WorldWideScience

Sample records for clinical imaging drugs

  1. Medical imaging in new drug clinical development.

    Science.gov (United States)

    Wang, Yi-Xiang; Deng, Min

    2010-12-01

    Medical imaging can help answer key questions that arise during the drug development process. The role of medical imaging in new drug clinical trials includes identification of likely responders; detection and diagnosis of lesions and evaluation of their severity; and therapy monitoring and follow-up. Nuclear imaging techniques such as PET can be used to monitor drug pharmacokinetics and distribution and study specific molecular endpoints. In assessing drug efficacy, imaging biomarkers and imaging surrogate endpoints can be more objective and faster to measure than clinical outcomes, and allow small group sizes, quick results and good statistical power. Imaging also has important role in drug safety monitoring, particularly when there is no other suitable biomarkers available. Despite the long history of radiological sciences, its application to the drug development process is relatively recent. This review highlights the processes, opportunities, and challenges of medical imaging in new drug development.

  2. Image-guided drug delivery: preclinical applications and clinical translation

    NARCIS (Netherlands)

    Ojha, Tarun; Rizzo, Larissa; Storm, Gert; Kiessling, Fabian; Lammers, Twan

    2015-01-01

    Image-guided drug delivery refers to the combination of drug targeting and imaging. Preclinically, image-guided drug delivery can be used for several different purposes, including for monitoring biodistribution, target site accumulation, off-target localization, drug release and drug efficacy. Clini

  3. Image-guided drug delivery : Preclinical applications and clinical translation

    NARCIS (Netherlands)

    Ojha, Tarun; Rizzo, Larissa; Storm, G; Kiessling, Fabian; Lammers, Twan

    2015-01-01

    Image-guided drug delivery refers to the combination of drug targeting and imaging. Preclinically, image-guided drug delivery can be used for several different purposes, including for monitoring biodistribution, target site accumulation, off-target localization, drug release and drug efficacy. Clini

  4. Imaging in drug discovery and early clinical trials

    National Research Council Canada - National Science Library

    Rudin, M

    2005-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Imaging modalities: principles and information content Tobias Schaeffter ... 15 Magnetic resonance and fluorescence based molecular imaging technologies David...

  5. Childhood extracranial neoplasms: the role of imaging in drug development and clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Fowkes, Lucy A.; Koh, Dow-Mu; MacVicar, David [Royal Marsden NHS Foundation Trust, Department of Radiology, Sutton, Surrey (United Kingdom); Collins, David J.; Jerome, Neil P. [Institute of Cancer Research, Cancer Research UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Chua, Sue C. [Royal Marsden NHS Foundation Trust, Nuclear Medicine and PET Department, Sutton, Surrey (United Kingdom); Pearson, Andrew D.J. [Royal Marsden NHS Foundation Trust, Paediatric Drug Development Unit, Children and Young People' s Unit, Sutton, Surrey (United Kingdom)

    2015-10-15

    Cancer is the leading cause of death in children older than 1 year of age and new drugs are necessary to improve outcomes. Imaging is crucial to the drug development process and assessment of therapeutic response. In adults, tumours are often assessed with CT using size criteria. Unfortunately, techniques established in adults are not necessarily applicable in children due to differing pathophysiology, ability to cooperate and increased susceptibility to ionising radiation. MRI, in particular quantitative MRI, has to date not been fully utilised in children with extracranial neoplasms. The specific challenges of imaging in children, the potential for functional imaging techniques to inform upon and their inclusion in clinical trials are discussed. (orig.)

  6. Drugs (image)

    Science.gov (United States)

    ... Drugs for fever, cough, stuffy nose, runny nose, diarrhea, and allergies are common drugs which are especially helpful during times of illness. All medications should be kept out of the reach of children.

  7. Use of functional imaging across clinical phases in CNS drug development

    OpenAIRE

    Borsook, D.; Becerra, L; Fava, M

    2013-01-01

    The use of novel brain biomarkers using nuclear magnetic resonance imaging holds potential of making central nervous system (CNS) drug development more efficient. By evaluating changes in brain function in the disease state or drug effects on brain function, the technology opens up the possibility of obtaining objective data on drug effects in the living awake brain. By providing objective data, imaging may improve the probability of success of identifying useful drugs to treat CNS diseases a...

  8. Imaging of illicit drug use

    Energy Technology Data Exchange (ETDEWEB)

    Venkatanarasimha, N., E-mail: nandashettykv@yahoo.co [Department of Radiology, Derriford Hospital, Plymouth (United Kingdom); Rock, B.; Riordan, R.D.; Roobottom, C.A.; Adams, W.M. [Department of Radiology, Derriford Hospital, Plymouth (United Kingdom)

    2010-12-15

    Illicit drug abuse is a continuing menace of epidemic proportions associated with serious medical and social problems. Drug abuse can have a wide variety of presentations some of which can be life-threatening. The clinical diagnosis can be challenging as the history is usually limited or absent. Radiologists need to be familiar with varied imaging presentations and the related complications of illicit drug abuse to ensure correct diagnosis and appropriate timely treatment. This review will illustrate the imaging spectrum of illicit drug abuse involving several organ systems and also discuss the pathophysiological consequences of drug abuse.

  9. Clinical features and {sup 123}I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Corrales, Francisco J.; Escobar-Delgado, Teresa [Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia, Instituto de Biomedicina de Sevilla, Seville (Spain); Sanz-Viedma, Salome [Hospital Universitario Virgen del Rocio, Unidad Diagnostica de Medicina Nuclear, Seville (Spain); Garcia-Solis, David [Hospital Universitario Virgen del Rocio, Unidad Diagnostica de Medicina Nuclear, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Mir, Pablo [Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia, Instituto de Biomedicina de Sevilla, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Hospital Universitario Virgen del Rocio, Unidad de Trastornos del Movimiento. Servicio de Neurologia, Seville (Spain)

    2010-03-15

    To determine clinical predictors and accuracy of {sup 123}I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD). Several clinical features and {sup 123}I-FP-CIT SPECT images in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs (PDu) and 22 patients with PD without a previous history of antidopaminergic treatment (PDc) were retrospectively evaluated. DIP and PD shared all clinical features except symmetry of parkinsonian signs which was more frequently observed in patients with DIP (46.9%) than in patients with PDu (16.0%, p<0.05) or PDc (4.5%, p<0.01). Qualitatively {sup 123}I-FP-CIT SPECT images were normal in 29 patients with DIP (90.6%) and abnormal in all patients with PD, and this imaging technique showed high levels of accuracy. DIP and PD are difficult to differentiate based on clinical signs. The precision of clinical diagnosis could be reliably enhanced by {sup 123}I-FP-CIT SPECT imaging. (orig.)

  10. Clinical Application of Insect Drugs

    Institute of Scientific and Technical Information of China (English)

    钟洪; 赵洁

    2003-01-01

    @@ Chinese insect drugs are drastic in nature, capable ofclearing channels and collaterals to promote a freeflow of qi and blood, and effective in someintractable and obstinate diseases due to long-termstagnation of phlegm and blood, which are hard to betreated by ordinary Chinese drugs. In clinic, properuse of insect drugs can often help raise thetherapeutic effects. Some commonly used pairs ofinsect drugs are introduced in the following.

  11. Vitiligo, drug induced (image)

    Science.gov (United States)

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat and depigmented, but maintains the ...

  12. Optimizing clinical drug product performance

    DEFF Research Database (Denmark)

    Dickinson, Paul A.; Kesisoglou, Filippos; Flanagan, Talia

    2016-01-01

    The aim of Biopharmaceutics Risk Assessment Roadmap (BioRAM) and the BioRAM Scoring Grid is to facilitate optimization of clinical performance of drug products. BioRAM strategy relies on therapy-driven drug delivery and follows an integrated systems approach for formulating and addressing critical...... questions and decision-making (J Pharm Sci. 2014,103(11): 3777-97). In BioRAM, risk is defined as not achieving the intended in vivo drug product performance, and success is assessed by time to decision-making and action. Emphasis on time to decision-making and time to action highlights the value of well...

  13. Cancer nanomedicine: from drug delivery to imaging.

    Science.gov (United States)

    Chow, Edward Kai-Hua; Ho, Dean

    2013-12-18

    Nanotechnology-based chemotherapeutics and imaging agents represent a new era of "cancer nanomedicine" working to deliver versatile payloads with favorable pharmacokinetics and capitalize on molecular and cellular targeting for enhanced specificity, efficacy, and safety. Despite the versatility of many nanomedicine-based platforms, translating new drug or imaging agents to the clinic is costly and often hampered by regulatory hurdles. Therefore, translating cancer nanomedicine may largely be application-defined, where materials are adapted only toward specific indications where their properties confer unique advantages. This strategy may also realize therapies that can optimize clinical impact through combinatorial nanomedicine. In this review, we discuss how particular materials lend themselves to specific applications, the progress to date in clinical translation of nanomedicine, and promising approaches that may catalyze clinical acceptance of nano.

  14. Differential X-ray phase contrast tomography of Alzheimer plaques in mouse models: perspectives for drug development and clinical imaging techniques

    Science.gov (United States)

    Pinzer, B. R.; Cacquevel, M.; Modregger, P.; Thuering, T.; Stampanoni, M.

    2013-05-01

    Alzheimer's disease (AD) is a looming threat on an ever-ageing population, with devastating effects on the human intellect. A particular characteristic lesion — the extracellular amyloid plaque — accumulates in the brain of AD patients during the course of the disease, and could therefore be used to monitor the progression of the disease, years before the first neurological symptoms appear. In addition, strategies for drug intervention in AD are often based on amyloid reduction, since amyloid plaques are hypothesized to be involved in a chain of reactions leading to the death of neurons. Developments in both fields would benefit from a microscopic technique that is capable of single plaque imaging, ideally in 3D. While such a non-destructive, single-plaque imaging technique does not yet exist for humans, it has been recently shown that synchrotron based differential X-ray phase contrast imaging can be used to visualize individual plaques at μm resolution in mouse models of AD ex-vivo. This method, which relies on a grating interferometer to measure refraction angles induced by fluctuations in the refractive index, yields a precise three-dimensional distribution of single plaques. These data could not only improve the understanding of the evolution of AD or the effectiveness of drugs, but could also help to improve reliable markers for current and future non-invasive clinical imaging techniques. In particular, validation of PET markers with small animal models could be rapidly carried out by co-registration of PET and DPC signals.

  15. Identification of clinically significant drug-drug interactions in cardiac ...

    African Journals Online (AJOL)

    Purpose: To identify clinically significant potential drug-drug interactions in cardiac intensive care units of two tertiary care ... Keywords: Pharmacy service, Drug interactions, Critical/intensive care, Adverse outcomes. Tropical .... Standard error.

  16. Progress with Drug-Eluting Stent Technology from Early to New Generation Devices : A comprehensive clinical and intravascular imaging evaluation

    NARCIS (Netherlands)

    L. Räber (Lorenz)

    2014-01-01

    markdownabstract__Abstract__ Percutaneous coronary interventions (PCI) are among the most frequently performed medical interventions worldwide reflecting the large burden of coronary atherosclerosis. Bare metal stents were associated with a high rate of repeat revascularization due to clinical

  17. Imaging of anticancer drug action in single cells.

    Science.gov (United States)

    Miller, Miles A; Weissleder, Ralph

    2017-06-23

    Imaging is widely used in anticancer drug development, typically for whole-body tracking of labelled drugs to different organs or to assess drug efficacy through volumetric measurements. However, increasing attention has been drawn to pharmacology at the single-cell level. Diverse cell types, including cancer-associated immune cells, physicochemical features of the tumour microenvironment and heterogeneous cell behaviour all affect drug delivery, response and resistance. This Review summarizes developments in the imaging of in vivo anticancer drug action, with a focus on microscopy approaches at the single-cell level and translational lessons for the clinic.

  18. CEST theranostics: label-free MR imaging of anticancer drugs

    Science.gov (United States)

    Xu, Jiadi; Yadav, Nirbhay N.; Chan, Kannie W. Y.; Luo, Liangping; McMahon, Michael T.; Vogelstein, Bert; van Zijl, Peter C.M.; Zhou, Shibin; Liu, Guanshu

    2016-01-01

    Image-guided drug delivery is of great clinical interest. Here, we explored a direct way, namely CEST theranostics, to detect diamagnetic anticancer drugs simply through their inherent Chemical Exchange Saturation Transfer (CEST) MRI signal, and demonstrated its application in image-guided drug delivery of nanoparticulate chemotherapeutics. We first screened 22 chemotherapeutic agents and characterized the CEST properties of representative agents and natural analogs in three major categories, i.e., pyrimidine analogs, purine analogs, and antifolates, with respect to chemical structures. Utilizing the inherent CEST MRI signal of gemcitabine, a widely used anticancer drug, the tumor uptake of the i.v.-injected, drug-loaded liposomes was successfully detected in CT26 mouse tumors. Such label-free CEST MRI theranostics provides a new imaging means, potentially with an immediate clinical impact, to monitor the drug delivery in cancer. PMID:26837220

  19. Clinically relevant drug interactions with anti-Alzheimer's drugs.

    Science.gov (United States)

    Caraci, Filippo; Sultana, Janet; Drago, Filippo; Spina, Edoardo

    2017-03-03

    The aging world population had led to an increase in the prevalence of Alzheimer's disease (AD). The drugs used to slow down the onset of AD, galantamine, donepezil, rivastigmine and memantine, are generally well-tolerated. However, drug interactions between these drugs and other drugs are an important aspect of patient safety that should be borne in mind, particularly given the high burden of polypharmacy in the elderly. The aim of this review is to provide an updated review of clinically significant drug-drug interactions concerning drugs approved for AD. PubMed was searched for relevant keywords. No time limit was imposed but only articles in English published in peer-reviewed journals were selected. Relevant literature was also identified from the references of identified articles. Further information was obtained from drug summary of product characteristics. The major pharmacokinetic interactions identified concerned fluoxetine, paroxetine and ketoconazole when used with galantamine or donepezil. On the other hand, the major potential pharmacodynamic interactions concerned anti-dementia drugs and general anesthesia agents, anti-cholinergic drugs, conventional antipsychotics and bradycardia-inducing drugs. In clinical practice memantine shows a lower potential for pharmacodynamic drug-drug interactions (DDIs) compared to other drug classes. In conclusion, the concomitant use of anti-dementia drugs with other drugs can have variable clinical effects, making appropriate prescribing of these drugs very challenging. A simple and coherent way of presenting evidence on complex drug interaction information from heterogenous sources to clinicians is needed in order for the voluminous data available to have an impact on clinical practice.

  20. Clinical Applications of Simultaneous PET/MR Imaging Using (R)-[11C]-Verapamil with Cyclosporin A: Preliminary Results on a Surrogate Marker of Drug-Resistant Epilepsy.

    Science.gov (United States)

    Shin, J-W; Chu, K; Shin, S A; Jung, K-H; Lee, S-T; Lee, Y-S; Moon, J; Lee, D Y; Lee, J S; Lee, D S; Lee, S K

    2016-04-01

    The development of resistance to antiepileptic drugs is explained well by the transporter hypothesis, which suggests that drug resistance is caused by inadequate penetration of drugs into the brain barrier as a result of increased levels of efflux transporter such as p-glycoprotein. To evaluate the brain expression of p-glycoprotein in patients with drug-resistant epilepsy, including neocortical epilepsy, we developed a noninvsive quantitative analysis including asymmetry indices based on (R)-[(11)C]-verapamil PET/MR imaging with cyclosporin A, a p-glycoprotein inhibitor. Six patients with drug-resistant epilepsy, 5 patients with drug-sensitive epilepsy, and 8 healthy controls underwent dynamic (R)-[(11)C]-verapamil PET/MR imaging with an intravenous infusion of cyclosporin A. Asymmetry indices [(Right Region - Left Region)/(Right Region + Left Region) × 200%] of the standard uptake values in each of the paired lobes were calculated. All patients with drug-resistant epilepsy had significantly different asymmetry from the healthy controls, whereas all patients with drug-sensitive epilepsy had asymmetry similar to that in healthy controls. In the temporal lobe, the asymmetry indices of patients with left temporal lobe drug-resistant epilepsy were more positive than those of healthy controls (healthy controls: 4.0413 ± 1.7452; patients: 7.2184 ± 1.8237; P = .048), and those of patients with right temporal drug-resistant epilepsy were more negative (patients: -1.6496 ± 3.4136; P = .044). In addition, specific regions that had significant asymmetry were different between the lateral and medial temporal lobe epilepsy groups. In the frontal lobe, the asymmetry index of patients with right frontal lobe drug-resistant epilepsy was more negative than that in healthy controls. We confirmed that statistical parametric mapping analysis by using asymmetry indices of (R)-[(11)C]-verapamil PET/MR imaging with cyclosporin A could be used as a surrogate marker for drug

  1. [Situation analysis for drug clinical trial institutions].

    Science.gov (United States)

    Chen, Yin-Ying; Wu, Ping; Wang, Jie

    2014-08-01

    Drug clinical trial is an important link in the chain of new drug research and development. The results of drug discovery and development directly depend on the extent of standardization of clinical trials. Therefore, improving the quality of drug clinical trials is of great importance, and drug clinical trial institutions play a crucial role in the quality management of drug clinical trials. After years of development, the overall level of drug clinical trials has advanced rapidly in China, and a large number of clinical trials of traditional Chinese medicine have also been carried out. However, there is still a big gap between our country and developed countries. Therefore, for the construction and management of Chinese drug clinical trial institutions, there is still a long way to go. This study aims to analyze the current development of drug clinical trial institutions in China and explore the existing problems from three aspects, including current situations of institutional organization and management, regional and professional distributions, and quality control. And some suggestions are put forward finally, including support of traditional Chinese medicine, introduction of drug-risk management system, and construction of information management.

  2. PET IMAGING STUDIES IN DRUG ABUSE RESEARCH.

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.; Volkow, N.D.; Ding, Y.S.; Logan, J.; Wang, G.J.

    2001-01-29

    There is overwhelming evidence that addiction is a disease of the brain (Leshner, 1997). Yet public perception that addiction is a reflection of moral weakness or a lack of willpower persists. The insidious consequence of this perception is that we lose sight of the fact that there are enormous medical consequences of addiction including the fact that a large fraction of the total deaths from cancer and heart disease are caused by smoking addiction. Ironically the medical school that educates physicians in addiction medicine and the cancer hospital that has a smoking cessation clinic are vanishingly rare and efforts at harm reduction are frequently met with a public indignation. Meanwhile the number of people addicted to substances is enormous and increasing particularly the addictions to cigarettes and alcohol. It is particularly tragic that addiction usually begins in adolescence and becomes a chronic relapsing problem and there are basically no completely effective treatments. Clearly we need to understand how drugs of abuse affect the brain and we need to be creative in using this information to develop effective treatments. Imaging technologies have played a major role in the conceptualization of addiction as a disease of the brain (Fowler et al., 1998a; Fowler et al., 1999a). New knowledge has been driven by advances in radiotracer design and chemistry and positron emission tomography (PET) instrumentation and the integration of these scientific tools with the tools of biochemistry, pharmacology and medicine. This topic cuts across the medical specialties of neurology, psychiatry, cancer and heart disease because of the high medical, social and economic toll that drugs of abuse, including and especially the legal drugs, cigarettes and alcohol, take on society. In this chapter we will begin by highlighting the important role that chemistry has played in making it possible to quantitatively image the movement of drugs as well as their effects on the human brain

  3. Image Guided Biodistribution of Drugs and Drug Delivery

    OpenAIRE

    Ding, Hong; Wu, Fang

    2012-01-01

    Image guided technique is playing an increasingly important role in the investigation of the biodistribution and pharmacokinetics of drugs or drug delivery systems. The application of these new materials and techniques with combined properties of diagnosis and therapy can benefit the development of targeted drug delivery system and modern personalized medicine This special issue provides an up-to-date collection of original research articles and review on the development of novel targeted dru...

  4. Clinical imaging of the pancreas

    Energy Technology Data Exchange (ETDEWEB)

    May, G.; Gardiner, R.

    1987-01-01

    Featuring more than 300 high-quality radiographs and scan images, clinical imaging of the pancreas systematically reviews all appropriate imaging modalities for diagnosing and evaluating a variety of commonly encountered pancreatic disorders. After presenting a succinct overview of pancreatic embryology, anatomy, and physiology, the authors establish the clinical indications-including postoperative patient evaluation-for radiologic examination of the pancreas. The diagnostic capabilities and limitations of currently available imaging techniques for the pancreas are thoroughly assessed, with carefully selected illustrations depicting the types of images and data obtained using these different techniques. The review of acute and chronic pancreatitis considers the clinical features and possible complications of their variant forms and offers guidance in selecting appropriate imaging studies.

  5. Pharmacometrics in early clinical drug development

    NARCIS (Netherlands)

    Keizer, R.J.

    2010-01-01

    Pharmacometrics, the science of quantitative clinical pharmacology, has been recognized as one of the main research fields able to improve efficiency in drug development, and to reduce attrition rates on the route from drug discovery to approval. This field of drug research, which builds heavily on

  6. Pharmacometrics in early clinical drug development

    NARCIS (Netherlands)

    Keizer, R.J.

    2010-01-01

    Pharmacometrics, the science of quantitative clinical pharmacology, has been recognized as one of the main research fields able to improve efficiency in drug development, and to reduce attrition rates on the route from drug discovery to approval. This field of drug research, which builds heavily on

  7. Clinical photoacoustic imaging of cancer

    Science.gov (United States)

    2016-01-01

    Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented. PMID:27669961

  8. Clinical photoacoustic imaging of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Valluru, Keerthi S.; Willmann, Juergen K. [Dept. of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford (United States)

    2016-08-15

    Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented.

  9. Clinical photoacoustic imaging of cancer

    Directory of Open Access Journals (Sweden)

    Keerthi S. Valluru

    2016-10-01

    Full Text Available Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented.

  10. Clinical photoacoustic imaging of cancer.

    Science.gov (United States)

    Valluru, Keerthi S; Willmann, Juergen K

    2016-10-01

    Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented.

  11. The Clinical Neurobiology of Drug Craving

    OpenAIRE

    Sinha, Rajita

    2013-01-01

    Drug craving has re-emerged as a relevant and important construct in the pathophysiology of addiction with its inclusion in DSM-V as a key clinical symptom of addictive disorders. This renewed focus has been due in part to the recent neurobiological evidence on craving- related neural activation and clinical evidence supporting its association with drug use, relapse and recovery processes. This review covers the neurobiology of drug craving and relapse risk with a primary focus on cocaine add...

  12. Chemical Imaging of Platinum-Based Drugs and their Metabolites.

    Science.gov (United States)

    Liu, Xin; Hummon, Amanda B

    2016-12-05

    Platinum-based drugs (cisplatin, carboplatin, and oxaliplatin) are widely used therapeutic agents for cancer treatment. Even though the platinum (Pt)-drugs are routinely used clinically, a clear picture of their distribution within tumor tissues is lacking. The current methods to image the distribution of Pt drugs are limited and do not enable the discrimination of the drug from its metabolites. In this manuscript, we demonstrate a methodology that enables chemical imaging of a Pt drug and its metabolites simultaneously and specifically. Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry Imaging (MSI) is combined with an on-tissue chemical derivatization using diethyldithiocarbamate (DDTC). DDTC abstracts the Pt atom to generate ionizable complexes that can be imaged by MALDI MSI. We demonstrate that Pt drugs and their metabolites can be specifically imaged. This approach was successfully applied to map the penetration and metabolism of oxaliplatin in hyperthermic intraperitoneal chemotherapy (HIPEC)-like treated 3D colorectal tumor mimics. The distribution of cisplatin and carboplatin was mapped in additional 3D tumor mimics. We demonstrate that the approach can also be used to image the distribution of copper ions in cells. This method has the potential to be used to evaluate the penetration and distribution of a wide range of compounds.

  13. Nanotech approaches to drug delivery and imaging.

    Science.gov (United States)

    Sahoo, Sanjeeb K; Labhasetwar, Vinod

    2003-12-15

    Nanotechnology, a multidisciplinary scientific undertaking, involves creation and utilization of materials, devices or systems on the nanometer scale. The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to create innovations and play a critical role in various biomedical applications, not only in drug delivery, but also in molecular imaging, biomarkers and biosensors. Target-specific drug therapy and methods for early diagnosis of pathologies are the priority research areas where nanotechnology would play a vital role. This review considers different nanotechnology-based drug delivery and imaging approaches, and their economic impact on pharmaceutical and biomedical industries.

  14. Microbubbles for Molecular Imaging and Drug Delivery

    NARCIS (Netherlands)

    I. Skachkov (Ilya)

    2016-01-01

    markdownabstractIn my thesis, microbubbles (MBs) for ultrasound (US) imaging, ultrasound molecular imaging, and drug delivery were studied. Microbubbles are gas-encapsulated lipid or polymer shell coated micro-particles, widely used as ultrasound contrast agents (UCA). MBs oscillate in response to t

  15. Clinically relevant drug interactions between anticancer drugs and psychotropic agents.

    Science.gov (United States)

    Yap, K Y-L; Tay, W L; Chui, W K; Chan, A

    2011-01-01

    Drug interactions are commonly seen in the treatment of cancer patients. Psychotropics are often indicated for these patients since they may also suffer from pre-existing psychological disorders or experience insomnia and anxiety associated with cancer therapy. Thus, the risk of anticancer drug (ACD)-psychotropic drug-drug interactions (DDIs) is high. Drug interactions were compiled from the British National Formulary (53rd edn), Lexi-Comp's Drug Information Handbook (15th edn), Micromedex (v5.1), Hansten & Horn's Drug Interactions (2000) and Drug Interaction Facts (2008 edn). Product information of the individual drugs, as well as documented literature on ACD-psychotropic interactions from PubMed and other databases was also incorporated. This paper identifies clinically important ACD-psychotropic DDIs that are frequently observed. Pharmacokinetic DDIs were observed for tyrosine kinase inhibitors, corticosteroids and antimicrotubule agents due to their inhibitory or inductive effects on cytochrome P450 isoenzymes. Pharmacodynamic DDIs were identified for thalidomide with central nervous system depressants, procarbazine with antidepressants, myelosuppressive ACDs with clozapine and anthracyclines with QT-prolonging psychotropics. Clinicians should be vigilant when psychotropics are prescribed concurrently with ACDs. Close monitoring of plasma drug levels should be carried out to avoid toxicity in the patient, as well as to ensure adequate chemotherapeutic and psychotropic coverage.

  16. Clinical efficacy of nebulized drugs

    DEFF Research Database (Denmark)

    Bisgaard, Hans

    1994-01-01

    There is a mandatory need for effortless drug administration to young children since the prevalence among them of recurrent wheezing is a 15-20%. It is becoming increasingly evident that many of these children respond dramatically well to beta2-agonists and topical steroids; accordingly this sub...

  17. Clinical Role of Hybrid Imaging.

    Science.gov (United States)

    Hsiao, Edward M; Ali, Bilal; Dorbala, Sharmila

    2010-10-01

    Recent technological advances have fueled the growth in hybrid radionuclide and CT imaging of the heart. Noninvasive imaging studies are reliable means to diagnose coronary artery disease (CAD), stratify risk, and guide clinical management. Myocardial perfusion scintigraphy is a robust, widely available noninvasive modality for the evaluation of ischemia from known or suspected CAD. Cardiac CT (coronary artery calcium score and coronary CT angiography) has emerged as a clinically robust noninvasive anatomic imaging test, capable of rapidly diagnosing or excluding obstructive CAD. Both anatomic and functional modalities have strengths and weaknesses, and can complement each other by offering integrated structural and physiologic information. As we discuss below, in selected patients, hybrid imaging may facilitate more accurate diagnosis, risk stratification, and management in a "one-stop shop" setting.

  18. CCCT - NCTN Steering Committees - Clinical Imaging

    Science.gov (United States)

    The Clinical Imaging Steering Committee serves as a forum for the extramural imaging and oncology communities to provide strategic input to the NCI regarding its significant investment in imaging activities in clinical trials.

