% of the tested MRSA strains, with fractional inhibitory concentration indices (FICIs) values ranged from 0.188 to 0.500. An additivity result was also observed for the Ber/AZM combination by time-kill curves. These results demonstrated for the first time that Ber and A-Ber enhanced the in vitro inhibitory efficacy of AZM and LEV to a same extent, which had potential for further investigation in combinatory therapeutic applications of patients infected with MRSA.

  12. Antibacterial and Synergy of Berberines with Antibacterial Agents against Clinical Multi-Drug Resistant Isolates of Methicillin-Resistant Staphylococcus aureus (MRSA

    Directory of Open Access Journals (Sweden)

    Zhong-Qi Bian

    2012-08-01

    Full Text Available Antibacterial activity of berberine (Ber and 8-acetonyl-dihydroberberine (A-Ber alone and combined uses with antibacterial agents ampicillin (AMP, azithromycin (AZM, cefazolin (CFZ and levofloxacin (LEV was studied on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA. Susceptibility to each agent alone was tested using a broth microdilution method and the chequerboard and time-kill tests for the combined evaluations, respectively. The alone MICs/MBCs (mg/mL ranges were 32–128/64–256 (Ber and 32-128/128-512 (A-Ber. Significant synergies were observed for the Ber (A-Ber/AZM and Ber (A-Ber/LEV combinations against 90% of the tested MRSA strains, with fractional inhibitory concentration indices (FICIs values ranged  from 0.188 to 0.500. An additivity result was also observed for the Ber/AZM combination by time-kill curves. These results demonstrated for the first time that Ber and A-Ber enhanced the in vitro inhibitory efficacy of AZM and LEV to a same extent, which had potential for further investigation in combinatory therapeutic applications of patients infected with MRSA.

  13. A self-controlled comparative clinical trial to explore the effectiveness of three topical hemostatic agents for stopping severe epistaxis in pediatrics with inherited coagulopathies.

    Science.gov (United States)

    Eshghi, P; Jenabzade, A; Habibpanah, B

    2014-09-01

    The aim of this study was to assess the effectiveness of localized treatments to persistently stop epistaxis in patients with inherited bleeding disorders. In a self-controlled comparative clinical trial, to offer the best solution to stop epistaxis at home (within 10 minutes), patients with inherited bleeding disorders were treated using three different topical hemostatic agents, including Tranexamic acid impregnated tampon, EpiCell tampon prepared from oxidized regenerated cellulose pad, and ChitoHem tampon (reinforced with chitosan). The results of using these different products on three groups of randomly selected patients were ultimately compared using the χ(2) and Fisher's exact test statistics. A total of 31 patients, 5 females and 26 males with a mean age of 5.6 years, were included in the study. Twenty-three patients had Glanzmann disease, four had von-Willebrand disease, two had Bernard soulier syndrome, two had activated factor VII deficiency, and one patient had impaired secretion of adenosine deaminase. The study exhibited that statistically there was no significant difference between EpiCell tampon and Tranexamic acid impregnated tampon treatments with respect to the hemostasis duration. However, ChitoHem tampon was more efficient than Tranexamic acid impregnated tampon (P value stop epistaxis. We recommend further research on the use of other hemostatic agents for localized bleeding in patients with inherited bleeding disorders.

  14. Clinical impact of the temporal relationship between depression and type 2 diabetes: the Fremantle diabetes study phase II.

    Directory of Open Access Journals (Sweden)

    David G Bruce

    Full Text Available BACKGROUND: The clinical features of type 2 diabetes may differ depending on whether first depression episode precedes or follows the diagnosis of diabetes. METHODS: Type 2 patients from the observational community-based Fremantle Diabetes Study Phase II underwent assessment of lifetime depression using the Brief Lifetime Depression Scale (developed and validated for this study supplemented by information on current depression symptoms (Patient Health Questionnaire, 9-item version and use of antidepressants. Patients were categorized as never depressed (Group 1, having had depression before diabetes diagnosis (Group 2, diagnosed with depression and diabetes within 2 years of each other (Group 3 and having depression after diabetes diagnosis (Group 4. RESULTS: Of 1391 patients, 20.8% were assigned to Group 2, 6.0% to Group 3 and 14.5% to Group 4. In Group 2, depression occurred a median 15.6 years before diabetes onset at age 37.2±14.7 years. These patients had similar clinical characteristics to never depressed patients except for reduced self-care behaviours and having more symptomatic peripheral arterial disease. In Group 4, depression occurred a median 9.9 years after diabetes onset at age 59.8±13.0 years. These patients had long duration diabetes, poor glycaemic control, more intensive management and more diabetic complications. Group 4 patients had more current depression than Group 2 but were less likely to be receiving antidepressants. CONCLUSIONS/INTERPRETATION: The clinical features of depression and type 2 diabetes are heterogeneous depending on their temporal relationship. There may be corresponding differences in the pathogenesis of depression in diabetes that have implications for diagnosis and management.

  15. In-vitro studies with 188Re-HEDP, a clinically used bone pain palliating agent, on bone cancer cells

    International Nuclear Information System (INIS)

    Sharma, Rohit; Kumar, Chandan; Mallia, Madhava B.; Banerjee, Sharmila; Kameswaran, Mythili

    2017-01-01

    Rhenium-188 is an attractive radioisotope for a wide variety of radiotherapy applications. 188 Re-HEDP (HEDPhydroxyethylidene- 1,1-diphosphonic acid) is one such, clinically useful, radiopharmaceutical for palliation of bone pain due to osseous metastasis. Herein, our aim was to study the uptake and retention of 188 Re-HEDP in mineralized bone and to assess its cellular toxicity, along with its underlying mechanism in human osteocarcinoma (MG-63 and Soas-2) cell lines. 188 Re-HEDP uptake was found to be significantly higher in mineralized bone. The 188 Re-HEDP complex also induces G2-M cell cycle arrest and thus contributing to apoptosis and cellular toxicity in bone cancer cells. (author)

  16. HPLC characterization of clinically used sup(99m)Tc bone agents. Relative tissue distribution of fractionated components in mice

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Meinken, G.E.; Richards, P.; Ford, L.A.; Benson, W.R.

    1982-01-01

    A study was undertaken to separate and characterize the components of clinically used (kit produced) 99m-Tc-Sn-MDP and 99m-Tc-Sn-EHDP preparations by high performance liquid chromatography (HPLC) using radioactivity detection mode. Tissue distribution studies of the HPLC fractionated species were carried out in mice in order to define the in vivo behavior of the individual components. Effect of many variables such as time, oxygen, pH, temperature, etc. on the above two systems was also studied in relation to the composition as determined by HPLC and changes, if any, in the biological behavior. The results demonstrate the unique capabilities of reverse phase HPLC for rapid and high resolution analysis of complex 99mTc radiopharmaceutical mixtures

  17. Demyelinizing neurological disease after treatment with tumor necrosis factor alpha-inhibiting agents in a rheumatological outpatient clinic

    DEFF Research Database (Denmark)

    Theibich, Ali; Dreyer, Lene; Magyari, Melinda

    2014-01-01

    Biological treatment with inhibitors of the pro-inflammatory cytokine TNF-alpha has dramatically improved the disease course of several chronic rheumatologic conditions. Adverse events (AEs) are primarily infections and hypersensitivity reactions. Demyelinizing neurological symptoms resembling...... multiple sclerosis (MS) have been described as a rare AE. During about 10-year use of anti TNF-alpha, the Danish Medicines Agency has recorded eight cases of MS like AEs. The objective of this study was to estimate the incidence of demyelinizing AEs both in the central and peripheral nervous system after...... treatment with anti TNF-alpha in a cohort of patients from a large rheumatologic outpatient clinic in Copenhagen. In a 4-year period from January 2008 to December 2011, approximately 550 patients annually were undergoing treatment with anti TNF-alpha inhibitors in our department. We collected data on all...

  18. Comparison of clinical imaging characteristics of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide: first result of a prospective phase II study

    International Nuclear Information System (INIS)

    Gabriel, M.; Decristoforo, C.; Wenger, M.; Guggenberg, E. von; Moncayo, R.; Mather, S.J.

    2002-01-01

    Full text: 99m Tc-EDDA/HYNIC-TOC(Tc-TOC) shows very similar clinical pharmacokinetics compared with 111 In-DTPA-octreotide (In-OCT), the gold standard for somatostatin receptor (SSTR) scintigraphy, and is a promising agent to image SSTR-positive tumors. Here we present the first results of a phase II trial comparing the clinical value of Tc-TOC in a prospective intra-patient comparison with In-OCT. Until now 26 oncological patients were enrolled in the study after giving informed consent. The patients presented with thyroid adeno-carcinomas (n=5), MW (n=3), GEP-tumors (n=10), carcinoid syndromes with unknown primary lesions (n=4), paragangliomas (n=2) and pituitary tumor (n=2), one of whom due to MEN. Posterior and anterior views and SPECT images of the corresponding ROIs were acquired at 4 hrs and 24 hrs alter injection of 111 MBq of In-OCT (octreoscan(r)). TcTOC was given at a dose of 300-350 MBq and imaging was done at 4 hrs p.i. including whole body planar and SPECT studies. Interpretations of these two sets of planar data were done independently by two different viewers. Final confirmation of suspected lesions was obtained by correlative inspection of matched CT or MR scans. In 7 patients SSTR-scintigraphy was negative with both Tc-TOC and In-OCT. Matching positive scintigraphic results with both tracers were obtained in 17 out of 19 patients. In-OCT failed to detect two CT-positive thoracic lesions in two patients with thyroid cancer, whereby these lesions were seen by Tc-TOC. In this series of patients 99m Tc-EDDA-HYNIC-TOC imaging resulted in equivalent diagnostic information on the SSTR-Status, with advantages of a single acquisition, one day protocol and lower radiation dose. The excellent imaging properties resulted in improved diagnosis in 2 of 26 patients when compared to 111 In-DTPA-octreotide. (author)

  19. Portable digital assistants (PDAs) in dentistry: part II--pilot study of PDA use in the dental clinic.

    Science.gov (United States)

    Reynolds, P A; Harper, J; Dunne, S; Cox, M; Myint, Y K

    2007-04-28

    To describe a simple technical evaluation of the access, security issues and uses of wireless networked PDAs in a dental clinic and report a pilot study investigating students' educational use of PDAs to access a Virtual Learning Environment (VLE) in a dental clinic. To undertake a technical evaluation of wireless networking to PDAs focusing on security issues, robustness of the system and accessibility particularly to educational resources. To evaluate the impact of using a PDA on undergraduate students in the dental clinic and at home. Part II describes the technical and educational evaluation of PDAs used by one group of 12 undergraduate fourth year students in the Primary Dental Care clinic. A cross over trial of six students with PDAs and six without was carried out during one semester of 12 weeks. Technical issues such as secure internet access using wireless connectivity were addressed. An assessment of the general and educational use and the students' attitudes towards using PDAs was undertaken using online questionnaires and focus group discussions. Over 90% of participants wanted PDAs as part of their dental kit. The potential of PDA use in dental training was demonstrated by a good to excellent response by over 75% of participants to having access to online support materials, particularly videos, being able to make notes for individual study and to keep a diary of their commitments to teaching sessions. Recreational use included a 100% good to excellent response to playing games and keeping a diary. The PDA proved to be a convenient and versatile mode of access to online education. Technical solutions enabled a substantial proportion of the functionality of WebCT (Web Course Tools) to be accessed by the students in a clinical environment. Both novice and experienced users were able to appreciate the use of the PDA and the less able considered that their ICT skills had improved. However, further research is needed to determine how students use a range of

  20. Clinical performance of cements as luting agents for telescopic double crown-retained removable partial and complete overdentures.

    Science.gov (United States)

    Behr, Michael; Kolbeck, Carola; Lang, Reinhold; Hahnel, Sebastian; Dirschl, Lisa; Handel, Gerhard

    2009-01-01

    The aim of this study was to investigate the survival rates and technical failures of removable prostheses (RPs) supported by telescopic double crown (TDC)-retained abutment teeth luted with zinc-phosphate or glass-ionomer cement. Clinical records of 577 patients (288 women, 289 men) who received 577 TDC-retained RPs supported by 1,807 abutments at the Department of Prosthodontics of the University Hospital Regensburg, Regensburg, Germany, between 1984 and 2007 were analyzed. The 577 prostheses included 200 attached to telescopic crowns with friction fit (FFs), 62 to conical crowns (CCs), and 315 to parallel-sided telescopic crowns with clearance fit (CFs). Survival probabilities were evaluated for the RPs, loss of cementation of the inner copings, secondary caries, and abutment teeth that required endodontic treatment using the Kaplan-Meier method. A Cox regression analysis determined the impact of covariates such as sex, denture location (maxilla/mandible), Eichner classification, number of abutment teeth, and the type of double crown system used. The 10-year survival probability was 98.8% +/- 0.09% for FFs, 92.9% +/- 0.41% for CCs, and 86.6% +/- 0.05% for CFs. During the observation period, loss of cementation was frequently observed (FFs: 32%, CCs: 53.2%, CFs: 21.3%). After 15 years, more than 75% of patients had experienced at least one "loss of cementation" event. In this respect, zinc-oxide phosphate and glass-ionomer cements did not show any significant difference. The long-term successful outcome of the RP experience was not compromised, although numerous clinical visits were required for maintenance. The predominant maintenance procedure was the need for recementation of the inner copings.

  1. Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis.

    Science.gov (United States)

    Cheng, Hui-Man; Wu, Yang-Chang; Wang, Qingmin; Song, Michael; Wu, Jackson; Chen, Dion; Li, Katherine; Wadman, Eric; Kao, Shung-Te; Li, Tsai-Chung; Leon, Francisco; Hayden, Karen; Brodmerkel, Carrie; Chris Huang, C

    2017-09-02

    Indigo naturalis is a Traditional Chinese Medicine (TCM) ingredient long-recognized as a therapy for several inflammatory conditions, including psoriasis. However, its mechanism is unknown due to lack of knowledge about the responsible chemical entity. We took a different approach to this challenge by investigating the molecular profile of Indigo naturalis treatment and impacted pathways. A randomized, double-blind, placebo-controlled clinical study was conducted using Indigo naturalis as topical monotherapy to treat moderate plaque psoriasis in a Chinese cohort (n = 24). Patients were treated with Indigo naturalis ointment (n = 16) or matched placebo (n = 8) twice daily for 8 weeks, with 1 week of follow-up. At week 8, significant improvements in Psoriasis Area and Severity Index (PASI) scores from baseline were observed in Indigo naturalis-treated patients (56.3% had 75% improvement [PASI 75] response) compared with placebo (0.0%). A gene expression signature of moderate psoriasis was established from baseline skin biopsies, which included the up-regulation of the interleukin (IL)-17 pathway as a key component; Indigo naturalis treatment resulted in most of these signature genes returning toward normal, including down-regulation of the IL-17 pathway. Using an in vitro keratinocyte assay, an IL-17-inhibitory effect was observed for tryptanthrin, a component of Indigo naturalis. This study demonstrated the clinical efficacy of Indigo naturalis in moderate psoriasis, and exemplified a novel experimental medicine approach to understand TCM targeting mechanisms. NCT01901705 .

  2. Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial.

    Science.gov (United States)

    Petrou, Philip A; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A; Ferris, Frederick L; Chew, Emily Y; Wong, Wai T

    2014-12-18

    To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA). The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline. Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye. While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. (ClinicalTrials.gov number, NCT01445548.). Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  3. Use of angiotensin II receptor blockers alone and in combination with other drugs: a large clinical experience trial

    Directory of Open Access Journals (Sweden)

    Matthew R Weir

    2001-03-01

    Full Text Available Angiotensin II (Ang II receptor blockers are the newest class of antihypertensive drugs to be developed. No large-scale clinical trials have been performed to evaluate their efficacy alone, or in combination with other drugs. A large-scale, eight week, open-label, non-placebo-controlled, single-arm trial evaluated the efficacy, tolerability and dose-response of candesartan cilexetil, 16—32 mg once-daily, either as monotherapy or as part of combination therapy, in a diverse hypertensive population in actual practice settings. 6465 patients with high blood pressure, of whom 52% were female and 16% African American, with a mean age of 58 years, were included. 5446 patients had essential hypertension and 1014 patients had isolated systolic hypertension. In order to be included in this study, patients had either untreated or uncontrolled hypertension (systolic blood pressure (SBP 140—179 mmHg and/or diastolic blood pressure (DBP 90—109 mmHg inclusive at baseline, despite a variety of other antihypertensive drugs. Of the 5156 patients with essential hypertension and at least one post baseline efficacy measurement, the mean pretreatment blood pressure (BP was 156/97 mmHg. Candesartan cilexetil monotherapy reduced mean SBP/DBP by 18.0/12.2 mmHg. Similarly, in the 964 patients with isolated systolic hypertension and at least one post baseline efficacy measurement, candesartan cilexetil monotherapy reduced SBP/DBP from 158/81 by 16.5/4.5 mmHg. Candesartan cilexetil was similarly effective when employed as add-on therapy. When added to baseline antihypertensive medication in 51% of the patients with essential hypertension not achieving BP control, additional reduction in BP was achieved regardless of the background therapy, including diuretics (17.8/11.7 mmHg calcium antagonists (16.6/11.2 mmHg, beta-blockers (16.5/10.4 mmHg, angiotensin-converting enzyme inhibitors (ACE-I (15.3/10.0 mmHg, and alpha blockers (16.4/10.4 mmHg. Likewise, when

  4. Loeys-Dietz syndrome type I and type II: clinical findings and novel mutations in two Italian patients

    Directory of Open Access Journals (Sweden)

    Calzavara-Pinton Pier

    2009-11-01

    Full Text Available Abstract Background Loeys-Dietz syndrome (LDS is a rare autosomal dominant disorder showing the involvement of cutaneous, cardiovascular, craniofacial, and skeletal systems. In particular, LDS patients show arterial tortuosity with widespread vascular aneurysm and dissection, and have a high risk of aortic dissection or rupture at an early age and at aortic diameters that ordinarily are not predictive of these events. Recently, LDS has been subdivided in LDS type I (LDSI and type II (LDSII on the basis of the presence or the absence of cranio-facial involvement, respectively. Furthermore, LDSII patients display at least two of the major signs of vascular Ehlers-Danlos syndrome. LDS is caused by mutations in the transforming growth factor (TGF beta-receptor I (TGFBR1 and II (TGFBR2 genes. The aim of this study was the clinical and molecular characterization of two LDS patients. Methods The exons and intronic flanking regions of TGFBR1 and TGFBR2 genes were amplified and sequence analysis was performed. Results Patient 1 was a boy showing dysmorphic signs, blue sclerae, high-arched palate, bifid uvula; skeletal system involvement, joint hypermobility, velvety and translucent skin, aortic root dilatation, tortuosity and elongation of the carotid arteries. These signs are consistent with an LDSI phenotype. The sequencing analysis disclosed the novel TGFBR1 p.Asp351Gly de novo mutation falling in the kinase domain of the receptor. Patient 2 was an adult woman showing ascending aorta aneurysm, with vascular complications following surgery intervention. Velvety and translucent skin, venous varicosities and wrist dislocation were present. These signs are consistent with an LDSII phenotype. In this patient and in her daughter, TGFBR2 genotyping disclosed in the kinase domain of the protein the novel p.Ile510Ser missense mutation. Conclusion We report two novel mutations in the TGFBR1 and TGFBR2 genes in two patients affected with LDS and showing marked

  5. Clinical significance of estimation of changes in serum IGF-II, TNF-α and TSGF levels after chemotherapy in patients with acute leukemia

    International Nuclear Information System (INIS)

    Liu Huijie

    2011-01-01

    Objective: To explore the clinical significance of changes in serum IGF-II, TNF-α and TSGF levels after chemotherapy in patients with acute leukemia. Methods: Serum IGF-II, TNF-α (with RIA) and TSGF (with biochemistry) levels were determined in 33 patients with acute leukemia both before and after chemotherapy as well as in 35 normal healthy Controls. Results: Before chemotherapy, serum IGF-II, TNF-α and TSGF levels in the patients were significantly higher than those in controls (P<0.01), 6 months after chemotherapy the levels in 28 patients without recurrence dropped markedly and approached those in controls. However, in the 5 eases with recurrence, the levels after return again, approaching those before chemotherapy. Conclusion: Changes of serum levels on IGF-II, TNF-α and TSGF might be useful as indicative parameters for diagnosis and curative effect in patients with acute leukemia. (authors)

  6. Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia

    International Nuclear Information System (INIS)

    Wang Guanghui; Chen Chuanbing; Wang Xianwu

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 (with RIA) and hs-CRP (with immunoturbidity method) levels were determined in 36 pediatric patients with bronchopneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and hs-CRP levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Determination of serum IGF-II, IL-6, IL-8 and hs-CRP levels in pediatric patients with bronchopneumonia was important for diagnosis and outcome prediction. (authors)

  7. Clinical significance of measurement of changes of serum IGF-II and NO levels after treatment in elderly patients with chronic bronchitis

    International Nuclear Information System (INIS)

    Gu Tao

    2006-01-01

    Objective: To study the clinical significance of changes of serum IGF-II and NO levels after treatment in elderly patients with chronic bronchitis. Methods: Serum IGF-II (with RIA) and NO (with Biochemical method) levels were measured in 42 elderly patients with chronic bronchitis both before and after treatment as well as in 30 controls. Results: Before treatment in the patients the serum IGF-II levels were significantly higher than those in controls (P<0.01), while the NO levels were significantly lower (P<0.01). After two weeks of treatment, the levels though dropped markedly, lemained higher than those in controls (P<0. 05). Conclusion: Serum IGF-II and NO levels changes could reflect the disease status as well as the progress of diseases. (authors)

  8. Clinical significance of changes of serum IGF-II, IL-2 and SOD levels after treatment in pediatric patients with bronchial pneumonia

    International Nuclear Information System (INIS)

    Zhou Hong; Hu Yan; Wei Guoyu; Huang Jufeng

    2011-01-01

    Objective: To investigate the clinical significance of changes of serum IGF-II, IL-2 and SOD levels after treatment in pediatric patients with bronchial pneumonia. Methods: Serum IGF-II, IL-2 and SOD (with RIA) levels were measured in 33 pediatric patients with bronchial pneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II levels in the patients were significantly higher than those in controls (P 0.05). Conclusion: Changes of serum IGF-II, IL-2 and SOD levels both before and after treatment could reflect the diseases status of the patients as well as the progress of diseases, and might be of prognostic importance in pediatric patients with bronchial pneumonia. (authors)

  9. Development and Evaluation of a Molecular Diagnostic Method for Rapid Detection of Histoplasma capsulatum var. farciminosum, the Causative Agent of Epizootic Lymphangitis, in Equine Clinical Samples.

    Science.gov (United States)

    Scantlebury, C E; Pinchbeck, G L; Loughnane, P; Aklilu, N; Ashine, T; Stringer, A P; Gordon, L; Marshall, M; Christley, R M; McCarthy, A J

    2016-12-01

    Histoplasma capsulatum var. farciminosum, the causative agent of epizootic lymphangitis (EZL), is endemic in parts of Africa. Diagnosis based on clinical signs and microscopy lacks specificity and is a barrier to further understanding this neglected disease. Here, a nested PCR method targeting the internal transcribed spacer (ITS) region of the rRNA operon was validated for application to equine clinical samples. Twenty-nine horses with signs of EZL from different climatic regions of Ethiopia were clinically examined. Blood samples and aspirates of pus from cutaneous nodules were taken, along with blood from a further 20 horses with no cutaneous EZL lesions. Among the 29 horses with suspected cases of EZL, H. capsulatum var. farciminosum was confirmed by extraction of DNA from pus and blood samples from 25 and 17 horses, respectively. Positive PCR results were also obtained with heat-inactivated pus (24 horses) and blood (23 horses) spotted onto Whatman FTA cards. Two positive results were obtained among blood samples from 20 horses that did not exhibit clinical signs of EZL. These are the first reports of the direct detection of H. capsulatum var. farciminosum in equine blood and at high frequency among horses exhibiting cutaneous lesions. The nested PCR outperformed conventional microscopic diagnosis, as characteristic yeast cells could be observed only in 14 pus samples. The presence of H. capsulatum var. farciminosum DNA was confirmed by sequencing the cloned PCR products, and while alignment of the ITS amplicons showed very little sequence variation, there was preliminary single nucleotide polymorphism-based evidence for the existence of two subgroups of H. capsulatum var. farciminosum This molecular diagnostic method now permits investigation of the epidemiology of EZL. Copyright © 2016 Scantlebury et al.

  10. Development and Evaluation of a Molecular Diagnostic Method for Rapid Detection of Histoplasma capsulatum var. farciminosum, the Causative Agent of Epizootic Lymphangitis, in Equine Clinical Samples

    Science.gov (United States)

    Pinchbeck, G. L.; Loughnane, P.; Aklilu, N.; Ashine, T.; Stringer, A. P.; Gordon, L.; Marshall, M.; Christley, R. M.

    2016-01-01

    Histoplasma capsulatum var. farciminosum, the causative agent of epizootic lymphangitis (EZL), is endemic in parts of Africa. Diagnosis based on clinical signs and microscopy lacks specificity and is a barrier to further understanding this neglected disease. Here, a nested PCR method targeting the internal transcribed spacer (ITS) region of the rRNA operon was validated for application to equine clinical samples. Twenty-nine horses with signs of EZL from different climatic regions of Ethiopia were clinically examined. Blood samples and aspirates of pus from cutaneous nodules were taken, along with blood from a further 20 horses with no cutaneous EZL lesions. Among the 29 horses with suspected cases of EZL, H. capsulatum var. farciminosum was confirmed by extraction of DNA from pus and blood samples from 25 and 17 horses, respectively. Positive PCR results were also obtained with heat-inactivated pus (24 horses) and blood (23 horses) spotted onto Whatman FTA cards. Two positive results were obtained among blood samples from 20 horses that did not exhibit clinical signs of EZL. These are the first reports of the direct detection of H. capsulatum var. farciminosum in equine blood and at high frequency among horses exhibiting cutaneous lesions. The nested PCR outperformed conventional microscopic diagnosis, as characteristic yeast cells could be observed only in 14 pus samples. The presence of H. capsulatum var. farciminosum DNA was confirmed by sequencing the cloned PCR products, and while alignment of the ITS amplicons showed very little sequence variation, there was preliminary single nucleotide polymorphism-based evidence for the existence of two subgroups of H. capsulatum var. farciminosum. This molecular diagnostic method now permits investigation of the epidemiology of EZL. PMID:27707938

  11. Three-year randomized controlled clinical study of a one step universal adhesive and a two-step self-etch adhesive in Class II resin composite restorations

    DEFF Research Database (Denmark)

    van Dijken, Jan WV; Pallesen, Ulla

    2017-01-01

    Purpose: To evaluate in a randomized clinical evaluation the 3-year clinical durability of a one-step universal adhesive bonding system and compare it intraindividually with a 2-step self-etch adhesive in Class II restorations. Materials and Methods: Each of 57 participants (mean age 58.3 yr......) received at least two, as similar as possible, extended Class II restorations. The cavities in each of the 60 individual pairs of cavities were randomly distributed to the 1-step universal adhesive (All Bond Universal: AU) and the control 2-step self-etch adhesive (Optibond XTR: OX). A low shrinkage resin......) success rates (p>0.05). Annual failure rates were 1.8% and 2.6%, respectively.The main reason for failure was resin composite fracture. Conclusion: Class II resin composite restorations placed with a one-step universal adhesive showed good short time effectiveness....

  12. Distinct genetic difference between the Duffy binding protein (PkDBPαII) of Plasmodium knowlesi clinical isolates from North Borneo and Peninsular Malaysia.

    Science.gov (United States)

    Fong, Mun-Yik; Rashdi, Sarah A A; Yusof, Ruhani; Lau, Yee-Ling

    2015-02-21

    Plasmodium knowlesi is one of the monkey malaria parasites that can cause human malaria. The Duffy binding protein of P. knowlesi (PkDBPαII) is essential for the parasite's invasion into human and monkey erythrocytes. A previous study on P. knowlesi clinical isolates from Peninsular Malaysia reported high level of genetic diversity in the PkDBPαII. Furthermore, 36 amino acid haplotypes were identified and these haplotypes could be separated into allele group I and allele group II. In the present study, the PkDBPαII of clinical isolates from the Malaysian states of Sarawak and Sabah in North Borneo was investigated, and compared with the PkDBPαII of Peninsular Malaysia isolates. Blood samples from 28 knowlesi malaria patients were used. These samples were collected between 2011 and 2013 from hospitals in North Borneo. The PkDBPαII region of the isolates was amplified by PCR, cloned into Escherichia coli, and sequenced. The genetic diversity, natural selection and phylogenetics of PkDBPαII haplotypes were analysed using MEGA5 and DnaSP ver. 5.10.00 programmes. Forty-nine PkDBPαII sequences were obtained. Comparison at the nucleotide level against P. knowlesi strain H as reference sequence revealed 58 synonymous and 102 non-synonymous mutations. Analysis on these mutations showed that PkDBPαII was under purifying (negative) selection. At the amino acid level, 38 different PkDBPαII haplotypes were identified. Twelve of the 28 blood samples had mixed haplotype infections. Phylogenetic analysis revealed that all the haplotypes were in allele group I, but they formed a sub-group that was distinct from those of Peninsular Malaysia. Wright's FST fixation index indicated high genetic differentiation between the North Borneo and Peninsular Malaysia haplotypes. This study is the first to report the genetic diversity and natural selection of PkDBPαII of P. knowlesi from Borneo Island. The PkDBPαII haplotypes found in this study were distinct from those from

  13. Oral minocycline for the treatment of diabetic macular edema (DME): results of a phase I/II clinical study.

    Science.gov (United States)

    Cukras, Catherine A; Petrou, Philip; Chew, Emily Y; Meyerle, Catherine B; Wong, Wai T

    2012-06-22

    Inflammation contributes significantly to the pathogenesis of diabetic macular edema (DME). In particular, retinal microglia demonstrate increased activation and aggregation in areas of DME. Study authors investigated the safety and potential efficacy of oral minocycline, a drug capable of inhibiting microglial activation, in the treatment of DME. A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with fovea-involving DME who received oral minocycline 100 mg twice daily for 6 months. Main outcome measurements included best-corrected visual acuity (BCVA), central retinal subfield thickness (CST), and central macular volume using spectral domain optical coherence tomography (SD-OCT) and late leakage on fluorescein angiography (FA). Findings indicated that the study drug was well tolerated and not associated with significant safety issues. In study eyes, mean BCVA improved continuously from baseline at 1, 2, 4, and 6 months by +1.0, +4.0, +4.0, and +5.8 letters, respectively, while mean retinal thickness (CST) on OCT decreased by -2.9%, -5.7%, -13.9, and -8.1% for the same time points. At month 6, mean area of late leakage on FA decreased by -34.4% in study eyes. Mean changes in contralateral fellow eyes also demonstrated similar trends. Improvements in outcome measures were not correlated with concurrent changes in systemic factors. In this pilot proof-of-concept study of DME, minocycline as primary treatment was associated with improved visual function, central macular edema, and vascular leakage, comparing favorably with historical controls from previous studies. Microglial inhibition with oral minocycline may be a promising therapeutic strategy targeting the inflammatory etiology of DME. (ClinicalTrials.gov number, NCT01120899.).

  14. Readability and Content Assessment of Informed Consent Forms for Phase II-IV Clinical Trials in China.

    Science.gov (United States)

    Wen, Gaiyan; Liu, Xinchun; Huang, Lihua; Shu, Jingxian; Xu, Nana; Chen, Ruifang; Huang, Zhijun; Yang, Guoping; Wang, Xiaomin; Xiang, Yuxia; Lu, Yao; Yuan, Hong

    2016-01-01

    To explore the readability and content integrity of informed consent forms (ICFs) used in China and to compare the quality of Chinese local ICFs with that of international ICFs. The length, readability and content of 155 consent documents from phase II-IV drug clinical trials from the Third Xiangya Hospital Ethics Committee from November 2009 to January 2015 were evaluated. Reading difficulty was tested using a readability formula adapted for the Chinese language. An ICF checklist containing 27 required elements was successfully constructed to evaluate content integrity. The description of alternatives to participation was assessed. The quality of ICFs from different sponsorships were also compared. Among the 155 evaluable trials, the ICFs had a median length of 5286 words, corresponding to 7 pages. The median readability score was 4.31 (4.02-4.41), with 63.9% at the 2nd level and 36.1% at the 3rd level. Five of the 27 elements were frequently neglected. The average score for the description of alternatives to participation was 1.06, and 27.7% of the ICFs did not mention any alternatives. Compared with Chinese local ICFs, international ICFs were longer, more readable and contained more of the required elements (P readability and content integrity than Chinese local ICFs. More efforts should thus be made to improve the quality of consent documents in China.

  15. Treatment of nonneovascular idiopathic macular telangiectasia type 2 with intravitreal ranibizumab: results of a phase II clinical trial.

    Science.gov (United States)

    Toy, Brian C; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

    2012-05-01

    To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for nonneovascular idiopathic macular telangiectasia Type 2. Single-center, open-label Phase II clinical trial enrolling five participants with bilateral nonneovascular idiopathic macular telangiectasia Type 2. Intravitreal ranibizumab (0.5 mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in best-corrected visual acuity, area of late-phase leakage on fluorescein angiography, and retinal thickness on optical coherence tomography. The study treatment was well tolerated and associated with few adverse events. Change in best-corrected visual acuity at 12 months was not significantly different between treated study eyes (0.0 ± 7.5 letters) and control fellow eyes (+2.2 ± 1.9 letters). However, decreases in the area of late-phase fluorescein angiography leakage (-33 ± 20% for study eyes, +1 ± 8% for fellow eyes) and in optical coherence tomography central subfield retinal thickness (-11.7 ± 7.0% for study eyes and -2.9 ± 3.5% for fellow eyes) were greater in study eyes compared with fellow eyes. Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with nonneovascular idiopathic macular telangiectasia Type 2.

  16. Treatment of Non-neovascular Idiopathic Macular Telangiectasia Type 2 with Intravitreal Ranibizumab: Results of a Phase II Clinical Trial

    Science.gov (United States)

    Toy, Brian C.; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

    2015-01-01

    Purpose To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for non-neovascular idiopathic macular telangiectasia, type 2 (IMT2). Methods Single-center, open-label phase II clinical trial enrolling 5 participants with bilateral non-neovascular IMT2. Intravitreal ranibizumab (0.5mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in: best corrected visual acuity (BCVA), area of late-phase leakage on fluorescein angiography (FA), and retinal thickness on optical coherence tomography (OCT). Results The study treatment was well-tolerated and associated with few adverse events. Change in BCVA at 12 months was not significantly different between treated study eyes (0.0±7.5 letters) and control fellow eyes (+2.2±1.9 letters). However, decreases in the area of late-phase FA leakage (−33±20% for study eyes, +1±8% for fellow eyes) and in OCT central subfield retinal thickness (−11.7±7.0% for study eyes and −2.9±3.5% for fellow eyes) were greater in study eyes compared to fellow eyes. Conclusions Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with non-neovascular IMT2. PMID:22266930

  17. Effectiveness and safety of exenatide in Korean patients with type 2 diabetes inadequately controlled with oral hypoglycemic agents: an observational study in a real clinical practice.