  19. [Adaptive clinical study methodologies in drug development].

    Science.gov (United States)

    Antal, János

    2015-11-29

    The evolution of drug development in human, clinical phase studies triggers the overview of those technologies and procedures which are labelled as adaptive clinical trials. The most relevant procedural and operational aspects will be discussed in this overview from points of view of clinico-methodological aspect.

  20. The clinical neurobiology of drug craving.

    Science.gov (United States)

    Sinha, Rajita

    2013-08-01

    Drug craving has re-emerged as a relevant and important construct in the pathophysiology of addiction with its inclusion in DSM-V as a key clinical symptom of addictive disorders. This renewed focus has been due in part to the recent neurobiological evidence on craving-related neural activation and clinical evidence supporting its association with drug use, relapse, and recovery processes. This review covers the neurobiology of drug craving and relapse risk with a primary focus on cocaine addiction and a secondary emphasis on alcohol addiction. A conceptualization of drug craving on the continuum of healthy desire and compulsive seeking, and the associated neurobiological adaptations associated with the development of an increased craving/wanting state is presented. Altered dopamine neurochemistry as well as disrupted prefrontal control and hyperactive striatal-limbic responses in experiencing drug cues, stress, drug intake and in basal relaxed states are identified as neurobiological signatures that predict drug craving and drug use. Thus, the clinical and neurobiological features of the craving/wanting state are presented with specific attention to alterations in these cortico-limbic-striatal and prefrontal self-control circuits that predict drug craving and relapse risk. The methodological challenges that need to be addressed to further develop the evolving conceptual approach to the neuroscience of drug craving is presented, with a focus on identification and validation of biomarkers associated with the craving state and treatment approaches that may be of benefit in reversing the neurobiological adaptations associated with drug craving to improve treatment outcomes in addiction.

  1. Ultrasound triggered, image guided, local drug delivery.

    Science.gov (United States)

    Deckers, Roel; Moonen, Chrit T W

    2010-11-20

    Ultrasound allows the deposition of thermal and mechanical energies deep inside the human body in a non-invasive way. Ultrasound can be focused within a region with a diameter of about 1mm. The bio-effects of ultrasound can lead to local tissue heating, cavitation, and radiation force, which can be used for 1) local drug release from nanocarriers circulating in the blood, 2) increased extravasation of drugs and/or carriers, and 3) enhanced diffusivity of drugs. When using nanocarriers sensitive to mechanical forces (the oscillating ultrasound pressure waves) and/or sensitive to temperature, the content of the nanocarriers can be released locally. Thermo-sensitive liposomes have been suggested for local drug release in combination with local hyperthermia more than 25 years ago. Microbubbles may be designed specifically to enhance cavitation effects. Real-time imaging methods, such as magnetic resonance, optical and ultrasound imaging have led to novel insights and methods for ultrasound triggered drug delivery. Image guidance of ultrasound can be used for: 1) target identification and characterization; 2) spatio-temporal guidance of actions to release or activate the drugs and/or permeabilize membranes; 3) evaluation of bio-distribution, pharmacokinetics and pharmacodynamics; and 4) physiological read-outs to evaluate the therapeutic efficacy.

  2. Liposomal drug delivery systems--clinical applications.

    Science.gov (United States)

    Goyal, Parveen; Goyal, Kumud; Vijaya Kumar, Sengodan Gurusamy; Singh, Ajit; Katare, Om Prakash; Mishra, Dina Nath

    2005-03-01

    Liposomes have been widely investigated since 1970 as drug carriers for improving the delivery of therapeutic agents to specific sites in the body. As a result, numerous improvements have been made, thus making this technology potentially useful for the treatment of certain diseases in the clinics. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. The current pharmaceutical preparations of liposome-based therapeutic systems mainly result from our understanding of lipid-drug interactions and liposome disposition mechanisms. The insight gained from clinical use of liposome drug delivery systems can now be integrated to design liposomes that can be targeted on tissues, cells or intracellular compartments with or without expression of target recognition molecules on liposome membranes. This review is mainly focused on the diseases that have attracted most attention with respect to liposomal drug delivery and have therefore yielded most progress, namely cancer, antibacterial and antifungal disorders. In addition, increased gene transfer efficiencies could be obtained by appropriate selection of the gene transfer vector and mode of delivery.

  3. [Drug resistant epilepsy. Clinical and neurobiological concepts].

    Science.gov (United States)

    Espinosa-Jovel, Camilo A; Sobrino-Mejía, Fidel E

    2015-08-16

    Drug-resistant epilepsy, is a condition defined by the International League Against Epilepsy as persistent seizures despite having used at least two appropriate and adequate antiepileptic drug treatments. Approximately 20-30% of patients with epilepsy are going to be resistant to antiepileptic drugs, with different patterns of clinical presentation, which are related to the biological basis of this disease (de novo resistance, relapsing-remitting and progressive). Drug resistant epilepsy, impacts negatively the quality of life and significantly increases the risk of premature death. From the neurobiological point of view, this medical condition is the result of the interaction of multiple variables related to the underlying disease, drug interactions and proper genetic aspects of each patient. Thanks to advances in pharmacogenetics and molecular biology research, currently some hypotheses may explain the cause of this condition and promote the study of new therapeutic options. Currently, overexpression of membrane transporters such as P-glycoprotein, appears to be one of the most important mechanisms in the development of drug resistant epilepsy. The objective of this review is to deepen the general aspects of this clinical condition, addressing the definition, epidemiology, differential diagnosis and the pathophysiological bases.

  4. [New antiepileptic drugs: characteristics and clinical applications].

    Science.gov (United States)

    Ohtsuka, Yoko

    2014-05-01

    New antiepileptic drugs (AEDs) that have been used in many other countries for more than 10 years have only recently became available for use in Japan. Gabapentin, topiramate, lamotrigine and levetiracetam were licensed for use in Japan between 2006 and 2010. Stiripentol for Dravet syndrome and rufinamide for Lennox-Gastaut syndrome were also approved in 2012 and 2013 as orphan drugs. Clinical trials of other new AEDs such as oxcarbazepine, vigabatrin, lacosamide, and perampanel are in progress. In this review, the general characteristics of the new AEDs are discussed with regards to their effectiveness, tolerability, drug interaction, safety and mechanisms of action. The effectiveness, of the new AEDs compared with established AEDs is also discussed. Clinical applications of the new AEDs, focusing on gabapentin, topiramate, lamotrigine and levetiracetam are also discussed based on our domestic experience as well as overseas reports.

  5. Advances in Lymphatic Imaging and Drug Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.; Thallapally, Praveen K.; Laird, Forrest M.

    2011-09-10

    Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastly improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.

  6. Clinics in diagnostic imaging (171)

    Science.gov (United States)

    Ooi, Su Kai Gideon; Tan, Tien Jin; Ngu, James Chi Yong

    2016-01-01

    A 46-year-old Chinese woman with a history of cholecystectomy and appendicectomy presented to the emergency department with symptoms of intestinal obstruction. Physical examination revealed central abdominal tenderness but no clinical features of peritonism. Plain radiography of the abdomen revealed a grossly distended large bowel loop with the long axis extending from the right lower abdomen toward the epigastrium, and an intraluminal air-fluid level. These findings were suspicious for an acute caecal volvulus, which was confirmed on subsequent contrast-enhanced computed tomography (CT) of the abdomen and pelvis. CT demonstrated an abnormal positional relationship between the superior mesenteric vein and artery, indicative of an underlying intestinal malrotation. This case highlights the utility of preoperative imaging in establishing the diagnosis of an uncommon cause of bowel obstruction. It also shows the importance of recognising the characteristic imaging features early, so as to ensure appropriate and expedient management, thus reducing patient morbidity arising from complications. PMID:27872936

  7. Ultrasound triggered image-guided drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Boehmer, Marcel R. [Philips Research Europe, Biomolecular Engineering, HTC11, 5656 AE Eindhoven (Netherlands); Department of Cardiology and Angiology, University Hospital Muenster, Albert Schweitzerstrasse 33, 48149 Muenster (Germany)], E-mail: marcel.bohmer@philips.com; Klibanov, Alexander L. [Cardiovascular Division, Department of Medicine, Cobb Hall, University of Virginia School of Medicine, Hospital Drive, Cobb Hall RM 1026, Charlottesville, VA 22908-158 (United States); Tiemann, Klaus [Department of Cardiology and Angiology, University Hospital Muenster, Albert Schweitzerstrasse 33, 48149 Muenster (Germany); Hall, Christopher S. [Philips Research North America, Ultrasound Imaging and Therapy, 345 Scarborough Road, Briarcliff Manor, NY 10510 (United States); Gruell, Holger; Steinbach, Oliver C. [Philips Research Europe, Biomolecular Engineering, HTC11, 5656 AE Eindhoven (Netherlands)

    2009-05-15

    The integration of therapeutic interventions with diagnostic imaging has been recognized as one of the next technological developments that will have a major impact on medical treatments. Important advances in this field are based on a combination of progress in guiding and monitoring ultrasound energy, novel drug classes becoming available, the development of smart delivery vehicles, and more in depth understanding of the mechanisms of the cellular and molecular basis of diseases. Recent research demonstrates that both pressure sensitive and temperature sensitive delivery systems hold promise for local treatment. The use of ultrasound for the delivery of drugs has been demonstrated in particular the field of cardiology and oncology for a variety of therapeutics ranging from small drug molecules to biologics and nucleic acids.

  8. 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.

  9. Chitosan-based formulations of drugs, imaging agents and biotherapeutics

    NARCIS (Netherlands)

    Amidi, M.; Hennink, W.E.

    2010-01-01

    This preface is part of the Advanced Drug Delivery Reviews theme issue on “Chitosan-Based Formulations of Drugs, Imaging Agents and Biotherapeutics”. This special Advanced Drug Delivery Reviews issue summarizes recent progress and different applications of chitosanbased formulations.

  10. Chitosan-based formulations of drugs, imaging agents and biotherapeutics

    NARCIS (Netherlands)

    Amidi, M.; Hennink, W.E.

    This preface is part of the Advanced Drug Delivery Reviews theme issue on “Chitosan-Based Formulations of Drugs, Imaging Agents and Biotherapeutics”. This special Advanced Drug Delivery Reviews issue summarizes recent progress and different applications of chitosanbased formulations.

  11. PET and SPECT Imaging of Tumor Biology: New Approaches towards Oncology Drug Discovery and Development

    OpenAIRE

    Van Dort, Marcian E.; Rehemtulla, Alnawaz; Brian D. Ross

    2008-01-01

    Spiraling drug developmental costs and lengthy time-to-market introduction are two critical challenges facing the pharmaceutical industry. The clinical trials success rate for oncology drugs is reported to be 5% as compared to other therapeutic categories (11%) with most failures often encountered late in the clinical development process. PET and SPECT nuclear imaging technologies could play an important role in facilitating the drug development process improving the speed, efficiency and cos...

  12. Advanced and controlled drug delivery systems in clinical disease management

    NARCIS (Netherlands)

    Brouwers, JRBJ

    1996-01-01

    Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted. Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative co

  13. Theranostic Multilayer Capsules for Ultrasound Imaging and Guided Drug Delivery.

    Science.gov (United States)

    Chen, Jun; Ratnayaka, Sithira; Alford, Aaron; Kozlovskaya, Veronika; Liu, Fei; Xue, Bing; Hoyt, Kenneth; Kharlampieva, Eugenia

    2017-03-28

    Despite the accessibility of ultrasound, the clinical potential of ultrasound-active theranostic agents has not been fully realized because it requires combining sufficient imaging contrast, high encapsulation efficiency, and ultrasound-triggered release in one entity. We report on theranostic polymer microcapsules composed of hydrogen-bonded multilayers of tannic acid and poly(N-vinylpyrrolidone) that produce high imaging contrast and deliver the anticancer drug doxorubicin upon low-power diagnostic or high-power therapeutic ultrasound irradiation. These capsules exhibit excellent imaging contrast in both brightness and harmonic modes and show prolonged contrast over six months, unlike commercially available microbubbles. We also demonstrate low-dose gradual and high-dose fast release of doxorubicin from the capsules by diagnostic (∼100 mW/cm(2)) and therapeutic (>10 W/cm(2)) ultrasound irradiation, respectively. We show that the imaging contrast of the capsules can be controlled by varying the number of layers, polymer type (relatively rigid tannic acid versus more flexible poly(methacrylic acid)), and polymer molecular weight. In vitro studies demonstrate that 50% doxorubicin release from ultrasound-treated capsules induces 97% cytotoxicity to MCF-7 human cancer cells, while no cytotoxicity is found without the treatment. Considering the strong ultrasound imaging contrast, high encapsulation efficiency, biocompatibility, and tunable drug release, these microcapsules can be used as theranostic agents for ultrasound-guided chemotherapy.

  14. [Clinical pharmacology of current antiplatelet drugs].

    Science.gov (United States)

    Trenk, D; Nührenberg, T; Stratz, C; Valina, C M; Hochholzer, W

    2014-11-01

    Dual antiplatelet therapy with low-dose acetylsalicylic acid (ASA) and an inhibitor of the P2Y12 adenosine diphosphate (ADP) receptor is the standard treatment for patients presenting with acute coronary syndrome (ACS) or undergoing elective coronary interventions according to the current guidelines published by the European Society of Cardiology (ESC). New generation P2Y12 inhibitors, such as prasugrel and ticagrelor exert stronger and more consistent inhibition of the P2Y12 receptor. In clinical studies enrolling patients with ACS these drugs decreased the incidence of ischemic events compared to the standard therapy with clopidogrel and ASA; however, this beneficial effect was associated with an increase in bleeding events. Alternative therapeutic approaches via addition of drugs with different modes of action showed an overall reduction of ischemic events but also failed to uncouple this beneficial effect from an increased bleeding risk.

  15. Clinically important drug-drug interactions in primary care.

    Science.gov (United States)

    Dhabali, A A H; Awang, R; Zyoud, S H

    2012-08-01

    Drug-drug interactions (DDIs) cause considerable morbidity and mortality worldwide and may lead to hospital admission. Sophisticated computerized drug information and monitoring systems, more recently established in many of the emerging economies, including Malaysia, are capturing useful information on prescribing. Our aim is to report on an investigation of potentially serious DDIs, using a university primary care-based system capturing prescription records from its primary care services. We retrospectively collected data from two academic years over 20 months from computerized databases at the Universiti Sains Malaysia (USM) from users of the USM primary care services. Three hundred and eighty-six DDI events were observed in a cohort of 208 exposed patients from a total of 23,733 patients, representing a 2-year period prevalence of 876·4 per 100,000 patients. Of the 208 exposed patients, 138 (66·3%) were exposed to one DDI event, 29 (13·9%) to two DDI events, 15 (7·2%) to three DDI events, 6 (2·9%) to four DDI events and 20 (9·6%) to more than five DDI events. Overall, an increasing mean number of episodes of DDIs was noted among exposed patients within the age category ≥70 years (P=0·01), an increasing trend in the number of medications prescribed (P<0·001) and an increasing trend in the number of long-term therapeutic groups (P<0·001). We describe the prevalence of clinically important DDIs in an emerging economy setting and identify the more common potentially serious DDIs. In line with the observations in developed economies, a higher number of episodes of DDIs were seen in patients aged ≥70 years and with more medications prescribed. The easiest method to reduce the frequency of DDIs is to reduce the number of medications prescribed. Therapeutic alternatives should be selected cautiously. © 2011 Blackwell Publishing Ltd.

  16. A Development of Hybrid Drug Information System Using Image Recognition

    Directory of Open Access Journals (Sweden)

    HwaMin Lee

    2015-04-01

    Full Text Available In order to prevent drug abuse or misuse cases and avoid over-prescriptions, it is necessary for medicine taker to be provided with detailed information about the medicine. In this paper, we propose a drug information system and develop an application to provide information through drug image recognition using a smartphone. We designed a contents-based drug image search algorithm using the color, shape and imprint of drug. Our convenient application can provide users with detailed information about drugs and prevent drug misuse.

  17. Clinical relevance of drug-drug interactions - A structured assessment procedure

    NARCIS (Netherlands)

    van Roon, EN; Flikweert, S; le Comte, M; Langendijk, PNJ; Kwee-Zuiderwijk, WJM; Smits, P; Brouwers, JRBJ

    2005-01-01

    Introduction: Computerised drug interaction surveillance systems (CIS) may be helpful in detecting clinically significant drug interactions. Experience with CIS C, reveals that they often yield alerts with questionable clinical significance, fail to provide relevant information on risk factors for t

  18. Clinical relevance of drug-drug interactions : a structured assessment procedure.

    NARCIS (Netherlands)

    Roon, E.N. van; Flikweert, S.; Comte, M. le; Langendijk, P.N.; Kwee-Zuiderwijk, W.J.; Smits, P.; Brouwers, J.R.B.J.

    2005-01-01

    INTRODUCTION: Computerised drug interaction surveillance systems (CIS) may be helpful in detecting clinically significant drug interactions. Experience with CIS reveals that they often yield alerts with questionable clinical significance, fail to provide relevant information on risk factors for the

  19. Ultrasound molecular imaging: Moving toward clinical translation

    Energy Technology Data Exchange (ETDEWEB)

    Abou-Elkacem, Lotfi; Bachawal, Sunitha V.; Willmann, Jürgen K., E-mail: willmann@stanford.edu

    2015-09-15

    Highlights: • Ultrasound molecular imaging is a highly sensitive modality. • A clinical grade ultrasound contrast agent has entered first in human clinical trials. • Several new potential future clinical applications of ultrasound molecular imaging are being explored. - Abstract: Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging.

  20. Polymer-Drug Conjugates: Recent Development in Clinical Oncology

    OpenAIRE

    Li, Chun; Wallace, Sidney

    2008-01-01

    Targeted drug delivery aims to increase the therapeutic index by making more drug molecules available at the diseased sites while reducing systemic drug exposure. In this update, we provide an overview of polymer-drug conjugates that have advanced into the clinical trials. These systems use synthetic water-soluble polymers as the drug carriers. The preclinical pharmacology and recent data in clinical trials with poly(L-glutamic acid)-paclitaxel (PG-TXL) are discussed first. This is followed b...

  1. Clinical pharmacokinetics of antibacterial drugs in neonates.

    Science.gov (United States)

    Paap, C M; Nahata, M C

    1990-10-01

    Neonatal patients are surviving longer due to the rapid advances in medical knowledge and technology. Our understanding of the developmental physiology of both preterm and full term neonates has also increased. It is now apparent that differences in body composition and organ function significantly affect the pharmacokinetics of antibacterial drugs in neonates, and dosage modifications are required to optimise antimicrobial therapy. The penicillins and cephalosporins are frequently used in neonates. Although ampicillin has replaced benzylpenicillin (penicillin G) for empirical treatment of neonatal sepsis, many of the other penicillins may be used in neonates for the management of various infections. Increased volume of distribution (Vd) and decreased total body clearance (CL) affect the disposition of penicillins and cephalosporins. Decreased renal clearance (CLR) due to decreased glomerular filtration and tubular secretion is responsible for the decreased CL for most of the beta-lactams. Aminoglycoside Vd is affected by the increased total body water content and extracellular fluid volume of neonates. The increased Vd, in part, accounts for the extended elimination half-life (t1/2) observed in neonates. Aminoglycoside CL is dependent on renal glomerular filtration which is markedly decreased in neonates, especially those preterm. These drugs appear to be less nephrotoxic and ototoxic in neonates than in older patients, and the role of serum concentration monitoring should be limited to specific neonatal patients. Other antibiotics such as vancomycin, teicoplanin, chloramphenicol, rifampicin, erythromycin, clindamycin, metronidazole and cotrimoxazole (trimethoprim plus sulfamethoxazole) may be used in certain clinical situations. The emergence of staphylococcal resistance to penicillins has increased the need for vancomycin. With the exceptions of vancomycin and chloramphenicol, the efficacy and safety of these other agents in neonates have not been established

  2. Drug interactions in controlled clinical trials.

    Science.gov (United States)

    Gershon, S

    1982-12-01

    As much information as possible should be obtained in clinical trials to assess possible interactions between test drugs and concomitant medications prescribed for other medical indications. Side effect profiles were compared in patients taking buspirone, mean = 20 mg/day; diazepam, 20 mg/day; clorazepate, 23 mg/day; and placebo, with or without concomitant medications. Approximately 1,000 anxious patients were included in the analysis; 700 received buspirone. The use of a variety of common medications did not affect the side effect profile in the buspirone, clorazepate, and placebo groups, but did increase the incidence of side effects in the diazepam group. The increased incidence of sedation noted with diazepam and clorazepate, however, was not due to concomitant medication.

  3. Principles and clinical applications of image analysis.

    Science.gov (United States)

    Kisner, H J

    1988-12-01

    Image processing has traveled to the lunar surface and back, finding its way into the clinical laboratory. Advances in digital computers have improved the technology of image analysis, resulting in a wide variety of medical applications. Offering improvements in turnaround time, standardized systems, increased precision, and walkaway automation, digital image analysis has likely found a permanent home as a diagnostic aid in the interpretation of microscopic as well as macroscopic laboratory images.

  4. Clinical pharmacology of novel anticancer drug formulations

    OpenAIRE

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The majority of new anti-cancer drugs are oral pharmaceutical formulations, consisting of new chemical entities, like molecular targeted agents and novel variants of existing drugs. The development of oral ...

  5. Clinical risk management in Dutch community pharmacies: the case of drug-drug interactions.

    NARCIS (Netherlands)

    Buurma, H.; Smet, P.A.G.M. de; Egberts, A.C.G.

    2006-01-01

    BACKGROUND: The prevention of drug-drug interactions requires a systematic approach for which the concept of clinical risk management can be used. The objective of our study was to measure the frequency, nature and management of drug-drug interaction alerts as these occur in daily practice of Dutch

  6. Clinical risk management in Dutch community pharmacies: the case of drug-drug interactions.

    NARCIS (Netherlands)

    Buurma, H.; Smet, P.A.G.M. de; Egberts, A.C.G.

    2006-01-01

    BACKGROUND: The prevention of drug-drug interactions requires a systematic approach for which the concept of clinical risk management can be used. The objective of our study was to measure the frequency, nature and management of drug-drug interaction alerts as these occur in daily practice of Dutch

  7. Stable cerasomes for simultaneous drug delivery and magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Cao Z

    2014-11-01

    Full Text Available Zhong Cao,1,* Wenjian Zhu,1,* Wei Wang,2 Chunyang Zhang,1 Ming Xu,2 Jie Liu,1 Shi-Ting Feng,3 Qing Jiang,1 Xiaoyan Xie2 1Department of Biomedical Engineering, College of Engineering, 2Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Institute of Diagnostic and Interventional Ultrasound, 3Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Magnetic liposomes have been frequently used as nanocarriers for targeted drug delivery and magnetic resonance imaging in recent years. Despite great potentials, their morphological/structural instability in the physiological environment still remains an intractable challenge for clinical applications. In this study, stable hybrid liposomal cerasomes (ie, liposomes partially coated with silica which can co-encapsulate Fe3O4 nanoparticles and the anticancer drug paclitaxel were developed using thin film hydration method. Compared with the drug loaded liposomes, the paclitaxel-loaded magnetic cerasomes (PLMCs exhibited much higher storage stability and better sustained release behavior. Cellular uptake study showed that the utilization of an external magnetic field significantly facilitated the internalization of PLMCs into cancer cells, resulting in potentiated drug efficacy of killing tumor cells. The T2 relaxivity (r2 of our PLMCs was much higher than that of free Fe3O4 nanoparticles, suggesting increased sensitivity in T2-weighted imaging. Given its excellent biocompatibility also shown in the study, such dual functional PLMC is potentially a promising nanosystem for effective cancer diagnosis and therapy. Keywords: MRI, paclitaxel, SPIO, superparamagnetic iron oxide

  8. Clinics in diagnostic imaging (175)

    Science.gov (United States)

    Krishnan, Vijay; Lim, Tze Chwan; Ho, Francis Cho Hao; Peh, Wilfred CG

    2017-01-01

    A 54-year-old man presented with change in behaviour, nocturnal enuresis, abnormal limb movement and headache of one week’s duration. The diagnosis of butterfly glioma (glioblastoma multiforme) was made based on imaging characteristics and was further confirmed by biopsy findings. As the corpus callosum is usually resistant to infiltration by tumours, a mass that involves and crosses the corpus callosum is suggestive of an aggressive neoplasm. Other neoplastic and non-neoplastic conditions that may involve the corpus callosum and mimic a butterfly glioma, as well as associated imaging features, are discussed. PMID:28361164

  9. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The

  10. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The major

  11. Ultrasound Molecular Imaging: Moving Towards Clinical Translation

    Science.gov (United States)

    Abou-Elkacem, Lotfi; Bachawal, Sunitha V.; Willmann, Jürgen K.

    2015-01-01

    Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging. PMID:25851932

  12. Ultrasound molecular imaging: Moving toward clinical translation.

    Science.gov (United States)

    Abou-Elkacem, Lotfi; Bachawal, Sunitha V; Willmann, Jürgen K

    2015-09-01

    Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging.

  13. Clinical PET/MR Imaging in Oncology

    DEFF Research Database (Denmark)

    Kjær, Andreas; Torigian, Drew A.

    2016-01-01

    . The question, therefore, arises regarding what the future clinical applications of PET/MR imaging will be. In this article, the authors discuss ways in which PET/MR imaging may be used in future applications that justify the added cost, predominantly focusing on oncologic applications. The authors suggest...

  14. PET and SPECT Imaging of Tumor Biology: New Approaches towards Oncology Drug Discovery and Development.

    Science.gov (United States)

    Van Dort, Marcian E; Rehemtulla, Alnawaz; Ross, Brian D

    2008-01-01

    Spiraling drug developmental costs and lengthy time-to-market introduction are two critical challenges facing the pharmaceutical industry. The clinical trials success rate for oncology drugs is reported to be 5% as compared to other therapeutic categories (11%) with most failures often encountered late in the clinical development process. PET and SPECT nuclear imaging technologies could play an important role in facilitating the drug development process improving the speed, efficiency and cost of drug development. This review will focus on recent studies of PET and SPECT radioligands in oncology and their application in the investigation of tumor biology. The use of clinically-validated radioligands as imaging-based biomarkers in oncology could significantly impact new cancer therapeutic development.

  15. Differences Between Clinical Trials of Medical Devices and Drugs

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhi-jun; LIU Wei

    2014-01-01

    How to design clinical trials for medical devices is a problem plaguing the industry today. As there are many differences in clinical trials of medical devices and drugs. This paper describes the differences of the two points from the perspectivs of defi-nition of medical devices and drugs, scope, phasing, subjects and design of clinical trials in details, aiming to help the related personnel make scientific decisions while conduct-ing clinical trial design for medical devices.

  16. Antiepleptic drug interactions: a clinical case demonstration.

    Science.gov (United States)

    Tesfaye, Hundie; Klapková, Eva; Tesfayeová, Alena; Komárek, Vladimír

    2011-01-01

    Epilepsy is a serious health disorder affecting both paediatric and adult population worldwide. Due to difficulties in identifying its aetiology, initial management is often guided by empiric therapy measures. Symptomatic control requires the use of antiepileptic drugs (AEDs), many of which have the potential for adverse drug interactions. Children are especially susceptible to drug interactions and frequently exhibit atypical adverse events, which may require special care. Aim. To demonstrate a case of a 15 year old girl suffering from refractory epilepsy with underlying focal cortical dysplasia (FCD), whose seizure deterioration was most probably associated with drug-drug interactions between prescribed common antiepileptic drugs, namely valproic acid, phenobarbital or the prodrug primidon and carbamazepine.

  17. Quantitative Imaging in Cancer Clinical Trials.

    Science.gov (United States)

    Yankeelov, Thomas E; Mankoff, David A; Schwartz, Lawrence H; Lieberman, Frank S; Buatti, John M; Mountz, James M; Erickson, Bradley J; Fennessy, Fiona M M; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L; Linden, Hannah M; Kinahan, Paul E; Zhao, Binsheng; Hylton, Nola M; Gillies, Robert J; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L

    2016-01-15

    As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies.

  18. Robust diffusion imaging framework for clinical studies

    CERN Document Server

    Maximov, Ivan I; Neuner, Irene; Shah, N Jon

    2015-01-01

    Clinical diffusion imaging requires short acquisition times and good image quality to permit its use in various medical applications. In turn, these demands require the development of a robust and efficient post-processing framework in order to guarantee useful and reliable results. However, multiple artefacts abound in in vivo measurements; from either subject such as cardiac pulsation, bulk head motion, respiratory motion and involuntary tics and tremor, or imaging hardware related problems, such as table vibrations, etc. These artefacts can severely degrade the resulting images and render diffusion analysis difficult or impossible. In order to overcome these problems, we developed a robust and efficient framework enabling the use of initially corrupted images from a clinical study. At the heart of this framework is an improved least trimmed squares diffusion tensor estimation algorithm that works well with severely degraded datasets with low signal-to-noise ratio. This approach has been compared with other...

  19. Ultrasound transducer selection in clinical imaging practice.

    Science.gov (United States)

    Szabo, Thomas L; Lewin, Peter A

    2013-04-01

    Many types of medical ultrasound transducers are used in clinical practice. They operate at different center frequencies, have different physical dimensions, footprints, and shapes, and provide different image formats. However, little information is available about which transducers are most appropriate for a given application, and the purpose of this article is to address this deficiency. Specifically, the relationship between the transducer, imaging format, and clinical applications is discussed, and systematic selection criteria that allow matching of transducers to specific clinical needs are presented. These criteria include access to and coverage of the region of interest, maximum scan depth, and coverage of essential diagnostic modes required to optimize a patient's diagnosis. Three comprehensive figures organize and summarize the imaging planes, scanning modes, and types of diagnostic transducers to facilitate their selection in clinical diagnosis.

  20. Clinical decision support tools: analysis of online drug information databases

    OpenAIRE

    Seamon Matthew J; Polen Hyla H; Marsh Wallace A; Clauson Kevin A; Ortiz Blanca I

    2007-01-01

    Abstract Background Online drug information databases are used to assist in enhancing clinical decision support. However, the choice of which online database to consult, purchase or subscribe to is likely made based on subjective elements such as history of use, familiarity, or availability during professional training. The purpose of this study was to evaluate clinical decision support tools for drug information by systematically comparing the most commonly used online drug information datab...

  1. [Clinical analysis of 410 cases of drug eruption].

    Science.gov (United States)

    Mo, Bao-han

    2003-02-01

    An clinical analysis was conducted among a cohort of 410 patients drug eruption with treated in our department from January 1995 to December 2001. We found that the common drugs likely to lead to anaphylactic reactions included cephalosporins, ampicillin types, antipyretic analgesic types, rabies vaccine, sulfonamides, tetracyclines types, etc. The drug eruption mostly presents diverse clinical features resembling the rashes as seen in cases of scarlet fever, measles, urtica, or mucosal edema or ulceration.

  2. Clinical practice - Drug desensitization in children

    NARCIS (Netherlands)

    de Groot, H.; Mulder, W.M.C.

    2010-01-01

    Immediate type allergic reactions to medication are potentially life threatening and can hamper drug therapy of several medical conditions. Exact incidence and prevalence data for these reactions in children are lacking. If no alternative drug treatment is available, a desensitization procedure may

  3. Clinical practice - Drug desensitization in children

    NARCIS (Netherlands)

    H. de Groot; W.M.C. Mulder

    2010-01-01

    Immediate type allergic reactions to medication are potentially life threatening and can hamper drug therapy of several medical conditions. Exact incidence and prevalence data for these reactions in children are lacking. If no alternative drug treatment is available, a desensitization procedure may

  4. Quantitative imaging for clinical dosimetry

    Science.gov (United States)

    Bardiès, Manuel; Flux, Glenn; Lassmann, Michael; Monsieurs, Myriam; Savolainen, Sauli; Strand, Sven-Erik

    2006-12-01

    Patient-specific dosimetry in nuclear medicine is now a legal requirement in many countries throughout the EU for targeted radionuclide therapy (TRT) applications. In order to achieve that goal, an increased level of accuracy in dosimetry procedures is needed. Current research in nuclear medicine dosimetry should not only aim at developing new methods to assess the delivered radiation absorbed dose at the patient level, but also to ensure that the proposed methods can be put into practice in a sufficient number of institutions. A unified dosimetry methodology is required for making clinical outcome comparisons possible.

  5. Clinical development of fenretinide as an antineoplastic drug: Pharmacology perspectives.

    Science.gov (United States)

    Cooper, Jason P; Reynolds, C Patrick; Cho, Hwangeui; Kang, Min H

    2017-06-01

    Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved drugs. Impact statement One of the critical components in drug development is understanding pharmacology (especially pharmacokinetics) of the drugs being developed. Often the pharmacokinetic properties, such as poor solubility leading to poor bioavailability, of the drug can limit further development of the drug. The development of numerous drugs has often halted at clinical testing stages, and several of them were due to the pharmacological properties of the agents, resulting in increased drug development cost. The current review provides an example of how improved clinical activity can be achieved by changing the formulations of a drug with poor bioavailability. Thus, it emphasizes the importance of understanding pharmacologic characteristics of the drug in drug development.

  6. Potential of metabolomics in preclinical and clinical drug development.

    Science.gov (United States)

    Kumar, Baldeep; Prakash, Ajay; Ruhela, Rakesh Kumar; Medhi, Bikash

    2014-12-01

    Metabolomics is an upcoming technology system which involves detailed experimental analysis of metabolic profiles. Due to its diverse applications in preclinical and clinical research, it became an useful tool for the drug discovery and drug development process. This review covers the brief outline about the instrumentation and interpretation of metabolic profiles. The applications of metabolomics have a considerable scope in the pharmaceutical industry, almost at each step from drug discovery to clinical development. These include finding drug target, potential safety and efficacy biomarkers and mechanisms of drug action, the validation of preclinical experimental models against human disease profiles, and the discovery of clinical safety and efficacy biomarkers. As we all know, nowadays the drug discovery and development process is a very expensive, and risky business. Failures at any stage of drug discovery and development process cost millions of dollars to the companies. Some of these failures or the associated risks could be prevented or minimized if there were better ways of drug screening, drug toxicity profiling and monitoring adverse drug reactions. Metabolomics potentially offers an effective route to address all the issues associated with the drug discovery and development. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  7. Barrett's esophagus: clinical features, obesity, and imaging.

    LENUS (Irish Health Repository)

    Quigley, Eamonn M M

    2011-09-01

    The following includes commentaries on clinical features and imaging of Barrett\\'s esophagus (BE); the clinical factors that influence the development of BE; the influence of body fat distribution and central obesity; the role of adipocytokines and proinflammatory markers in carcinogenesis; the role of body mass index (BMI) in healing of Barrett\\'s epithelium; the role of surgery in prevention of carcinogenesis in BE; the importance of double-contrast esophagography and cross-sectional images of the esophagus; and the value of positron emission tomography\\/computed tomography.

  8. Novel in vivo imaging analysis of an inner ear drug delivery system: Drug availability in inner ear following different dose of systemic drug injections.

    Science.gov (United States)

    Kanzaki, Sho; Watanabe, Kotaro; Fujioka, Masato; Shibata, Shinsuke; Nakamura, Masaya; Okano, Hirotaka James; Okano, Hideyuki; Ogawa, Kaoru

    2015-12-01

    Systemic application of drugs is commonly used in clinical situations. Some of these drugs are ototoxic. Since there are few studies on in vivo monitoring of drug delivery dynamics, the time course or bioavailability of drugs in the inner ear of live animals following systemic drug application remains unknown. For instance, it is unknown whether the volume of a drug delivered systemically correlates with its inner ear pharmacokinetics. We previously established a new in vivo imaging system to monitor drug delivery in live mice. In the present study, we used this system to compare drug concentration in the inner ear over time after systemic drug injections. We used transgenic GFAP-Luc mice that harbor a firefly luciferase gene expression cassette regulated by 12 kb of murine GFAP promoter and human beta-globin intron 2. Luciferin delivered into the inner ear of these mice reacts with luciferase, and the resulting signals are detected in GFAP-expressing cells in the cochlear nerve. Thus, we assessed in the inner ear the intensity and duration of luciferin/luciferase signals after systemic injections of different volumes of luciferin. An IVIS(®) imaging system was used to observe signals, and these signals were compared to the drug dynamics of luciferin delivered through subcutaneous (sc) injections. The volume of sc-injected drug correlated significantly with photon counts measured in the inner ear. Photons were detected almost immediately after injection, peaking 20 min after injection. Drug concentration did not affect inner ear signals. Luciferin injected systemically appeared in the inner ear between highest and lowest concentration. Drug volume is an important parameter to know if the inner ear requires a higher level of the drug. We observed that it is the volume of a drug-not its concentration-that is the important factor. Indeed, the more volume of a drug injected systemically increased the concentration of that drug in the inner ear. This study provides a

  9. New Antituberculosis Drugs: From Clinical Trial to Programmatic Use.

    Science.gov (United States)

    Gualano, Gina; Capone, Susanna; Matteelli, Alberto; Palmieri, Fabrizio

    2016-06-24

    Treatment of multidrug-resistant tuberculosis (MDR-TB) cases is challenging because it relies on second-line drugs that are less potent and more toxic than those used in the clinical management of drug-susceptible TB. Moreover, treatment outcomes for MDR-TB are generally poor compared to drug sensitive disease, highlighting the need for of new drugs. For the first time in more than 50 years, two new anti-TB drugs were approved and released. Bedaquiline is a first-in-class diarylquinoline compound that showed durable culture conversion at 24 weeks in phase IIb trials. Delamanid is the first drug of the nitroimidazole class to enter clinical practice. Similarly to bedaquiline results of phase IIb studies showed increased sputum-culture conversion at 2 months and better final treatment outcomes in patients with MDR-TB. Among repurposed drugs linezolid and carbapenems may represent a valuable drug to treat cases of MDR and extensively drug-resistant TB. The recommended regimen for MDR-TB is the combination of at least four drugs to which M. tuberculosis is likely to be susceptible for the duration of 20 months. Drugs are chosen with a stepwise selection process through five groups on the basis of efficacy, safety, and cost. Clinical phase III trials on new regimen are ongoing that could prove transformative against MDR-TB, by being shorter (six months), simpler (an all-oral regimen) and safer than current standard therapy. It is fundamental that the adoption of the new drugs is done responsibly to avoid inappropriate use. Concentration of in-patient MDR-TB treatment in specialized centers could be considered in countries with low numbers of cases in order to provide appropriate clinical case management and to prevent emergence of drug resistance.

  10. Optical Molecular Imaging of Ultrasound-mediated Drug Delivery

    NARCIS (Netherlands)

    Derieppe, M.P.P.

    2015-01-01

    The goal of this PhD project was to develop optical molecular imaging methods to study drug delivery facilitated by ultrasound waves (US) and hyperthermia. Fibered confocal fluorescence microscopy (FCFM), together with dedicated image analysis, was used in vitro on a cell monolayer, and in vivo at

  11. Bioavailability studies and the clinical pharmacologist: correlation of drug distribution with clinical effects.

    Science.gov (United States)

    Ogilvie, R I

    1975-06-01

    Bioavailability studies can be interpreted only when clinical information is available which correlates drug distribution with both efficacious and toxic clinical effects. The clinical pharmacologist should be instrumental in the development of safe and effective drug therapy by the systematic application of well designed clinical trials, the clear definition of therapeutically desirable clinical responses, and the development and application of improved techniques of measuring these effects.

  12. Clinical study of cutaneous drug eruptions in 200 patients

    Directory of Open Access Journals (Sweden)

    Patel Raksha

    2008-01-01

    Full Text Available Background: Cutaneous drug reactions are the most common adverse reactions attributed to drugs. Any skin disorder can be imitated, induced or aggravated by drugs. Aims: The present study was carried out to determine the age, sex incidence and clinical pattern of drug eruptions, to recognize offending drugs (self medication or prescribed, to evaluate mortality and morbidity associated with drugs, to educate the patients, and to avoid self-administration of drugs and re-administration of the offending drugs. Methods: The diagnosis of cutaneous drug reactions is mainly based on detailed history and correlation between drug intake and the onset of rash. Two hundred patients (112 males and 88 females presenting with cutaneous drug reactions were studied. Results: Fixed drug eruption was seen in 61 patients; others being urticaria and angioedema, morbilliform rash in 37, pruritus in 25, Stevens Johnson (SJ syndrome in six, purpura in six, exfoliative dermatitis in five, photosensitivity in five, Toxic Epidermal Necrolysis in two, acneiform eruption in three, and erythema multiforme in two patients. The most frequently affected age group was 41-50 years, followed by the 21-30 and 31-40 years age groups. The youngest patient was one year old and the oldest was 80 years old. The period of development of lesions after the intake of drug(s varies from 01-45 days. Cotrimoxazole was the offending drug in 26 cases, followed by Ibuprofen in 20 cases. Conclusions: Fixed drug eruption was the most common drug eruption seen. Cotrimoxazole was the most common cause of drug eruptions.

  13. Therapeutic drug monitoring in clinical research

    NARCIS (Netherlands)

    Neef, Cees; Touw, Daniel J.; Stolk, Leo M.

    2008-01-01

    The development of a new drug is characterized by distinct developmental stages, usually described as phases I to IV. Dose tolerance and dose response exploration studies are undertaken in phase II or III. Pharmacokinetic studies are often involved in these phases, but frequently only as an objectiv

  14. Therapeutic drug monitoring in clinical research

    NARCIS (Netherlands)

    Neef, Cees; Touw, Daniel J.; Stolk, Leo M.

    2008-01-01

    The development of a new drug is characterized by distinct developmental stages, usually described as phases I to IV. Dose tolerance and dose response exploration studies are undertaken in phase II or III. Pharmacokinetic studies are often involved in these phases, but frequently only as an

  15. World Antimalarial Resistance Network I: Clinical efficacy of antimalarial drugs

    Directory of Open Access Journals (Sweden)

    Olliaro Piero

    2007-09-01

    Full Text Available Abstract The proliferation of antimalarial drug trials in the last ten years provides the opportunity to launch a concerted global surveillance effort to monitor antimalarial drug efficacy. The diversity of clinical study designs and analytical methods undermines the current ability to achieve this. The proposed World Antimalarial Resistance Network (WARN aims to establish a comprehensive clinical database from which standardised estimates of antimalarial efficacy can be derived and monitored over time from diverse geographical and endemic regions. The emphasis of this initiative is on five key variables which define the therapeutic response. Ensuring that these data are collected at the individual patient level in a consistent format will facilitate better data management and analytical practices, and ensure that clinical data can be readily collated and made amenable for pooled analyses. Such an approach, if widely adopted will permit accurate and timely recognition of trends in drug efficacy. This will guide not only appropriate interventions to deal with established multidrug resistant strains of malaria, but also facilitate prompt action when new strains of drug resistant plasmodia first emerge. A comprehensive global database incorporating the key determinants of the clinical response with in vitro, molecular and pharmacokinetic parameters will bring together relevant data on host, drug and parasite factors that are fundamental contributors to treatment efficacy. This resource will help guide rational drug policies that optimize antimalarial drug use, in the hope that the emergence and spread of resistance to new drugs can be, if not prevented, at least delayed.

  16. Clinical applications of biomedical microdevices for controlled drug delivery.

    Science.gov (United States)

    Gurman, Pablo; Miranda, Oscar R; Clayton, Kevin; Rosen, Yitzhak; Elman, Noel M

    2015-01-01

    Miniaturization of devices to micrometer and nanometer scales, combined with the use of biocompatible and functional materials, has created new opportunities for the implementation of drug delivery systems. Advances in biomedical microdevices for controlled drug delivery platforms promise a new generation of capabilities for the treatment of acute conditions and chronic illnesses, which require high adherence to treatment, in which temporal control over the pharmacokinetic profiles is critical. In addition, clinical conditions that require a combination of drugs with specific pharmacodynamic profiles and local delivery will benefit from drug delivery microdevices. This review provides a summary of various clinical applications for state-of-the-art controlled drug delivery microdevices, including cancer, endocrine and ocular disorders, and acute conditions such as hemorrhagic shock. Regulatory considerations for clinical translation of drug delivery microdevices are also discussed. Drug delivery microdevices promise a remarkable gain in clinical outcomes and a substantial social impact. A review of articles covering the field of microdevices for drug delivery was performed between January 1, 1990, and January 1, 2014, using PubMed as a search engine.

  17. Phase 0 clinical trials in oncology new drug development.

    Science.gov (United States)

    Gupta, Umesh Chandra; Bhatia, Sandeep; Garg, Amit; Sharma, Amit; Choudhary, Vaibhav

    2011-01-01

    Research focus of pharmaceutical industry has expanded to a larger extent in last few decades putting many more new molecules, particularly targeted agents, for the clinical development. On the other hand, researchers are facing serious challenges due to high failure rates of new molecules in clinical studies. The United States Food and Drug Administration (FDA) in combination with academia and industry experts identified many factors responsible for failures of new molecules, and with a vision of taking traditional drug development model toward an innovative paradigm shift, issued regulatory guidance on conduct of exploratory investigational new drug (exploratory IND) studies, often called as phase 0 clinical trials, requiring reduced preclinical testing, which has special relevance to life-threatening diseases such as cancer. Phase 0 trials, utilizing much lower drug doses, provide an opportunity to explore the clinical behavior of new molecules very early in the drug development pathway, helping to identify the promising candidates and eliminating non-promising molecules, thus improving the efficiency of overall drug development with significant savings of resources. Being non-therapeutic in nature, these studies, however, pose certain ethical challenges requiring careful study designing and informed consent process. This article reviews the insights and perspectives for the feasibility, utility, planning, designing and conduct of phase 0 clinical trials, in addition to ethical issues and industrial perspective focused at oncology new drug development.

  18. Phase 0 clinical trials in oncology new drug development

    Directory of Open Access Journals (Sweden)

    Umesh Chandra Gupta

    2011-01-01

    Full Text Available Research focus of pharmaceutical industry has expanded to a larger extent in last few decades putting many more new molecules, particularly targeted agents, for the clinical development. On the other hand, researchers are facing serious challenges due to high failure rates of new molecules in clinical studies. The United States Food and Drug Administration (FDA in combination with academia and industry experts identified many factors responsible for failures of new molecules, and with a vision of taking traditional drug development model toward an innovative paradigm shift, issued regulatory guidance on conduct of exploratory investigational new drug (exploratory IND studies, often called as phase 0 clinical trials, requiring reduced preclinical testing, which has special relevance to life-threatening diseases such as cancer. Phase 0 trials, utilizing much lower drug doses, provide an opportunity to explore the clinical behavior of new molecules very early in the drug development pathway, helping to identify the promising candidates and eliminating non-promising molecules, thus improving the efficiency of overall drug development with significant savings of resources. Being non-therapeutic in nature, these studies, however, pose certain ethical challenges requiring careful study designing and informed consent process. This article reviews the insights and perspectives for the feasibility, utility, planning, designing and conduct of phase 0 clinical trials, in addition to ethical issues and industrial perspective focused at oncology new drug development.

  19. Antibody Positron Emission Tomography Imaging in Anticancer Drug Development

    NARCIS (Netherlands)

    Lamberts, Laetitia E.; Williams, Simon P.; Terwisscha Van Scheltinga, Anton; Lub-de Hooge, Marjolijn N.; Schroeder, Carolien P.; Gietema, Jourik A.; Brouwers, Adrienne H.; de Vries, Elisabeth G. E.

    2015-01-01

    More than 50 monoclonal antibodies (mAbs), including several antibody-drug conjugates, are in advanced clinical development, forming an important part of the many molecularly targeted anticancer therapeutics currently in development. Drug development is a relatively slow and expensive process,

  20. Clinical Prediction Rule of Drug Resistant Epilepsy in Children

    OpenAIRE

    2015-01-01

    Background and Purpose: Clinical prediction rules (CPR) are clinical decision-making tools containing variables such as history, physical examination, diagnostic tests by developing scoring model from potential risk factors. This study is to establish clinical prediction scoring of drug-resistant epilepsy (DRE) in children using clinical manifestationa and only basic electroencephalography (EEG). Methods: Retrospective cohort study was conducted. A total of 308 children with diagnosed epileps...

  1. Specification of phase I of new drugs' clinical tolerance trials

    Institute of Scientific and Technical Information of China (English)

    LI Guo-xin

    2008-01-01

    Phase I of clinical trials is the first stage of clinical pharmacology and body safety evaluation, including body tolerance test and pharmacokinetics test. The aim is providing evidence for dosage regimen and be the cornerstone of the preliminary assessment of efficacy and safety of phase II of clinical trials. This text discussed the technique and requirement of phase I of new drugs' clinical tolerance trials.

  2. Imaging of drug smuggling by body packing.

    Science.gov (United States)

    Sica, Giacomo; Guida, Franco; Bocchini, Giorgio; Iaselli, Francesco; Iadevito, Isabella; Scaglione, Mariano

    2015-02-01

    Body packing, pushing, and stuffing are hazardous practices with complex medicolegal and social implications. A radiologist plays both a social and a medicolegal role in their assessment, and it should not be limited only to the identification of the packages but must also provide accurate information about their number and their exact location so as to prevent any package remains in the body packer. Radiologists must also be able to recognize the complications associated with these risky practices. Imaging assessment of body packing is performed essentially through plain abdominal X-ray and computed tomography scans. Ultrasound and magnetic resonance imaging, although with some advantages, actually have a limited use.

  3. 75 FR 14448 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2010-03-25

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practices; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug Administration (FDA) Los...

  4. Multiscale Modeling in the Clinic: Drug Design and Development

    Energy Technology Data Exchange (ETDEWEB)

    Clancy, Colleen E.; An, Gary; Cannon, William R.; Liu, Yaling; May, Elebeoba E.; Ortoleva, Peter; Popel, Aleksander S.; Sluka, James P.; Su, Jing; Vicini, Paolo; Zhou, Xiaobo; Eckmann, David M.

    2016-02-17

    A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multi-scale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multi-scale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multi-scale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical techniques employed for multi-scale modeling approaches used in pharmacology and present several examples illustrating the current state-of-the-art regarding drug development for: Excitable Systems (Heart); Cancer (Metastasis and Differentiation); Cancer (Angiogenesis and Drug Targeting); Metabolic Disorders; and Inflammation and Sepsis. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multi-scale models.

  5. Delays in clinical development of neurological drugs in Japan.

    Science.gov (United States)

    Ikeda, Masayuki

    2017-06-28

    The delays in the approval and development of neurological drugs between Japan and other countries have been a major issue for patients with neurological diseases. The objective of this study was to analyze factors contributing to the delay in the launching of neurological drugs in Japan. We analyzed data from Japan and the US for the approval of 42 neurological drugs, all of which were approved earlier in the US than in Japan, and examined the potential factors that may cause the delay of their launch. Introductions of the 42 drugs in Japan occurred at a median of 87 months after introductions in the US. The mean review time of new drug applications for the 20 drugs introduced in Japan in January 2011 or later (15 months) was significantly shorter than that for the other 22 drugs introduced in Japan in December 2010 or earlier (24 months). The lag in the Japan's review time behind the US could not explain the approval delays. In the 31 of the 42 drugs, the application data package included overseas data. The mean review time of these 31 drugs (17 months) was significantly shorter than that of the other 11 drugs without overseas data (26 months). The mean approval lag behind the US of the 31 drugs (78 months) was also significantly shorter than that of the other 11 drugs (134 months). These results show that several important reforms in the Japanese drug development and approval system (e.g., inclusion of global clinical trial data) have reduced the delays in the clinical development of neurological drugs.

  6. Physics and instrumentation for imaging in-vivo drug distribution.

    Science.gov (United States)

    Singh, M; Waluch, V

    2000-03-15

    Several imaging methods are currently available to measure drugs noninvasively. Of these, two techniques are today central to such measurements: nuclear imaging and magnetic resonance imaging/spectroscopy (MRI and MRS). While other methods, such as optical techniques, are rapidly gaining in interest, they have not yet attained the degree of development that makes them effective in measuring drugs in living systems, except in a small number of examples. The following introduction provides some basic elements of the potential and the limitations of both nuclear imaging and MRI/MRS techniques, methods that will be used in the studies described in the articles in this issue. However, and for those desiring to gain a better understanding of both methods, the reader is advised to consult much more extensive reviews and books describing such methods. A suggested list of books and articles on Nuclear Imaging and MRI/MRS is given.

  7. 76 FR 45578 - Request for Nominations for Members on a Public Advisory Committee; Medical Imaging Drugs...

    Science.gov (United States)

    2011-07-29

    ... Committee; Medical Imaging Drugs Advisory Committee AGENCY: Food and Drug Administration, HHS. ACTION... on the Medical Imaging Drugs Advisory Committee in the Center for Drug Evaluation and Research. FDA... requesting nominations for voting members on the Medical Imaging Drugs Advisory Committee (the Committee...

  8. 78 FR 12762 - Joint Meeting of the Medical Imaging Drugs Advisory Committee and the Oncologic Drugs Advisory...

    Science.gov (United States)

    2013-02-25

    ... HUMAN SERVICES Food and Drug Administration Joint Meeting of the Medical Imaging Drugs Advisory...: Medical Imaging Drugs Advisory Committee and the Oncologic Drugs Advisory Committee. General Function of... Hartzler Warner, Acting Associate Commissioner for Special Medical Programs. BILLING CODE 4160-01-P ...

  9. Clinical Neuroprotective Drugs for Treatment and Prevention of Stroke

    Directory of Open Access Journals (Sweden)

    Eiichiro Tanaka

    2012-06-01

    Full Text Available Stroke is an enormous public health problem with an imperative need for more effective therapies. In therapies for ischemic stroke, tissue plasminogen activators, antiplatelet agents and anticoagulants are used mainly for their antithrombotic effects. However, free radical scavengers, minocycline and growth factors have shown neuroprotective effects in the treatment of stroke, while antihypertensive drugs, lipid-lowering drugs and hypoglycemic drugs have shown beneficial effects for the prevention of stroke. In the present review, we evaluate the treatment and prevention of stroke in light of clinical studies and discuss new anti-stroke effects other than the main effects of drugs, focusing on optimal pharmacotherapy.

  10. Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs

    DEFF Research Database (Denmark)

    Sulochana, Suresh P; Syed, Muzeeb; Chandrasekar, Devaraj V

    2016-01-01

    of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along...

  11. Drug delivery from engineered organisms and nanocarriers as monitored by multimodal imaging technologies

    Directory of Open Access Journals (Sweden)

    Daniel Calle

    2017-03-01

    Full Text Available In recent years, while the research budget and development times increased for different phases of drug development, the number of clinically approved new medicines declined. In fact, many promising drug candidates failed to demonstrate their full therapeutic potential in vivo. Reasons for unfavorable outcome include some intrinsic properties of drugs, like biodegradation, solubility, and systemic toxicity, as well as the ways in which they are administered or the time elapsed until therapeutic efficiency is demonstrated. Therefore, to develop the full therapeutic potential of drug candidates in vivo, there is a need for advanced drug delivery systems that would carry the drug specifically to the target and release it there at desired concentrations. In addition, there is a requirement for non-invasive biomedical imaging technologies allowing for rapid and sensitive evaluations of drug performance in vivo. This review will present recent developments in bioengineered drug delivery systems, highlighting the biomedical imaging tools needed to evaluate the success of drug delivery strategies.