    Science.gov (United States)

    Hwang, You-Cheol; Kim, Ari; Jo, Euna; Yang, Yeoree; Cho, Jae-Hyoung; Lee, Byung-Wan

    2017-10-25

    Randomized clinical trials have shown the efficacy and safety of short-acting exenatide in patients with type 2 diabetes mellitus (T2DM). The aim of this observational study was to investigate the effectiveness and safety of exenatide twice a day in Korean patients with T2DM who are suboptimally controlled with oral hypoglycemic agents. This study was a post hoc analysis of multi-center (71 centers), prospective, observational, single-arm, post-marketing study of short-acting exenatide 5 to 10 μg twice a day from March 2008 to March 2014 and analyzed those who finished the follow-up over 20 weeks of medication. Changes of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight values before and after exenatide treatment were analyzed. Adverse events and adverse drug reactions were estimated in patients who were treated with exenatide at least once and for whom follow-up for safety has been completed. After 20 weeks treatment with exenatide, mean HbA1c and body weight were significantly reduced from 8.4% to 7.7% and from 83.4 kg to 80.2 kg, respectively (both p levels showed an independent association with a greater reduction in glucose level. In addition, short duration of diabetes less than 5 years was an independent predictor for the improvement in glucose level. The majority of study subjects showed a reduction in both body weight and glucose level (63.3%) after exenatide treatment. In terms of safety profile, exenatide treatment was generally well-tolerated and the incidence of severe adverse event was rare (0.8%). The gastrointestinal side effects were most common and hypoglycemia was reported in 1.7% of subjects. In real clinical practice, 20 weeks treatment with short-acting exenatide was well tolerated and showed a significant body weight and glucose reduction in Korean patients with T2D who are suboptimally controlled with oral hypoglycemic agents. ClinicalTirals.gov , number NCT02090673 , registered 14 February 2008.

  18. HTLV-I/II prevalence in different geographic locations

    NARCIS (Netherlands)

    Vrielink, Hans; Reesink, Henk W.

    2004-01-01

    Human T-cell lymphotropic virus (HTLV) type I (HTLV-I) is the etiological agent of adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-II is a closely related virus, and this infection is not clearly associated with clinical disease, although

  19. Pharmacophore Modelling and 4D-QSAR Study of Ruthenium(II) Arene Complexes as Anticancer Agents (Inhibitors) by Electron Conformational- Genetic Algorithm Method.

    Science.gov (United States)

    Yavuz, Sevtap Caglar; Sabanci, Nazmiye; Saripinar, Emin

    2018-01-01

    The EC-GA method was employed in this study as a 4D-QSAR method, for the identification of the pharmacophore (Pha) of ruthenium(II) arene complex derivatives and quantitative prediction of activity. The arrangement of the computed geometric and electronic parameters for atoms and bonds of each compound occurring in a matrix is known as the electron-conformational matrix of congruity (ECMC). It contains the data from HF/3-21G level calculations. Compounds were represented by a group of conformers for each compound rather than a single conformation, known as fourth dimension to generate the model. ECMCs were compared within a certain range of tolerance values by using the EMRE program and the responsible pharmacophore group for ruthenium(II) arene complex derivatives was found. For selecting the sub-parameter which had the most effect on activity in the series and the calculation of theoretical activity values, the non-linear least square method and genetic algorithm which are included in the EMRE program were used. In addition, compounds were classified as the training and test set and the accuracy of the models was tested by cross-validation statistically. The model for training and test sets attained by the optimum 10 parameters gave highly satisfactory results with R2 training= 0.817, q 2=0.718 and SEtraining=0.066, q2 ext1 = 0.867, q2 ext2 = 0.849, q2 ext3 =0.895, ccctr = 0.895, ccctest = 0.930 and cccall = 0.905. Since there is no 4D-QSAR research on metal based organic complexes in the literature, this study is original and gives a powerful tool to the design of novel and selective ruthenium(II) arene complexes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Topical antifungal agents: an update.

    Science.gov (United States)

    Diehl, K B

    1996-10-01

    So many topical antifungal agents have been introduced that it has become very difficult to select the proper agent for a given infection. Nonspecific agents have been available for many years, and they are still effective in many situations. These agents include Whitfield's ointment, Castellani paint, gentian violet, potassium permanganate, undecylenic acid and selenium sulfide. Specific antifungal agents include, among others, the polyenes (nystatin, amphotericin B), the imidazoles (metronidazole, clotrimazole) and the allylamines (terbinafine, naftifine). Although the choice of an antifungal agent should be based on an accurate diagnosis, many clinicians believe that topical miconazole is a relatively effective agent for the treatment of most mycotic infections. Terbinafine and other newer drugs have primary fungicidal effects. Compared with older antifungal agents, these newer drugs can be used in lower concentrations and shorter therapeutic courses. Studies are needed to evaluate the clinical efficacies and cost advantages of both newer and traditional agents.

  1. Gadolinium-ethoxybenzyl-DTPA as a hepatobiliary contrast agent for use in MR cholangiography: results of an in vivo phase-I clinical evaluation

    International Nuclear Information System (INIS)

    Bollow, M.; Taupitz, M.; Hamm, B.; Staks, T.; Wolf, K.J.; Weinmann, H.J.

    1997-01-01

    The purpose of this study was to investigate the time course of contrast enhancement in bile ducts and the gallbladder (GB) after injection of gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA). In a clinical phase-I study, MR imaging at 1.5T was performed in 16 healthy volunteers with four different doses of Gd-EOB-DTPA (10, 25, 50, and 100 μmol/kg b. w., four volunteers per dosage). The study protocol comprised a heavily T1-weighted fast multiplanar gradient-echo (GE) sequence before and at increasing intervals for up to 360 min after injection of Gd-EOB-DTPA. The signal enhancement was evaluated in extra-and intrahepatic bile ducts as well as in the GB. In all 16 volunteers the common bile duct showed intense signal enhancement beginning 5-16 min after injection (mean 10 min) and persisting for at least 120 min in 4 subjects and for 360 min in 12 subjects. The duration of signal enhancement was significantly (p < 0.05) longer for higher doses (50, 100 μmol/kg) than for lower doses (10, 25 μmol/kg). Intrahepatic bile ducts were hyperintense as compared with liver parenchyma in all subjects receiving 10 μmol/kg from approximately 50-120 min after contrast agent application. Intrahepatic bile ducts were not displayed using the higher doses, probably because of the strong enhancement of the liver parenchyma. Gallbladder contrasting was achieved in all cases beginning 7-33 min after injection (mean 19 min) and remained visible for up to 360 min in 94 %. Hyperintense visualization of normal extrahepatic bile ducts as well as the GB is regularly achieved with the hepatobiliary contrast agent Gd-EOB-DTPA. The dosage for hyperintense visualization of intrahepatic bile ducts is 10 μmol/kg. (orig.). With 8 figs., 2 tabs

  2. Clinical significance of determination of serum NSE and plasma ET, IGF-II, CNP levels in patients with acute brain injury

    International Nuclear Information System (INIS)

    Chen Bo

    2010-01-01

    Objective: To investigate the clinical significance of changes of plasma ET, IGF-II, CNP and serum NSE contents in patients with acute brain injury. Methods: Serum contents of neuron specific enolase (NSE) were measured with chemiluminescence immunoassay and plasma endothelin (ET), insulin-like growth factor-II (IGF-II) and C-type natriuretic peptide (CNP) were measured with radioimmunoassay in 30 patients with acute brain injury and 35 controls. Results: Serum contents of NSE and plasma IGF-II, CNP were not much different in patients with mild brain injury from those in controls (P >0.05), but plasma contents of ET were already significantly higher in patients with mild brain injury than those in controls(P < 0.01). The serum NSE and plasma ET levels in patients with moderate and severe brain injury were significantly higher than those in patients with mild brain injury and controls (P < 0.01). Decrease of plasma levels of IGF-II and CNP was not significant in patients with mild brain injury (vs controls). However, the plasma levels of IGF-II and CNP were significantly lower in patients with moderate and severe brain injury than those in patients with mild brain injury and controls (P <0.01). As a whole, the magnitude of changes of these parameters was proportional to the severity of the injury. Conclusion: Changes of serum NSE and plasma IGF-II, ET and CNP levels were closely related to the pathological process of brain injury. Determination of these parameters was of clinical importance for evaluation of the severity of injury and outcome prediction. (authors)

  3. Clinical utility of the DSM-5 alternative model for borderline personality disorder: Differential diagnostic accuracy of the BFI, SCID-II-PQ, and PID-5.

    Science.gov (United States)

    Fowler, J Christopher; Madan, Alok; Allen, Jon G; Patriquin, Michelle; Sharp, Carla; Oldham, John M; Frueh, B Christopher

    2018-01-01

    With the publication of DSM 5 alternative model for personality disorders it is critical to assess the components of the model against evidence-based models such as the five factor model and the DSM-IV-TR categorical model. This study explored the relative clinical utility of these models in screening for borderline personality disorder (BPD). Receiver operator characteristics and diagnostic efficiency statistics were calculated for three personality measures to ascertain the relative diagnostic efficiency of each measure. A total of 1653 adult inpatients at a specialist psychiatric hospital completed SCID-II interviews. Sample 1 (n=653) completed the SCID-II interviews, SCID-II Questionnaire (SCID-II-PQ) and the Big Five Inventory (BFI), while Sample 2 (n=1,000) completed the SCID-II interviews, Personality Inventory for DSM5 (PID-5) and the BFI. BFI measure evidenced moderate accuracy for two composites: High Neuroticism+ low agreeableness composite (AUC=0.72, SE=0.01, ptrait constellation for diagnosing BPD. Limitations of the study include the single inpatient setting and use of two discrete samples to assess PID-5 and SCID-II-PQ. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Synthesis and characterization of Ruthenium (II) amines with the chelating agent 4-4' dithio-pyridine occluded in Na Y zeolite

    International Nuclear Information System (INIS)

    Marques, Clelia Mara de Paula; Franco, Douglas Wagner; Sanches, Rosemary

    1993-01-01

    The aim of this work is to study the chemical behavior of metallic complexes of Ru(II) encapsulated in Na Y zeolites. We chose systems with well known chemical behaviour in solution and which present a great interest, because of the bridging ligand used (4,4-Dithiodipyridine). This ligand is the first example of the great efficiency of the S-S bridge in conducting electrons. In this work we describe the ionic exchange reactions between the Na Y zeolite and the complex ion [Ru (N H 3 ) 5 DTDP] 2+ to obtain [Ru (N H 3 ) 5 DTDP]-Y sample. The [Ru (N H 3 ) 5 ] 2 DTDP)-Y sample is prepared through the reaction between [Ru (N H 3 ) 5 H 2 O] 2+ and [Ru (N H 3 ) 5 DTDP]-Y. These sample were characterized by spectroscopic techniques. (author)

  5. Fundamentos del uso clínico de la eritropoyetina como neuroprotector Foundations of the clinical use of erythropoietin as a neuroprotective agent

    Directory of Open Access Journals (Sweden)

    Alain Valdivia Acosta

    2008-08-01

    Full Text Available Hace aproximadamente una década, se reportaron por primera vez, las propiedades neuroprotectoras de la eritropoyetina en estudios preclínicos. Todavía no se ha podido esclarecer con firmeza el posible mecanismo de acción neuroprotector de esta hormona, pero existen varias hipótesis. La eritropoyetina ha mostrado buenos resultados en preclínica como agente neuroprotector y todavía queda mucho camino por recorrer para lograr una adecuada efectividad y seguridad en la clínica en este sentido. Se investiga para lograr una eritropoyetina con actividad neuroprotectora que carezca, o al menos tenga disminuida su actividad hematopoyética. Disminuir sus efectos adversos, lograr una significativa biodisponibilidad al sistema nervioso central, alargar el tiempo de vida media y con ello evitar una alta frecuencia de administración al paciente, es lo que principalmente se está buscando. En este trabajo se realizó una búsqueda sobre los mecanismos de acción neuroprotectora hasta ahora propuestos para la eritropoyetina y se detallaron importantes consideraciones a tomar en cuenta, que pudieran influir sobre su utilización en la clínica.The neuroprotective properties of erythropoietin were reported for the first time in preclinical studies approximately a decade ago. The possible mechanism of neuroprotective action of this hormone has not been cleared yet, but here are diverse hypotheses. Erythropoietin has showed good results in preclinic as a neuroprotective agent and there is still a long way to go to attain an adequate effectivity and safety in the clinic in this sense. Research is being carried out to obtain an erythropoietin with neuroprotective activity that lacks or at least has a diminished hematopoietic activity. To reduce its adverse effects, to achieve a significant bioavailability to the central nervous system, to prolong its mean life and to avoid this way a high frequency of administration to the patient, is our main objective. In

  6. Type II diabetes and its therapy in clinical practice - results from the standardised non-interventional registry SIRTA.

    Science.gov (United States)

    Gallwitz, B; Kusterer, K; Hildemann, S; Fresenius, K

    2014-12-01

    Modern antidiabetic therapies should achieve low HbA1c values and avoid hypoglycaemic complications. The registry SIRTA included 1522 patients with type II diabetes mellitus (T2DM) from 306 German medical practices. Patients had an HbA1c > 6.5% under the maximum tolerated metformin dose. If required, they received combination therapy with other antidiabetics according to the guideline of the German Diabetes Society [Deutsche Diabetes Gesellschaft (DDG)] or usual medical practice. Patients were followed up for 6 months. The target criteria included the achievement of HbA1c target values and the emergence of severe hypoglycaemic episodes. Most patients (64.0%) were planned to achieve an HbA1c target < 6.5%, the standard target recommended by the 2009 DDG guideline valid throughout the registry. Primarily to reduce the individual risk for hypoglycaemia, 32.4% of patients had a less strict HbA1c-target of 6.5-7.0%. These targets were achieved by 31.3% and 44.3% of patients, respectively. Combination therapies increased from 45% to 56% over the 6 months registry. Four patients had severe hypoglycaemias (0.26%). The registry confirms results from other epidemiologic studies on the therapy of T2DM in everyday practice. The treatment strategies applied effectively reduced blood glucose and avoided severe hypoglycaemias. An early therapy of insufficiently controlled patients with T2DM is important, as lower baseline values facilitated achieving HbA1c targets. © 2014 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

  7. A randomized, double-blind, multicenter, controlled clinical trial of chicken type II collagen in patients with rheumatoid arthritis.

    Science.gov (United States)

    Zhang, Ling-Ling; Wei, Wei; Xiao, Feng; Xu, Jian-Hua; Bao, Chun-De; Ni, Li-Qing; Li, Xing-Fu

    2008-07-15

    To assess the efficacy and safety of chicken type II collagen (CCII) in rheumatoid arthritis (RA) compared with methotrexate (MTX). We conducted a prospective, 24-week, followup, multicenter, double-blind, controlled study of CCII (0.1 mg/day) versus MTX (10 mg/week) in patients with active RA. Clinical assessments were performed at screening and at 12, 18, and 24 weeks of treatment. A total of 236 RA patients were included; 211 patients (89.4%) completed the 24-week followup. In both groups there was a decrease in pain, morning stiffness, tender joint count, swollen joint count, Health Assessment Questionnaire score, and investigator and patient assessment of function; all differences were statistically significant. In the MTX group, erythrocyte sedimentation rate and C-reactive protein level decreased. Rheumatoid factor did not change in either group. At 24 weeks, 68.57% of patients in the CCII group and 83.02% in the MTX group met the American College of Rheumatology 20% improvement criteria (ACR20), and 40.95% and 57.54%, respectively, met the ACR50 criteria. The ACR20 and ACR50 response rates in the CCII group were lower than those in the MTX group, and this difference was statistically significant (P < 0.05). Gastrointestinal symptoms were common in both groups. There were fewer and milder side effects in the CCII group than the MTX group. The difference in incidence of adverse events between the 2 groups was statistically significant (P < 0.05). CCII is effective in the treatment of RA. CCII is well tolerated, and the incidence of adverse events of CCII is lower than that of MTX.

  8. Comparison of VATS and Robotic Approaches For Clinical Stage I and II NSCLC Using the STS Database

    Science.gov (United States)

    Louie, Brian E.; Wilson, Jennifer L.; Kim, Sunghee; Cerfolio, Robert J.; Park, Bernard J.; Farivar, Alexander S.; Vallières, Eric; Aye, Ralph W.; Burfeind, William R.; Block, Mark I.

    2016-01-01

    Background Data from selected centers show that robotic lobectomy (RL) is safe, effective and has comparable 30-day mortality to video assisted lobectomy (VATS). However, widespread adoption of RL is controversial. We used the STS-GTS-Database to evaluate quality metrics for these two minimally invasive lobectomy techniques. Methods A database query for primary clinical stage I or II NSCLC at high volume centers from 2009 to 2013 identified 1,220 RLs and 12,378 VATS. Quality metrics evaluated included operative morbidity, 30-day mortality and nodal upstaging (NU), defined as cN0 to pN1. Multivariable logistic regression was used to evaluate NU. Results RL patients were older, less active, less likely to be an ever smoker, and had higher BMI (all p<0.05). They were also more likely to have coronary heart disease or hypertension (all p<0.001) and to have had preoperative mediastinal staging (p<0.0001). RL operative times were longer (median 186 vs 173 min, p<0.001); all other operative parameters were similar. All postoperative outcomes were similar including complications and 30-day mortality (RL 0.6% vs VATS 0.8%, p=0.4). Median length of stay was 4 days for both, but a higher proportion of RLs stayed < 4 days: 48% vs 39%, p<0.001. NU overall was similar (p=0.6), but with trends favoring VATS in the cT1b group, and RL in the cT2a group. Conclusions RL patients had more co-morbidities and RL operative times were longer, but quality outcome measures including complications, hospital stay, 30-day mortality, and NU suggest RL and VATS are equivalent. PMID:27209613

  9. Glycemia in Acute Stroke II study: a call to improve post-stroke hyperglycemia management in clinical practice.

    Science.gov (United States)

    Fuentes, B; Sanz-Cuesta, B E; Gutiérrez-Fernández, M; Martínez-Sánchez, P; Lisbona, A; Madero-Jarabo, R; Delgado-Mederos, R; Gállego-Cullere, J; Rodríguez-Yáñez, M; Martínez-Zabaleta, M; Freijo, M; Alonso de Leciñana, M; Portilla, J C; Gil-Núñez, A; Díez-Tejedor, E

    2017-09-01

    The aim of the study was to analyze the effect of conventional glucose management, which aimed to maintain glucose levels stroke (IS) in a clinical practice setting. This was a multicenter, prospective cohort study of patients with acute IS. Patients were classified into four groups based on their initial 48-h capillary glucose levels and the administration of and response to corrective treatment: (i) untreated and maximum glucose levels <155 mg/dL (8.5 mmol/L) within the first 48 h; (ii) treated and good responders [glucose levels persistently <155 mg/dL (8.5 mmol/L)]; (iii) treated and non-responders [any glucose values ≥155 mg/dL (8.5 mmol/L) during the 24 h after the start of corrective treatment]; and (iv) untreated with any glucose value ≥155 mg/dL (8.5 mmol/L). The primary outcome was death or dependence at 3 months (blinded rater). A total of 213 patients were included. Ninety-seven (45.5%) patients developed glucose levels ≥155 mg/dL (8.5 mmol/L), 69 (71.1%) underwent corrective treatment and 31 patients underwent no corrective treatment at the physician's discretion [28 of whom had isolated values ≥155 mg/dL (8.5 mmol/L)]. Only 11 (16%) patients responded to conventional treatment, whereas 58 (84%) patients were non-responsive. Non-responders showed a twofold higher risk of death or dependence at 3 months (odds ratio, 2.472; 95% confidence interval, 1.096-5.576; P = 0.029). Lack of response to conventional treatment for glucose management in acute IS is frequent and associated with poor outcomes. © 2017 EAN.