  12. Multiscale Modeling in the Clinic: Drug Design and Development.

    Science.gov (United States)

    Clancy, Colleen E; An, Gary; Cannon, William R; Liu, Yaling; May, Elebeoba E; Ortoleva, Peter; Popel, Aleksander S; Sluka, James P; Su, Jing; Vicini, Paolo; Zhou, Xiaobo; Eckmann, David M

    2016-09-01

    A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multiscale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multiscale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multiscale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical and computational techniques employed for multiscale modeling approaches used in pharmacometric and systems pharmacology models in drug development and present several examples illustrating the current state-of-the-art models for (1) excitable systems and applications in cardiac disease; (2) stem cell driven complex biosystems; (3) nanoparticle delivery, with applications to angiogenesis and cancer therapy; (4) host-pathogen interactions and their use in metabolic disorders, inflammation and sepsis; and (5) computer-aided design of nanomedical systems. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multiscale models.

  13. Challenges and guidelines for clinical trial of herbal drugs

    Directory of Open Access Journals (Sweden)

    Abida Parveen

    2015-01-01

    Full Text Available World Health Organization (WHO has defined herbal medicines as finished labeled medicinal product that contain an active ingredient, aerial, or underground parts of the plant or other plant material or combinations. According to a report of WHO, about 80% of the world population is reported to rely on traditional medicine for their primary health care needs. Even in the developed countries, complementary or alternative medicine is gaining popularity. A report of a global survey on national policy on traditional medicine and regulation of herbal medicines indicated that about 50 countries including China, Japan, and Germany already have their national policy and laws on regulations of traditional medicines. Herbal drugs possess a long history of its use and better patient tolerance. These are cheaper and easily available in countries like India due to rich agro culture conditions. However, reckless utilization of resources threatens the sustainability of several plant species. Traditional medicines are governed by the Drugs and Cosmetics Act of 1940 and the Drugs and Cosmetics Rules of 1945. In 1959, the Government of India amended the Drugs and Cosmetics Act to include drugs that are derived from traditional Indian medicine. In 1993, the guidelines for the safety and efficacy of herbal medicines developed by an expert committee directed that the procedures laid down by the office of the Drug Controller General of India for allopathic drugs should be followed for all traditional and herbal products to enter into clinical trials for any therapeutic condition. However, there are certain loop holes in the clinical trials of herbal drugs as the lack of stringent bylaws and regulations. Hence, a deep insight of important challenges and major regulatory guidelines for clinical trial of herbal drugs and botanicals is discussed in the present communication. There is lack of scientific evidence to evaluate safety and efficacy of herbal drugs. The quality

  14. Clinical risk management of herb-drug interactions.

    NARCIS (Netherlands)

    Smet, P.A.G.M. de

    2007-01-01

    The concomitant use of conventional and herbal medicines can lead to clinically relevant herb-drug interactions. Clinical risk management offers a systematic approach to minimize the untoward consequences of these interactions by paying attention to: (i) risk identification and assessment; (ii) deve

  15. 78 FR 20664 - Society of Clinical Research Associates-Food and Drug Administration: Food and Drug...

    Science.gov (United States)

    2013-04-05

    ... Clinical Practice AGENCY: Food and Drug Administration, HHS. ACTION: Notice of conference. SUMMARY: The... 8 a.m. to 5 p.m. Location: The conference will be held at the Renaissance Seattle Hotel, 515 Madison... community a high priority to help ensure the quality of FDA-regulated drugs and devices. The workshop helps...

  16. Clinically relevant QTc prolongation due to overridden drug-drug interaction alerts: A retrospective cohort study

    NARCIS (Netherlands)

    I.H. van der Sijs (Heleen); R. Kowlesar (Ravi); A.P.J. Klootwijk (Peter); S.P. Nelwan (Stefan); A.G. Vulto (Arnold); T. van Gelder (Teun)

    2009-01-01

    textabstractAIMS: To investigate whether, in patients in whom drug-drug interaction (DDI) alerts on QTc prolongation were overridden, the physician had requested an electrocardiogram (ECG), and if these ECGs showed clinically relevant QTc prolongation. METHODS: For all patients with overridden DDI a

  17. Multifunctional Nanoparticles for Drug Delivery Applications Imaging, Targeting, and Delivery

    CERN Document Server

    Prud'homme, Robert

    2012-01-01

    This book clearly demonstrates the progression of nanoparticle therapeutics from basic research to applications. Unlike other books covering nanoparticles used in medical applications, Multifunctional Nanoparticles for Drug Delivery Applications presents the medical challenges that can be reduced or even overcome by recent advances in nanoscale drug delivery. Each chapter highlights recent progress in the design and engineering of select multifunctional nanoparticles with topics covering targeting, imaging, delivery, diagnostics, and therapy.

  18. Clinical applications of cardiovascular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Marcu, C.B.; Beek, A.M.; Van Rossum, A.C. [Hospital of Saint Raphael, Cardiac Diagnostic Unit, New Haven, CT (United States)], E-mail: bogmarcu@pol.net

    2006-10-15

    Cardiovascular magnetic resonance imaging (MRI) has evolved from an effective research tool into a clinically proven, safe and comprehensive imaging modality. It provides anatomic and functional information in acquired and congenital heart disease and is the most precise technique for quantification of ventricular volumes, function and mass. Owing to its excellent interstudy reproducibility, cardiovascular MRI is the optimal method for assessment of changes in ventricular parameters after therapeutic intervention. Delayed contrast enhancement is an accurate and robust method used in the diagnosis of ischemic and nonischemic cardiomyopathies and less common diseases, such as cardiac sarcoidosis and myocarditis. First-pass magnetic contrast myocardial perfusion is becoming an alternative to radionuclide techniques for the detection of coronary atherosclerotic disease. In this review we outline the techniques used in cardiovascular MRI and discuss the most common clinical applications. (author)

  19. Hereditary angioedema: imaging manifestations and clinical management.

    Science.gov (United States)

    Gakhal, Mandip S; Marcotte, Gregory V

    2015-02-01

    Hereditary angioedema is a genetic disorder typically related to insufficient or dysfunctional C1-esterase inhibitor. Patients present with episodic swelling of various body parts, such as the face, neck, bowel, genitals, and extremities. Acute or severe symptoms can lead to patients presenting to the emergency room, particularly when the neck and abdominopelvic regions are affected, which is often accompanied by radiologic imaging evaluation. Patients with hereditary angioedema can pose a diagnostic challenge for emergency department physicians and radiologists at initial presentation, and the correct diagnosis may be missed or delayed, due to lack of clinical awareness of the disease or lack of its consideration in the radiologic differential diagnosis. Timely diagnosis of hereditary angioedema and rapid initiation of appropriate therapy can avoid potentially life-threatening complications. This article focuses on the spectrum of common and characteristic acute imaging manifestations of hereditary angioedema and provides an update on important recent developments in its clinical management and treatment.

  20. Clinically Relevant Imaging in Tuberous Sclerosis

    Directory of Open Access Journals (Sweden)

    Rupa Radhakrishnan

    2011-01-01

    Full Text Available Tuberous sclerosis (TS, also known as Bourneville disease or Bourneville-Pringle disease, is an autosomal dominant genetic disorder classically characterized by the presence of hamartomatous growths in multiple organs. TS and tuberous sclerosis complex (TSC are different terms for the same genetic condition. Both terms describe clinical changes due to mutations involving either of the two genes named TSC1 and TSC2, which regulate cell growth. The diagnosis of TSC is established using diagnostic criteria based on clinical and imaging findings. Routine screening and surveillance of patients with TSC is needed to determine the presence and extent of organ involvement, especially the brain, kidneys, and lungs, and identify the development of associated complications. As the treatment is organ specific, imaging plays a crucial role in the management of patients with TSC.

  1. Clinical and imaging features of fludarabine neurotoxicity.

    Science.gov (United States)

    Lee, Michael S; McKinney, Alexander M; Brace, Jeffrey R; Santacruz, Karen

    2010-03-01

    Neurotoxicity from intravenous fludarabine is a rare but recognized clinical entity. Its brain imaging features have not been extensively described. Three patients received 38.5 mg or 40 mg/m per day fludarabine in a 5-day intravenous infusion before bone marrow transplantation in treatment of hematopoietic malignancies. Several weeks later, each patient developed progressive neurologic decline, including retrogeniculate blindness, leading to coma and death. Brain MRI showed progressively enlarging but mild T2/FLAIR hyperintensities in the periventricular white matter. The lesions demonstrated restricted diffusion but did not enhance. Because the neurotoxicity of fludarabine appears long after exposure, neurologic decline in this setting is likely to be attributed to opportunistic disease. However, the imaging features are distinctive in their latency and in being mild relative to the profound clinical features. The safe dose of fludarabine in this context remains controversial.

  2. Intracranial Infections: Clinical and Imaging Characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Foerster, B.R.; Thurnher, M.M.; Malani, P.N.; Petrou, M.; Carets-Zumelzu, F.; Sundgren, P.C. [Dept. of Radiology, and Divisions of Infectious Diseases and G eriatric Medicine, Dept. of Internal Medicine, Univ. of Michigan Medical Center, Ann Arbor, MI (United States)

    2007-10-15

    The radiologist plays a crucial role in identifying and narrowing the differential diagnosis of intracranial infections. A thorough understanding of the intracranial compartment anatomy and characteristic imaging findings of specific pathogens, as well incorporation of the clinical information, is essential to establish correct diagnosis. Specific types of infections have certain propensities for different anatomical regions within the brain. In addition, the imaging findings must be placed in the context of the clinical setting, particularly in immunocompromised and human immunodeficiency virus (HIV)-positive patients. This paper describes and depicts infections within the different compartments of the brain. Pathology-proven infectious cases are presented in both immunocompetent and immunocompromised patients, with a discussion of the characteristic findings of each pathogen. Magnetic resonance spectroscopy (MRS) characteristics for several infections are also discussed.

  3. Vertigo Imaging; Clinical Radiology'

    Directory of Open Access Journals (Sweden)

    Jalal Jalal Shokouhi

    2009-01-01

    ;' and anxiety in psychiatry. "n- Clinical differentiating of peripheral and central vestibular lesion should be done by separating harmonic and disharmonic vestibular syndrome. "n- Examination of the patient with vertigo '' laboratory and imaging'' "n•Electronystagmography "n•Video-oculography "n•Audiometry "n•BAEP "n•CT "n•MRI "n - Common cause of vertigo '' all by image '' "nPeripheral: Physiological '' motion sickness'', benign paroxysmal positional vertigo , vestibular neuronitis , labyrinthitis , meniere disease , perilymph fistula. "nCentral: Brain stem TIA/infarct , post. fossa tumors , M.sclerosis, syringobulbia ,Arnold -chiari , temporal lobe epilepsy and basilar migraine. "nOthers: Cardiac , GI , psycogenic , mediacations , anemia and  hypotension , toxin and drugs: "n''aminoglycoside antibiotics,anticonvulsants,salycilates , alcohol , sedatives , antihistamins , antidepressants '' , cervical spondylosis , sensory deprivation ''neuropathy , visual impairment '',anemia , hypoglycemia , orthostatic hypotension and hyperventilation.  

  4. Metanephric Adenoma: clinical, imaging, and histological findings

    Energy Technology Data Exchange (ETDEWEB)

    Torricelli, Fabio Cesar Miranda; Marchini, Giovanni Scala, E-mail: fabio_torri@yahoo.com.b [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina. Dept. de Urologica; Campos, Rodrigo Sousa Madeira [Hospital do Servidor Publico Estadual, Sao Paulo, SP (Brazil). Dept. de Urologia; Gil, Antonio Otero [Instituto Dante Pazanezzi, Sao Paulo, SP (Brazil)

    2011-07-01

    Metanephric adenoma (MA), also designated nephrogenic nephroma or renal epithelial tumor resembling immature nephron, has just been recently recognized as a special type of benign renal epithelial tumor. Only few reports are found in the literature regarding this rare renal tumor. The purpose of this paper is to describe our clinical, imaging and histological / immunohistochemical observations of MA diagnosed in two patients and compare these data to previous information reported in medical databases (author)

  5. Clinical application of several tumor imaging agents

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Neoplasms is one of the main diseases for harming health.It is difficult to prevent the neoplasms because the factors of bringing out them are complex.To raise survival rate the early diagnosis of tumors is very important.Radionuclide imaging is useful to detect recurrent or residual diseaseand to identificate benign or malignant tumor.Several tumorimaging agents as following have clinical significance indiagnosing tumors.

  6. Can Functional Magnetic Resonance Imaging Improve Success Rates in CNS Drug Discovery?

    Science.gov (United States)

    Borsook, David; Hargreaves, Richard; Becerra, Lino

    2011-01-01

    Introduction The bar for developing new treatments for CNS disease is getting progressively higher and fewer novel mechanisms are being discovered, validated and developed. The high costs of drug discovery necessitate early decisions to ensure the best molecules and hypotheses are tested in expensive late stage clinical trials. The discovery of brain imaging biomarkers that can bridge preclinical to clinical CNS drug discovery and provide a ‘language of translation’ affords the opportunity to improve the objectivity of decision-making. Areas Covered This review discusses the benefits, challenges and potential issues of using a science based biomarker strategy to change the paradigm of CNS drug development and increase success rates in the discovery of new medicines. The authors have summarized PubMed and Google Scholar based publication searches to identify recent advances in functional, structural and chemical brain imaging and have discussed how these techniques may be useful in defining CNS disease state and drug effects during drug development. Expert opinion The use of novel brain imaging biomarkers holds the bold promise of making neuroscience drug discovery smarter by increasing the objectivity of decision making thereby improving the probability of success of identifying useful drugs to treat CNS diseases. Functional imaging holds the promise to: (1) define pharmacodynamic markers as an index of target engagement (2) improve translational medicine paradigms to predict efficacy; (3) evaluate CNS efficacy and safety based on brain activation; (4) determine brain activity drug dose-response relationships and (5) provide an objective evaluation of symptom response and disease modification. PMID:21765857

  7. [Consideration on molecular imaging technology as a tool for drug research and development].

    Science.gov (United States)

    Yajima, Kazuyoshi; Nishimura, Shintaro

    2009-03-01

    Molecular imaging technology such as positron emission tomography (PET) and magnetic resonance imaging (MRI) are known as powerful tools for clinical diagnosis in neurology, oncology and so on. As applications to new drug research and development, there are three methodologies which are PK (Pharmacokinetics study), PD (Pharmacodynamic study), and efficacy study. When we use these methodologies for the drug research, we must consider construction of technological environment (tracer, animal model, imaging analysis software, and clinical database) and regulatory environment for GMP (Good Manufacturing Practice) and GCP (Good Clinical Practice) level. Additionally, concept of microdosing and exploratory clinical study was proposed in western countries and the guidance on microdosing study was also announced by Health, Labor and Welfare Ministry on June 3rd 2008. However they may be still in learning phase, we must meet with complexity, high cost, and indigestion. To promote molecular imaging technology into the drug research, integration of the scientists between academia and industry is important because it needs much type of the advanced technologies and skills.

  8. Photoacoustic imaging for transvascular drug delivery to the rat brain

    Science.gov (United States)

    Watanabe, Ryota; Sato, Shunichi; Tsunoi, Yasuyuki; Kawauchi, Satoko; Takemura, Toshiya; Terakawa, Mitsuhiro

    2015-03-01

    Transvascular drug delivery to the brain is difficult due to the blood-brain barrier (BBB). Thus, various methods for safely opening the BBB have been investigated, for which real-time imaging methods are desired both for the blood vessels and distribution of a drug. Photoacoustic (PA) imaging, which enables depth-resolved visualization of chromophores in tissue, would be useful for this purpose. In this study, we performed in vivo PA imaging of the blood vessels and distribution of a drug in the rat brain by using an originally developed compact PA imaging system with fiber-based illumination. As a test drug, Evans blue (EB) was injected to the tail vein, and a photomechanical wave was applied to the targeted brain tissue to increase the permeability of the blood vessel walls. For PA imaging of blood vessels and EB distribution, nanosecond pulses at 532 nm and 670 nm were used, respectively. We clearly visualized blood vessels with diameters larger than 50 μm and the distribution of EB in the brain, showing spatiotemporal characteristics of EB that was transvascularly delivered to the target tissue in the brain.

  9. Fixed drug eruption at a dermatology clinic in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Olusola Olabisi Ayanlowo

    2015-01-01

    Full Text Available Background: Fixed drug eruption (FDE is common cutaneous drug eruption characterized by the development of one or more annular, oval, erythematous, and hyperpigmented patches as a result of systemic exposure to a drug. Drugs causing FDE vary with prevailing diseases and prescription pattern in different parts of the world. This study is aimed at reviewing cases of FDE seen at the dermatology outpatient clinic of Lagos University Teaching Hospital (LUTH over a 9-year period, highlighting the spectrum of drugs implicated and the clinical characteristics. Materials and Methods: Data were obtained from the clinic records and patients' case notes. These included the demographic details, duration of presentation, drugs implicated, and clinical characteristics. Results: FDE was diagnosed in 1.8% (295/16,160 of patients seen. There was a slight female preponderance. Antimalarials were the commonest group of medications implicated (51.0% followed by antibiotics (27.9%; analgesics (10.2%, herbal toothpaste (6.1%, and oral hypoglycemic agents (4.1%. Sulfonamides were the commonest group of drugs found in 78 patients (53.1% predominantly as sulfadoxine/pyrimethamine antimalarials and trimethoprim/sulfamethoxazole antibiotics (co-trimoxazole. Conclusion: Concerted efforts are needed to discourage over-the-counter sales and purchase of nonprescription sulfonamide-based medications. A change in prescription pattern from sulfonamides to other classes of antimalarials and antibiotics is desirable and/or recommended. Patients should inform their caregivers at any point of care about their reaction to drugs. It is advised that they have a list of common implicating drugs and they wear a medic alert or carry an ID card bearing this information.

  10. Drug repurposing: translational pharmacology, chemistry, computers and the clinic.

    Science.gov (United States)

    Issa, Naiem T; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2013-01-01

    The process of discovering a pharmacological compound that elicits a desired clinical effect with minimal side effects is a challenge. Prior to the advent of high-performance computing and large-scale screening technologies, drug discovery was largely a serendipitous endeavor, as in the case of thalidomide for erythema nodosum leprosum or cancer drugs in general derived from flora located in far-reaching geographic locations. More recently, de novo drug discovery has become a more rationalized process where drug-target-effect hypotheses are formulated on the basis of already known compounds/protein targets and their structures. Although this approach is hypothesis-driven, the actual success has been very low, contributing to the soaring costs of research and development as well as the diminished pharmaceutical pipeline in the United States. In this review, we discuss the evolution in computational pharmacology as the next generation of successful drug discovery and implementation in the clinic where high-performance computing (HPC) is used to generate and validate drug-target-effect hypotheses completely in silico. The use of HPC would decrease development time and errors while increasing productivity prior to in vitro, animal and human testing. We highlight approaches in chemoinformatics, bioinformatics as well as network biopharmacology to illustrate potential avenues from which to design clinically efficacious drugs. We further discuss the implications of combining these approaches into an integrative methodology for high-accuracy computational predictions within the context of drug repositioning for the efficient streamlining of currently approved drugs back into clinical trials for possible new indications.

  11. Clinical drugs that interact with St. John's wort and implication in drug development.

    Science.gov (United States)

    Di, Yuan Ming; Li, Chun Guang; Xue, Charlie Changli; Zhou, Shu-Feng

    2008-01-01

    St. John's wort (Hypericum perforatum, SJW) is one of the most commonly used herbal antidepressants for the treatment of minor to moderate depression. A major safety concern about SJW is its ability to alter the pharmacokinetics and/or clinical response of a variety of clinically important drugs that have distinctive chemical structure, mechanism of action and metabolic pathways. This review highlights and updates the knowledge on clinical interactions of prescribed drugs with SJW and the implication in drug development. A number of clinically significant interactions of SJW have been identified with conventional drugs, including anticancer agents (imatinib and irinotecan), anti-HIV agents (e.g. indinavir, lamivudine and nevirapine), anti-inflammatory agents (e.g. ibuprofen and fexofenadine), antimicrobial agents (e.g. erythromycin and voriconazole), cardiovascular drugs (e.g. digoxin, ivabradine, warfarin, verapamil, nifedipine and talinolol), central nervous system agents (e.g. amitriptyline, buspirone, phenytoin, methadone, midazolam, alprazolam, and sertraline), hypoglycaemic agents (e.g. tolbutamide and gliclazide), immuno-modulating agents (e.g. cyclosporine and tacrolimus), oral contraceptives, proton pump inhibitor (e.g. omeprazole), respiratory system agent (e.g. theophylline), statins (e.g. atorvastatin and pravastatin). Both pharmacokinetic and pharmacodynamic components may play a role in the interactions of drugs with SJW. For pharmacokinetic changes of drugs by SJW, induction of cytochrome P450s (e.g. CYP2C9 and 3A4) and P-glycoprotein (P-gp) are considered the major mechanism. Thus, it is not a surprise that many drugs that interact with SJW are substrates of CYP3A4, CYP2C9 and P-gp. A comprehensive understanding of clinical drugs that interact with SJW has important implications in drug development. New drugs may be designed to minimize interactions with SJW; and new SJW formulations may be designed to avoid drug interactions. Further clinical and

  12. Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials

    NARCIS (Netherlands)

    B.M. Ellingson (Benjamin M.); M. Bendszus (Martin); J. Boxerman (Jerrold); D. Barboriak (Daniel); B.J. Erickson (Bradley J.); M. Smits (Marion); S.J. Nelson (Sarah J.); E. Gerstner (Elizabeth); B. Alexander (Brian); G. Goldmacher (Gregory); W. Wick (Wolfgang); M.A. Vogelbaum (Michael); M. Weller (Michael); E. Galanis (Evanthia); J. Kalpathy-Cramer (Jayashree); L. Shankar; P. Jacobs (Paula); W.B. Pope (Whitney B.); D. Yang (Dewen); C. Chung (Caroline); R.H. Knopp; S. Cha (Soonme); M.J. van den Bent (Martin); S.M. Chang (Susan); W.K. Al Yung; T.F. Cloughesy (Timothy F.); P.Y. Wen (Patrick Y.); M.R. Gilbert (Mark R.); A. Whitney (Andrew); D. Sandak (David); A. Musella (Al); C. Haynes (Chas); M. Wallace (Max); D.F. Arons (David F.); A. Kingston (Ann)

    2015-01-01

    textabstractA recent joint meeting was held on January 30, 2014, with the US Food and Drug Administration (FDA), National Cancer Institute (NCI), clinical scientists, imaging experts, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocate groups to discuss ima

  13. Use of diffusion and perfusion magnetic resonance imaging as a tool in acute stroke clinical trials

    Directory of Open Access Journals (Sweden)

    Warach Steven

    2001-01-01

    Full Text Available Abstract In light of the slow progress in developing effective therapies for ischemic stroke, magnetic resonance imaging techniques have emerged as new tools in stroke clinical trials. Rapid imaging with magnetic resonance imaging, diffusion weighted imaging, perfusion imaging and angiography are being incorporated into phase II and phase III stroke trials to optimize patient selection based on positive imaging diagnosis of the ischemic pathophysiology specifically related to a drug's mechanism of action and as a direct biomarker of the effect of a treatment's effect on the brain.

  14. Translating Clinical Findings into Knowledge in Drug Safety Evaluation - Drug Induced Liver Injury Prediction System (DILIps)

    Science.gov (United States)

    Liu, Zhichao; Shi, Qiang; Ding, Don; Kelly, Reagan; Fang, Hong; Tong, Weida

    2011-01-01

    Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects) seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps). The DILIps yielded 60–70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the “Rule of Three” was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91%) when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity. PMID:22194678

  15. The status of platinum anticancer drugs in the clinic and in clinical trials.

    Science.gov (United States)

    Wheate, Nial J; Walker, Shonagh; Craig, Gemma E; Oun, Rabbab

    2010-09-21

    Since its approval in 1979 cisplatin has become an important component in chemotherapy regimes for the treatment of ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and melanoma. Unfortunately its continued use is greatly limited by severe dose limiting side effects and intrinsic or acquired drug resistance. Over the last 30 years, 23 other platinum-based drugs have entered clinical trials with only two (carboplatin and oxaliplatin) of these gaining international marketing approval, and another three (nedaplatin, lobaplatin and heptaplatin) gaining approval in individual nations. During this time there have been more failures than successes with the development of 14 drugs being halted during clinical trials. Currently there are four drugs in the various phases of clinical trial (satraplatin, picoplatin, Lipoplatin and ProLindac). No new small molecule platinum drug has entered clinical trials since 1999 which is representative of a shift in focus away from drug design and towards drug delivery in the last decade. In this perspective article we update the status of platinum anticancer drugs currently approved for use, those undergoing clinical trials and those discontinued during clinical trials, and discuss the results in the context of where we believe the field will develop over the next decade.

  16. Drug screening in clinical or forensic toxicology: are there differences?

    Science.gov (United States)

    Gerostamoulos, Dimitri; Beyer, Jochen

    2010-09-01

    Legal and medical practitioners need to remember that, with respect to drug analysis, there are two distinct disciplines in analytical toxicology concerned with human biological matrices, namely clinical and forensic toxicology. Both fields use similar analytical techniques designed to detect and quantify drugs, chemicals and poisons in fluids or tissues. In clinical toxicology, analytical results help to specify the appropriate treatment of a poisoned or intoxicated patient. In forensic toxicology, the results often play a vital role in determining the possible impairment or behavioural changes in an individual, or the contribution of drugs or poisons to death in a medico-legal investigation. This column provides an overview of the similarities and differences inherent in clinical and forensic toxicology.

  17. Photoacoustic image-guided drug delivery in the prostate

    Science.gov (United States)

    Tang, Shanshan; Chen, Jian; Samant, Pratik; Xiang, Liangzhong

    2016-03-01

    Image guided drug delivery is a novel strategy that combines the effect of therapy and visibility into one system. Here we apply photoacoustic (PA) imaging to visualize the drug delivery process, and perform a simulation study on monitoring the photosensitizer concentration in a prostate tumor during photodynamic therapy (PDT). A 3D optical model of the human prostate is developed, and the light absorption distribution in the prostate is estimated by the Monte Carlo simulation method. The filtered back-projection algorithm is used to reconstruct PA images. PA images of transurethral laser/transrectal ultrasound are compared to those of transrectal laser/ultrasound. Results show that the transurethral laser has a better penetration depth in the prostate compared with transrectal one. Urethral thermal safety is investigated via COMSOL Multiphysics, and the results show that the proposed pulsed transurethral laser will cause no thermal damage on the urethral surface. Regression analysis for PA signal amplitude and drug concentration demonstrates that the PA technique has the potential to monitor drug distributions in PDT, as well as in other laser-based prostate therapy modalities.

  18. Seeing is believing, looks are deceiving: what does one see in images of drugs and drug use(rs)?

    Science.gov (United States)

    Montagne, Michael

    2015-03-01

    Images of drugs and drug use(rs) convey meaning, feelings, and beliefs, and what is being seen is often believed. Images can also deceive in content, meaning, and belief. Drug use(r) researchers, who use images as data, must be cautious in interpreting what is being conveyed and why. As technological advances continue to shape the creation, modification, storage, and analysis of images, researchers must be ever more vigilant about what they are seeing and believing.

  19. Army Drug Development Program. Phase 1. Clinical Testing

    Science.gov (United States)

    1981-02-01

    done as clinically indicated. * Part III of Experiment 114 was cancelled. 35 ( H+r rDrug Assay: The schedule of blood sampling will be de...Indicated. * Part III of Experiment #14 was cancelled. 79 ■■— ’( mmmm ■H-K. rDrug Assay: The schedule of blood sampling will be de...reading of phototoxicity tests. 89 tDrug Assay? 10 ml of venous blood were taXen from each sub- ject for each of 20

  20. Liposomal drug delivery systems: from concept to clinical applications.

    Science.gov (United States)

    Allen, Theresa M; Cullis, Pieter R

    2013-01-01

    The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future.

  1. Weaving single photon imaging into new drug development.

    Science.gov (United States)

    Mozley, P David

    2005-01-01

    The specific aim of this review is to assess the potential contribution of single photon emitting radiopharmaceutical technologies to new drug development. For each phase of therapeutic drug development, published literature was sought that shows single photon emitters can add value by quantifying pharmacokinetics, visualizing mechanisms of drug action, estimating therapeutic safety indices, or measuring dose-dependent pharmacodynamic effects. Not any published reports were found that describe using nuclear medicine techniques to help manage the progress of a new drug development program. As a consequence, most of the case in favor of weaving single photon imaging into the process had to be built on extrapolations from studies that showed feasibility post hoc. The strongest evidence of potential value was found for drug candidates that hope to influence diseases characterized by cell proliferation or cell death, particularly in the fields of oncology, cardiology, nephrology, and inflammation. Receptor occupancy studies were observed to occasionally offer unique advantages over analogous studies with positron emission tomography (PET). Enough hard data sets were found to justify the costs of using single photon imaging in a variety of new drug development paradigms.

  2. 76 FR 45402 - Advisory Committee; Medical Imaging Drugs Advisory Committee; Re-Establishment

    Science.gov (United States)

    2011-07-29

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 14 Advisory Committee; Medical Imaging Drugs.... SUMMARY: The Food and Drug Administration (FDA) is announcing the re- establishment of the Medical Imaging... language for the Medical Imaging Drugs Advisory Committee in the Agency's list of standing advisory...

  3. 76 FR 25357 - Advisory Committee; Medical Imaging Drugs Advisory Committee; Reestablishment

    Science.gov (United States)

    2011-05-04

    ... HUMAN SERVICES Food and Drug Administration Advisory Committee; Medical Imaging Drugs Advisory Committee... Administration (FDA) is announcing the ] reestablishment of the Medical Imaging Drugs Advisory Committee in the.... 101-635); and 21 CFR 14.40(b), FDA is announcing the reestablishment of the Medical Imaging Drugs...

  4. Co-targeting cancer drug escape pathways confers clinical advantage for multi-target anticancer drugs.

    Science.gov (United States)

    Tao, Lin; Zhu, Feng; Xu, Feng; Chen, Zhe; Jiang, Yu Yang; Chen, Yu Zong

    2015-12-01

    Recent investigations have suggested that anticancer therapeutics may be enhanced by co-targeting the primary anticancer target and the corresponding drug escape pathways. Whether this strategy confers statistically significant clinical advantage has not been systematically investigated. This question was probed by the evaluation of the clinical status and the multiple targets of 23 approved and 136 clinical trial multi-target anticancer drugs with particular focus on those co-targeting EGFR, HER2, Abl, VEGFR2, mTOR, PI3K, Alk, MEK, KIT, and DNA topoisomerase, and some of the 14, 7, 13, 20, 6, 5, 7, 2, 4 and 10 cancer drug escape pathways respectively. Most of the approved (73.9%) and phase III (75.0%), the majority of the Phase II (62.8%) and I (53.6%), and the minority of the discontinued (35.3%) multi-target drugs were found to co-target cancer drug escape pathways. This suggests that co-targeting anticancer targets and drug escape pathways confer significant clinical advantage and such strategy can be more extensively explored. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Clinical herbal interactions with conventional drugs: from molecules to maladies.

    Science.gov (United States)

    Chen, X-W; Serag, E S; Sneed, K B; Liang, J; Chew, H; Pan, S-Y; Zhou, S-F

    2011-01-01

    Clinical studies and case reports have identified a number of herb-drug interactions potentiated by the concurrent use of herbal medicines with prescription drugs. The purpose of this paper is to discuss the mechanisms and clinical implications of such herb-drug interactions by reviewing published human studies. Both pharmacokinetic and pharmacodynamic components may be involved in herbdrug interactions, although metabolic induction or inhibition is a common underlying mechanism for many herb-drug interactions. Drugs that have a high potential to interact with herbal medicines usually have a narrow therapeutic index, including warfarin, digoxin, cyclosporine, tacrolimus, amitriptyline, midazolam, indinavir, and irinotecan. Many of them are substrates of cytochrome P450s (CYPs) and/or P-glycoprotein (P-gp). Herbal medicines that are reported to interact with drugs include garlic (Allium sativum), ginger (Zingiber officinale), ginkgo (Ginkgo biloba), ginseng (Panax ginseng), and St. John's wort (Hypericum perforatum). For example, garlic has been shown to increase the clotting time and international normalized ratio (INR) of warfarin, cause hypoglycaemia when taken with chlorpropamide, and reduce the area under the plasma concentration-time curve (AUC) and maximum concentration of saquinavir in humans. Similarly, case reports have demonstrated that ginkgo may potentiate bleeding when combined with warfarin or aspirin, increases blood pressure when combined with thiazide diuretics, and has even led to a coma when combined with trazodone, a serotonin antagonist and reuptake inhibitor used to treat depression. Furthermore, ginseng reduced the blood levels of warfarin and alcohol as well as induced mania if taken concomitantly with phenelzine, a non-selective and irreversible monoamine oxidase inhibitor used as an antidepressant and anxiolytic agent. Lastly, multiple herb-drug interactions have been identified with St. John's wort that involve significantly reduced AUC

  6. Imaging of Drug-induced Complications in the Gastrointestinal System.

    Science.gov (United States)

    McGettigan, Melissa J; Menias, Christine O; Gao, Zhenqiang J; Mellnick, Vincent M; Hara, Amy K

    2016-01-01

    Drug-induced injury commonly affects the gastrointestinal and hepatobiliary systems because of the mechanisms of absorption and metabolism. In pill esophagitis, injury is frequently related to direct contact with the esophageal mucosa, resulting in small superficial ulcers in the mid esophagus. Nonsteroidal anti-inflammatory drugs can lead to gastrointestinal tract ulcers and small bowel mucosal diaphragms (thin weblike strictures). Injury to the pancreatic and hepatobiliary systems can manifest as pancreatitis, acute or chronic hepatitis, cholestasis, or steatosis and steatohepatitis (which may progress to cirrhosis). Various drugs may also insult the hepatic vasculature, resulting in Budd-Chiari and sinusoidal obstructive syndromes. Focal lesions such as hepatic adenomas may develop after use of oral contraceptives or anabolic steroids. Ultrasonography, computed tomography, and magnetic resonance imaging can aid in diagnosis of drug-induced injuries and often are necessary to exclude other causes.

  7. Phase 0 clinical trials in oncology new drug development

    OpenAIRE

    Umesh Chandra Gupta; Sandeep Bhatia; Amit Garg; Amit Sharma; Vaibhav Choudhary

    2011-01-01

    Research focus of pharmaceutical industry has expanded to a larger extent in last few decades putting many more new molecules, particularly targeted agents, for the clinical development. On the other hand, researchers are facing serious challenges due to high failure rates of new molecules in clinical studies. The United States Food and Drug Administration (FDA) in combination with academia and industry experts identified many factors responsible for failures of new molecules, and with a visi...

  8. Pharmacokinetic drug-drug interaction and their implication in clinical management

    Directory of Open Access Journals (Sweden)

    Palleria Caterina

    2013-01-01

    Full Text Available Drug-drug interactions (DDIs are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In this review, using Medline, PubMed, Embase, Cochrane library and Reference lists we searched articles published until June 30 2012, and we described the mechanism of pharmacokinetic DDIs focusing the interest on their clinical implications.

  9. Comparative clinic research of dysthymia patients used drugs and patients with drug addiction

    Directory of Open Access Journals (Sweden)

    Iliya Gubin

    2012-10-01

    Full Text Available The paper presents comparative research on the clinical picture and distinctive features of the therapy in dysthymia patients who used opiate drugs and drug addiction. 26 patients with dysthymia complicated by addiction to opiate drugs and 22 heroin addicts were examined.The received results will allow doctors to pay attention to the necessary details for the detection of relevant affective disorders, reduce the period of detecting affective disorders that significantly influence the choice of a rational therapy in the status of patients and also to build specific projections regarding patients.

  10. Clinical information in drug package inserts in India

    Directory of Open Access Journals (Sweden)

    Shivkar Y

    2009-01-01

    Full Text Available Background: It is widely recognized that accurate and reliable product information is essential for the safe and effective use of medications. Pharmaceutical companies are the primary source of most drug information, including package inserts. Package inserts are printed leaflets accompanying marketed drug products and contain information approved by the regulatory agencies. Studies on package inserts in India, in 1996, had shown that crucial information was often missing and they lacked uniformity. Aim: To assess the presentation and completeness of clinically important information provided in the currently available package inserts in India. Materials and Methods: Package inserts accompanying allopathic drug products marketed by pharmaceutical companies in India were collected. These package inserts were analyzed for the content of clinically important information in various sections. Statistical Analysis: The results were expressed as absolute numbers and percentages. Results: Preliminary analyses revealed that most package inserts did contain information under headings, such as, therapeutic indications, contraindications, undesirable effects, etc., listed in the Drugs and Cosmetics Rules 1945. The findings indicated considerable improvement in package inserts since 1996. However, on critical evaluation it was revealed that clinically important information was not well presented and was often incomplete. Information with regard to pediatric and geriatric use was present in only 44% and 13% of the package inserts, respectively. Only five of the inserts had information on the most frequent adverse drug reactions associated with the drug. Also, information on interactions and overdosage was often missing. Conclusion: Although the package inserts appear to have improved over the past decade there is still a definite need to further refine the clinical information contained, to minimize the risks to patients. This could be brought about by self

  11. Introduction: feature issue on optical molecular probes, imaging, and drug delivery.

    Science.gov (United States)

    Campagnola, Paul; French, Paul M W; Georgakoudi, Irene; Mycek, Mary-Ann

    2014-02-01

    The editors introduce the Biomedical Optics Express feature issue "Optical Molecular Probes, Imaging, and Drug Delivery," which is associated with a Topical Meeting of the same name held at the 2013 Optical Society of America (OSA) Optics in the Life Sciences Congress in Waikoloa Beach, Hawaii, April 14-18, 2013. The international meeting focused on the convergence of optical physics, photonics technology, nanoscience, and photochemistry with drug discovery and clinical medicine. Papers in this feature issue are representative of meeting topics, including advances in microscopy, nanotechnology, and optics in cancer research.

  12. Clinical decision support tools: analysis of online drug information databases

    Directory of Open Access Journals (Sweden)

    Seamon Matthew J

    2007-03-01

    Full Text Available Abstract Background Online drug information databases are used to assist in enhancing clinical decision support. However, the choice of which online database to consult, purchase or subscribe to is likely made based on subjective elements such as history of use, familiarity, or availability during professional training. The purpose of this study was to evaluate clinical decision support tools for drug information by systematically comparing the most commonly used online drug information databases. Methods Five commercially available and two freely available online drug information databases were evaluated according to scope (presence or absence of answer, completeness (the comprehensiveness of the answers, and ease of use. Additionally, a composite score integrating all three criteria was utilized. Fifteen weighted categories comprised of 158 questions were used to conduct the analysis. Descriptive statistics and Chi-square were used to summarize the evaluation components and make comparisons between databases. Scheffe's multiple comparison procedure was used to determine statistically different scope and completeness scores. The composite score was subjected to sensitivity analysis to investigate the effect of the choice of percentages for scope and completeness. Results The rankings for the databases from highest to lowest, based on composite scores were Clinical Pharmacology, Micromedex, Lexi-Comp Online, Facts & Comparisons 4.0, Epocrates Online Premium, RxList.com, and Epocrates Online Free. Differences in scope produced three statistical groupings with Group 1 (best performers being: Clinical Pharmacology, Micromedex, Facts & Comparisons 4.0, Lexi-Comp Online, Group 2: Epocrates Premium and RxList.com and Group 3: Epocrates Free (p Conclusion Online drug information databases, which belong to clinical decision support, vary in their ability to answer questions across a range of categories.

  13. Unique roles of SPET brain imaging in clinical and research studies. Lessons from Parkinson's disease research.

    Science.gov (United States)

    Seibyl, J; Jennings, D; Tabamo, R; Marek, K

    2005-06-01

    The increasing availability of PET imaging in nuclear medicine expands the armamentarium of clinical and research tools for improving diagnosis and treatment of neuropsychiatric disorders. Nonetheless, the role of SPECT imaging remains critical to both research and clinical practice. The development of rational strategies for guiding the selection of imaging modalities flows from primarily the nature of the clinical or research question and the availability of appropriate radiopharmaceuticals. There has been extensive SPECT and PET work in Parkinson's disease (PD) which highlights the value of both these scintigraphic modalities. Three main areas of interest in PD include imaging for improving diagnostic accuracy, for monitoring the progression of disease, and for assessing the therapeutic efficacy of drugs with neuroprotective potential. The demands of the clinical or research question posed to imaging dictates the selection of radiotracer and imaging modality. Diagnosis of PD represents the easiest challenge with many imaging biomarkers showing high sensitivity for detecting abnormal reduction of dopaminergic function based on qualitative review of images. On the other hand, using imaging to evaluate treatments which purportedly slow the rate of disease progression, indicated by the reduction in the rate of loss in a quantitative imaging signal in patients studied over time, represents the most rigorous requirement of the imaging measure. In each of these applications presynaptic markers of dopaminergic function using SPECT and PET have been extremely valuable. Review of neuroimaging studies of PD provides a useful example of optimized approaches to clinical and research studies in neuropsychiatric disorders.

  14. Clinical micro-CT for dental imaging

    Science.gov (United States)

    Youn, Hanbean; Cho, Min Kook; Shon, Cheol-Soon; Cho, Bong Hae; Kim, Chang Hyuk; Kim, Ho Kyung

    2009-02-01

    We exploit the development of a clinical computed microtomography (micro-CT) system for dental imaging. While the conventional dental CT simply serves implant treatment, the clinical dental micro-CT may provide clinicians with a histologic evaluation. To investigate the feasibility of the realization of a dental micro-CT, we have constructed an experimental test system which mainly consists of a microfocus x-ray source, a rotational subject holder, and a flat-panel detector. The flat-panel detector is based on a matrix-addressed photodiode array coupled to a CsI:Tl scintillator. The detective quantum efficiency (DQE) of the detector was measured as a function of magnification based on the measured modulation-transfer function (MTF) and noise-power spectrum (NPS). The best MTF and DQE performances were achieved at the magnification factor of 3. Similar tendency of the spatial resolving power in tomography was also observed with a wire phantom having a 25 μm diameter. From the investigation of tomographs reconstructed from a humanoid skull phantom, the application of magnification in the system largely reduced both signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for a fixed dose at the entrance surface of the detector, 1.2 mGy, while this setup increased the dose at the object plane from 4.7 mGy to 19.1 mGy for the magnification factor from 2 to 4, respectively. Although the quantum mottles at the high magnification factor tackled the practical use in the clinic, the information contained in the magnified CT images was quite promising.

  15. The Smart Drug Delivery System and Its Clinical Potential.

    Science.gov (United States)

    Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

    2016-01-01

    With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications.

  16. Perfusion MRI in the early clinical development of antivascular drugs: decorations or decision making tools?

    Energy Technology Data Exchange (ETDEWEB)

    Zweifel, Martin [Mount Vernon Cancer Centre, Department of Medical Oncology, Northwood, Middlesex (United Kingdom); Padhani, Anwar R. [Mount Vernon Hospital, Paul Strickland Scanner Centre, Northwood, Middlesex (United Kingdom)

    2010-08-15

    Classically, the first step in the clinical development of drugs in oncology involves assessments of dose limiting toxicity (DLT) and maximum tolerated dose (MTD). New paradigms are needed for antiangiogenic drugs and vascular disrupting agents (VDAs) as they are active at doses well below the MTD and as single agents their use might not translate into anti-tumour efficacy. MRI is able to assess the antivascular effects of antivascular drugs via changes in functional kinetic parameters; however, the usefulness of MRI in decision making has been questioned by many. Our aim is to review the experience of using dynamic contrast-enhanced MRI (DCE-MRI) in early clinical development of vascular directed anticancer therapies over the last decade. Thirty-nine phase I and II studies including data on more than 700 patients have been published as abstracts and/or papers, documenting DCE-MRI changes after the administration of antiangiogenic drugs and VDAs. Perfusion MRI is helpful in assessing whether mechanistic goals are achieved, in assisting dose selection for phase II studies, in selecting subpopulations enriched for response and in predicting patient benefit. Imaging tools are increasingly available. Future challenges for imaging include correlation with clinical measures of efficacy and determining relationships with blood and serum biomarkers. (orig.)

  17. Nanotechnology: from In Vivo Imaging System to Controlled Drug Delivery

    Science.gov (United States)

    Mir, Maria; Ishtiaq, Saba; Rabia, Samreen; Khatoon, Maryam; Zeb, Ahmad; Khan, Gul Majid; ur Rehman, Asim; ud Din, Fakhar

    2017-08-01

    Science and technology have always been the vitals of human's struggle, utilized exclusively for the development of novel tools and products, ranging from micro- to nanosize. Nanotechnology has gained significant attention due to its extensive applications in biomedicine, particularly related to bio imaging and drug delivery. Various nanodevices and nanomaterials have been developed for the diagnosis and treatment of different diseases. Herein, we have described two primary aspects of the nanomedicine, i.e., in vivo imaging and drug delivery, highlighting the recent advancements and future explorations. Tremendous advancements in the nanotechnology tools for the imaging, particularly of the cancer cells, have recently been observed. Nanoparticles offer a suitable medium to carryout molecular level modifications including the site-specific imaging and targeting. Invention of radionuclides, quantum dots, magnetic nanoparticles, and carbon nanotubes and use of gold nanoparticles in biosensors have revolutionized the field of imaging, resulting in easy understanding of the pathophysiology of disease, improved ability to diagnose and enhanced therapeutic delivery. This high specificity and selectivity of the nanomedicine is important, and thus, the recent advancements in this field need to be understood for a better today and a more prosperous future.

  18. DNA nanostructure-based imaging probes and drug carriers.

    Science.gov (United States)

    Zhan, Pengfei; Jiang, Qiao; Wang, Zhen-Gang; Li, Na; Yu, Haiyin; Ding, Baoquan

    2014-09-01

    Self-assembled DNA nanostructures are well-defined nanoscale shapes, with uniform sizes, precise spatial addressability, and excellent biocompatibility. With these features, DNA nanostructures show great potential for biomedical applications; various DNA-based biomedical imaging probes or payload delivery carriers have been developed. In this review, we summarize the recent developments of DNA-based nanostructures as tools for diagnosis and cancer therapy. The biological effects that are brought about by DNA nanostructures are highlighted by in vitro and in vivo imaging, antitumor drug delivery, and immunostimulatory therapy. The challenges and perspectives of DNA nanostructures in the field of nanomedicine are discussed.

  19. Relationship between drug interactions and drug-related negative clinical outcomes in two community pharmacies

    Directory of Open Access Journals (Sweden)

    Gonzalo M

    2009-03-01

    Full Text Available Drug interactions may represent an iatrogenic risk that should be controlled in community pharmacies at the dispensing level. Aim: We analyzed the association between potential drug-drug interactions (DDIs and negative clinical outcomes.Methods: We used dispensing data from two community pharmacies: instances where drug dispensing was associated with a potential DDI and a comparison group of randomized dispensing operations with no potential DDI. In cases where potential DDIs were detected, we analyzed the underlying negative clinical outcomes. Age and gender data were included in the analysis.Results: During the study period, we registered 417 potential DDIs. The proportion of women and age were higher in the study group than in the comparison group. The average potential DDIs per patient was 1.31 (SD=0.72. The Consejo General de Colegios Oficiales de Farmacéuticos (CGCOF database did not produce an alert in 2.4% of the cases. Over-the-counter medication use was observed in 5% of the potential DDI cases. The drugs most frequently involved in potential DDIs were acenocoumarol, calcium salts, hydrochlorothiazide, and alendronic acid, whereas the most predominant potential DDIs were calcium salts and bisphosphonates, oral antidiabetics and thiazide diuretics, antidiabetics and glucose, and oral anticoagulant and paracetamol. The existence of a drug-related negative clinical outcome was observed only in 0.96% of the potential DDI cases (50% safety cases and 50% effectiveness cases. Conclusions: Only a small proportion of the detected potential DDIs lead to medication negative outcomes. Considering the drug-related negative clinical outcomes encountered, tighter control would be recommended in potential DDIs with NSAIDs or benzodiazepines.

  20. Appropriate Use of Drug Testing in Clinical Addiction Medicine.

    Science.gov (United States)

    Jarvis, Margaret; Williams, Jessica; Hurford, Matthew; Lindsay, Dawn; Lincoln, Piper; Giles, Leila; Luongo, Peter; Safarian, Taleen

    : Biological drug testing is a tool that provides information about an individual's recent substance use. Like any tool, its value depends on using it correctly; that is, on selecting the right test for the right person at the right time. This document is intended to clarify appropriate clinical use of drug testing in addiction medicine and aid providers in their decisions about drug testing for the identification, diagnosis, treatment, and recovery of patients with, or at risk for, addiction. The RAND Corporation (RAND)/University of California, Los Angeles (UCLA) Appropriateness Method (RAM) process for combining scientific evidence with the collective judgment of experts was used to identify appropriate clinical practices and highlight areas where research is needed. Although consensus panels and expert groups have offered guidance on the use of drug testing for patients with addiction, very few addressed considerations for patients across settings and in different levels of care. This document will focus primarily on patients in addiction treatment and recovery, where drug testing is used to assess patients for a substance use disorder, monitor the effectiveness of a treatment plan, and support recovery. Inasmuch as the scope includes the recognition of addiction, which often occurs in general healthcare settings, selected special populations at risk for addiction visiting these settings are briefly included.

  1. A new wide field-of-view confocal imaging system and its applications in drug discovery and pathology

    Science.gov (United States)

    Li, Gang; Damaskinos, Savvas; Dixon, Arthur E.; Lee, Lucy E. J.

    2005-11-01

    Conventional widefield light microscopy and confocal scanning microscopy have been indispensable for pathology and drug discovery research. Clinical specimens from diseased tissues are examined, new drug candidates are tested on drug targets, and the morphological and molecular biological changes of cells and tissues are observed. High throughput screening of drug candidates requires highly efficient screening instruments. A standard biomedical slide is 1 by 3 inches (25.4 by 76.2 mm) in size. A typical tissue specimen is 10 mm in diameter. To form a high resolution image of the entire specimen, a conventional widefield light microscope must acquire a large number of small images of the specimen, and then tile them together, which is tedious, inefficient and error-prone. A patented new wide field-of-view confocal scanning laser imaging system has been developed for tissue imaging, which is capable of imaging an entire microscope slide without tiling. It is capable of operating in brightfield, reflection and epi-fluorescence imaging modes. Three (red, green and blue (RGB)) lasers are used to produce brightfield and reflection images, and to excite various fluorophores. This new confocal system makes examination of large biomedical specimens more efficient, and makes fluorescence examination of large specimens possible for the first time without tiling. Description of the new confocal technology and applications of the imaging system in pathology and drug discovery research, for example, imaging large tissue specimens, tissue microarrays, and zebrafish sections, are reported in this paper.

  2. Magnetic nanoparticles with dual functional properties: drug delivery and magnetic resonance imaging.

    Science.gov (United States)

    Jain, Tapan K; Richey, John; Strand, Michelle; Leslie-Pelecky, Diandra L; Flask, Chris A; Labhasetwar, Vinod

    2008-10-01

    There is significant interest in recent years in developing magnetic nanoparticles (MNPs) having multifunctional characteristics with complimentary roles. In this study, we investigated the drug delivery and magnetic resonance imaging (MRI) properties of our novel oleic acid-coated iron-oxide and pluronic-stabilized MNPs. The drug incorporation efficiency of doxorubicin and paclitaxel (alone or in combination) in MNPs was 74-95%; the drug release was sustained and the incorporated drugs had marginal effects on physical (size and zeta potential) and magnetization properties of the MNPs. The drugs in combination incorporated in MNPs demonstrated highly synergistic antiproliferative activity in MCF-7 breast cancer cells. The T2 relaxivity (r(2)) was higher for our MNPs than Feridex IV, whereas the T1 relaxivity (r(1)) was better for Feridex IV than for our MNPs, suggesting greater sensitivity of our MNPs than Feridex IV in T2 weighted imaging. The circulation half-life (t(1/2)), determined from the changes in the MRI signal intensity in carotid arteries in mice, was longer for our MNPs than Feridex IV (t(1/2)=31.2 vs. 6.4 min). MNPs with combined characteristics of MRI and drug delivery could be of high clinical significance in the treatment of various disease conditions.

  3. Mouse models for pre-clinical drug testing in leukemia.

    Science.gov (United States)

    Bhatia, Sanil; Daschkey, Svenja; Lang, Franziska; Borkhardt, Arndt; Hauer, Julia

    2016-11-01

    The development of novel drugs which specifically target leukemic cells, with the overall aim to increase complete remission and to reduce toxicity and morbidity, is the most important prerequisite for modern leukemia treatment. In this regard, the current transition rate of potential novel drugs from bench to bedside is remarkably low. Although many novel drugs show promising data in vitro and in vivo, testing of these medications in clinical phase I trials is often sobering with intolerable toxic side effects leading to failure in FDA approval. Areas covered: In this review, the authors discuss the development of murine model generation in the context of targeted therapy development for the treatment of childhood leukemia, aiming to decrease the attrition rate of progressively complex targeted therapies ranging from small molecules to cell therapy. As more complex therapeutic approaches develop, more complex murine models are needed, to recapitulate closely the human phenotype. Expert opinion: Combining xenograft models for efficacy testing and GEMMs for toxicity testing will be a global approach for pre-clinical testing of complex therapeutics and will contribute to the clinical approval of novel compounds. Finally, this approach is likely to increase clinical approval of novel compounds.

  4. Drug Development and Challenges for Neuromuscular Clinical Trials.

    Science.gov (United States)

    El Mouelhi, Mohamed

    2016-03-01

    Drug development process faces many challenges, including those encountered in clinical trials for neuromuscular diseases. Drug development is a lengthy and highly costly process. Out of 10 compounds entering first study in man (phase 1), only one compound reaches the market after an average of 14 years with a cost of $2.7 billion. Nevertheless, according to the Centers for Medicare and Medicaid services, prescription drugs constituted only 9 % of each health care dollar spent in USA in 2013. Examples of challenges encountered in neuromuscular clinical trials include lack of validated patient-reported outcome tools, blinding issues, and the use of placebo in addition to lack of health authority guidance for orphan diseases. Patient enrollment challenge is the leading cause of missed clinical trial deadlines observed in about 80 % of clinical trials, resulting in delayed availability of potentially life-saving therapies. Another specific challenge introduced by recent technology is the use of social media and risk of bias. Sharing personal experiences while in the study could easily introduce bias among patients that would interfere with accurate interpretation of collected data. To minimize this risk, recent neuromuscular studies incorporate as an inclusion criterion the patient's agreement not to share any of study experiences through social media with other patients during the study conduct. Consideration of these challenges will allow timely response to the high unmet medical needs for many neuromuscular diseases.

  5. Hypericum perforatum: pharmacokinetic, mechanism of action, tolerability, and clinical drug-drug interactions.

    Science.gov (United States)

    Russo, Emilio; Scicchitano, Francesca; Whalley, Benjamin J; Mazzitello, Carmela; Ciriaco, Miriam; Esposito, Stefania; Patanè, Marinella; Upton, Roy; Pugliese, Michela; Chimirri, Serafina; Mammì, Maria; Palleria, Caterina; De Sarro, Giovambattista

    2014-05-01

    Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP.

  6. 78 FR 734 - Medical Imaging Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-01-04

    ... HUMAN SERVICES Food and Drug Administration Medical Imaging Drugs Advisory Committee; Notice of Meeting... the public. Name of Committee: Medical Imaging Drugs Advisory Committee. General Function of the... resonance imaging in brain (intracranial), spine, and associated tissues in adults and pediatric patients...