  10. Prospective double blind randomized placebo-controlled clinical trial of the pectoral nerves (Pecs) block type II.

    Science.gov (United States)

    Versyck, Barbara; van Geffen, Geert-Jan; Van Houwe, Patrick

    2017-08-01

    The aim of this clinical trial was to test the hypothesis whether adding the pectoral nerves (Pecs) block type II to the anesthetic procedure reduces opioid consumption during and after breast surgery. A prospective randomized double blind placebo-controlled study. A secondary hospital. 140 breast cancer stage 1-3 patients undergoing mastectomy or tumorectomy with sentinel node or axillary node dissection. Patients were randomized to receive either a Pecs block with levobupivacaine 0.25% (n=70) or placebo block with saline (n=70). The pain levels were evaluated by Numeric Rating Scale (NRS) pain scores at 15-minute intervals during the post anesthesia care unit stay time (PACU), at 2-hour intervals for the first 24h on the ward and at 4-hour intervals for the next 24h. Intraoperative and postoperative opioid consumption were recorded during the full stay. Patient satisfaction was evaluated upon discharge using a 10-point scale. Intraoperative sufentanil requirements were comparable for the Pecs and placebo group (8.0±3.5μg and 7.8±3.0μg, P=0.730). Patients in the Pecs group experienced significantly less pain than patients in the control group (P=0.048) during their PACU stay. Furthermore, patients in the Pecs group required significant less postoperative opioids (9.16±10.15mg and 14.97±14.38mg morphine equivalent, P=0.037) and required significant fewer postsurgical opioid administration interventions than patients in the control group (P=0.045). Both patient-groups were very satisfied about their management (9.6±0.6 and 9.1±1.8 on a 10-point scale, P=0.211). The Pecs block reduces postsurgical opioid consumption during the PACU stay time for patients undergoing breast surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Treatment of geographic atrophy by the topical administration of OT-551: results of a phase II clinical trial.

    Science.gov (United States)

    Wong, Wai T; Kam, Waynekid; Cunningham, Denise; Harrington, Molly; Hammel, Keri; Meyerle, Catherine B; Cukras, Catherine; Chew, Emily Y; Sadda, Srinivas R; Ferris, Frederick L

    2010-12-01

    To investigate the safety and preliminary efficacy of OT-551, a disubstituted hydroxylamine with antioxidant properties, for the treatment of geographic atrophy (GA), the advanced atrophic form of age-related macular degeneration (AMD). The study was a single-center, open-label phase II trial, enrolling 10 participants with bilateral GA. Topical 0.45% OT-551 was administered in one randomly assigned eye three times daily for 2 years. Safety measures were assessed by complete ophthalmic examination, fundus photography, and review of symptoms. The primary efficacy outcome measure was the change in best corrected visual acuity at 24 months. Secondary efficacy measures included changes in area of GA, contrast sensitivity, microperimetry measurements, and total drusen area from baseline. Study drug was well tolerated and was associated with few adverse events. The mean change in BCVA at 2 years was +0.2 ± 13.3 letters in the study eyes and -11.3 ± 7.6 letters in fellow eyes (P = 0.0259). However, no statistically significant differences were found between the study and fellow eyes for all other secondary outcome measures. OT-551 was well tolerated by study participants and was not associated with any serious adverse effects. Efficacy measurements in this small study indicate a possible effect in maintaining visual acuity. However, the absence of significant effects on other outcomes measures in this study suggests that OT-551, in the current concentration and mode of delivery, may have limited or no benefit as a treatment for GA (ClinicalTrials.gov number, NCT00306488).

  12. Clinical significance of measurement of serum insulin-like growth factor II and adrenomedulion levels in patients with essential hypertension

    International Nuclear Information System (INIS)

    Fan Bifu; Ji Naijun; Mei Yibin; Wang Chengyao; Chen Donghai; Li Fuyuan; Guan Lihua; Gao Meiying

    2003-01-01

    Objective: To investigate the changes of serum levels of insulin-like growth factor II (IGF II) and adrenomedullin (ADM) in patients with essential hypertension. Methods: Serum IGF II and ADM levels were measured in 62 cases of hypertension and 40 controls with RIA. Results: Serum IGF II and ADM levels were significantly bigger in hypertensive patients than those in the controls (t = 4.454, p < 0.01; t = 3.992, p < 0.01). The serum IGF II level was significantly positively correlated to the serum ADM levels (r = 0.379, p < 0.05) and both were significantly positively correlated to the mean arterial pressure (r = 0.346, r = 0.353, p < 0.05) but not with BMI. Serum ADM levels increased gradually as the disease progressed from stage I to stage III (p < 0.05) with levels in stage III markedly higher than those in stage I (p < 0.01). In EH patients with heart and/or brain and/or renal complications the serum ADM levels were significantly higher than those in EH patients without complications (t = 2.050, p < 0.05). Such differences did not exist in the case of IGF II. Conclusion: Serum IGF II and ADM levels were increased markedly in hypertensive patients. These two factors were mutually positively correlated and both were positively correlated to mean arterial pressure. ADM levels increased gradually as the disease progressing but IGF II levels remained stable

  13. Zn(II)-cyclam based chromogenic sensors for recognition of ATP in aqueous solution under physiological conditions and their application as viable staining agents for microorganism.

    Science.gov (United States)

    Mahato, Prasenjit; Ghosh, Amrita; Mishra, Sanjiv K; Shrivastav, Anupama; Mishra, Sandhya; Das, Amitava

    2011-05-02

    Two chromogenic complexes, L.Zn (where L is (E)-4-((4-(1,4,8,11-tetraazacyclotetradecan-1-ylsulfonyl)phenyl)diazenyl)-N,N-dimethylaniline) and its [2]pseudorotaxane form (α-CD.L.Zn), were found to bind preferentially to adenosine triphosphate (ATP), among all other common anions and biologically important phosphate (AMP, ADP, pyrophosphate, and phosphate) ions in aqueous HEPES buffer medium of pH 7.2. Studies with live cell cultures of prokaryotic microbes revealed that binding of these two reagents to intercellular ATP, produced in situ, could be used in delineating the gram-positive and the gram-negative bacteria. More importantly, these dyes were found to be nontoxic to living microbes (eukaryotes and prokaryotes) and could be used for studying the cell growth dynamics. Binding to these two viable staining agents to intercellular ATP was also confirmed by spectroscopic studies on cell growth in the presence of different respiratory inhibitors that influence the intercellular ATP generation. © 2011 American Chemical Society

  14. Assimilate unloading from maize (Zea mays L.) pedicel tissues. II. Effects of chemical agents on sugar, amino acid, and 14C-assimilate unloading

    International Nuclear Information System (INIS)

    Porter, G.A.; Knievel, D.P.; Shannon, J.C.

    1987-01-01

    Sugar, amino acid, and 14 C-assimilate release from attached maize (Zea mays L.) pedicels was studied following treatment with several chemical inhibitors. In the absence of these agents, sugar release was nearly linear over a 7-hour period. At least 13 amino acids were released with glutamine comprising over 30% of the total. Release was not affected by potassium concentration, 10-minute pretreatments with p-chloromercuribenzene sulfonic acid (PCMBS) or dithiothreitol, and low concentrations of CaCl 2 . Three hours or more exposure to PCMBS, dinitrophenol, N-ethylmaleimide, or 2,4,6-trinitrobenzene sulfonic acid strongly inhibited 14 C-assimilate, sugar, and amino acid release from the pedicel. These treatments also reduced 14 C-assimilate movement into the kernel bases. It is, therefore, likely that reduced unloading, caused by these relatively long-term exposures to chemical inhibitors, was related to reduced translocation of assimilates into treated kernels. Whether this effect is due to disruption of kernel metabolism and sieve element function or reduced assimilate unloading and subsequent accumulation of unlabeled assimilates within the pedicel tissues cannot be determined at this time

  15. Association of time-to-surgery with outcomes in clinical stage I-II pancreatic adenocarcinoma treated with upfront surgery.

    Science.gov (United States)

    Swords, Douglas S; Zhang, Chong; Presson, Angela P; Firpo, Matthew A; Mulvihill, Sean J; Scaife, Courtney L

    2018-04-01

    Time-to-surgery from cancer diagnosis has increased in the United States. We aimed to determine the association between time-to-surgery and oncologic outcomes in patients with resectable pancreatic ductal adenocarcinoma undergoing upfront surgery. The 2004-2012 National Cancer Database was reviewed for patients undergoing curative-intent surgery without neoadjuvant therapy for clinical stage I-II pancreatic ductal adenocarcinoma. A multivariable Cox model with restricted cubic splines was used to define time-to-surgery as short (1-14 days), medium (15-42), and long (43-120). Overall survival was examined using Cox shared frailty models. Secondary outcomes were examined using mixed-effects logistic regression models. Of 16,763 patients, time-to-surgery was short in 34.4%, medium in 51.6%, and long in 14.0%. More short time-to-surgery patients were young, privately insured, healthy, and treated at low-volume hospitals. Adjusted hazards of mortality were lower for medium (hazard ratio 0.94, 95% confidence interval, .90, 0.97) and long time-to-surgery (hazard ratio 0.91, 95% confidence interval, 0.86, 0.96) than short. There were no differences in adjusted odds of node positivity, clinical to pathologic upstaging, being unresectable or stage IV at exploration, and positive margins. Medium time-to-surgery patients had higher adjusted odds (odds ratio 1.11, 95% confidence interval, 1.03, 1.20) of receiving an adequate lymphadenectomy than short. Ninety-day mortality was lower in medium (odds ratio 0.75, 95% confidence interval, 0.65, 0.85) and long time-to-surgery (odds ratio 0.72, 95% confidence interval, 0.60, 0.88) than short. In this observational analysis, short time-to-surgery was associated with slightly shorter OS and higher perioperative mortality. These results may suggest that delays for medical optimization and referral to high volume surgeons are safe. Published by Elsevier Inc.

  16. Efficacy of the clinical agent VT-1161 against fluconazole-sensitive and -resistant Candida albicans in a murine model of vaginal candidiasis.

    Science.gov (United States)

    Garvey, E P; Hoekstra, W J; Schotzinger, R J; Sobel, J D; Lilly, E A; Fidel, P L

    2015-09-01

    Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) remain major health problems for women. VT-1161, a novel fungal CYP51 inhibitor which has potent antifungal activity against fluconazole-sensitive Candida albicans, retained its in vitro potency (MIC50 of ≤0.015 and MIC90 of 0.12 μg/ml) against 10 clinical isolates from VVC or RVVC patients resistant to fluconazole (MIC50 of 8 and MIC90 of 64 μg/ml). VT-1161 pharmacokinetics in mice displayed a high volume of distribution (1.4 liters/kg), high oral absorption (73%), and a long half-life (>48 h) and showed rapid penetration into vaginal tissue. In a murine model of vaginal candidiasis using fluconazole-sensitive yeast, oral doses as low as 4 mg/kg VT-1161 significantly reduced the fungal burden 1 and 4 days posttreatment (P < 0.0001). Similar VT-1161 efficacy was measured when an isolate highly resistant to fluconazole (MIC of 64 μg/ml) but fully sensitive in vitro to VT-1161 was used. When an isolate partially sensitive to VT-1161 (MIC of 0.12 μg/ml) and moderately resistant to fluconazole (MIC of 8 μg/ml) was used, VT-1161 remained efficacious, whereas fluconazole was efficacious on day 1 but did not sustain efficacy 4 days posttreatment. Both agents were inactive in treating an infection with an isolate that demonstrated weaker potency (MICs of 2 and 64 μg/ml for VT-1161 and fluconazole, respectively). Finally, the plasma concentrations of free VT-1161 were predictive of efficacy when in excess of the in vitro MIC values. These data support the clinical development of VT-1161 as a potentially more efficacious treatment for VVC and RVVC. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Case Report: Diagnosis of hypogeusia after oral exposure to commercial cleaning agent and considerations for clinical taste testing [version 2; referees: 2 approved, 1 not approved

    Directory of Open Access Journals (Sweden)

    Marie Jetté

    2017-06-01

    Full Text Available Few reports in the literature document acute taste disturbance following exposure to toxic chemicals. We describe the case of a 54-year-old man who presented with primary complaint of tongue numbness and persistent problems with taste 1.5 years following oral exposure to a commercial cleaning agent. A test of olfaction revealed normosmia for age and gender. Lingual tactile two-point discrimination testing showed reduced somatosensation. Taste threshold testing using a 3-drop method demonstrated severe hypogeusia, though the patient was able to discriminate tastants at lower concentrations with a whole mouth swish and spit test. We conclude that clinical evaluation of dysgeusia can be performed using a number of previously published testing methods, however, determining causative factors may be confounded by duration since exposure, lack of knowledge of baseline taste function, and medications. Although many testing options exist, basic taste testing can be performed with minimal expertise or specialized equipment, depending on the patient history and goals of evaluation.

  18. Human T-cell Lymphotropic Virus types I and II (HTLV-I/II in French Guiana: clinical and molecular epidemiology

    Directory of Open Access Journals (Sweden)

    Kazanji Mirdad

    2003-01-01

    Full Text Available We review here the epidemiological studies performed by our group on human retrovirus HTLV-I and HTLV-II infections and the associated diseases in French Guiana since 1984. French Guiana is an overseas French administrative district located between Brazil and Surinam. Its population is characterized by a large variety of ethnic groups, including several populations of African origin and various populations of Amerindian origin. Several epidemiological studies of large samples of pregnant women and in remote villages showed that HTLV-I is highly endemic in this area but is restricted to groups of African origin, especially the Noir-Marrons. In this endemic population, the results of segregation analysis in a genetic epidemiological study were consistent with the presence of a dominant major gene predisposing to HTLV-I infection, especially in children. In contrast, HTLV-II infection appears to be rare in French Guiana, having been found in only a few individuals of Brazilian origin. From a molecular point of view, the HTLV-I strains present in the Noir-Marrons, Creoles and Amerindians appear to originate from Africa, as they belong to the large cosmopolitan molecular subtype A.

  19. Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for Topical Treatment of Onychomycosis: II. Prenatal and Postnatal Developmental Toxicity and Maternal Function Study.

    Science.gov (United States)

    Ciaravino, Vic; Coronado, Dina; Lanphear, Cheryl; Hoberman, Alan; Chanda, Sanjay

    2016-09-01

    Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. The effects of tavaborole on gestation, parturition (delivery, labor), offspring development, and survival during the perinatal and postnatal periods were assessed in mated female rats. Females (F0 generation) were administered single daily oral (gavage) doses of 15, 60, or 100 mg/kg/d from gestation day 6 through lactation day 20. The females were allowed to deliver naturally and rear their offspring until lactation day 21, at which time the F0 females were euthanized. One male and female from each litter were selected (F1 generation) and retained for assessments, including growth, neurobehavior, fertility, and their ability to produce an F2 generation. Reproductive and offspring parameters were determined for the F1 and F2 generations, as applicable. F1 females and F2 pups were euthanized on postnatal day 7. In the F0 females, decreased activity was observed in the 100 mg/kg/d dose group. Excess salivation was observed in the 60 and 100 mg/kg/d dose groups (slight to moderate), however, this finding was not considered adverse. There were no tavaborole-related effects on the growth, viability, development, neurobehavioral assessments, or reproductive performance of the F1 generation. Survivability and mean body weight of the F2 pups were unaffected. The no observed adverse effect level (NOAEL) for maternal toxicity (F0 generation) was 60 mg/kg/d, based on the decreased activity observed in the 100 mg/kg/d dose group. The NOAEL for the offspring effects was ≥100 mg/kg/d, based on the lack of test article-related changes. © The Author(s) 2016.