  7. Novel Polysaccharide Based Polymers and Nanoparticles for Controlled Drug Delivery and Biomedical Imaging

    Science.gov (United States)

    Shalviri, Alireza

    The use of polysaccharides as building blocks in the development of drugs and contrast agents delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, upgradability, multiple reacting groups and low cost. The focus of this thesis was to develop and characterize novel starch based hydrogels and nanoparticles for delivery of drugs and imaging agents. To this end, two different systems were developed. The first system includes polymer and nanoparticles prepared by graft polymerization of polymethacrylic acid and polysorbate 80 onto starch. This starch based platform nanotechnology was developed using the design principles based on the pathophysiology of breast cancer, with applications in both medical imaging and breast cancer chemotherapy. The nanoparticles exhibited a high degree of doxorubicin loading as well as sustained pH dependent release of the drug. The drug loaded nanoparticles were significantly more effective against multidrug resistant human breast cancer cells compared to free doxorubicin. Systemic administration of the starch based nanoparticles co-loaded with doxorubicin and a near infrared fluorescent probe allowed for non-invasive real time monitoring of the nanoparticles biodistribution, tumor accumulation, and clearance. Systemic administration of the clinically relevant doses of the drug loaded particles to a mouse model of breast cancer significantly enhanced therapeutic efficacy while minimizing side effects compared to free doxorubicin. A novel, starch based magnetic resonance imaging (MRI) contrast agent with good in vitro and in vivo tolerability was formulated which exhibited superior signal enhancement in tumor and vasculature. The second system is a co-polymeric hydrogel of starch and xanthan gum with adjustable swelling and permeation properties. The hydrogels exhibited excellent film forming capability, and appeared to be particularly useful in

  8. Liposomal drug delivery system from laboratory to clinic

    Directory of Open Access Journals (Sweden)

    Kshirsagar N

    2005-01-01

    Full Text Available The main objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action and to achieve greater efficacy and minimise the toxic effects compared to conventional drugs. Amongst various carrier systems, liposomes have generated a great interest because of their versatility. Liposomes are vesicular concentric bilayered structures, which are biocompatible, biodegradable and nonimmumnogenic. They can control the delivery of drugs by targeting the drug to the site of action or by site avoidance drug delivery or by prolonged circulation of drugs. Amphotericin B (Amp B remains the drug of choice in most systemic mycoses and also as a second line treatment for Kala azar. However, its toxic effects often limit its use. Although the liposome delivery system has been tried for several drugs, only a few have been used in patients due to the slow development of necessary large-scale pharmaceutical procedures. This paper reviews the development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, FungisomeTM drug delivery system in our laboratory in collaboration with the department of Biochemistry, Delhi University in India and proving the safety and efficacy of this preparation in clinical practice. It also attempts to compare the efficacy and benefits of our product for Indian patients with those of similar products and it includes facts from the publications that flowed from our work. As compared to conventional Amp B, Fungisome is infused over a much shorter period requiring a smaller volume and no premedication. It was found to be safe in patients who had developed serious unacceptable toxicity with conventional Amp B. In renal transplant patients, Fungisome did not produce any nephrotoxicity. Fungisome is effective in fungal infections resistant to fluconazole, conventional Amp B and in virgin and resistant cases of visceral leishmaniasis. The cost of any drug is of great significance, especially in India

  9. The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

    Science.gov (United States)

    Sacramento, Carolina Q.; de Melo, Gabrielle R.; de Freitas, Caroline S.; Rocha, Natasha; Hoelz, Lucas Villas Bôas; Miranda, Milene; Fintelman-Rodrigues, Natalia; Marttorelli, Andressa; Ferreira, André C.; Barbosa-Lima, Giselle; Abrantes, Juliana L.; Vieira, Yasmine Rangel; Bastos, Mônica M.; de Mello Volotão, Eduardo; Nunes, Estevão Portela; Tschoeke, Diogo A.; Leomil, Luciana; Loiola, Erick Correia; Trindade, Pablo; Rehen, Stevens K.; Bozza, Fernando A.; Bozza, Patrícia T.; Boechat, Nubia; Thompson, Fabiano L.; de Filippis, Ana M. B.; Brüning, Karin; Souza, Thiago Moreno L.

    2017-01-01

    Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma (Huh-7) cells, neuroblastoma (SH-Sy5y) cells, neural stem cells (NSC) and brain organoids. In addition to the direct inhibition of the viral RNA polymerase, we observed that sofosbuvir also induced an increase in A-to-G mutations in the viral genome. Together, our data highlight a potential secondary use of sofosbuvir, an anti-HCV drug, against ZIKV. PMID:28098253

  10. Emerging drugs of abuse: clinical and legal considerations.

    Science.gov (United States)

    Aoun, Elie G; Christopher, Paul P; Ingraham, James W

    2014-06-02

    Over the past several decades, nontraditional drugs of abuse, including bath salts, synthetic cannabinoids, and salvia, have increased in popularity and use. Despite this fact, they remain unfamiliar to many healthcare providers. Commonly marketed as "legal highs," these substances are being used for their desired neuropsychiatric effects, taking advantage of their accessibility, low cost, variable legality, and limited detection on traditional urine drug screens. Similar to traditional drugs of abuse, these substances have varying degrees of toxicity and may lead to potentially adverse effects, ranging from benign to life threatening. This paper offers a review of three of the more widely-used emerging drugs (or classes of drugs): bath salts, synthetic cannabinoids, and salvia. For each we review its history and development, the neurochemical basis for its clinical effects, the nature and route of ingestion, the range of desired effects, potential toxicities, diagnostic and therapeutic approaches, as well as social and legal considerations. [Full text available at http://rimed.org/rimedicaljournal-2014-06.asp, free with no login].

  11. BACE1 inhibitor drugs in clinical trials for Alzheimer's disease.

    Science.gov (United States)

    Vassar, Robert

    2014-01-01

    β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the β-secretase enzyme required for the production of the neurotoxic β-amyloid (Aβ) peptide that is widely considered to have a crucial early role in the etiology of Alzheimer's disease (AD). As a result, BACE1 has emerged as a prime drug target for reducing the levels of Aβ in the AD brain, and the development of BACE1 inhibitors as therapeutic agents is being vigorously pursued. It has proven difficult for the pharmaceutical industry to design BACE1 inhibitor drugs that pass the blood-brain barrier, however this challenge has recently been met and BACE1 inhibitors are now in human clinical trials to test for safety and efficacy in AD patients and individuals with pre-symptomatic AD. Initial results suggest that some of these BACE1 inhibitor drugs are well tolerated, although others have dropped out because of toxicity and it is still too early to know whether any will be effective for the prevention or treatment of AD. Additionally, based on newly identified BACE1 substrates and phenotypes of mice that lack BACE1, concerns have emerged about potential mechanism-based side effects of BACE1 inhibitor drugs with chronic administration. It is hoped that a therapeutic window can be achieved that balances safety and efficacy. This review summarizes the current state of progress in the development of BACE1 inhibitor drugs and the evaluation of their therapeutic potential for AD.

  12. The addicted brain: imaging neurological complications of recreational drug abuse.

    Science.gov (United States)

    Montoya-Filardi, A; Mazón, M

    Recreational drug abuse represents a serious public health problem. Neuroimaging traditionally played a secondary role in this scenario, where it was limited to detecting acute vascular events. However, thanks to advances in knowledge about disease and in morphological and functional imaging techniques, radiologists have now become very important in the diagnosis of acute and chronic neurological complications of recreational drug abuse. The main complications are neurovascular disease, infection, toxicometabolic disorders, and brain atrophy. The nonspecific symptoms and denial of abuse make the radiologist's involvement fundamental in the management of these patients. Neuroimaging makes it possible to detect early changes and to suggest an etiological diagnosis in cases with specific patterns of involvement. We aim to describe the pattern of abuse and the pathophysiological mechanisms of the drugs with the greatest neurological repercussions as well as to illustrate the depiction of the acute and chronic cerebral complications on conventional and functional imaging techniques. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Counterfeiting in performance- and image-enhancing drugs.

    Science.gov (United States)

    Graham, Michael R; Ryan, Paul; Baker, Julien S; Davies, Bruce; Thomas, Non-Eleri; Cooper, Stephen-Mark; Evans, Peter; Easmon, Sue; Walker, Christopher J; Cowan, David; Kicman, Andrew T

    2009-03-01

    The current drastic escalation in obesity may be contributing to the exponential rise in drugs used for image enhancement. Drugs such as anabolic-androgenic steroids (AAS) are perceived as a viable method of achieving a perfect physique. They are also the most widely abused drugs in sport. The Internet has encouraged the abuse of expensive drugs, particularly human growth hormone (hGH), resulting in increased importation for personal use. The substantial increase in this market has opened up avenues for counterfeiting, estimated as a multi-million pound business. The acute adverse effects from contaminated vials may result in a variety of pathologies including communicable diseases. In 2007, in the UK, a series of intramuscular abscesses, requiring surgical treatment, led us to study samples obtained from the underground market. The analysis of 38 parenteral samples and 19 oral samples of tablets was performed by a World Anti-Doping Agency (WADA) accredited laboratory, in an attempt to establish the extent of available counterfeit products. Fifty-three per cent (20) of the injectable AAS esters and 21% (4) of the oral tablets were counterfeit. Culture and sensitivity revealed the presence of skin commensal organisms, which may have contributed to the development of the abscesses. Users of AAS and hGH for sport, including bodybuilding, are currently risking their health because of counterfeit and poorly controlled products.

  14. Advances in functional magnetic resonance imaging: technology and clinical applications.

    Science.gov (United States)

    Dickerson, Bradford C

    2007-07-01

    Functional MRI (fMRI) is a valuable method for use by clinical investigators to study task-related brain activation in patients with neurological or neuropsychiatric illness. Despite the relative infancy of the field, the rapid adoption of this functional neuroimaging technology has resulted from, among other factors, its ready availability, its relatively high spatial and temporal resolution, and its safety as a noninvasive imaging tool that enables multiple repeated scans over the course of a longitudinal study, and thus may lend itself well as a measure in clinical drug trials. Investigators have used fMRI to identify abnormal functional brain activity during task performance in a variety of patient populations, including those with neurodegenerative, demyelinating, cerebrovascular, and other neurological disorders that highlight the potential utility of fMRI in both basic and clinical spheres of research. In addition, fMRI studies reveal processes related to neuroplasticity, including compensatory hyperactivation, which may be a universally-occurring, adaptive neural response to insult. Functional MRI is being used to study the modulatory effects of genetic risk factors for neurological disease on brain activation; it is being applied to differential diagnosis, as a predictive biomarker of disease course, and as a means to identify neural correlates of neurotherapeutic interventions. Technological advances are rapidly occurring that should provide new applications for fMRI, including improved spatial resolution, which promises to reveal novel insights into the function of fine-scale neural circuitry of the human brain in health and disease.

  15. The drug discovery by nanomedicine and its clinical experience.

    Science.gov (United States)

    Matsumura, Yasuhiro

    2014-06-01

    It is expected that the incidence of various adverse effects of anticancer agents maybe decreased owing to the reduced drug distribution in normal tissue. Anticancer agent incorporating nanoparticles including micelles and liposomes can evade non-specific capture by the reticuloendothelial system because the outer shell of the nanoparticles is covered with polyethylene glycol. Consequently, the micellar and liposomal carrier can be delivered selectively to a tumor by utilizing the enhanced permeability and retention effect. Presently, several anticancer agent-incorporating nano-carrier systems are under preclinical and clinical evaluation. Several drug delivery system formulations have been approved worldwide. Regarding a pipeline of clinical development of anticancer agent incorporating micelle carrier system, several clinical trials are now underway not only in Japan but also in other countries. A Phase 3 trial of NK105, a paclitaxel incorporating micelle is now underway. In this paper, preclinical and clinical studies of NK105, NC-6004, cisplatin incorporating micelle, NC-6300, epirubicin incorporating micelle and the concept of cancer stromal targeting therapy using nanoparticles and monoclonal antibodies against cancer related stromal components are reviewed.

  16. PROPOSAL OF GUIDELINE FOR CLINICAL TRIAL PROTOCOLS WITH HERBAL DRUGS

    Directory of Open Access Journals (Sweden)

    Migdacelys Arboláez Estrada.

    2007-04-01

    Full Text Available SUMMARYCuba has extensive experience about herbal drugs, however only a few products get to the clinical phase of drug development. Our objective was to design new guidelines for clinical trials with herbal drugs.A detailed bibliographic search about regulatory aspects about clinical trials in Cuba and the world was done for development of the guideline. The guideline's proposed format includes: 1 Index, including the classification of the content. 2 Summary, 3 Fifteen chapters, related to the clinical trials. The guideline also propose the inclusion of annexes.A new guideline containing 15 chapters allows for writing more clear and detailed clinical trial protocols. The guideline contains the information required to guide the research staff who is interested in the validation of herbal drugs pharmacological activations from the perspective of clinical trials. RESUMEN Cuba tiene experiencia extensa sobre plantas medicinales, aunque solo algunos productos llegan a una fase clínica del desarrollo. Nuestro objetivo fué diseñar una nueva guía para ensayos clínicos con plantas medicinales.Hemos realizado una detallada búsqueda bibliográfica sobre aspectos reguladores de ensayos clínicos en Cuba y el resto del mundo para el desarrollo de la guía. El formato propuesto de la guia incluye: 1 Índice, incluyendo la clasificación de los contenidos. 2 Resumen, 3 Quince capítulos, relacionados con los ensayos clínicos. La guía también propone la inclusión de anexos.La nueva guía que contiene 15 capítulos que orientan la redacción de protocolos de ensayos clínicos más claros y más detallados. La guía contiene la información requerida para orientar al personal investigador interesado en la validación de la actividad farmacológica de las plantas medicinales desde la perspectiva de los ensayos clínicos.

  17. IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer

    Science.gov (United States)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M.; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui; Yang, Lily

    2016-05-01

    Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

  18. Multi-regional clinical trials and global drug development

    Directory of Open Access Journals (Sweden)

    Premnath Shenoy

    2016-01-01

    Full Text Available Drug development has been globalized, and multi-regional clinical trial (MRCT for regulatory submission has widely been conducted by many discovery based global pharmaceutical companies with the objective of reducing the time lag of launch in key markets and improve patient access to new and innovative treatments. Sponsors are facing several challenges while conducting multiregional clinical trials. Challenges under the heads statistics, clinical, regulatory operational, and ethics have been discussed. Regulators in different countries such as USA, EU-Japan, and China have issued guidance documents in respect of MRCT's. Lack of harmonization in the design and planning of MRCT is perceived to create a difficult situation to sponsors adversely affecting progressing MRCT in more and more discoveries. International conference on hormonisation (ICH has initiated the process for having a harmonized guidance document on MRCT. This document is likely to be issued in early 2017.

  19. The pre-clinical discovery of Amyotrophic Lateral Sclerosis Drugs

    Science.gov (United States)

    Glicksman, Marcie A.

    2012-01-01

    Introduction Amyotrophic Lateral Sclerosis, also referred to as Lou Gehrig’s disease is characterized by the progressive loss of cells in the brain and spinal cord that leads to debilitation and death in 3–5 years. Only one therapeutic drug, Riluzole, has been approved for ALS and that drug improves survival by 2–3 months. The need for new therapeutics, either that can postpone or slow the progression of the motor deficits and prolong survival, is still a strong unmet medical need. Areas Covered Although there are a number of drugs currently in clinical trials for ALS, this review provides an overview of the most promising biological targets and preclinical strategies that are currently being developed and deployed. The list of targets for ALS was compiled from a variety of websites including: individual companies that have ALS programs, and the author’s experience. Expert Opinion Progress is being made in the identification of possible new therapeutics for ALS with recent efforts in: understanding the genetic causes of the disease, susceptibility factors, and the development of additional preclinical animal models. However, many challenges remain in the identification of new ALS therapeutics including: the use of relevant biomarkers, the need for earlier diagnosis of the disease, and additional animal models. Multiple strategies need to be tested, in the clinic, in order to determine what will be effective in patients. PMID:22646982

  20. 75 FR 51824 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2010-08-23

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practice; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. ] SUMMARY: The Food and Drug Administration (FDA) New Jersey...

  1. 3-D Image Analysis of Fluorescent Drug Binding

    Directory of Open Access Journals (Sweden)

    M. Raquel Miquel

    2005-01-01

    Full Text Available Fluorescent ligands provide the means of studying receptors in whole tissues using confocal laser scanning microscopy and have advantages over antibody- or non-fluorescence-based method. Confocal microscopy provides large volumes of images to be measured. Histogram analysis of 3-D image volumes is proposed as a method of graphically displaying large amounts of volumetric image data to be quickly analyzed and compared. The fluorescent ligand BODIPY FL-prazosin (QAPB was used in mouse aorta. Histogram analysis reports the amount of ligand-receptor binding under different conditions and the technique is sensitive enough to detect changes in receptor availability after antagonist incubation or genetic manipulations. QAPB binding was concentration dependent, causing concentration-related rightward shifts in the histogram. In the presence of 10 μM phenoxybenzamine (blocking agent, the QAPB (50 nM histogram overlaps the autofluorescence curve. The histogram obtained for the 1D knockout aorta lay to the left of that of control and 1B knockout aorta, indicating a reduction in 1D receptors. We have shown, for the first time, that it is possible to graphically display binding of a fluorescent drug to a biological tissue. Although our application is specific to adrenergic receptors, the general method could be applied to any volumetric, fluorescence-image-based assay.

  2. Clinically relevant transmitted drug resistance to first line antiretroviral drugs and implications for recommendations.

    Directory of Open Access Journals (Sweden)

    Susana Monge

    Full Text Available BACKGROUND: The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR defined by the 2009 update of the WHO SDRM list. METHODS: We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain between 2007-2011. Using the Stanford algorithm "Low-level resistance", "Intermediate resistance" and "High-level resistance" categories were considered as "Resistant". RESULTS: 70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8-7.7], and 221 harbored TDR using the WHO list [7.9% (6.9-9.0]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8-2.9 vs. 3.6% (2.9-4.3 by the WHO list] and PIs [0.8% (0.4-1.1 vs. 1.7% (1.2-2.2], while it was higher for NNRTIs [4.6% (3.8-5.3 vs. 3.7% (3.0-4.7]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02. CONCLUSIONS: Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations.

  3. Perinatal clinical and imaging features of CLOVES syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Pineda, Israel [Virgen del Rocio Children' s Hospital, Department of Pediatric Surgery, Seville (Spain); Fajardo, Manuel [Virgen del Rocio Children' s Hospital, Department of Pediatric Radiology, Seville (Spain); Chaudry, Gulraiz; Alomari, Ahmad I. [Children' s Hospital Boston and Harvard Medical School, Division of Vascular and Interventional Radiology, Boston, MA (United States)

    2010-08-15

    We report a neonate with antenatal imaging features suggestive of CLOVES syndrome. Postnatal clinical and imaging findings confirmed the diagnosis, with the constellation of truncal overgrowth, cutaneous capillary malformation, lymphatic and musculoskeletal anomalies. The clinical, radiological and histopathological findings noted in this particular phenotype help differentiate it from other overgrowth syndromes with complex vascular anomalies. (orig.)

  4. Radionuclide imaging technologies and their use in evaluating asthma drug deposition in the lungs.

    Science.gov (United States)

    Newman, Stephen P; Pitcairn, Gary R; Hirst, Peter H; Rankin, Lisa

    2003-07-18

    Whole lung and regional lung deposition of inhaled asthma drugs in the lungs can be quantified using either two-dimensional or three-dimensional radionuclide imaging methods. The two-dimensional method of gamma scintigraphy has been the most widely used, and is currently considered the industry standard, but the three-dimensional methods (SPECT, single photon emission computed tomography; and PET, positron emission tomography) give superior regional lung deposition data and will undoubtedly be used more frequently in future. Recent developments in radionuclide imaging are described, including an improved algorithm for assessing regional lung deposition in gamma scintigraphy, and a patent-protected radiolabelling method (TechneCoat), applicable to both gamma scintigraphy and SPECT. Radionuclide imaging data on new inhaled asthma products provide a milestone assessment, and the data form a bridge between in vitro testing and a full clinical trials program, allowing the latter to be entered with increased confidence.

  5. Application of aptamers in diagnostics, drug-delivery and imaging

    Indian Academy of Sciences (India)

    CHETAN CHANDOLA; SHEETAL KALME; MARCO G CASTELEIJN; ARTO URTTI; MUNIASAMY NEERATHILINGAM

    2016-09-01

    Aptamers are small, single-stranded oligonucleotides (DNA or RNA) that bind to their target with high specificity andaffinity. Although aptamers are analogous to antibodies for a wide range of target recognition and variety ofapplications, they have significant advantages over antibodies. Since aptamers have recently emerged as a class ofbiomolecules with an application in a wide array of fields, we need to summarize the latest developments herein. Inthis review we will discuss about the latest developments in using aptamers in diagnostics, drug delivery and imaging.We begin with diagnostics, discussing the application of aptamers for the detection of infective agents itself, antigens/toxins (bacteria), biomarkers (cancer), or a combination. The ease of conjugation and labelling of aptamers makesthem a potential tool for diagnostics. Also, due to the reduced off-target effects of aptamers, their use as a potentialdrug delivery tool is emerging rapidly. Hence, we discuss their use in targeted delivery in conjugation with siRNAs,nanoparticles, liposomes, drugs and antibodies. Finally, we discuss about the conjugation strategies applicable forRNA and DNA aptamers for imaging. Their stability and self-assembly after heating makes them superior overprotein-based binding molecules in terms of labelling and conjugation strategies.

  6. Photoacoustic Imaging in Oncology: Translational Preclinical and Early Clinical Experience.

    Science.gov (United States)

    Valluru, Keerthi S; Wilson, Katheryne E; Willmann, Jürgen K

    2016-08-01

    Photoacoustic imaging has evolved into a clinically translatable platform with the potential to complement existing imaging techniques for the management of cancer, including detection, characterization, prognosis, and treatment monitoring. In photoacoustic imaging, tissue is optically excited to produce ultrasonographic images that represent a spatial map of optical absorption of endogenous constituents such as hemoglobin, fat, melanin, and water or exogenous contrast agents such as dyes and nanoparticles. It can therefore provide functional and molecular information that allows noninvasive soft-tissue characterization. Photoacoustic imaging has matured over the years and is currently being translated into the clinic with various clinical studies underway. In this review, the current state of photoacoustic imaging is presented, including techniques and instrumentation, followed by a discussion of potential clinical applications of this technique for the detection and management of cancer. (©) RSNA, 2016.

  7. Methodological issues in clinical drug development for essential tremor.

    Science.gov (United States)

    Carranza, Michael A; Snyder, Madeline R; Elble, Rodger J; Boutzoukas, Angelique E; Zesiewicz, Theresa A

    2012-01-01

    Essential tremor (ET) is one of the most common tremor disorders in the world. Despite this, only two medications have received Level A recommendations from the American Academy of Neurology to treat it (primidone and propranolol). Even though these medications provide relief to a large group of ET patients, up to 50% of patients are non-responders. Additional medications to treat ET are needed. This review discusses some of the methodological issues that should be addressed for quality clinical drug development in ET.

  8. Brain imaging with synthetic MR in children: clinical quality assessment

    Energy Technology Data Exchange (ETDEWEB)

    Betts, Aaron M.; Serai, Suraj [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Leach, James L.; Jones, Blaise V. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); University of Cincinnati College of Medicine, Cincinnati, OH (United States); Zhang, Bin [Cincinnati Children' s Hospital Medical Center, Biostatistics and Epidemiology, Cincinnati, OH (United States)

    2016-10-15

    Synthetic magnetic resonance imaging is a quantitative imaging technique that measures inherent T1-relaxation, T2-relaxation, and proton density. These inherent tissue properties allow synthesis of various imaging sequences from a single acquisition. Clinical use of synthetic MR imaging has been described in adult populations. However, use of synthetic MR imaging has not been previously reported in children. The purpose of this study is to report our assessment of diagnostic image quality using synthetic MR imaging in children. Synthetic MR acquisition was obtained in a sample of children undergoing brain MR imaging. Image quality assessments were performed on conventional and synthetic T1-weighted, T2-weighted, and FLAIR images. Standardized linear measurements were performed on conventional and synthetic T2 images. Estimates of patient age based upon myelination patterns were also performed. Conventional and synthetic MR images were evaluated on 30 children. Using a 4-point assessment scale, conventional imaging performed better than synthetic imaging for T1-weighted, T2-weighted, and FLAIR images. When the assessment was simplified to a dichotomized scale, the conventional and synthetic T1-weighted and T2-weighted images performed similarly. However, the superiority of conventional FLAIR images persisted in the dichotomized assessment. There were no statistically significant differences between linear measurements made on T2-weighted images. Estimates of patient age based upon pattern of myelination were also similar between conventional and synthetic techniques. Synthetic MR imaging may be acceptable for clinical use in children. However, users should be aware of current limitations that could impact clinical utility in the software version used in this study. (orig.)

  9. Use of "big data" in drug discovery and clinical trials.

    Science.gov (United States)

    Taglang, Guillaume; Jackson, David B

    2016-04-01

    Oncology is undergoing a data-driven metamorphosis. Armed with new and ever more efficient molecular and information technologies, we have entered an era where data is helping us spearhead the fight against cancer. This technology driven data explosion, often referred to as "big data", is not only expediting biomedical discovery, but it is also rapidly transforming the practice of oncology into an information science. This evolution is critical, as results to-date have revealed the immense complexity and genetic heterogeneity of patients and their tumors, a sobering reminder of the challenge facing every patient and their oncologist. This can only be addressed through development of clinico-molecular data analytics that provide a deeper understanding of the mechanisms controlling the biological and clinical response to available therapeutic options. Beyond the exciting implications for improved patient care, such advancements in predictive and evidence-based analytics stand to profoundly affect the processes of cancer drug discovery and associated clinical trials.

  10. Clinical applications of choroidal imaging technologies

    Directory of Open Access Journals (Sweden)

    Jay Chhablani

    2015-01-01

    Full Text Available Choroid supplies the major blood supply to the eye, especially the outer retinal structures. Its understanding has significantly improved with the advent of advanced imaging modalities such as enhanced depth imaging technique and the newer swept source optical coherence tomography. Recent literature reports the findings of choroidal changes, quantitative as well as qualitative, in various chorioretinal disorders. This review article describes applications of choroidal imaging in the management of common diseases such as age-related macular degeneration, high myopia, central serous chorioretinopathy, chorioretinal inflammatory diseases, and tumors. This article briefly discusses future directions in choroidal imaging including angiography.

  11. Imaging of a targeted PDT drug with fluorescence tomography

    Science.gov (United States)

    Muffoletto, Dan; Gupta, Anurag; Xu, Zhiqiang; Mahrer, Chris; Bauer, Gretchen; Galas, Scott; Pandey, Ravindra K.; Sunar, Ulas

    2009-02-01

    We constructed a whole-body fluorescence tomography instrument to monitor novel bifunctional phototherapeutic drugs (e.g., HPPH-Cyanine dye conjugate) in small animals. The instrument allows dense source and detector sampling with a fast galvo scanner and a CCD detector for improved resolution and sensitivity (Patwardhan et al., 2005). Here we report tissue phantom measurements to evaluate the imaging performance with a newly constructed tomography instrument. Phantom measurements showed that strong fluorescence generated by HPPH-Cyanine dye (HPPH-CD), having high fluorescence quantum yield and long wavelength fluorescence emission, allowed deep tissue imaging. We also report in vivo fluorescence measurements of the conjugate in Nude mice bearing A549 human non-small cell lung carcinoma (NSCLC) tumors at 24 hr post injection to evaluate tumor detection ability of the conjugate. Our results indicate that the HPPH-CD shows preferential uptake in tumors compared to surrounding normal tissue at 24 hr post injection. This study demonstrates a potential use of HPPH-CD in detection (fluorescence imaging) and treatment (PDT) of deeply seated tumors.