  20. Neoadjuvant Treatment With Single-Agent Cetuximab Followed by 5-FU, Cetuximab, and Pelvic Radiotherapy: A Phase II Study in Locally Advanced Rectal Cancer

    International Nuclear Information System (INIS)

    Bertolini, Federica; Chiara, Silvana; Bengala, Carmelo; Antognoni, Paolo; Dealis, Cristina; Zironi, Sandra; Malavasi, Norma; Scolaro, Tindaro; Depenni, Roberta; Jovic, Gordana; Sonaglio, Claudia; Rossi, Aldo; Luppi, Gabriele; Conte, Pier Franco

    2009-01-01

    Purpose: Preoperative chemoradiotherapy followed by surgery represents the standard of care for locally advanced rectal cancer (LARC). Cetuximab has proved activity in advanced colorectal cancer, and its incorporation in preoperative treatment may increase tumor downstaging. Methods and Materials: After biopsy and staging, uT3/uT4 N0/+ LARC received single-agent cetuximab in three doses, followed by weekly cetuximab plus 5-fluorouracil (5-FU), concomitantly with RT. Sample size was calculated according to Bryant and Day test, a two-stage design with at least 10 pathologic complete remissions observed in 60 patients (pts) able to complete the treatment plan. Results: Forty pts with LARC were entered: male/female = 34/6; median age: 61 (range, 28-77); 12 uT3N0 Ed(30%); 25 uT3N1 (62%); 3 uT4N1 (8%); all Eastern Cooperative Oncology Group = 0. Thirty-five pts completed neoadjuvant treatment; 5 (12%) withdrew therapy after one cetuximab administration: three for hypersensitivity reactions, one for rapid progression, and one for purulent arthritis. They continued 5-FU in continuous infusion in association with RT. Thirty-one pts (77%) presented with acnelike rash; dose reduction/interruption of treatment was necessary in six pts (15%): two for Grade 3 acnelike rash, two for Grade 3 gastrointestinal toxicity, and two for refusal. Thirty-eight pts were evaluable for pathological response (one patient refused surgery, and one was progressed during neoadjuvant treatment). Pathological staging was: pT0N0 three pts (8%), pT1N0 1 pt (3%); pT2N0 13 pts (34%), and pT3 19 pts (50%) (N0:9, N1:5; N2:5); pT4 2 pts (5%). Conclusions: Preoperative treatment with 5-FU, cetuximab, and pelvic RT is feasible with acceptable toxicities; however, the rate of pathologic responses is disappointingly low

  1. SURVEYING THE AGENTS OF GALAXY EVOLUTION IN THE TIDALLY STRIPPED, LOW METALLICITY SMALL MAGELLANIC CLOUD (SAGE-SMC). II. COOL EVOLVED STARS

    International Nuclear Information System (INIS)

    Boyer, Martha L.; Meixner, Margaret; Gordon, Karl D.; Shiao, Bernie; Srinivasan, Sundar; Van Loon, Jacco Th.; McDonald, Iain; Kemper, F.; Zaritsky, Dennis; Block, Miwa; Engelbracht, Charles W.; Misselt, Karl; Babler, Brian; Bracker, Steve; Meade, Marilyn; Whitney, Barbara; Hora, Joe; Robitaille, Thomas; Indebetouw, Remy; Sewilo, Marta

    2011-01-01

    We investigate the infrared (IR) properties of cool, evolved stars in the Small Magellanic Cloud (SMC), including the red giant branch (RGB) stars and the dust-producing red supergiant (RSG) and asymptotic giant branch (AGB) stars using observations from the Spitzer Space Telescope Legacy program entitled 'Surveying the Agents of Galaxy Evolution in the Tidally Stripped, Low Metallicity SMC', or SAGE-SMC. The survey includes, for the first time, full spatial coverage of the SMC bar, wing, and tail regions at IR wavelengths (3.6-160 μm). We identify evolved stars using a combination of near-IR and mid-IR photometry and point out a new feature in the mid-IR color-magnitude diagram that may be due to particularly dusty O-rich AGB stars. We find that the RSG and AGB stars each contribute ∼20% of the global SMC flux (extended + point-source) at 3.6 μm, which emphasizes the importance of both stellar types to the integrated flux of distant metal-poor galaxies. The equivalent SAGE survey of the higher-metallicity Large Magellanic Cloud (SAGE-LMC) allows us to explore the influence of metallicity on dust production. We find that the SMC RSG stars are less likely to produce a large amount of dust (as indicated by the [3.6] - [8] color). There is a higher fraction of carbon-rich stars in the SMC, and these stars appear to reach colors as red as their LMC counterparts, indicating that C-rich dust forms efficiently in both galaxies. A preliminary estimate of the dust production in AGB and RSG stars reveals that the extreme C-rich AGB stars dominate the dust input in both galaxies, and that the O-rich stars may play a larger role in the LMC than in the SMC.

  2. Coordination chemistry of two heavy metals: I, Ligand preferences in lead(II) complexation, toward the development of therapeutic agents for lead poisoning: II, Plutonium solubility and speciation relevant to the environment

    Energy Technology Data Exchange (ETDEWEB)

    Neu, Mary Patricia [Univ. of California, Berkeley, CA (United States)

    1993-11-01

    The coordination chemistry and solution behavior of the toxic ions lead(II) and plutonium(IV, V, VI) have been investigated. The ligand pKas and ligand-lead(II) stability constants of one hydroxamic acid and four thiohydroaxamic acids were determined. Solution thermodynamic results indicate that thiohydroxamic acids are more acidic and slightly better lead chelators than hydroxamates, e.g., N-methylthioaceto-hydroxamic acid, pKa = 5.94, logβ120 = 10.92; acetohydroxamic acid, pKa = 9.34, logβ120 = 9.52. The syntheses of lead complexes of two bulky hydroxamate ligands are presented. The X-ray crystal structures show the lead hydroxamates are di-bridged dimers with irregular five-coordinate geometry about the metal atom and a stereochemically active lone pair of electrons. Molecular orbital calculations of a lead hydroxamate and a highly symmetric pseudo octahedral lead complex were performed. The thermodynamic stability of plutonium(IV) complexes of the siderophore, desferrioxamine B (DFO), and two octadentate derivatives of DFO were investigated using competition spectrophotometric titrations. The stability constant measured for the plutonium(IV) complex of DFO-methylterephthalamide is logβ120 = 41.7. The solubility limited speciation of 242Pu as a function of time in near neutral carbonate solution was measured. Individual solutions of plutonium in a single oxidation state were added to individual solutions at pH = 6.0, T = 30.0, 1.93 mM dissolved carbonate, and sampled over intervals up to 150 days. Plutonium solubility was measured, and speciation was investigated using laser photoacoustic spectroscopy and chemical methods.

  3. Coordination chemistry of two heavy metals: I, Ligand preferences in lead(II) complexation, toward the development of therapeutic agents for lead poisoning: II, Plutonium solubility and speciation relevant to the environment

    International Nuclear Information System (INIS)

    Neu, M.P.

    1993-11-01

    The coordination chemistry and solution behavior of the toxic ions lead(II) and plutonium(IV, V, VI) have been investigated. The ligand pK a s and ligand-lead(II) stability constants of one hydroxamic acid and four thiohydroaxamic acids were determined. Solution thermodynamic results indicate that thiohydroxamic acids are more acidic and slightly better lead chelators than hydroxamates, e.g., N-methylthioaceto-hydroxamic acid, pK a = 5.94, logβ 120 = 10.92; acetohydroxamic acid, pK a = 9.34, logβ l20 = 9.52. The syntheses of lead complexes of two bulky hydroxamate ligands are presented. The X-ray crystal structures show the lead hydroxamates are di-bridged dimers with irregular five-coordinate geometry about the metal atom and a stereochemically active lone pair of electrons. Molecular orbital calculations of a lead hydroxamate and a highly symmetric pseudo octahedral lead complex were performed. The thermodynamic stability of plutonium(IV) complexes of the siderophore, desferrioxamine B (DFO), and two octadentate derivatives of DFO were investigated using competition spectrophotometric titrations. The stability constant measured for the plutonium(IV) complex of DFO-methylterephthalamide is logβ 110 = 41.7. The solubility limited speciation of 242 Pu as a function of time in near neutral carbonate solution was measured. Individual solutions of plutonium in a single oxidation state were added to individual solutions at pH = 6.0, T = 30.0, 1.93 mM dissolved carbonate, and sampled over intervals up to 150 days. Plutonium solubility was measured, and speciation was investigated using laser photoacoustic spectroscopy and chemical methods

  4. Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone

    DEFF Research Database (Denmark)

    Horwich, A.; Specht, L.; Ashley, S.

    1997-01-01

    relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial......To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first...... radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate...

  5. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Recommendations of the Panel on Clinical Practices for Treatment of HIV.

    Science.gov (United States)

    Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

    2002-05-17

    The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions is critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. Treatment should

  6. Study of the Prevalence of Causative Bacterial&Protozoal Agents of in Stool Samples of 470 Gastroenteritis Patients Referring to the Nikoopour Clinic in Yazd,Iran

    Directory of Open Access Journals (Sweden)

    MR Sharifi

    2004-04-01

    Full Text Available Interoduction: Gasteroenteritis is one of the problems worth consideration all over the world. It is one of the important causes of mortality, especially in children < 5 years of age, in developing countries including Iran. The aim of this descriptive study was to determine the demographic conditions influencing the presence of causative bacteria and protozoa, followed by antibiograms of isolated bacteria from stool samples of patients with gasteroenteritis referring to Nikoopour Clinic in the city of Yazd, Iran from 1998 – 2001. Materials and method: A total of 470 samples were microbiologically examined by direct method, culture and then antibiogramed. In order to isolate the possible bacteria, differential and selected media were used. Also, wet – mount technique was applied for detection of protozoa. Results: Results revealed that 272 samples (57.9% were infected by pathogenic bacteria or protozoa. 138 (50.8% pathogenic specimens were from male patients and the remaining 134(49.3% were from female patients. Isolated species were: Enteropathogenic E.coli 117(43%, Shigella 51(18.8%, Salmonella.interetidis 25(9.2%, C.jejuni 16(5.9%, Giardia lambdia 51(18.8% and Amoebae spp 12(4.4%. The most commonly detected shigella species was dysenteriae, (74.5% while boydii with 2% was the least common type observed in the specimens. Except shigella, all the other bacteria were more common in males than female, but insignificant statistically. In order to determine the sensitivity and/or resistance of pathogenic bacteria, antibiogram test was performed using selected antibiotic disks such as Ampicillin, Nalidixic Acid, Ciprofloxacin, Gentamycin and Sulfamethaxazole. Conclusion: Results revealed that some patients were probably infected by pathogenic factors other than bacteria or protozoa. Since all viruses and parasites are almost resistant to antibiotics and on the other hand, administration of antibiotics may lead to resistance of bacterial agents

  7. Chemical Agents

    Science.gov (United States)

    ... CR) see Riot Control Agents Digitalis Distilled mustard (HD) see Sulfur mustard E Ethylene glycol F Fentanyls and other opioids H Hydrazine Hydrofluoric acid (hydrogen fluoride) Hydrogen chloride Hydrogen cyanide (AC) Hydrogen ...

  8. Clinical Comparison of Autogenous Bone Graft with and without Plasma Rich in Growth Factors in the Treatment of Grade II Furcation Involvement of Mandibular Molars

    Directory of Open Access Journals (Sweden)

    Ardeshir Lafzi

    2013-03-01

    Full Text Available Background and aims. Plasma rich in growth factors (PRGF is a concentrated suspension of growth factors, which is used to promote periodontal tissue regeneration. The aim of this randomized, controlled, clinical trial was to evaluate of the treatment of grade II mandibular molar furcation involvement using autogenous bone graft with and without PRGF. Materials and methods. In this double-blind clinical trial, thirty mandibular molars with grade II furcation involvement in 30 patients were selected. The test group received bone graft combined with PRGF, while the control group was treated with bone graft only. Clinical parameters included clinical probing depth (CPD, vertical clinical attachment level (V-CAL, horizontal clinical attachment level (H-CAL, location of gingival margin (LGM, surgically exposed horizontal probing depth of bony defect (E-HPD, vertical depth of bone crest (V-DBC, vertical depth of the base of bony defect (V-DBD, and length of the intrabony defect (LID. After six months, a re-entry surgery was performed. Data were analyzed by SPSS 14, using Kolmogorov, Mann-Whitney U, and paired t-test. Results. After 6 months, both treatment methods led to significant improvement in V-CAL and H-CAL and significant decreases in CPD, E-HPD, V-DBD and LID; there was no significant difference in LGM and V-DBC in any of the treated groups compared to the baseline values. Also, none of the parameters showed significant differences between the study groups. Conclusion. Although autogenous bone grafts, with or without PRGF, were successful in treating grade II furcation involvement, no differences between the study groups were observed.

  9. Clinical Comparison of Autogenous Bone Graft with and without Plasma Rich in Growth Factors in the Treatment of Grade II Furcation Involvement of Mandibular Molars

    Science.gov (United States)

    Lafzi, Ardeshir; Shirmohammadi, Adileh; Faramarzi, Masoumeh; Jabali, Sahar; Shayan, Arman

    2013-01-01

    Background and aims Plasma rich in growth factors (PRGF) is a concentrated suspension of growth factors, which is used to promote periodontal tissue regeneration. The aim of this randomized, controlled, clinical trial was to evaluate of the treatment of grade II mandibular molar furcation involvement using autogenous bone graft with and without PRGF. Materials and methods In this double-blind clinical trial, thirty mandibular molars with grade II furcation involvement in 30 patients were selected. The test group received bone graft combined with PRGF, while the control group was treated with bone graft only. Clinical parameters included clinical probing depth (CPD), vertical clinical attachment level (V-CAL), horizontal clinical attachment level (H-CAL), location of gingival margin (LGM), surgically exposed horizontal probing depth of bony defect (E-HPD), vertical depth of bone crest (V-DBC), vertical depth of the base of bony defect (V-DBD), and length of the intrabony defect (LID). After six months, a re-entry surgery was performed. Data were analyzed by SPSS 14, using Kolmogorov, Mann-Whitney U, and paired t-test. Results After 6 months, both treatment methods led to significant improvement in V-CAL and H-CAL and significant decreases in CPD, E-HPD, V-DBD and LID; there was no significant difference in LGM and V-DBC in any of the treated groups compared to the baseline values. Also, none of the parameters showed significant differences between the study groups. Conclusion Although autogenous bone grafts, with or without PRGF, were successful in treating grade II furcation involvement, no differences between the study groups were observed. PMID:23486928

  10. Guided tissue regeneration and platelet rich growth factor for the treatment of Grade II furcation defects: A randomized double-blinded clinical trial - A pilot study

    Directory of Open Access Journals (Sweden)

    Niloofar Jenabian

    2017-01-01

    Results: Eight patients were finally enrolled for this study. Overly, general and specific clinical and furcation parameters were improved except REC that was deteriorated insignificantly and FAC improved not significantly. Intergroup comparison revealed better improvement of FHC in GTR/PRGF group (P = 0.02. Conclusion: A significant improvement in the Grade II furcation defects treated with either GTR or PRGF/GTR was noticed. Further large-scale trials are needed to reveal differences of mentioned treatment in more details.

  11. Antisocial Personality Disorder Subscale (Chinese Version) of the Structured Clinical Interview for the DSM-IV Axis II disorders: validation study in Cantonese-speaking Hong Kong Chinese.

    Science.gov (United States)

    Tang, D Y Y; Liu, A C Y; Leung, M H T; Siu, B W M

    2013-06-01

    OBJECTIVE. Antisocial personality disorder (ASPD) is a risk factor for violence and is associated with poor treatment response when it is a co-morbid condition with substance abuse. It is an under-recognised clinical entity in the local Hong Kong setting, for which there are only a few available Chinese-language diagnostic instruments. None has been tested for its psychometric properties in the Cantonese-speaking population in Hong Kong. This study therefore aimed to assess the reliability and validity of the Chinese version of the ASPD subscale of the Structured Clinical Interview for the DSM-IV Axis II Disorders (SCID-II) in Hong Kong Chinese. METHODS. This assessment tool was modified according to dialectal differences between Mainland China and Hong Kong. Inpatients in Castle Peak Hospital, Hong Kong, who were designated for priority follow-up based on their assessed propensity for violence and who fulfilled the inclusion criteria for the study, were recruited. To assess the level of agreement, best-estimate diagnosis made by a multidisciplinary team was compared with diagnostic status determined by the SCID-II ASPD subscale. The internal consistency, sensitivity, and specificity of the subscale were also calculated. RESULTS. The internal consistency of the subscale was acceptable at 0.79, whereas the test-retest reliability and inter-rater reliability showed an excellent and good agreement of 0.90 and 0.86, respectively. Best-estimate clinical diagnosis-SCID diagnosis agreement was acceptable at 0.76. The sensitivity, specificity, positive and negative predictive values were 0.91, 0.86, 0.83, and 0.93, respectively. CONCLUSION. The Chinese version of the SCID-II ASPD subscale is reliable and valid for diagnosing ASPD in a Cantonese-speaking clinical population.

  12. Clinical analysis of the changes of plasma PRA, AT-II and Aid levels in patients with acute renal failure

    International Nuclear Information System (INIS)

    Zhang Qiuyue; Yang Yongqing

    2002-01-01

    Objective: To investigate the role of changes of plasma PRA, AT-II and Ald levels in the pathogenesis of acute renal failure. Methods: Plasma PRA, AT-II and Ald levels were determined with RIA in 40 normal subjects and 72 cases of acute renal failure. Results: Plasma PRA, AT-II and Ald levels in the patients were markedly increased as compared with those in normal subjects (p < 0.05, p < 0.01, p < 0.001 respectively). There were no linearity and exponential relationship between plasma PRA, AT-II, Ald levels and the 24 h urinary sodium excretion amount (within the range of 89.1 - 365.2 mEq). Conclusion: Acute renal failure could activate the RAAS function

  13. Clinical evaluation of the Byk LIA-mat CA125 II assay: discussion of a reference value.

    Science.gov (United States)

    Bonfrer, J M; Korse, C M; Verstraeten, R A; van Kamp, G J; Hart, G A; Kenemans, P

    1997-03-01

    The Byk LIA-mat CA125 II assay was compared with the Centocor IRMA CA125 II. Serum samples studied (n = 1012) were obtained from 652 apparently healthy females, 61 pregnant women, and 299 patients with benign and malignant gynecological tumors. The CA125 II assay value at the 95th percentile of the total healthy group was 29 kU/L for the LIA-mat and 32 kU/L for the Centocor assay. For the LIA-mat assay the 95th percentile was 31 kU/L (Centocor 36 kU/L) for the group 55 years of age. By using ROC curves we found the optimal pretreatment Byk LIA-mat CA125 II value differentiating between benign and malignant ovarian tumors to be 95 kU/L. Pretreatment CA125 values > 1000 kU/L were detected in serum samples of patients with advanced epithelial ovarian cancer.

  14. Photoacoustic imaging at 1064nm wavelength with exogenous contrast agents

    Science.gov (United States)

    Upputuri, Paul Kumar; Jiang, Yuyan; Pu, Kanyi; Pramanik, Manojit

    2018-02-01

    Photoacoustic (PA) imaging is a promising imaging modality for both preclinical research and clinical practices. Laser wavelengths in the first near infrared window (NIR-I, 650-950 nm) have been widely used for photoacoustic imaging. As compared with NIR-I window, scattering of photons by biological tissues is largely reduced in the second NIR (NIR-II) window, leading to enhanced imaging fidelity. However, the lack of biocompatible NIR-II absorbing exogenous agents prevented the use of this window for in vivo imaging. In recent years, few studies have been reported on photoacoustic imaging in NIR-II window using exogenous contrast agents. In this work, we discuss the recent work on PA imaging using 1064 nm wavelength, the fundamental of Nd:YAG laser, as an excitation wavelength. The PA imaging at 1064 nm is advantageous because of the low and homogeneous signal from tissue background, enabling high contrast in PA imaging when NIR-II absorbing contrast agents are employed.

  15. Thymidine phosphorylase and hypoxia-inducible factor 1-α expression in clinical stage II/III rectal cancer: association with response to neoadjuvant chemoradiation therapy and prognosis.

    Science.gov (United States)

    Lin, Shuhan; Lai, Hao; Qin, Yuzhou; Chen, Jiansi; Lin, Yuan

    2015-01-01

    The aim of this study was to determine whether pretreatment status of thymidine phosphorylase (TP), and hypoxia-inducible factor alpha (HIF-1α) could predict pathologic response to neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine (XELOXART) and outcomes for clinical stage II/III rectal cancer patients. A total of 180 patients diagnosed with clinical stage II/III rectal cancer received XELOXART. The status of TP, and HIF-1α were determined in pretreatment biopsies by immunohistochemistry (IHC). Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. 5-year disease free survival (DFS) and 5-year overall survival (OS) were evaluated with the Kaplan-Meier method and were compared by the log-rank test. Over expression of TP and low expression of HIF-1α were associated with pathologic response to XELOXART and better outcomes (DFS and OS) in clinical stage II/III rectal cancer patients (P rectal cancer received XELOXART. Additional well-designed, large sample, multicenter, prospective studies are needed to confirm the result of this study.

  16. Efficacy and tolerability of lodenafil carbonate for oral therapy in erectile dysfunction: a phase II clinical trial.

    Science.gov (United States)

    Glina, Sidney; Toscano, Iderpol; Gomatzky, Celso; de Góes, Plínio Moreira; Júnior, Archimedes Nardozza; Claro, Joaquim Francisco de Almeida; Pagani, Eduardo

    2009-02-01

    Oral treatment with phosphodiesterase type 5 inhibitor (PDE5) is considered the first-line treatment for patients with erectile dysfunction (ED). Lodenafil carbonate (LC) is a novel PDE5. This is a phase II, prospective, randomized, double-blind, and placebo controlled clinical trial of LC. Efficacy end points were International Index of Sexual Function (IIEF) erectile domain, IIEF questions 3 and 4, and Sexual Encounter Profile (SEP) questions 2 and 3, before and after the use of LC or placebo. Seventy-two men older than 18 years, with ED for at least 6 months with stable sexual relationship were enrolled. Patients were randomized to placebo or LC 80 mg, 40 mg, or 20 mg and followed for 4 weeks. IIEF erectile domain scores before and after the use of medications were (mean +/- standard deviation [SD]): placebo: 11.9 +/- 3.4 and 12.6 +/- 5.5; LC 20 mg: 15.8 +/- 4.1 and 18.9 +/- 6.6; LC 40 mg: 11.9 +/- 4.4 and 15.4 +/- 8.1; LC 80 mg: 14.2 +/- 4.7 and 22.8 +/- 6.0 (ANOVA P < 0.01). The SEP-2 scores before and after the use of medications were (Mean +/- SD): placebo: 71.0 +/- 33.1 and 51.2 +/- 43.1; LC 20 mg 70.3 +/- 34.2 and 75.5 +/- 31.5; LC 40 mg: 48.4 +/- 42.1 and 60.8 +/- 42.5; LC 80 mg: 68.6 +/- 33.5 and 89.6 +/- 26.0. The SEP-3 scores were: placebo 23.3 +/- 27.6 and 33.6 +/- 42.3; LC 20 mg: 32.3 +/- 38.9 and 51.2 +/- 41.7; LC 40 mg: 39.7 +/- 44.7 and 46.7 +/- 41.1; LC 80 mg* 17.2 +/- 29.5 and 74.3 +/- 36.4 (*P < 0.05 for difference to placebo). The drug was well tolerated. Adverse reactions were mild and self-limited and included headache, rhinitis, flushing, color visual disorders, and dyspepsia. This study showed that the dosage of 80 mg of LC was significantly more efficacious than placebo and well tolerated.

  17. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors

    Directory of Open Access Journals (Sweden)

    Spugnini Enrico P

    2011-12-01

    Full Text Available Abstract Background The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study. Methods Thirty-four companion animals (27 dogs and 7 cats were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols. Results The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6% the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17% experienced short lived partial responses (1-3 months duration while all the others died of progressive disease within two months. Conclusions high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of

  18. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors.

    Science.gov (United States)

    Spugnini, Enrico P; Baldi, Alfonso; Buglioni, Sabrina; Carocci, Francesca; de Bazzichini, Giulia Milesi; Betti, Gianluca; Pantaleo, Ilaria; Menicagli, Francesco; Citro, Gennaro; Fais, Stefano

    2011-12-28

    The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI) increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study. Thirty-four companion animals (27 dogs and 7 cats) were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats) whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols. The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6%) the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17%) experienced short lived partial responses (1-3 months duration) while all the others died of progressive disease within two months. high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of the quality of life in pets with down staged cancer and in

  19. Efficacy and safety of a novel pharmacological stress test agent-higenamine in radionuclide myocardial perfusion imaging: phase Ⅱ clinical trial

    International Nuclear Information System (INIS)

    Du Yanrong; Li Fang; Wang Qian; Li Dianfu; Long Mingqing; Liu Yimin; Li Bilu

    2014-01-01

    Objective: To evaluate the effectiveness and safety of higenamine (HG), a pharmaco logical stress agent, for the detection of myocardial ischemia using SPECT. Methods: This study was an open,multi-center, randomized and positively controlled trial with crossover references. It consisted of 120 patients clinically confirmed or suspected of myocardial ischemia. Each patient underwent a resting MPI and two separate stress MPI in a randomized crossover manner with intravenous administration of HG or adenosine (Ad) on different days. The severity and extent of myocardial ischemia were diagnosed on stress MPI. The degree of vascular stenosis in terms of percentage narrowing was measured by CAG (>50% was defined as coronary disease), thus defined as gold standard. The diagnostic efficacy of HG and Ad was compared. Vital signs, routine blood and urine tests,blood biochemical items and side effects were documented for evaluation of procedure safety. Two-sample t test, χ 2 or Fisher's exact test, and Kappa test were used. Results: A total of 109 patients completed the trim and CAG. The diagnostic sensitivity, specificity, accuracy, positive predictive value, negative predictive value of HG MPI were 56.1% (32/57), 78.8% (41/52), 67.0%(73/109), 74.4% (32/43) and 62.1% (41/66), respectively, which were not significantly different from those of Ad MPI (52.6% (30/57), 82.7% (43/52), 67.0% (73/109), 76.9% (30/39) and 61.4%(43/70) ; χ 2 =0-0.2476, all P>0.05). The sensitivity of HG vs Ad MPI in the diagnosis of single-, double-and triple-vessel ischemia was 29.6% (8/27) vs 22.2% (6/27), 64.7% (11/17) vs 64.7% (11/17) and 100% (13/13) vs 100% (13/13), respectively. The concordance between HG and Ad for the detection of LAD, LCX and RCA ischemia was 95.41% (104/109), 97.25% (106/109) and 97.25% (106/109) (Kappa=0.8905, 0.8420 and 0.8874). HG did not induce significant systolic blood pressure change during or after administration. Both HG and Ad could induce temporary decrease

  20. Pseudomonas aeruginosa cells adapted to benzalkonium chloride show resistance to other membrane-active agents but not to clinically relevant antibiotics.

    Science.gov (United States)

    Loughlin, M F; Jones, M V; Lambert, P A

    2002-04-01

    Our objective was to determine whether strains of Pseudomonas aeruginosa can adapt to growth in increasing concentrations of the disinfectant benzalkonium chloride (BKC), and whether co-resistance to clinically relevant antimicrobial agents occurs. Attempts were made to determine what phenotypic alterations accompanied resistance and whether these explained the mechanism of resistance. Strains were serially passaged in increasing concentrations of BKC in static nutrient broth cultures. Serotyping and genotyping were used to determine purity of the cultures. Two strains were examined for cross-resistance to other disinfectants and antibiotics by broth dilution MIC determination. Alterations in outer membrane proteins and lipopolysaccharide (LPS) expressed were examined by SDS-PAGE. Cell surface hydrophobicity and charge, uptake of disinfectant and proportion of specific fatty acid content of outer and cytoplasmic membranes were determined. Two P. aeruginosa strains showed a stable increase in resistance to BKC. Co-resistance to other quaternary ammonium compounds was observed in both strains; chloramphenicol and polymyxin B resistance were observed in one and a reduction in resistance to tobramycin observed in the other. However, no increased resistance to other biocides (chlorhexidine, triclosan, thymol) or antibiotics (ceftazidime, imipenem, ciprofloxacin, tobramycin) was detected. Characteristics accompanying resistance included alterations in outer membrane proteins, uptake of BKC, cell surface charge and hydrophobicity, and fatty acid content of the cytoplasmic membrane, although no evidence was found for alterations in LPS. Each of the two strains had different alterations in phenotype, indicating that such adaptation is unique to each strain of P. aeruginosa and does not result from a single mechanism shared by the whole species.

  1. Clinical results of Hi-tech Knee II total knee arthroplasty in patients with rheumatoid athritis: 5- to 12-year follow-up

    Directory of Open Access Journals (Sweden)

    Yamanaka Hajime

    2012-02-01

    Full Text Available Abstract Background Total knee arthroplasty (TKA is a common form of treatment to relieve pain and improve function in cases of rheumatoid arthritis (RA. Good clinical outcomes have been reported with a variety of TKA prostheses. The cementless Hi-Tech Knee II cruciate-retaining (CR-type prosthesis, which has 6 fins at the anterior of the femoral component, posterior cruciate ligament (PCL retention, flat-on-flat surface component geometry, all-polyethylene patella, strong initial fixation by the center screw of the tibial base plate, 10 layers of titanium alloy fiber mesh, and direct compression molded ultra high molecular weight polyethylene (UHMWPE, is appropriate for TKA in the Japanese knee. The present study was performed to evaluate the clinical results of primary TKA in RA using the cementless Hi-Tech Knee II CR-type prosthesis. Materials and methods We performed 32 consecutive primary TKAs using cementless Hi-Tech Knee II CR-type prosthesis in 31 RA patients. The average follow-up period was 8 years 3 months. Clinical evaluations were performed according to the American Knee Society (KS system, knee score, function score, radiographic evaluation, and complications. Results The mean postoperative maximum flexion angle was 115.6°, and the KS knee score and function score improved to 88 and 70 after surgery, respectively. Complications, such as infection, occurred in 1 patient and revision surgery was performed. There were no cases of loosening in this cohort, and prosthesis survival rate was 96.9% at 12 years postoperatively. Conclusion These results suggest that TKA using the cementless Hi-Tech Knee II CR-type prosthesis is a very effective form of treatment in RA patients at 5 to 12 years postoperatively. Further long-term follow-up studies are required to determine the ultimate utility of this type of prosthesis.

  2. Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents.

    Science.gov (United States)

    Runge, Val M

    2017-06-01

    For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was

  3. Clinical significance of measurement of changes of serum IGF-II, SCC and CYFRA21-1 levels after operation in patients with carcinoma of uterine cervix

    International Nuclear Information System (INIS)

    Kuang Lei

    2010-01-01

    Objective: To explore the clinical significance of changes of serum IGF-II, SCC and CYFRA21-1 levels after operation in patients with carcinoma uterine cervix. Methods: Serum levels of IGF-II, SCC and CYFRA21-1 were determined with RIA repeatedly in 31 patients with carcinoma of uterine cervix (before operation 1 month after operation and 6 month after operation) and once in 35 controls. Results: Before operation,serum levels of IGF-II, SCC and CYFRA21-1 in the patients were significantly higher than those in the controls (P<0.01). One month after operation all the serum levels were approaching normal. Six month later,the levels in the patients without recurrence remained normal. However, the levels in the 6 patients with recurrence returned to those before operation again. Conclusion: Changes of serum IGF-II, SCC and CYFRA21-1 levels are closely related to the tumor burden and may be of prognostic importance. (authors)

  4. Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV).

    Science.gov (United States)

    Okada, Kenji; Miyazaki, Chiaki; Kino, Yoichiro; Ozaki, Takao; Hirose, Mizuo; Ueda, Kohji

    2013-07-15

    Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. DTaP-sIPV was shown to be a safe and immunogenic vaccine. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).

  5. A comparison of DNA binding profiles of dinuclear platinum compounds with polyamine linkers and the trinuclear platinum phase II clinical agent BBR3464

    Czech Academy of Sciences Publication Activity Database

    McGregor, T. D.; Hegmans, A.; Kašpárková, Jana; Neplechová, Kamila; Nováková, Olga; Peňázová, Hana; Vrána, Oldřich; Brabec, Viktor; Farrel, N.

    2002-01-01

    Roč. 7, 4/5 (2002), s. 397-404 ISSN 0949-8257 R&D Projects: GA ČR GA305/99/0695; GA ČR GA301/00/0556; GA ČR GA301/98/P231; GA AV ČR IAA5004101; GA AV ČR IAA7004805 Institutional research plan: CEZ:AV0Z5004920 Keywords : unwinding * dinuclear platinum * hydrogen bonding Subject RIV: BO - Biophysics Impact factor: 3.911, year: 2002

  6. [Clinical efficacy of alprostan in combination with "Bioptron-II" rays and iruxol-miramistin in the treatment of the diabetic foot complicated by atherosclerosis].

    Science.gov (United States)

    Tomashuk, I P; Tomashuk, I I

    2001-08-01

    Experience of clinical treatment of 9 patients with diabetes mellitus and diabetic angiopathy using alprostan in combination with rays "Bioptron-II" and iruxol-miramistinum in conditions of polyclinic was summarized. Antidiabetic preparations, mainly insulin, were administered to all patients together with abovementioned treatment. Optimal scheme of treatment constitutes daily slow (no less than 6 h) dropper intravenous infusion of alprostan in 0.1 mg dosage in 150-200 ml isotonic solution of sodium chloride during 15 days. Before and after infusion of alprostan ulcer was locally irradiated using "Bioptron-II" lamp from 5 cm distance during 6 min, bandage with iruxol-miramistinum ointment was applied in ratio 1:1. In 6 patients pain in lower extremities disappeared, ulcers epithelized, in 3--ulcers reduced by 50%.

  7. Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

    Science.gov (United States)

    Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

    2016-12-12

    The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

  8. Diagnostic Efficiency among Psychiatric Outpatients of a Self-Report Version of a Subset of Screen Items of the Structured Clinical Interview for DSM-IV-TR Personality Disorders (SCID-II)

    Science.gov (United States)

    Germans, Sara; Van Heck, Guus L.; Masthoff, Erik D.; Trompenaars, Fons J. W. M.; Hodiamont, Paul P. G.

    2010-01-01

    This article describes the identification of a 10-item set of the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) items, which proved to be effective as a self-report assessment instrument in screening personality disorders. The item selection was based on the retrospective analyses of 495 SCID-II interviews. The…

  9. DEMO-II trial. Aerobic exercise versus stretching exercise in patients with major depression-a randomised clinical trial

    DEFF Research Database (Denmark)

    Krogh, Jesper; Videbech, Poul; Thomsen, Carsten

    2012-01-01

    The effect of referring patients from a clinical setting to a pragmatic exercise intervention for depressive symptoms, cognitive function, and metabolic variables has yet to be determined.......The effect of referring patients from a clinical setting to a pragmatic exercise intervention for depressive symptoms, cognitive function, and metabolic variables has yet to be determined....

  10. World Endometriosis Research Foundation Endometriosis Phenome and biobanking harmonization project: II. Clinical and covariate phenotype data collection in endometriosis research

    DEFF Research Database (Denmark)

    Vitonis, Allison F.; Vincent, Katy; Rahmioglu, Nilufer

    2014-01-01

    ObjectiveTo harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration.......ObjectiveTo harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration....

  11. [Orthopedic treatment of dento-skeletal Class II by the association minivis + Forsus(TM): a clinical case].

    Science.gov (United States)

    Pujol, Pierre

    2014-06-01

    The use of customized combination mechanics with two auxillaries such as mini screws and Forsus(TM) Springs that up to now have been used independently, achieved unexpected results in the correction of a non-surgical skeletal Class II malocclusion. The use of mini implants to control the canting of the occlusal plane that is frequently reported during the use of hyperpropulsors with fixed appliances made it possible to achieve a better mandibular outcome. © EDP Sciences, SFODF, 2014.

  12. Adjuvant chemotherapy for stage II colon cancer: influence of care structures' characteristics on a controversial clinical practice.

    Science.gov (United States)

    Alter, Eléonore; Phelip, Jean-Marc; Guilhot, Jean-Noel; Matysiak, Michel; Vermorel, Michel; Roblin, Xavier

    2007-11-01

    Adjuvant chemotherapy for stage II colon cancer is a controversial practice and is not recommended by the French Consensus Conference outside of therapeutic trial. To assess, within a well-defined population, the influence of hospital characteristics in this practice. In the Rhône-Alpes region (10% of the French population), 534 patients presenting with colon cancer stage II were operated on in 81 hospitals in the year 2000. The influence of hospital characteristics on the use of adjuvant chemotherapy was assessed using a multivariate logistic regression. Overall, 19.5% of patients received adjuvant chemotherapy. Younger age, T4 tumour, hospital volume lower than 20 colon cancer surgeries [odds ratio (OR) 2.96; Pclinical complications at diagnosis were independently associated with higher rates of chemotherapy. On the other hand, a number of examined lymph nodes lower than recommendations did not have any influence on chemotherapy use. Hospital characteristics had independently influenced the practice of adjuvant chemotherapy in stage II colon cancer. The more important institutional factor was the hospital procedure volume. The decisions of the multidisciplinary committees appeared at times paradoxical; a more comprehensive evaluation of this practice is needed.