  12. Liver Effects of Clinical Drugs Differentiated in Human Liver Slices

    Directory of Open Access Journals (Sweden)

    Alison E. M. Vickers

    2017-03-01

    Full Text Available Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM, diclofenac (DCF, 1 mM and etomoxir (ETM, 100 μM. Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM and cyclosporin A (CSA, 10 μM, while GSH was affected more than ATP by methimazole (MMI, 500 μM, terbinafine (TBF, 100 μM, and carbamazepine (CBZ 100 μM. Oxidative stress genes were affected by TBF (18%, CBZ, APAP, and ETM (12%–11%, and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%–6%. Apoptosis genes were affected by DCF (14%, while apoptosis plus necrosis were altered by APAP and ETM (15%. Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%, ETM (66%, DCF, TBF, MMI (61%–60%, APAP, CBZ (57%–56%, and DTL (48%. Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%, CBZ and ETM (44%–43%, APAP and DCF (40%–38%, MMI, TBF and CSA (37%–35%. This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

  13. Smart drug delivery systems: from fundamentals to the clinic.

    Science.gov (United States)

    Alvarez-Lorenzo, Carmen; Concheiro, Angel

    2014-07-25

    Forty years after the first reports on stimuli-responsive phase transitions in synthetic hydrogels, the first medicines based on responsive components are approaching the market. Sensitiveness to internal or external signals of the body can be achieved by means of materials (mostly polymers, but also lipids and metals) that modify their properties as a function of the intensity of the signal and that enable the transduction into changes in the delivery system that affect its ability to host/release a therapeutic substance. Integration of responsive materials into implantable depots, targetable nanocarriers and even insertable medical devices can endow them with activation-modulated and feedback-regulated control of drug release. This review offers a critical overview of therapeutically-interesting stimuli to trigger drug release and the evolution of responsive materials suitable as functional excipients, illustrated with recent examples of formulations in clinical trials or already commercially available, which can provide a perspective on the current state of the art on smart drug delivery systems.

  14. Liver Effects of Clinical Drugs Differentiated in Human Liver Slices.

    Science.gov (United States)

    Vickers, Alison E M; Ulyanov, Anatoly V; Fisher, Robyn L

    2017-03-07

    Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM), diclofenac (DCF, 1 mM) and etomoxir (ETM, 100 μM). Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM) and cyclosporin A (CSA, 10 μM), while GSH was affected more than ATP by methimazole (MMI, 500 μM), terbinafine (TBF, 100 μM), and carbamazepine (CBZ 100 μM). Oxidative stress genes were affected by TBF (18%), CBZ, APAP, and ETM (12%-11%), and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%-6%). Apoptosis genes were affected by DCF (14%), while apoptosis plus necrosis were altered by APAP and ETM (15%). Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%), ETM (66%), DCF, TBF, MMI (61%-60%), APAP, CBZ (57%-56%), and DTL (48%). Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%), CBZ and ETM (44%-43%), APAP and DCF (40%-38%), MMI, TBF and CSA (37%-35%). This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

  15. Application of Personal Drug (P-Drug) Seminar to Clinical Pharmacy Education in the Graduate School of Pharmaceutical Sciences

    OpenAIRE

    2002-01-01

    The P-drug seminar, a novel method of teaching the process of rational pharmacotherapy, was introduced in 2000 into the practice program of the clinical pharmacy course in the Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University (TMPU). The P-drug concept is evidence-based drug selection according to criteria (i.e., efficacy, safety, suitability and cost) deter mined in advance and rational prescribing by each physician. The P-drug seminar originated from e...

  16. Salivary Secretory Disorders, Inducing Drugs, and Clinical Management

    Science.gov (United States)

    Miranda-Rius, Jaume; Brunet-Llobet, Lluís; Lahor-Soler, Eduard; Farré, Magí

    2015-01-01

    Background: Salivary secretory disorders can be the result of a wide range of factors. Their prevalence and negative effects on the patient's quality of life oblige the clinician to confront the issue. Aim: To review the salivary secretory disorders, inducing drugs and their clinical management. Methods: In this article, a literature search of these dysfunctions was conducted with the assistance of a research librarian in the MEDLINE/PubMed Database. Results: Xerostomia, or dry mouth syndrome, can be caused by medication, systemic diseases such as Sjögren's Syndrome, glandular pathologies, and radiotherapy of the head and neck. Treatment of dry mouth is aimed at both minimizing its symptoms and preventing oral complications with the employment of sialogogues and topical acting substances. Sialorrhea and drooling, are mainly due to medication or neurological systemic disease. There are various therapeutic, pharmacologic, and surgical alternatives for its management. The pharmacology of most of the substances employed for the treatment of salivary disorders is well-known. Nevertheless, in some cases a significant improvement in salivary function has not been observed after their administration. Conclusion: At present, there are numerous frequently prescribed drugs whose unwanted effects include some kind of salivary disorder. In addition, the differing pathologic mechanisms, and the great variety of existing treatments hinder the clinical management of these patients. The authors have designed an algorithm to facilitate the decision making process when physicians, oral surgeons, or dentists face these salivary dysfunctions. PMID:26516310

  17. 77 FR 35689 - Guidance for Industry on Irritable Bowel Syndrome-Clinical Evaluation of Drugs for Treatment...

    Science.gov (United States)

    2012-06-14

    ... Evaluation of Drugs for Treatment; Availability; Correction AGENCY: Food and Drug Administration, HHS. ACTION... guidance for industry entitled ``Irritable Bowel Syndrome--Clinical Evaluation of Drugs for Treatment...

  18. Antipsychotic drug treatment for patients with schizophrenia: theoretical background, clinical considerations and patients preferences

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Nielsen, Jimmi

    2009-01-01

      The cornerstone in treatment of psychosis is antipsychotic drugs. Treatment options have increased over the years; newer antipsychotic drugs with a proposed efficacy regarding negative and cognitive symptoms, but also a shift in side-effects from neurological side-effects to metabolic side-effe...... treatment. The clinically relevant aspects of antipsychotic drug treatment are reviewed; mechanism of antipsychotic drug action, clinical considerations in treatment, switching antipsychotic drugs, polypharmacy, safety and patient preference.  ...

  19. Programmable Real-time Clinical Photoacoustic and Ultrasound Imaging System.

    Science.gov (United States)

    Kim, Jeesu; Park, Sara; Jung, Yuhan; Chang, Sunyeob; Park, Jinyong; Zhang, Yumiao; Lovell, Jonathan F; Kim, Chulhong

    2016-10-12

    Photoacoustic imaging has attracted interest for its capacity to capture functional spectral information with high spatial and temporal resolution in biological tissues. Several photoacoustic imaging systems have been commercialized recently, but they are variously limited by non-clinically relevant designs, immobility, single anatomical utility (e.g., breast only), or non-programmable interfaces. Here, we present a real-time clinical photoacoustic and ultrasound imaging system which consists of an FDA-approved clinical ultrasound system integrated with a portable laser. The system is completely programmable, has an intuitive user interface, and can be adapted for different applications by switching handheld imaging probes with various transducer types. The customizable photoacoustic and ultrasound imaging system is intended to meet the diverse needs of medical researchers performing both clinical and preclinical photoacoustic studies.

  20. Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials.

    Science.gov (United States)

    Van Heertum, Ronald L; Scarimbolo, Robert; Ford, Robert; Berdougo, Eli; O'Neal, Michael

    2015-01-01

    In the era of personalized medicine, diagnostic approaches are helping pharmaceutical and biotechnology sponsors streamline the clinical trial process. Molecular assays and diagnostic imaging are routinely being used to stratify patients for treatment, monitor disease, and provide reliable early clinical phase assessments. The importance of diagnostic approaches in drug development is highlighted by the rapidly expanding global cancer diagnostics market and the emergent attention of regulatory agencies worldwide, who are beginning to offer more structured platforms and guidance for this area. In this paper, we highlight the key benefits of using companion diagnostics and diagnostic imaging with a focus on oncology clinical trials. Nuclear imaging using widely available radiopharmaceuticals in conjunction with molecular imaging of oncology targets has opened the door to more accurate disease assessment and the modernization of standard criteria for the evaluation, staging, and treatment responses of cancer patients. Furthermore, the introduction and validation of quantitative molecular imaging continues to drive and optimize the field of oncology diagnostics. Given their pivotal role in disease assessment and treatment, the validation and commercialization of diagnostic tools will continue to advance oncology clinical trials, support new oncology drugs, and promote better patient outcomes.

  1. Assuring the Proper Analytical Performance of Measurement Procedures for Immunosuppressive Drug Concentrations in Clinical Practice: Recommendations of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology Immunosuppressive Drug Scientific Committee.

    Science.gov (United States)

    Seger, Christoph; Shipkova, Maria; Christians, Uwe; Billaud, Elaine M; Wang, Ping; Holt, David W; Brunet, Mercè; Kunicki, Paweł K; Pawiński, Thomasz; Langman, Loralie J; Marquet, Pierre; Oellerich, Michael; Wieland, Eberhard; Wallemacq, Pierre

    2016-04-01

    Monitoring immunosuppressive drugs (ISDs) in blood or plasma is still a key therapeutic drug monitoring (TDM) application in clinical settings. Narrow target ranges and severe side effects at drug underexposure or overexposure make accurate and precise measurements a must. This overview prepared by the Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology is intended to serve as a summary and guidance document describing the current state-of-the-art in the TDM of ISDs.

  2. Differentiation of true anophthalmia from clinical anophthalmia using neuroradiological imaging

    Institute of Scientific and Technical Information of China (English)

    Ali; Riza; Cenk; Celebi; Hadi; Sasani

    2014-01-01

    Anophthalmia is a condition of the absence of an eye and the presence of a small eye within the orbit.It is associated with many known syndromes.Clinical findings,as well as imaging modalities and genetic analysis,are important in making the diagnosis.Imaging modalities are crucial scanning methods.Cryptophthalmos,cyclopia,synophthalmia and congenital cystic eye should be considered in differential diagnoses.We report two clinical anophthalmic siblings,emphasizing the importance of neuroradiological and orbital imaging findings in distinguishing true congenital anophthalmia from clinical anophthalmia.

  3. 78 FR 13070 - Guidance for Clinical Investigators, Industry, and Food and Drug Administration Staff: Financial...

    Science.gov (United States)

    2013-02-26

    ..., Industry, and Food and Drug Administration Staff: Financial Disclosure by Clinical Investigators..., Industry, and FDA Staff: Financial Disclosure by Clinical Investigators.'' This guidance is intended to... governing financial disclosure by clinical investigators. This guidance provides FDA's responses to the...

  4. Comparison of 5 health care professionals’ratings of the clinical significance of drug related problems

    DEFF Research Database (Denmark)

    Villesen, Christine; Hojsted, Jette; Kjeldsen, Lene Juel

    2014-01-01

    Background Patients have medicines reviews conducted by different health care professionals in different settings. Introducing a clinical panel to drug related problems (DRPs) to evaluate their clinical significance is common practice. The clinical panel discuss the potential consequences and com...

  5. Clinical role of indium-111 antimyosin imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, S.; Lahiri, A. (Northwich Park Hospital and Clinical Research Centre, Harrow (UK). Dept. of Cardiology Northwich Park Hospital and Clinical Research Centre, Harrow (UK). Div. of Cardiovascular Sciences)

    1991-11-01

    Myocyte necrosis occurs in ischaemic, inflammatory and toxic heart diseases and can be detected by indium 111 antimyosin imaging. This allows a non-invasive evaluation of the site, extent and quantitation of the severity of myocardial necrosis. Simultaneous imaging of perfusion in patients with myocardial infarction allows the differentiation of necrosed and perfused areas and the varying degrees of mismatch and overlap, which has prognostic significance. Indium 111 antimyosin imaging is useful in the assessment of patients with unstable angina and in those for whom the diagnosis of infarction or unstable angina is not clear. In suspected myocarditis, a positive scan indicates the necessity for endomyocardial biopsy to confirm inflammation, whereas a negative scan makes the diagnosis of myocarditis unlikely. Antimyosin imaging is not useful as a marker of rejection in the 1 year-post-transplant, but uptake after this period is associated with an increased rejection rate and is therefore an important tool in planning management strategies. Most patients on anthracycline treatment have demonstrable uptake, which is related to the cumulative dose and to the ejection fraction. Its role in this situation is as yet unclear. The use of new ligands and radioisotopes ({sup 99m}Tc) is likely to allow earlier imaging and produce improved quality. (orig.).

  6. Liver imaging. Clinical applications and future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Rummeny, E.J. [Muenster Univ. (Germany). Dept. of Clinical Radiology; Marchal, G. [Dept. of Radiology, Univ. Hospitals, KU Leuven (Belgium)

    1997-07-01

    Primary hepatocellular carcinoma and liver metastases affect several millon people each year. The main imaging modalities to detect and assist diagnosis of primary and secondary liver tumours include MR imaging, CT, and US. The value of these techniques is further increased by the use of contrast agents which increase the sensitivity, and sometimes also the specificity, of the investigations. The relative advantages and drawbacks of the different contrast agents and imaging modalities in the detection and characterisation of liver tumours are discussed. Currently there is no consensus amongst investigators as to which is superior, due to the technical complexities and number of combinations possible within each of the different modalities. There continues to be advances in the hardware and software of imaging equipment, as well as a trend to develop new contrast agents with more organ-specificity. These include those targeting the hepatocytes, such as mangafodipir trisodium (MnDPDP, Teslascan), and those with reticuloendothelial cell specificity, such as the superparamagnetic iron oxides. These developments have the potential for making significant contributions to the diagnostic value of imaging procedures and, by reducing the number of investigations necessary to reach a final diagnosis, having a significant and beneficial impact on the pharmaco-economics of patient health care. (orig.).

  7. IMPACT OF CLINICAL-TRIALS ON THE ADOPTION OF NEW DRUGS WITHIN A UNIVERSITY HOSPITAL

    NARCIS (Netherlands)

    DENIG, P; HAAIJER-RUSKAMP, FM; WESSELING, H

    1991-01-01

    To assess the influence that clinical trials may have on the introduction of new drugs into prescribing routines, the adoption of drugs has been studied in a university hospital in the Netherlands. A significant relation was found between the testing of semi-innovative drugs in clinical trials in th

  8. IMPACT OF CLINICAL-TRIALS ON THE ADOPTION OF NEW DRUGS WITHIN A UNIVERSITY HOSPITAL

    NARCIS (Netherlands)

    DENIG, P; HAAIJER-RUSKAMP, FM; WESSELING, H

    1991-01-01

    To assess the influence that clinical trials may have on the introduction of new drugs into prescribing routines, the adoption of drugs has been studied in a university hospital in the Netherlands. A significant relation was found between the testing of semi-innovative drugs in clinical trials in

  9. Drugs in early clinical development for the treatment of osteosarcoma.

    Science.gov (United States)

    Heymann, Marie-Françoise; Brown, Hannah K; Heymann, Dominique

    2016-11-01

    Osteosarcomas are the main malignant primary bone tumours found in children and young adults. Conventional treatment is based on diagnosis and resection surgery, combined with polychemotherapy. This is a protocol that was established in the 1970s. Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient survival rate has not improved in the last four decades. New therapeutic approaches are thus required to improve the prognosis for osteosarcoma patients. Areas covered: From the databases available and published scientific literature, the present review gives an overview of the drugs currently in early clinical development for the treatment of osteosarcoma. For each drug, a short description is given of the relevant scientific data supporting its development. Expert opinion: Multidrug targeted approaches are set to emerge, given the heterogeneity of osteosarcoma subtypes and the multitude of therapeutic responses. The key role played by the microenvironment in the disease increases the number of therapeutic targets (such as macrophages or osteoclasts), as well as the master proteins that control cell proliferation or cell death. Ongoing phase I/II trials are important steps, not only for identifying new therapies with greater safety and efficacy, but also for better defining the role played by the microenvironment in the pathogenesis of osteosarcoma.

  10. clinical features and patterns of imaging in cerebral venous sinus ...

    African Journals Online (AJOL)

    2013-09-01

    Sep 1, 2013 ... study was conducted at Kenyatta National Hospital. Clinical and imaging records ... loss of memory, abdominal pain and senile dementia. Aetiological factors .... with a large study by Khealani in Pakistan and. Middle East that ...

  11. Multimodal tissue perfusion imaging using multi-spectral and thermographic imaging systems applied on clinical data

    Science.gov (United States)

    Klaessens, John H. G. M.; Nelisse, Martin; Verdaasdonk, Rudolf M.; Noordmans, Herke Jan

    2013-03-01

    Clinical interventions can cause changes in tissue perfusion, oxygenation or temperature. Real-time imaging of these phenomena could be useful for surgical strategy or understanding of physiological regulation mechanisms. Two noncontact imaging techniques were applied for imaging of large tissue areas: LED based multispectral imaging (MSI, 17 different wavelengths 370 nm-880 nm) and thermal imaging (7.5 to 13.5 μm). Oxygenation concentration changes were calculated using different analyzing methods. The advantages of these methods are presented for stationary and dynamic applications. Concentration calculations of chromophores in tissue require right choices of wavelengths The effects of different wavelength choices for hemoglobin concentration calculations were studied in laboratory conditions and consequently applied in clinical studies. Corrections for interferences during the clinical registrations (ambient light fluctuations, tissue movements) were performed. The wavelength dependency of the algorithms were studied and wavelength sets with the best results will be presented. The multispectral and thermal imaging systems were applied during clinical intervention studies: reperfusion of tissue flap transplantation (ENT), effectiveness of local anesthetic block and during open brain surgery in patients with epileptic seizures. The LED multispectral imaging system successfully imaged the perfusion and oxygenation changes during clinical interventions. The thermal images show local heat distributions over tissue areas as a result of changes in tissue perfusion. Multispectral imaging and thermal imaging provide complementary information and are promising techniques for real-time diagnostics of physiological processes in medicine.

  12. [The importance of clinical data management in improvement of drug evaluation].

    Science.gov (United States)

    Huang, Qin; Wang, Jun

    2015-11-01

    Although the importance of clinical data is drawing more attention in drug development in China, the clinical data management is not good enough in the clinical trials right now. With the development of internet and progress of information technology, especially with the setup of the state innovation strategy for drug development, it is necessary and urgent to improve the clinical data quality. Good data quality is the primary basis of technical evaluation of drug at the marketing authorization. So Center for Drug Evaluation of CFDA has made some endeavors to enhance data management in the clinical trials in recent years. This article is focused on these aspects of data managment.

  13. Novel cardiac imaging technologies : implications in clinical decision making

    NARCIS (Netherlands)

    Delgado, Victoria

    2010-01-01

    The objectives of this thesis were to investigate the role of novel cardiac imaging technologies in the current clinical daily practice with the advent of novel therapies. In Part I, the role of novel imaging modalities to assess left ventricular mechanics will be discussed, focusing on 1) the

  14. Clinics in diagnostic imaging (58). Chronic cerebral paragonimiasis.

    Science.gov (United States)

    Kaw, G J; Sitoh, Y Y

    2001-02-01

    A 36-year-old Korean man presented with a history of epilepsy. MR imaging of the brain revealed multiple conglomerated round nodules that were hypointense on both T1-and-T2 weighted images. These were located at the left temporal and occipital lobes and had surrounding encephalomalacia. CT scan confirmed the presence of large calcified nodules in the corresponding regions. These imaging findings were typical of chronic cerebral paragonimiasis. The clinical, CT and MR features of cerebral paragonimiasis are reviewed.

  15. Multimodal imaging of bone metastases: From preclinical to clinical applications

    Directory of Open Access Journals (Sweden)

    Stephan Ellmann

    2015-10-01

    Full Text Available Metastases to the skeletal system are commonly observed in cancer patients, highly affecting the patients' quality of life. Imaging plays a major role in detection, follow-up, and molecular characterisation of metastatic disease. Thus, imaging techniques have been optimised and combined in a multimodal and multiparametric manner for assessment of complementary aspects in osseous metastases. This review summarises both application of the most relevant imaging techniques for bone metastasis in preclinical models and the clinical setting.

  16. Incidental ferumoxytol artifacts in clinical brain MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bowser, Bruce A.; Campeau, Norbert G.; Carr, Carrie M.; Diehn, Felix E.; McDonald, Jennifer S.; Miller, Gary M.; Kaufmann, Timothy J. [Mayo Clinic, Department of Radiology, Rochester, MN (United States)

    2016-11-15

    Ferumoxytol (Feraheme) is a parenteral therapy approved for treatment of iron deficiency anemia. The product insert for ferumoxytol states that it may affect the diagnostic ability of MRI for up to 3 months. However, the expected effects may not be commonly recognized among clinical neuroradiologists. Our purpose is to describe the artifacts we have seen at our institution during routine clinical practice. We reviewed the patients at our institution that had brain MRI performed within 90 days of receiving intravenous ferumoxytol. The imaging was reviewed for specific findings, including diffusion-weighted imaging vascular susceptibility artifact, gradient-echo echo-planar T2*-weighted vascular susceptibility artifact, SWI/SWAN vascular susceptibility artifact, hypointense vascular signal on T2-weighted images, pre-gadolinium contrast vascular enhancement on magnetization-prepared rapid acquisition gradient echo (MPRAGE) imaging, and effects on post-gadolinium contrast T1 imaging. Multiple artifacts were observed in patients having a brain MRI within 3 days of receiving intravenous ferumoxytol. These included susceptibility artifact on DWI, GRE, and SWAN/SWI imaging, pre-gadolinium contrast increased vascular signal on MPRAGE imaging, and decreased expected enhancement on post-gadolinium contrast T1-weighted imaging. Ferumoxytol can create imaging artifacts which complicate clinical interpretation when brain MRI is performed within 3 days of administration. Recognition of the constellation of artifacts produced by ferumoxytol is important in order to obviate additional unnecessary examinations and mitigate errors in interpretation. (orig.)

  17. Automated spectral imaging for clinical diagnostics

    Science.gov (United States)

    Breneman, John; Heffelfinger, David M.; Pettipiece, Ken; Tsai, Chris; Eden, Peter; Greene, Richard A.; Sorensen, Karen J.; Stubblebine, Will; Witney, Frank

    1998-04-01

    Bio-Rad Laboratories supplies imaging equipment for many applications in the life sciences. As part of our effort to offer more flexibility to the investigator, we are developing a microscope-based imaging spectrometer for the automated detection and analysis of either conventionally or fluorescently labeled samples. Immediate applications will include the use of fluorescence in situ hybridization (FISH) technology. The field of cytogenetics has benefited greatly from the increased sensitivity of FISH producing simplified analysis of complex chromosomal rearrangements. FISH methods for identification lends itself to automation more easily than the current cytogenetics industry standard of G- banding, however, the methods are complementary. Several technologies have been demonstrated successfully for analyzing the signals from labeled samples, including filter exchanging and interferometry. The detection system lends itself to other fluorescent applications including the display of labeled tissue sections, DNA chips, capillary electrophoresis or any other system using color as an event marker. Enhanced displays of conventionally stained specimens will also be possible.

  18. Associating Drugs, Targets and Clinical Outcomes into an Integrated Network Affords a New Platform for Computer-Aided Drug Repurposing

    DEFF Research Database (Denmark)

    Oprea, Tudor; Nielsen, Sonny Kim; Ursu, Oleg

    2011-01-01

    benefit from an integrated, semantic-web compliant computer-aided drug repurposing (CADR) effort, one that would enable deep data mining of associations between approved drugs (D), targets (T), clinical outcomes (CO) and SE. We report preliminary results from text mining and multivariate statistics, based...

  19. Microencapsulation of indocyanine green for potential applications in image-guided drug delivery.

    Science.gov (United States)

    Zhu, Zhiqiang; Si, Ting; Xu, Ronald X

    2015-02-07

    We present a novel process to encapsulate indocyanine green (ICG) in liposomal droplets at high concentration for potential applications in image-guided drug delivery. The microencapsulation process follows two consecutive steps of droplet formation by liquid-driven coaxial flow focusing (LDCFF) and solvent removal by oil phase dewetting. These biocompatible lipid vesicles may have important applications in drug delivery and fluorescence imaging.

  20. Big Data Mining and Adverse Event Pattern Analysis in Clinical Drug Trials.

    Science.gov (United States)

    Federer, Callie; Yoo, Minjae; Tan, Aik Choon

    2016-12-01

    Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov ( https://clinicaltrials.gov/ ), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning. To our knowledge, current AE databases contain mainly U.S. Food and Drug Administration (FDA)-approved drugs. However, our database contains both FDA-approved and experimental compounds extracted from ClinicalTrials.gov . Our database contains 8,161 clinical trials of 3,102,675 patients and 713,103 reported AEs. We extracted the information from ClinicalTrials.gov using a set of python scripts, and then used regular expressions and a drug dictionary to process and structure relevant information into a relational database. We performed data mining and pattern analysis of drug-AEs in our database. Our database can serve as a tool to assist researchers to discover drug-AE relationships for developing, repositioning, and repurposing drugs.

  1. Clinical image: MRI during migraine with aura

    Energy Technology Data Exchange (ETDEWEB)

    McNeal, A.C. [Brooklyn VA Medical Center, NY (United States)

    1996-03-01

    Migraine refers to severe headaches that are usually unilateral, throbbing, and associated with nausea, vomiting, photophobia, and phonophobia. Migraine with aura (formerly called {open_quotes}classic migraine{close_quotes}) consists of the headache preceded or accompanied by neurological dysfunction. This dysfunction (aura) usually involves visual and sensory symptoms. The patient described herein experienced migraine with aura. MRI during and after the attack showed a reversible abnormality of the right posterior cerebral artery, with no parenchymal lesions. This appears to be the first report of abnormal MR vascular imaging during migraine with aura. 10 refs., 2 figs.

  2. Clinical Trial Risk in Hepatitis C: Endpoint Selection and Drug Action

    OpenAIRE

    Tillie, Nicole A.; Parker, Jayson L.; Jordan J. Feld

    2016-01-01

    Background and Aims. This study analyzed the risk of clinical trial failure of new drugs for hepatitis C between January 1998 and January 2015. Methods. Hepatitis C drug development trials that were in phases I–III of clinical trial testing were obtained from the publicly accessible clinical trial repository and other publicly available databases. Drug compounds were excluded from the study if they began their phase I testing before 1998, if they were not industry sponsored, or if they treate...

  3. Challenges and perspective of drug repurposing strategies in early phase clinical trials

    OpenAIRE

    Kato, Shumei; Moulder, Stacy L.; Ueno, Naoto T; Wheler, Jennifer J.; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

    2015-01-01

    Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment ...

  4. Cutaneous malignant melanoma: clinical aspects, imaging modalities and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ak, I.; Stokkel, M.P.M.; Pauwels, E.K.J. [Leiden University Medical Centre, Department of Radiology, Division of Nuclear Medicine, Leiden (Netherlands); Bergman, W. [Department of Dermatology, Leiden University Medical Centre, Leiden (Netherlands)

    2000-04-01

    Cutaneous melanoma is a highly malignant tumour of the melanocytes presenting characteristic metabolic and biological features. Early detection decreases mortality and morbidity and provides the best chance for optimal clinical management. Imaging techniques, including scintigraphy, have assumed an important role in detection strategies. As a functional modality, nuclear medicine offers a variety of possibilities to assist in the clinical management of malignant melanoma. This review discusses the clinical aspects and treatment of melanoma, and the imaging techniques used for its diagnosis, staging and follow-up. A survey of currently available techniques is presented. (orig.)

  5. Shortcomings in the clinical evaluation of new drugs: acute myeloid leukemia as paradigm

    OpenAIRE

    Walter, Roland B.; Appelbaum, Frederick R.; Tallman, Martin S.; Weiss, Noel S.; Larson, Richard A.; Estey, Elihu H.

    2010-01-01

    Drugs introduced over the past 25 years have benefitted many patients with acute myeloid leukemia (AML) and provided cure for some. Still, AML remains difficult to treat, and most patients will eventually die from their disease. Therefore, novel drugs and drug combinations are under intense investigation, and promising results eagerly awaited and embraced. However, drug development is lengthy and costs are staggering. While the phase 1–phase 2–phase 3 sequence of clinical drug testing has rem...