  13. Bone radioisotope scanning: usefulness in the evaluation and observation of patients with breast cancer in clinical stage II, III, IV; Gammagrafia osea: utilidad en la evaluacion y seguimiento de pacientes con cancer de mama en estadio clinico II, III, IV

    Energy Technology Data Exchange (ETDEWEB)

    Cano P, R A

    1996-12-31

    The clinical records of 420 patients with diagnosis of breast cancer well documented by the pathological anatomy in clinical stage II, III and IV were reviewed. In each one of them has been done at least a bone scanning during the diagnosis. In 52 cases carried out sericeous dosages of CA 15-3 and in some cases it was necessary to administer Samarium-153 EDTMP as palliative therapy of bone pain. The presence of secondary gamma-graphic focuses was 0/84 cases (0%) in clinical stage II, 54/265 cases (20%) in III and 41/91 cases (45%) in IV. The one focus appeared in 6.7% of the cases. In 7 of the 52 cases that received sericeous dosages of CA 15-3 were detected secondary osseous lesions, and 5 of them presented a marker elevation. The bone scanning has shown in many cases the presence of getters focuses in singular places of skeleton, urinary excretory system or mammary tissue. The gamma rays from Sm-153 allowed us to get some appropriate basal views post-therapy of the secondary lesions. The results show that the great incidence of secondary lesions in the skeleton occurred in cases of stages III and IV unlike other countries. The serial repetition of the radioisotope scanning. The presence of one focus in the skeleton of a patient with a well-known neoplasia makes us to do a careful evaluation of the focus nature. The presence of tracer accumulation in the kidney, ureter and bladder allows us to infer the pathology of excretory system that is the first evidence of its presence in many cases. (author). 71 refs., 7 figs., 6 tabs.

  14. A surgeon, a rabbi and a lawyer walk in to an OR… Absorbable haemostatic agents and the dangers of product evolution – clinical, religious and legal implications

    Directory of Open Access Journals (Sweden)

    Laurence Gluch

    2018-01-01

    Full Text Available Adjunctive haemostatic agents have been used in surgery for over 70 years. What surgeons may not know is that products intended for similar applications may have very different biological properties and that occasionally product upgrades may introduce a change in the material’s behaviour. Many of the agents employed to assist in haemostasis may have a biological (animal origin. A recent case brought to light the need to recognise the possibility of biological interactions. As consideration into this surgical problem unfolded, religious and legal questions began to arise.

  15. Clinical application of removable partial dentures using thermoplastic resin. Part II: Material properties and clinical features of non-metal clasp dentures.

    Science.gov (United States)

    Fueki, Kenji; Ohkubo, Chikahiro; Yatabe, Masaru; Arakawa, Ichiro; Arita, Masahiro; Ino, Satoshi; Kanamori, Toshikazu; Kawai, Yasuhiko; Kawara, Misao; Komiyama, Osamu; Suzuki, Tetsuya; Nagata, Kazuhiro; Hosoki, Maki; Masumi, Shin-ichi; Yamauchi, Mutsuo; Aita, Hideki; Ono, Takahiro; Kondo, Hisatomo; Tamaki, Katsushi; Matsuka, Yoshizo; Tsukasaki, Hiroaki; Fujisawa, Masanori; Baba, Kazuyoshi; Koyano, Kiyoshi; Yatani, Hirofumi

    2014-04-01

    This position paper reviews physical and mechanical properties of thermoplastic resin used for non-metal clasp dentures, and describes feature of each thermoplastic resin in clinical application of non-metal clasp dentures and complications based on clinical experience of expert panels. Since products of thermoplastic resin have great variability in physical and mechanical properties, clinicians should utilize them with careful consideration of the specific properties of each product. In general, thermoplastic resin has lower color-stability and higher risk for fracture than polymethyl methacrylate. Additionally, the surface of thermoplastic resin becomes roughened more easily than polymethyl methacrylate. Studies related to material properties of thermoplastic resin, treatment efficacy and follow-up are insufficient to provide definitive conclusions at this time. Therefore, this position paper should be revised based on future studies and a clinical guideline should be provided. Copyright © 2014 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  16. [Anniversaries of the foundation of the dental clinics. II. The dental clinics at the Mikszáth Kálmán Square in Budapest, Hungary].

    Science.gov (United States)

    Kóbor, András

    2010-03-01

    After 1952 the building of the Department of Stomatology was no more able to fulfill the increased demands, when the independent dental education had been started at the Medical University of Budapest. The leadership of the new Dental Faculty--officially founded in 1955--was looking for a solution to find a new building for clinical purposes. Finally in 1959 the new dental departments moved to a once residential building at Mikszáth Kálmán Square converted into dental clinics. This site had been in operation until the opening of the New Dental Education Center in 2007.

  17. cobalt (ii), nickel (ii)

    African Journals Online (AJOL)

    DR. AMINU

    Department of Chemistry Bayero University, P. M. B. 3011, Kano, Nigeria. E-mail: hnuhu2000@yahoo.com. ABSTRACT. The manganese (II), cobalt (II), nickel (II) and .... water and common organic solvents, but are readily soluble in acetone. The molar conductance measurement [Table 3] of the complex compounds in.

  18. Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group.

    Science.gov (United States)

    Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

    2011-05-01

    There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3-4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity.

  19. A comparison of DNA extraction procedures for the detection of Mycobacterium ulcerans, the causative agent of Buruli ulcer, in clinical and environmental specimens

    DEFF Research Database (Denmark)

    Durnez, Lies; Stragier, Pieter; Roebben, Karen

    2008-01-01

    Mycobacterium ulcerans is the causative agent of Buruli ulcer, the third most common mycobacterial disease in humans after tuberculosis and leprosy. Although the disease is associated with aquatic ecosystems, cultivation of the bacillus from the environment is difficult to achieve. Therefore...

  20. Initial formal toxicity evaluation of APC-2, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate in preparation for a first-in-man clinical trial

    Science.gov (United States)

    Bugaj, Joseph E.; Dorshow, Richard B.

    2014-03-01

    The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated APC-2, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in preparation. A battery of formal toxicity tests necessary for regulatory clearance to proceed with a clinical trial has been recently completed on this new fluorescent tracer agent. These include single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Blood samples were collected to assess pharmacokinetic parameters including half-life, area under the curve, and clearance. Urine samples were collected to assess distribution. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly fluorescent compound and was not considered pathological. Thus initial toxicology studies of this new fluorescent tracer agent APC-2 have resulted in no demonstrable pathological test article concerns.

  1. Quinone-fused porphyrins as contrast agents for photoacoustic imaging

    KAUST Repository

    Banala, Srinivas

    2017-06-27

    Photoacoustic (PA) imaging is an emerging non-invasive diagnostic modality with many potential clinical applications in oncology, rheumatology and the cardiovascular field. For this purpose, there is a high demand for exogenous contrast agents with high absorption coefficients in the optical window for tissue imaging, i.e. the near infrared (NIR) range between 680 and 950 nm. We herein report the photoacoustic properties of quinone-fused porphyrins inserted with different transition metals as new highly promising candidates. These dyes exhibit intense NIR absorption, a lack of fluorescence emission, and PA sensitivity in concentrations below 3 nmol mL. In this context, the highest PA signal was obtained with a Zn(ii) inserted dye. Furthermore, this dye was stable in blood serum and free thiol solution and exhibited negligible cell toxicity. Additionally, the Zn(ii) probe could be detected with an up to 3.2 fold higher PA intensity compared to the clinically most commonly used PA agent, ICG. Thus, further exploration of the \\'quinone-fusing\\' approach to other chromophores may be an efficient way to generate highly potent PA agents that do not fluoresce and shift their absorption into the NIR range.

  2. Audiovisual biofeedback breathing guidance for lung cancer patients receiving radiotherapy: a multi-institutional phase II randomised clinical trial.

    Science.gov (United States)

    Pollock, Sean; O'Brien, Ricky; Makhija, Kuldeep; Hegi-Johnson, Fiona; Ludbrook, Jane; Rezo, Angela; Tse, Regina; Eade, Thomas; Yeghiaian-Alvandi, Roland; Gebski, Val; Keall, Paul J

    2015-07-18

    There is a clear link between irregular breathing and errors in medical imaging and radiation treatment. The audiovisual biofeedback system is an advanced form of respiratory guidance that has previously demonstrated to facilitate regular patient breathing. The clinical benefits of audiovisual biofeedback will be investigated in an upcoming multi-institutional, randomised, and stratified clinical trial recruiting a total of 75 lung cancer patients undergoing radiation therapy. To comprehensively perform a clinical evaluation of the audiovisual biofeedback system, a multi-institutional study will be performed. Our methodological framework will be based on the widely used Technology Acceptance Model, which gives qualitative scales for two specific variables, perceived usefulness and perceived ease of use, which are fundamental determinants for user acceptance. A total of 75 lung cancer patients will be recruited across seven radiation oncology departments across Australia. Patients will be randomised in a 2:1 ratio, with 2/3 of the patients being recruited into the intervention arm and 1/3 in the control arm. 2:1 randomisation is appropriate as within the interventional arm there is a screening procedure where only patients whose breathing is more regular with audiovisual biofeedback will continue to use this system for their imaging and treatment procedures. Patients within the intervention arm whose free breathing is more regular than audiovisual biofeedback in the screen procedure will remain in the intervention arm of the study but their imaging and treatment procedures will be performed without audiovisual biofeedback. Patients will also be stratified by treating institution and for treatment intent (palliative vs. radical) to ensure similar balance in the arms across the sites. Patients and hospital staff operating the audiovisual biofeedback system will complete questionnaires to assess their experience with audiovisual biofeedback. The objectives of this

  3. Inflammation's Association with Metabolic Profiles before and after a Twelve-Week Clinical Trial in Drug-Naïve Patients with Bipolar II Disorder.

    Directory of Open Access Journals (Sweden)

    Sheng-Yu Lee

    Full Text Available Inflammation is thought to be involved in the pathophysiology of bipolar disorder (BP and metabolic syndrome. Prior studies evaluated the association between metabolic profiles and cytokines only during certain mood states instead of their changes during treatment. We enrolled drug-naïve patients with BP-II and investigated the correlation between changes in mood symptoms and metabolic indices with changes in plasma cytokine levels after 12 weeks of pharmacological treatment. Drug-naïve patients (n = 117 diagnosed with BP-II according to DSM-IV criteria were recruited. Metabolic profiles (cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI and plasma cytokines (TNF-α, CRP, IL-6, and TGF-β were measured at baseline and 2, 8, and 12 weeks post-treatment. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. Seventy-six (65.0% patients completed the intervention. Changes in plasma CRP were significantly associated with changes in BMI (P = 1.7E-7 and triglyceride (P = 0.005 levels. Changes in plasma TGF-β1 were significantly associated with changes in BMI (P = 8.2E-6, cholesterol (P = 0.004, and triglyceride (P = 0.006 levels. However, changes in plasma TNF-α and IL-6 were not associated with changes in any of the metabolic indices. Changes in Hamilton Depression Rating Scale scores were significantly associated with changes in IL-6 (P = 0.003 levels; changes in Young Mania Rating Scale scores were significantly associated with changes in CRP (P = 0.006 and TNF-α (P = 0.039 levels. Plasma CRP and TGF-β1 levels were positively correlated with several metabolic indices in BP-II after 12 weeks of pharmacological intervention. We also hypothesize that clinical symptoms are correlated with certain cytokines. These new findings might be important evidence that inflammation is the pathophysiology

  4. Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research Practices Task Force report.

    Science.gov (United States)

    Ramsey, Scott D; Willke, Richard J; Glick, Henry; Reed, Shelby D; Augustovski, Federico; Jonsson, Bengt; Briggs, Andrew; Sullivan, Sean D

    2015-03-01

    Clinical trials evaluating medicines, medical devices, and procedures now commonly assess the economic value of these interventions. The growing number of prospective clinical/economic trials reflects both widespread interest in economic information for new technologies and the regulatory and reimbursement requirements of many countries that now consider evidence of economic value along with clinical efficacy. As decision makers increasingly demand evidence of economic value for health care interventions, conducting high-quality economic analyses alongside clinical studies is desirable because they broaden the scope of information available on a particular intervention, and can efficiently provide timely information with high internal and, when designed and analyzed properly, reasonable external validity. In 2005, ISPOR published the Good Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials: The ISPOR RCT-CEA Task Force report. ISPOR initiated an update of the report in 2014 to include the methodological developments over the last 9 years. This report provides updated recommendations reflecting advances in several areas related to trial design, selecting data elements, database design and management, analysis, and reporting of results. Task force members note that trials should be designed to evaluate effectiveness (rather than efficacy) when possible, should include clinical outcome measures, and should obtain health resource use and health state utilities directly from study subjects. Collection of economic data should be fully integrated into the study. An incremental analysis should be conducted with an intention-to-treat approach, complemented by relevant subgroup analyses. Uncertainty should be characterized. Articles should adhere to established standards for reporting results of cost-effectiveness analyses. Economic studies alongside trials are complementary to other evaluations (e.g., modeling studies) as information for decision

  5. Coronally positioned flap with or without acellular dermal matrix graft in the treatment of class II gingival recession defects: A randomized controlled clinical study

    Directory of Open Access Journals (Sweden)

    Sunitha Jagannathachary

    2010-01-01

    Full Text Available The aim of the randomized controlled single blind study is to evaluate the treatment of Miller′s class II gingival recessions by coronally positioned flap (CPF with or without acellular dermal matrix allograft (ADMA. Ten patients with 20 sites with maxillary bilateral Miller′s class II facial recession defects were selected randomly into two groups of test (ADMA+CPF and control (CPF alone group with each group having 10 recession defects to be treated. The clinical parameters included plaque index (PI, gingival index (GI, probing pocket depth (PPD, clinical attachment level (CAL, recession height (RH, recession width (RW, height of the keratinized tissue (HKT, and thickness of the keratinized tissue (TKT. These measurements were recorded at baseline and after 6 months post-surgery. Statistical analysis was made by the paired "t" test for intragroup and intergroup comparison was done by the unpaired "t" test. The percentage of root coverage for both the experimental and control groups were 82.2% and 50%, respectively. The changes from baseline to 6 months were significant in both the groups for PD, CAL, and RH; however, for parameters such as RW, HKT, and TKT significance was seen only in the experimental group. On comparison between two groups, only TKT showed statistically significance. It can be concluded that the amount of root coverage obtained with ADMA + CPF was superior compared to CPF alone.

  6. The World Health Organisation Disability Assessment Scale (WHODAS II: Links between self-rated health and objectively defined and clinical parameters in the population of spinal cord injury

    Directory of Open Access Journals (Sweden)

    Steinerte V.

    2016-01-01

    Full Text Available There are many clinical and objectively defined parameters that are used to evaluate a person's disability. Since the World Health Organisation has presented the WHODAS II as a means of objectively measuring subjectively defined functions, greater attention has been focused on self-rated health. Only a few studies, however, have been conducted about differences between self-rated health and objectively defined parameters. The survey for this study was conducted on the basis of WHODAS II and the population in Latvia with spinal cord injury. Respondents were between 18 and 65, and 98 questionnaires were analysed. The results show that people with spinal cord injury on average rate their functioning as limited (33–40 points of 100. Most respondents have been declared to be disabled, which is defined as very serious or severe functional disorders. More than 40% have paid jobs, while one-third do not work for reasons of health. The research shows that there is a close coherence (p< 0.05 between individual, objectively and clinically defined indicators on the one hand and the aspects of the questionnaire in which physical functioning was an important factor on the other hand. In order to understand the real functional abilities of patients and the individual factors that influence those abilities, it is necessary to define functional self-rated health in addition to objectively defined indicators.

  7. An Immature Type II Dens Invaginatus in a Mandibular Lateral Incisor with Talon’s Cusp: A Clinical Dilemma to Confront

    Directory of Open Access Journals (Sweden)

    Anshul Gangwar

    2014-01-01

    Full Text Available Dens invaginatus (DI is a malformation of teeth probably resulting from an infolding of the dental papilla during tooth development. DI is classified as type I, II, and III by Oehlers depending on the severity of malformation. The maxillary lateral incisor is the most commonly affected tooth. Structural defects do exist in the depth of the invagination pits, and as a consequence, the early development of caries and the subsequent necrosis of the dental pulp, as well as abscess and cyst formation are clinical implications associated with DI. Occasionally, we can see more than one developmental anomaly occurring in a single tooth. In such cases it becomes important to identify the anomalies and initiate a proper treatment plan for good prognosis. In this paper, an unusual case of DI which clinically presented as a huge talons cusp affecting a mandibular lateral incisor tooth is described. This case report illustrates grinding of the talons cusp followed by nonsurgical endodontic management of dens invaginatus type II with an immature apex and periapical lesions, in which Mineral Trioxide Aggregate (MTA shows a complete periapical healing with bone formation at the site of the lesions.

  8. Trading Agents

    CERN Document Server

    Wellman, Michael

    2011-01-01

    Automated trading in electronic markets is one of the most common and consequential applications of autonomous software agents. Design of effective trading strategies requires thorough understanding of how market mechanisms operate, and appreciation of strategic issues that commonly manifest in trading scenarios. Drawing on research in auction theory and artificial intelligence, this book presents core principles of strategic reasoning that apply to market situations. The author illustrates trading strategy choices through examples of concrete market environments, such as eBay, as well as abst

  9. Audiovisual biofeedback breathing guidance for lung cancer patients receiving radiotherapy: a multi-institutional phase II randomised clinical trial

    International Nuclear Information System (INIS)

    Pollock, Sean; O’Brien, Ricky; Makhija, Kuldeep; Hegi-Johnson, Fiona; Ludbrook, Jane; Rezo, Angela; Tse, Regina; Eade, Thomas; Yeghiaian-Alvandi, Roland; Gebski, Val; Keall, Paul J

    2015-01-01

    There is a clear link between irregular breathing and errors in medical imaging and radiation treatment. The audiovisual biofeedback system is an advanced form of respiratory guidance that has previously demonstrated to facilitate regular patient breathing. The clinical benefits of audiovisual biofeedback will be investigated in an upcoming multi-institutional, randomised, and stratified clinical trial recruiting a total of 75 lung cancer patients undergoing radiation therapy. To comprehensively perform a clinical evaluation of the audiovisual biofeedback system, a multi-institutional study will be performed. Our methodological framework will be based on the widely used Technology Acceptance Model, which gives qualitative scales for two specific variables, perceived usefulness and perceived ease of use, which are fundamental determinants for user acceptance. A total of 75 lung cancer patients will be recruited across seven radiation oncology departments across Australia. Patients will be randomised in a 2:1 ratio, with 2/3 of the patients being recruited into the intervention arm and 1/3 in the control arm. 2:1 randomisation is appropriate as within the interventional arm there is a screening procedure where only patients whose breathing is more regular with audiovisual biofeedback will continue to use this system for their imaging and treatment procedures. Patients within the intervention arm whose free breathing is more regular than audiovisual biofeedback in the screen procedure will remain in the intervention arm of the study but their imaging and treatment procedures will be performed without audiovisual biofeedback. Patients will also be stratified by treating institution and for treatment intent (palliative vs. radical) to ensure similar balance in the arms across the sites. Patients and hospital staff operating the audiovisual biofeedback system will complete questionnaires to assess their experience with audiovisual biofeedback. The objectives of this

  10. The fitness for the Ageing Brain Study II (FABS II: protocol for a randomized controlled clinical trial evaluating the effect of physical activity on cognitive function in patients with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ames David

    2010-12-01

    Full Text Available Abstract Background Observational studies have documented a potential protective effect of physical exercise in older adults who are at risk for developing Alzheimer's disease. The Fitness for the Ageing Brain II (FABS II study is a multicentre randomized controlled clinical trial (RCT aiming to determine whether physical activity reduces the rate of cognitive decline among individuals with Alzheimer's disease. This paper describes the background, objectives of the study, and an overview of the protocol including design, organization and data collection methods. Methods/Design The study will recruit 230 community-dwelling participants diagnosed with Alzheimer's disease. Participants will be randomly allocated to two treatment groups: usual care group or 24-week home-based program consisting of 150 minutes per week of tailored moderate physical activity. The primary outcome measure of the study is cognitive decline as measured by the change from baseline in the total score on the Alzheimer's disease Assessment Scale-Cognitive section. Secondary outcomes of interest include behavioral and psychological symptoms, quality of life, functional level, carer burden and physical function (strength, balance, endurance, physical activity. Primary endpoints will be measured at six and twelve months following the baseline assessment. Discussion This RCT will contribute evidence regarding the potential benefits of a systematic program of physical activity as an affordable and safe intervention for people with Alzheimer's disease. Further, if successful, physical activity in combination with usual care has the potential to alleviate the symptoms of Alzheimer's disease and improve its management and the quality of life of patients and their carers. Trial Registration Australia New Zealand Clinical Trials Registry ACTRN12609000755235

  11. Beating the odds: Successful establishment of a Phase II/III clinical research trial in resource-poor Liberia during the largest-ever Ebola outbreak

    Directory of Open Access Journals (Sweden)

    J. Doe-Anderson

    2016-12-01

    Full Text Available It has been argued that a country such as Liberia, not fully recovered from the devastation of decades of civil unrest, lacked the appropriate ethical and regulatory framework, basic human and health care services, and infrastructure to carry out clinical trials according to international standards of quality during a public health emergency. However, as Liberia, Sierra Leone, and Guinea were being ravaged by the largest and most devastating Ebola Virus Disease (EVD outbreak ever recorded, the topic of conducting clinical trials of experimental vaccine and treatment candidates in these resource-poor countries generated the keen interest and concern of scientists, researchers, physicians, bioethicists, philanthropists, and even politicians. Decisive action on behalf of the Liberian government, and a timely positive and supportive response from the United States (U.S. government, led to the formation of PREVAIL (Partnership for Research on Ebola Vaccines in Liberia – a clinical research partnership between the two governments. Within a span of 12 weeks, this partnership accomplished the unimaginable: the successful initiation of a Phase II/III vaccine clinical trial for EVD in Liberia. This paper will discuss the dynamics of the research collaboration, barriers encountered, breakthroughs realized, key elements of success, and lessons learned in the process.

  12. Long term results of mantle irradiation(MRT) alone in 261 patients with clinical stage I-II supradiaphragmatic Hodgkin's disease

    International Nuclear Information System (INIS)

    Wirth, A.; Byram, D.; Chao, M.; Corry, J.; Davis, S.; Kiffer, J.; Laidlaw, C.; Quong, G.; Ryan, G.; Liew, K.

    1997-01-01

    Purpose: We report our results using MRT for clinical stage I-II HD and assess the value of published prognostic criteria in our study population. Pts and Methods: Between 1969 and 1994, 261 pts were treated with MRT alone for clinical stage I-II supradiaphragmatic HD. Pt characteristics: median age-30; M-54%/F-46%; stage IA-52%, IB-2%, IIA-37%, IIB-8%; histology LP-21%, NS-51%, MC-23%, other 5%; median ESR 18. CT abdomen and LAG were performed in 61% and 60% respectively. No pt had prior staging laparotomy. No pt received infradiaphragmatic RT. Central axis dose was 32 Gy-36 Gy. Univariate analysis was performed for prognostic factors for progression-free (PFS) and overall survival(OS). Outcome was assessed in favourable subsets as defined by: EORTC (v. favourable: CSIA, LP or NS histology, age < 40, female, no bulk, ESR < 50; favourable: CSI-II, age < 50, < 4 sites, no bulky mediastinal mass, ESR < 50 with no B symptoms or ESR < 30 with B symptoms); Princess Margaret Hospital (PMH) (IA-IIA, LP or NS histology, ESR < 40, age < 50, no large mediastinal mass, no E lesion). Results: 261 pts completed RT, with 5% requiring treatment interruption for toxicity. Significant factors (P<0.05) for PFS were stage, performance status, histology, B symptoms, number of sites, ESR and bulk. Significant factors (P<0.05) for OS were age, performance status, histology and B symptoms. (The results of a multivariate analysis will be presented.) Results in our study population using published prognostic criteria (in %): Thirty-six percent progressed following RT: 8% in-field; 24% out of field only (including 10% in the paraaortic/splenic region alone); 4% marginal; Fifty-seven percent of relapsed pts remain progression free after subsequent salvage treatment. Two cases of acute leukaemia, 8 cases of non-Hodgkin's lymphoma and 14 (non-skin) carcinomas occurred, of which 11 were in-field. Seventy pts have died. The cause was: HD 41%; other malignancy 20%; cardiovascular 17%; other 15

  13. Sham surgery versus labral repair or biceps tenodesis for type II SLAP lesions of the shoulder: a three-armed randomised clinical trial.

    Science.gov (United States)

    Schrøder, Cecilie Piene; Skare, Øystein; Reikerås, Olav; Mowinckel, Petter; Brox, Jens Ivar

    2017-12-01

    Labral repair and biceps tenodesis are routine operations for superior labrum anterior posterior (SLAP) lesion of the shoulder, but evidence of their efficacy is lacking. We evaluated the effect of labral repair, biceps tenodesis and sham surgery on SLAP lesions. A double-blind, sham-controlled trial was conducted with 118 surgical candidates (mean age 40 years), with patient history, clinical symptoms and MRI arthrography indicating an isolated type II SLAP lesion. Patients were randomly assigned to either labral repair (n=40), biceps tenodesis (n=39) or sham surgery (n=39) if arthroscopy revealed an isolated SLAP II lesion. Primary outcomes at 6 and 24 months were clinical Rowe score ranging from 0 to 100 (best possible) and Western Ontario Shoulder Instability Index (WOSI) ranging from 0 (best possible) to 2100. Secondary outcomes were Oxford Instability Shoulder Score, change in main symptoms, EuroQol (EQ-5D and EQ-VAS), patient satisfaction and complications. There were no significant between-group differences at any follow-up in any outcome. Between-group differences in Rowe scores at 2 years were: biceps tenodesis versus labral repair: 1.0 (95% CI -5.4 to 7.4), p=0.76; biceps tenodesis versus sham surgery: 1.6 (95% CI -5.0 to 8.1), p=0.64; and labral repair versus sham surgery: 0.6 (95% CI -5.9 to 7.0), p=0.86. Similar results-no differences between groups-were found for WOSI scores. Postoperative stiffness occurred in five patients after labral repair and in four patients after tenodesis. Neither labral repair nor biceps tenodesis had any significant clinical benefit over sham surgery for patients with SLAP II lesions in the population studied. ClinicalTrials.gov identifier: NCT00586742. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Management of Major Bleeding in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants Compared With Warfarin in Clinical Practice (from Phase II of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF II]).

    Science.gov (United States)

    Steinberg, Benjamin A; Simon, DaJuanicia N; Thomas, Laine; Ansell, Jack; Fonarow, Gregg C; Gersh, Bernard J; Kowey, Peter R; Mahaffey, Kenneth W; Peterson, Eric D; Piccini, Jonathan P

    2017-05-15

    Non-vitamin K antagonist oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the management of bleeding in contemporary, clinical use of NOACs. We aimed to assess the frequency, management, and outcomes of major bleeding in the setting of community use of NOACs. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry, we analyzed rates of International Society on Thrombosis and Haemostasis major bleeding and subsequent outcomes in patients treated with NOACs versus warfarin. Outcomes of interest included acute and chronic bleeding management, recurrent bleeding, thromboembolic events, and death. In total, 344 patients with atrial fibrillation experienced major bleeding events over a median follow-up of 360 days follow-up: n = 273 on NOAC (3.3 per 100 patient-years) and n = 71 on warfarin (3.5 per 100 patient-years). Intracranial bleeding was uncommon but similar (0.34 per 100 patient-years for NOAC vs 0.44 for warfarin, p = 0.5), as was gastrointestinal bleeding (1.8 for NOAC vs 1.3 for warfarin, p = 0.1). Blood products and correction agents were less commonly used in NOAC patients with major bleeds compared with warfarin-treated patients (53% vs 76%, p = 0.0004 for blood products; 0% vs 1.5% for recombinant factor; p = 0.0499); no patients received pharmacologic hemostatic agents (aminocaproic acid, tranexamic acid, desmopressin, aprotinin). Within 30 days, 23 NOAC-treated patients (8.4%) died versus 5 (7.0%) on warfarin (p = 0.7). At follow-up, 126 NOAC-treated (46%) and 29 warfarin-treated patients (41%) were not receiving any anticoagulation. In conclusion, rates of major bleeding are similar in warfarin and NOAC-treated patients in clinical practice. However, NOAC-related bleeds require less blood product administration and rarely require factor replacement. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights

  15. Clinical librarianship in the UK: temporary trend or permanent profession? Part II: present challenges and future opportunities.

    Science.gov (United States)

    Harrison, Janet; Sargeant, Sally J E

    2004-12-01

    This article is the second part of a two-part series reporting a study of the role of the Clinical Librarian (CL) in the UK. A qualitative method of semi-structured interviews was used to explore in-depth the role of the CL. The interviews provided a rich source of data and give insight into this new and emerging role as practised in the National Health Service (NHS). Similarities and differences are examined between the CL population and reported within themes, specifically: personal qualities and skills required, training for the CLs, marketing the CL service, working in the clinical environment, monitoring and evaluation and the acceptance of the CL in the NHS. A common understanding of the skills and knowledge required to undertake the CL role was shared by the respondents. However, practice differed as this was often dictated by local circumstances. The study confirmed the need for the CLs to work with clinical colleagues in the clinical setting to enhance patient care. The importance of using best evidence to support patient care is a message that is slowly becoming the norm in the NHS and the CL role in this practice is demonstrated by this study.

  16. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Directory of Open Access Journals (Sweden)

    L John Hoffer

    Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type

  17. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Science.gov (United States)

    Hoffer, L John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H

    2015-01-01

    Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy

  18. Immunological effects of hypomethylating agents.

    Science.gov (United States)

    Lindblad, Katherine E; Goswami, Meghali; Hourigan, Christopher S; Oetjen, Karolyn A

    2017-08-01

    Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets. We summarized the effects of hypomethylating agents on the frequency and function of natural killer cells, T cells, and dendritic cells. In particular, we highlight the effects of hypomethylating agents on expression of immune checkpoint inhibitors, leukemia-associated antigens, and endogenous retroviral elements. Expert commentary: In vitro and ex vivo studies indicate mixed effects on the function of natural killer, dendritic cells and T cells following treatment with hypomethylating agents. Clinical correlates of immune function have suggested that hypomethylating agents have immunomodulatory functions with the potential to synergize with immune checkpoint therapy for the treatment of hematologic malignancy, and has become an active area of clinical research.

  19. Looking for the new preparations for antibacterial therapy. II. Clinical trials; new beta-lactam antibiotics and beta-lactamase inhibitors.

    Science.gov (United States)

    Karpiuk, Izabela; Tyski, Stefan

    2013-01-01

    To obtain a status of a medicinal product, a compound possessing potential antimicrobial activity and displaying no cytotoxicity, must undergo three phases of clinical trials to prove its therapeutic efficacy, safety and quality. Properties of the compound should be based on the results of studies meeting specific criteria. Studies should be: randomized, double-blind, involving sufficient number of volunteers, concerning the infections localized in strictly defined area and caused by identified microorganisms. After the medicinal product is authorized to be on the market, clinical trials of the fourth phase are carried out to detect adverse effects, overdose symptoms, interactions of the new drug with other medicinal products and to establish characteristic of activity among groups such as children, elderly, women in pregnancy and patients suffering from other diseases, but only if the benefits of receiving treatment outweigh the risks. This article is a second part of the series associated with searching for new antibacterial agents and it relates to performance of clinical trials and the new compounds belonging to the class of beta-lactams. Among the 9 presented compounds, candidates to become medicinal products, two belong to the cephalosporins (CXA-101, S-649266), one to carbapenems (razupenem), three to monobactams (BAL30072, BAL30376, MC-1) and three to beta-lactamase inhibitors (NXL-104, MK-7655, ME1071).

  20. Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

    Science.gov (United States)

    Vogel, Moritz; Bayi, Pierre F; Ruf, Marie-Thérèse; Bratschi, Martin W; Bolz, Miriam; Um Boock, Alphonse; Zwahlen, Marcel; Pluschke, Gerd; Junghanss, Thomas

    2016-02-01

    Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. ISRCT 72102977. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  1. Appropriate customization of radiation therapy for stage II and III rectal cancer: Executive summary of an ASTRO Clinical Practice Statement using the RAND/UCLA Appropriateness Method.

    Science.gov (United States)

    Goodman, Karyn A; Patton, Caroline E; Fisher, George A; Hoffe, Sarah E; Haddock, Michael G; Parikh, Parag J; Kim, John; Baxter, Nancy N; Czito, Brian G; Hong, Theodore S; Herman, Joseph M; Crane, Christopher H; Hoffman, Karen E

    2016-01-01

    To summarize results of a Clinical Practice Statement on radiation therapy for stage II-III rectal cancer, which addressed appropriate customization of (neo)adjuvant radiation therapy and use of non-surgical therapy for patients who are inoperable or refuse abdominoperineal resection. The RAND/University of California, Los Angeles, Appropriateness Method was applied to combine current evidence with multidisciplinary expert opinion. A systematic literature review was conducted and used by the expert panel to rate appropriateness of radiation therapy options for different clinical scenarios. Treatments were categorized by median rating as Appropriate, May Be Appropriate, or Rarely Appropriate. In the neoadjuvant setting, chemoradiation was rated Appropriate and the ratings indicated short-course radiation therapy, chemotherapy alone, and no neoadjuvant therapy are potential options in selected patients. However, neoadjuvant endorectal brachytherapy was rated Rarely Appropriate. For adjuvant therapy, chemoradiation (plus ≥4 months of chemotherapy) was rated Appropriate and chemotherapy alone May Be Appropriate for most scenarios. For medically inoperable patients, definitive external beam radiation therapy and chemotherapy alone were rated May Be Appropriate, whereas endorectal brachytherapy and chemoradiation plus endorectal brachytherapy were possible approaches for some scenarios. The last option, definitive chemoradiation, was rated Appropriate to May Be Appropriate based on performance status. Finally, for patients with low-lying tumors refusing abdominoperineal resection, definitive chemoradiation alone, chemoradiation plus endorectal brachytherapy, and chemoradiation plus external beam radiation therapy were all rated Appropriate. This Clinical Practice Statement demonstrated the central role of radiation therapy in stage II-III rectal cancer management and evaluated ways to better individualize its use in the neoadjuvant, adjuvant, and definitive settings

  2. Four-year clinical evaluation of Class II nano-hybrid resin composite restorations bonded with a one-step self-etch and a two-step etch-and-rinse adhesive

    DEFF Research Database (Denmark)

    van Dijken, Jan W V; Pallesen, Ulla

    2011-01-01

    The objective of this prospective clinical trial was to evaluate the 4-year clinical performance of an ormocer-based nano-hybrid resin composite (Ceram X; Dentsply/DeTrey) in Class II restorations placed with a one-step self-etch (Xeno III; Dentsply/DeTrey) and two-step etch-and-rinse adhesive (I...

  3. Clinical and radiographic evaluation of Bio-Gen with biocollagen compared with Bio-Gen with connective tissue in the treatment of class II furcation defects: a randomized clinical trial

    Science.gov (United States)

    JENABIAN, Niloofar; HAGHANIFAR, Sina; MABOUDI, Avideh; BIJANI, Ali

    2013-01-01

    Objective Treatment of furcation defects are thought to be challenging. The purpose of this study was to evaluate the clinical and radiographic parameters of Bio-Gen with Biocollagen compared with Bio-Gen with connective tissue in the treatment of Class II furcation defects. Material and Methods In this clinical trial, 24 patients with Class II furcation defect on a buccal or lingual mandibular molar were recruited. After oral hygiene instruction, scaling and root planing and achievement of acceptable plaque control, the patients were randomly chosen to receive either connective tissue and Bio-Gen (case group) or Biocollagen and Bio-Gen (control group). The following parameters were re