  6. Imaging and Data Acquisition in Clinical Trials for Radiation Therapy.

    Science.gov (United States)

    FitzGerald, Thomas J; Bishop-Jodoin, Maryann; Followill, David S; Galvin, James; Knopp, Michael V; Michalski, Jeff M; Rosen, Mark A; Bradley, Jeffrey D; Shankar, Lalitha K; Laurie, Fran; Cicchetti, M Giulia; Moni, Janaki; Coleman, C Norman; Deye, James A; Capala, Jacek; Vikram, Bhadrasain

    2016-02-01

    Cancer treatment evolves through oncology clinical trials. Cancer trials are multimodal and complex. Assuring high-quality data are available to answer not only study objectives but also questions not anticipated at study initiation is the role of quality assurance. The National Cancer Institute reorganized its cancer clinical trials program in 2014. The National Clinical Trials Network (NCTN) was formed and within it was established a Diagnostic Imaging and Radiation Therapy Quality Assurance Organization. This organization is Imaging and Radiation Oncology Core, the Imaging and Radiation Oncology Core Group, consisting of 6 quality assurance centers that provide imaging and radiation therapy quality assurance for the NCTN. Sophisticated imaging is used for cancer diagnosis, treatment, and management as well as for image-driven technologies to plan and execute radiation treatment. Integration of imaging and radiation oncology data acquisition, review, management, and archive strategies are essential for trial compliance and future research. Lessons learned from previous trials are and provide evidence to support diagnostic imaging and radiation therapy data acquisition in NCTN trials.

  7. Photoacoustic imaging system for peripheral small-vessel imaging based on clinical ultrasound technology

    Science.gov (United States)

    Irisawa, Kaku; Hirota, Kazuhiro; Hashimoto, Atsushi; Murakoshi, Dai; Ishii, Hiroyasu; Tada, Takuji; Wada, Takatsugu; Hayakawa, Toshiro; Azuma, Ryuichi; Otani, Naoki; Itoh, Kenji; Ishihara, Miya

    2016-03-01

    One of the features of photoacoustic (PA) imaging is small-vessel visualization realized without injection of a contrast agent or exposure to X-rays. For carrying out clinical studies in this field, a prototype PA imaging system has been developed. The PA imaging system utilizes a technological platform of FUJIFILM's clinical ultrasound (US) imaging system mounting many-core MPU for enhancing the image quality of US B-mode and US Doppler mode, which can be superposed onto PA images. By evaluating the PA and US Doppler images of the prototyped system, the applicability of the prototype system to small-vessel visualization has been discussed. The light source for PA imaging was on a compact cart of a US unit and emitted 750 nm wavelength laser pulses. The laser light was transferred to illumination optics in a handheld US transducer, which was connected to the US unit. Obtained PA rf data is reconstructed into PA images in the US unit. 3D images were obtained by scanning a mechanical stage, which the transducer is attached to. Several peripheral parts such as fingers, palms and wrists were observed by PA and US Doppler imaging. As for small arteries, US Doppler images were able to visualize the bow-shaped artery in the tip of the finger. Though PA images cannot distinguish arteries and veins, it could visualize smaller vessels and showed good resolution and vascular connectivity, resulting in a complementary image for the US Doppler images. Therefore, superposed images of the PA, US B-mode and US Doppler can visualize from large to small vessels without a contrast agent, which should be a differentiating feature of US/PA combined technology from other clinical vascular imaging modalities.

  8. Idiopathic granulomatous hypophysitis: clinical and imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Vasile, M. [Service de Radiologie, Hopital Saint-Antoine, 75 - Paris (France); Marsot-Dupuch, K. [Service de Radiologie, Hopital Saint-Antoine, 75 - Paris (France); Kujas, M. [Service d`Histologie Embryologie Cytogenetique, Hopital Pitie-Salpetriere, 75 - Paris (France); Brunereau, L. [Service de Radiologie, Hopital Saint-Antoine, 75 - Paris (France); Bouchard, P. [Service d`Histologie Embryologie Cytogenetique, Hopital Pitie-Salpetriere, 75 - Paris (France); Comoy, J. [Service de Neurochirurgie, Hopital Kremlin Bicetre, 94 (France); Tubiana, J.M. [Service de Radiologie, Hopital Saint-Antoine, 75 - Paris (France)

    1997-01-01

    Idiopathic pituitary granuloma is a rare disorder similar to lymphocytic adenohypophysitis. Few cases have been reported. We report a new histologically case proven with MRI. The patterns of clinical and radiological presentation and the management of this disorder are discussed. MRI findings suggestive of this condition include an intensely enhancing pituitary mass, associated with dural enhancement. Steroid therapy may be suggested avoiding unnecessary surgery. (orig.)

  9. ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials.

    Science.gov (United States)

    Schwartz, Lisa M; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A

    2016-09-20

    Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA. ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews). 100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015). 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths. Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant. Unknown generalizability to uncontrolled or crossover trial results. Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials. National Library of Medicine.

  10. Clinical application of functional magnetic resonance imaging

    CERN Document Server

    Alwatban, A Z W

    2002-01-01

    The work described in this thesis was carried out at the Magnetic Resonance Centre of the University of Nottingham during the time from May 1998 to April 2001, and is the work of the except where indicated by reference. The main source of signal changes in functional magnetic resonance imaging (fMRJ) is the fluctuation of paramagnetic deoxyhaemoglobin in the venous blood during different states of functional performance. For the work of this thesis, fMRI studies were carried out using a 3 T MR system with an echo planar imaging (EPI) pulse sequence. Hearing research utilising fMRI has been previously reported in normal subjects. Hearing fMRI is normally performed by stimulating the auditory cortex via an acoustic task presentation such as music, tone, etc. However, performing the same research on deaf subjects requires special equipment to be designed to allow direct stimulation of the auditory nerve. In this thesis, a new method of direct electrical stimulation of the auditory nerve is described that uses a ...

  11. Introduction to Pre-clinical Imaging Techniques; Introduccion a las tecnicas de imagen preclinica

    Energy Technology Data Exchange (ETDEWEB)

    Mulero, F.

    2008-07-01

    Biomedical research poses increasingly complex problems regarding the biochemical processes that take place in living organisms. Just as in clinical research, medical imaging techniques are an excellent tool to study these processes. One of the most outstanding techniques is what is called molecular imaging, the best tool for which is positron emission tomography (PET). PET is capable of monitoring those processes in vivo at a molecular level and it can be used in multiple applications, including the development of new drugs, the study of human disease models in animals, and the characterization of gene expression and phenotype changes caused by genetic manipulation (transgenic and knockout animals). (Author) 5 refs.

  12. Chirality and drugs in clinical practice and its ethical aspect.

    Science.gov (United States)

    Banerjee, Molly; Biswas, Indranil; Halder, Swaraj

    2009-01-01

    Recently specific enantiomer of different chiral molecules are being launched in the market as drugs. Here the rationality of scopes and uses of these drugs in therapeutic medicine is discussed including the ethical aspect.

  13. Systematic drug repositioning through mining adverse event data in ClinicalTrials.gov.

    Science.gov (United States)

    Su, Eric Wen; Sanger, Todd M

    2017-01-01

    Drug repositioning (i.e., drug repurposing) is the process of discovering new uses for marketed drugs. Historically, such discoveries were serendipitous. However, the rapid growth in electronic clinical data and text mining tools makes it feasible to systematically identify drugs with the potential to be repurposed. Described here is a novel method of drug repositioning by mining ClinicalTrials.gov. The text mining tools I2E (Linguamatics) and PolyAnalyst (Megaputer) were utilized. An I2E query extracts "Serious Adverse Events" (SAE) data from randomized trials in ClinicalTrials.gov. Through a statistical algorithm, a PolyAnalyst workflow ranks the drugs where the treatment arm has fewer predefined SAEs than the control arm, indicating that potentially the drug is reducing the level of SAE. Hypotheses could then be generated for the new use of these drugs based on the predefined SAE that is indicative of disease (for example, cancer).

  14. Systematic drug repositioning through mining adverse event data in ClinicalTrials.gov

    Directory of Open Access Journals (Sweden)

    Eric Wen Su

    2017-03-01

    Full Text Available Drug repositioning (i.e., drug repurposing is the process of discovering new uses for marketed drugs. Historically, such discoveries were serendipitous. However, the rapid growth in electronic clinical data and text mining tools makes it feasible to systematically identify drugs with the potential to be repurposed. Described here is a novel method of drug repositioning by mining ClinicalTrials.gov. The text mining tools I2E (Linguamatics and PolyAnalyst (Megaputer were utilized. An I2E query extracts “Serious Adverse Events” (SAE data from randomized trials in ClinicalTrials.gov. Through a statistical algorithm, a PolyAnalyst workflow ranks the drugs where the treatment arm has fewer predefined SAEs than the control arm, indicating that potentially the drug is reducing the level of SAE. Hypotheses could then be generated for the new use of these drugs based on the predefined SAE that is indicative of disease (for example, cancer.

  15. Multispectral photoacoustic imaging of nerves with a clinical ultrasound system

    Science.gov (United States)

    Mari, Jean Martial; West, Simeon; Beard, Paul C.; Desjardins, Adrien E.

    2014-03-01

    Accurate and efficient identification of nerves is of great importance during many ultrasound-guided clinical procedures, including nerve blocks and prostate biopsies. It can be challenging to visualise nerves with conventional ultrasound imaging, however. One of the challenges is that nerves can have very similar appearances to nearby structures such as tendons. Several recent studies have highlighted the potential of near-infrared optical spectroscopy for differentiating nerves and adjacent tissues, as this modality can be sensitive to optical absorption of lipids that are present in intra- and extra-neural adipose tissue and in the myelin sheaths. These studies were limited to point measurements, however. In this pilot study, a custom photoacoustic system with a clinical ultrasound imaging probe was used to acquire multi-spectral photoacoustic images of nerves and tendons from swine ex vivo, across the wavelength range of 1100 to 1300 nm. Photoacoustic images were processed and overlaid in colour onto co-registered conventional ultrasound images that were acquired with the same imaging probe. A pronounced optical absorption peak centred at 1210 nm was observed in the photoacoustic signals obtained from nerves, and it was absent in those obtained from tendons. This absorption peak, which is consistent with the presence of lipids, provides a novel image contrast mechanism to significantly enhance the visualization of nerves. In particular, image contrast for nerves was up to 5.5 times greater with photoacoustic imaging (0.82 +/- 0.15) than with conventional ultrasound imaging (0.148 +/- 0.002), with a maximum contrast of 0.95 +/- 0.02 obtained in photoacoustic mode. This pilot study demonstrates the potential of photoacoustic imaging to improve clinical outcomes in ultrasound-guided interventions in regional anaesthesia and interventional oncology.

  16. Clinical application of functional magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Alwatban, Adnan Z.W

    2002-07-01

    The work described in this thesis was carried out at the Magnetic Resonance Centre of the University of Nottingham during the time from May 1998 to April 2001, and is the work of the author except where indicated by reference. The main source of signal changes in functional magnetic resonance imaging (fMRJ) is the fluctuation of paramagnetic deoxyhaemoglobin in the venous blood during different states of functional performance. For the work of this thesis, fMRI studies were carried out using a 3 T MR system with an echo planar imaging (EPI) pulse sequence. Hearing research utilising fMRI has been previously reported in normal subjects. Hearing fMRI is normally performed by stimulating the auditory cortex via an acoustic task presentation such as music, tone, etc. However, performing the same research on deaf subjects requires special equipment to be designed to allow direct stimulation of the auditory nerve. In this thesis, a new method of direct electrical stimulation of the auditory nerve is described that uses a transtympanic electrode implanted onto the surface of the cochlea. This approach would however, result in electromotive forces (EMFs) being induced by the time varying magnetic field, which would lead to current flow and heating, as well as deflection of the metallic electrode within the static magnetic field, and image distortion due to the magnetic susceptibility difference. A gold-plated tungsten electrode with a zero magnetic susceptibility was developed to avoid image distortion. Used with carbon leads and a carbon reference pad, it enabled safe, distortion-free fMRI studies of deaf subjects. The study revealed activation of the primary auditory cortex. This fMRI procedure can be used to demonstrate whether the auditory pathway is fully intact, and may provide a useful method for pre-operative assessment of candidates for cochlear implantation. Glucose is the energy source on which the function of the human brain is entirely dependent. Failure to

  17. Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).

    Science.gov (United States)

    Liu, Zhichao; Shi, Qiang; Ding, Don; Kelly, Reagan; Fang, Hong; Tong, Weida

    2011-12-01

    Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects) seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps). The DILIps yielded 60-70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the "Rule of Three" was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91%) when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity.

  18. Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps.

    Directory of Open Access Journals (Sweden)

    Zhichao Liu

    2011-12-01

    Full Text Available Drug-induced liver injury (DILI is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps. The DILIps yielded 60-70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the "Rule of Three" was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91% when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity.

  19. MALDI imaging mass spectrometry: bridging biology and chemistry in drug development.

    Science.gov (United States)

    Castellino, Stephen; Groseclose, M Reid; Wagner, David

    2011-11-01

    Our understanding of drug tissue distribution impacts a number of areas in drug development, including: pharmacology, pharmacokinetics, safety, drug-drug interactions, transport and metabolism. Despite their extensive use, autoradiography and tissue homogenate LC-MS analysis have limitations in providing a comprehensive assessment of tissue distributions. In the case of autoradiography, it is the inability to distinguish between parent drug and drug metabolites. In LC-MS analysis of tissue homogenate, all tissue localization information is lost. The emerging technique of MALDI imaging mass spectrometry has the capability to distinguish between parent and metabolites while maintaining spatial distribution in tissues. In this article, we will review the MALDI imaging MS methodology as applied to drug development and provide examples highlighting the impact of this important technique in drug development.

  20. Role of clinical images based teaching as a supplement to conventional clinical teaching in dermatology

    Directory of Open Access Journals (Sweden)

    Gurumoorthy Rajesh Kumar

    2015-01-01

    Full Text Available Introduction : Clinical Dermatology is a visually oriented specialty, where visually oriented teaching is more important than it is in any other specialty. It is essential that students must have repeated exposure to common dermatological disorders in the limited hours of Dermatology clinical teaching. Aim: This study was conducted to assess the effect of clinical images based teaching as a supplement to the patient based clinical teaching in Dermatology, among final year MBBS students. Methods: A clinical batch comprising of 19 students was chosen for the study. Apart from the routine clinical teaching sessions, clinical images based teaching was conducted. This teaching method was evaluated using a retrospective pre-post questionnaire. Students′ performance was assessed using Photo Quiz and an Objective Structured Clinical Examination (OSCE. Feedback about the addition of images based class was collected from students. Results: A significant improvement was observed in the self-assessment scores following images based teaching. Mean OSCE score was 6.26/10, and that of Photo Quiz was 13.6/20. Conclusion : This Images based Dermatology teaching has proven to be an excellent supplement to routine clinical cases based teaching.

  1. Niacin revisited: clinical observations on an important but underutilized drug.

    Science.gov (United States)

    Henkin, Y; Oberman, A; Hurst, D C; Segrest, J P

    1991-09-01

    To evaluate the efficacy and side effects of niacin therapy in dyslipidemic individuals. A retrospective analysis of patients' charts. An outpatient referral-based clinic specializing in the treatment of lipid disorders. All patients with dyslipidemia treated by niacin (n = 82) at the Atherosclerosis Detection and Prevention Clinic during 1987 to 1990, including a subgroup of 17 dyslipidemic heart transplant recipients. Niacin was well tolerated in 83% of the nontransplant group (n = 65) at an average dose of 2.5 +/- 0.9 g/day. Similar beneficial lipoprotein effects were found in the transplant and nontransplant patients. The high-density lipoprotein cholesterol (HDL-C) response to niacin therapy was independent of the baseline (HDL-C level. In the transplant group, 11 patients (65%) discontinued treatment, primarily because of hyperglycemia; this was especially prominent in those patients with pretreatment diabetes mellitus. Of the 15 patients using sustained-release niacin, eight cases of hepatitis were recorded, some during therapy with relatively low niacin doses. Several different sustained-release preparations were responsible for this phenomenon, suggesting that the cause was not a contaminant in the preparation. No cases of hepatitis were documented in the 67 patients using regular niacin. One case of hepatitis was recently observed in a patient who switched from one type to regular niacin to another; however, we have data to suggest that the substituted preparation was not an immediate-release niacin. A familial predisposition to hepatitis is suggested by the occurrence of this side effect in identical twin brothers and two sisters. A pharmacy survey disclosed that most pharmacists are unaware of the relationship of sustained-release niacin to hepatitis, have a negative impression of regular niacin, and do not stock this formulation. Finally, we found that in this small sample of patients, niacin used with lovastatin is a particularly effective drug

  2. Clinical use of gadobutrol for contrast-enhanced magnetic resonance imaging of neurological diseases

    Directory of Open Access Journals (Sweden)

    Cheng KT

    2012-02-01

    Full Text Available Kenneth T Cheng1, Hannah Y Cheng2, Kam Leung31Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA; 2Freelance Technical Writer, New Orleans, LA, USA; 3National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USAAbstract: Contrast-enhanced magnetic resonance imaging (CE-MRI is an important clinical tool for diagnosing neurological diseases. The appropriate use of a suitable MRI contrast agent or contrast pharmaceutical is essential for CE-MRI to produce desirable diagnostic images. Currently, there are seven contrast agents (CAs or pharmaceuticals approved for clinical imaging of the central nervous system (CNS in the US, Europe, or Japan. All of the clinically approved CAs are water-soluble gadolinium-based contrast agents (GBCAs which do not penetrate the CNS blood–brain barrier (BBB. These agents are used for imaging CNS areas without a BBB, or various pathologies, such as tumors and infection that break down the BBB and allow CAs to enter into the surrounding parenchyma. Clinically, GBCAs are most useful for detecting primary and secondary cerebral neoplastic lesions. Among these CNS GBCAs, gadobutrol (Gd-BT-DO3A, Gadovist™ is a neutral, nonionic, macrocyclic compound that showed promising results from clinical trials of CNS imaging. In comparison with other GBCAs, Gd-BT-DO3A has relatively high in vitro kinetic stability and r1 relaxivity. Gd-BT-DO3A has been recently approved by the US Food and Drug Administration (FDA in 2011 for CNS imaging. A review of available literature shows that Gd-BT-DO3A exhibits similar safety and clinical efficacy profiles to other GBCAs. Gd-BT-DO3A has the distinguishing feature that it is the only clinical agent commercially available in a formulation of 1.0 M concentration with a relatively higher in vitro T1 shortening per unit volume than other clinical GBCAs which are only

  3. An adaptive optics imaging system designed for clinical use.

    Science.gov (United States)

    Zhang, Jie; Yang, Qiang; Saito, Kenichi; Nozato, Koji; Williams, David R; Rossi, Ethan A

    2015-06-01

    Here we demonstrate a new imaging system that addresses several major problems limiting the clinical utility of conventional adaptive optics scanning light ophthalmoscopy (AOSLO), including its small field of view (FOV), reliance on patient fixation for targeting imaging, and substantial post-processing time. We previously showed an efficient image based eye tracking method for real-time optical stabilization and image registration in AOSLO. However, in patients with poor fixation, eye motion causes the FOV to drift substantially, causing this approach to fail. We solve that problem here by tracking eye motion at multiple spatial scales simultaneously by optically and electronically integrating a wide FOV SLO (WFSLO) with an AOSLO. This multi-scale approach, implemented with fast tip/tilt mirrors, has a large stabilization range of ± 5.6°. Our method consists of three stages implemented in parallel: 1) coarse optical stabilization driven by a WFSLO image, 2) fine optical stabilization driven by an AOSLO image, and 3) sub-pixel digital registration of the AOSLO image. We evaluated system performance in normal eyes and diseased eyes with poor fixation. Residual image motion with incremental compensation after each stage was: 1) ~2-3 arc minutes, (arcmin) 2) ~0.5-0.8 arcmin and, 3) ~0.05-0.07 arcmin, for normal eyes. Performance in eyes with poor fixation was: 1) ~3-5 arcmin, 2) ~0.7-1.1 arcmin and 3) ~0.07-0.14 arcmin. We demonstrate that this system is capable of reducing image motion by a factor of ~400, on average. This new optical design provides additional benefits for clinical imaging, including a steering subsystem for AOSLO that can be guided by the WFSLO to target specific regions of interest such as retinal pathology and real-time averaging of registered images to eliminate image post-processing.

  4. Modern Trends in Imaging X: Spectral Imaging in Preclinical Research and Clinical Pathology

    Directory of Open Access Journals (Sweden)

    Richard Levenson

    2012-01-01

    Full Text Available Spectral imaging methods are attracting increased interest from researchers and practitioners in basic science, pre-clinical and clinical arenas. A combination of better labeling reagents and better optics creates opportunities to detect and measure multiple parameters at the molecular and cellular level. These tools can provide valuable insights into the basic mechanisms of life, and yield diagnostic and prognostic information for clinical applications. There are many multispectral technologies available, each with its own advantages and limitations. This chapter will present an overview of the rationale for spectral imaging, and discuss the hardware, software and sample labeling strategies that can optimize its usefulness in clinical settings.

  5. Ultrasound Image Quality Assessment: A framework for evaluation of clinical image quality

    DEFF Research Database (Denmark)

    Hemmsen, Martin Christian; Pedersen, Mads Møller; Nikolov, Svetoslav Ivanov

    2010-01-01

    Improvement of ultrasound images should be guided by their diagnostic value. Evaluation of clinical image quality is generally performed subjectively, because objective criteria have not yet been fully developed and accepted for the evaluation of clinical image quality. Based on recommendation 500...... from the International Telecommunication Union - Radiocommunication (ITU-R) for such subjective quality assessment, this work presents equipment and a methodology for clinical image quality evaluation for guiding the development of new and improved imaging. The system is based on a BK-Medical 2202 Pro......Focus scanner equipped with a UA2227 research interface, connected to a PC through X64-CL Express camera link. Data acquisition features subject data recording, loading/saving of exact scanner settings (for later experiment reproducibility), free access to all system parameters for beamformation...

  6. Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy.

    Science.gov (United States)

    Biju, Vasudevanpillai

    2014-02-07

    As prepared nanomaterials of metals, semiconductors, polymers and carbon often need surface modifications such as ligand exchange, and chemical and bioconjugate reactions for various biosensor, bioanalytical, bioimaging, drug delivery and therapeutic applications. Such surface modifications help us to control the physico-chemical, toxicological and pharmacological properties of nanomaterials. Furthermore, introduction of various reactive functional groups on the surface of nanomaterials allows us to conjugate a spectrum of contrast agents, antibodies, peptides, ligands, drugs and genes, and construct multifunctional and hybrid nanomaterials for the targeted imaging and treatment of cancers. This tutorial review is intended to provide an introduction to newcomers about how chemical and bioconjugate reactions transform the surface of nanomaterials such as silica nanoparticles, gold nanoparticles, gold quantum clusters, semiconductor quantum dots, carbon nanotubes, fullerene and graphene, and accordingly formulate them for applications such as biosensing, bioimaging, drug and gene delivery, chemotherapy, photodynamic therapy and photothermal therapy. Nonetheless, controversial reports and our growing concerns about toxicity and pharmacokinetics of nanomaterials suggest the need for not only rigorous in vivo experiments in animal models but also novel nanomaterials for practical applications in the clinical settings. Further reading of original and review articles cited herein is necessary to buildup in-depth knowledge about the chemistry, bioconjugate chemistry and biological applications of individual nanomaterials.

  7. Application of imaging mass spectrometry approaches to facilitate metal-based anticancer drug research.

    Science.gov (United States)

    Lee, Ronald F S; Theiner, Sarah; Meibom, Anders; Koellensperger, Gunda; Keppler, Bernhard K; Dyson, Paul J

    2017-02-03

    Mass spectrometry imaging is being increasingly used in metal-based anticancer drug development to study elemental and/or molecular drug distributions in different biological systems. The main analytical tools employed are SIMS (especially nanoSIMS), LA-ICP-MSI and MALDI-MSI as well as a combination of complementary imaging techniques. Main challenges are appropriate sample preparation methods, reliable and validated quantification strategies and a trade-off between sensitivity and spatial resolution. So far, research has mostly focused on the development of analytical methods for imaging with the long term goal to study drug uptake into tumor tissue and toxicity affected organs and to identify cellular targets of metal-based drugs. In this review we cover the technological features of the mass spectrometry imaging methods used and give an overview of the applications in metal-based anticancer drug research as well as some future perspectives.

  8. Clinical applications for diffusion magnetic resonance imaging in radiotherapy.

    Science.gov (United States)

    Tsien, Christina; Cao, Yue; Chenevert, Thomas

    2014-07-01

    In this article, we review the clinical applications of diffusion magnetic resonance imaging (MRI) in the radiotherapy treatment of several key clinical sites, including those of the central nervous system, the head and neck, the prostate, and the cervix. Diffusion-weighted MRI (DWI) is an imaging technique that is rapidly gaining widespread acceptance owing to its ease and wide availability. DWI measures the mobility of water within tissue at the cellular level without the need of any exogenous contrast agent. For radiotherapy treatment planning, DWI improves upon conventional imaging techniques, by better characterization of tumor tissue properties required for tumor grading, diagnosis, and target volume delineation. Because DWI is also a sensitive marker for alterations in tumor cellularity, it has potential clinical applications in the early assessment of treatment response following radiation therapy.

  9. Interconnecting smartphone, image analysis server, and case report forms in clinical trials for automatic skin lesion tracking in clinical trials

    Science.gov (United States)

    Haak, Daniel; Doma, Aliaa; Gombert, Alexander; Deserno, Thomas M.

    2016-03-01

    Today, subject's medical data in controlled clinical trials is captured digitally in electronic case report forms (eCRFs). However, eCRFs only insufficiently support integration of subject's image data, although medical imaging is looming large in studies today. For bed-side image integration, we present a mobile application (App) that utilizes the smartphone-integrated camera. To ensure high image quality with this inexpensive consumer hardware, color reference cards are placed in the camera's field of view next to the lesion. The cards are used for automatic calibration of geometry, color, and contrast. In addition, a personalized code is read from the cards that allows subject identification. For data integration, the App is connected to an communication and image analysis server that also holds the code-study-subject relation. In a second system interconnection, web services are used to connect the smartphone with OpenClinica, an open-source, Food and Drug Administration (FDA)-approved electronic data capture (EDC) system in clinical trials. Once the photographs have been securely stored on the server, they are released automatically from the mobile device. The workflow of the system is demonstrated by an ongoing clinical trial, in which photographic documentation is frequently performed to measure the effect of wound incision management systems. All 205 images, which have been collected in the study so far, have been correctly identified and successfully integrated into the corresponding subject's eCRF. Using this system, manual steps for the study personnel are reduced, and, therefore, errors, latency and costs decreased. Our approach also increases data security and privacy.

  10. Doing the right things and doing things right : inpatient drug surveillance assisted by clinical decision support

    NARCIS (Netherlands)

    Helmons, Pieter J.; Suijkerbuijk, Bas O.; Nannan Panday, Prashant V.; Kosterink, Jos G. W.

    Increased budget constraints and a continuous focus on improved quality require an efficient inpatient drug surveillance process. We describe a hospital-wide drug surveillance strategy consisting of a multidisciplinary evaluation of drug surveillance activities and using clinical decision support to

  11. Comparison of MMPI Scores of Drug Abusers and Mayo Clinic Normative Groups.

    Science.gov (United States)

    Patalano, Frank

    1980-01-01

    Compared MMPIs of 80 male and 80 female drug abusers with MMPIs of 550 male and 695 female medical patients. Male drug abusers obtained significantly higher scores than male medical patients on all clinical scales. Female drug abusers obtained significantly higher scores than female medical patients on seven scales. (Author)

  12. Doing the right things and doing things right : inpatient drug surveillance assisted by clinical decision support

    NARCIS (Netherlands)

    Helmons, Pieter J.; Suijkerbuijk, Bas O.; Nannan Panday, Prashant V.; Kosterink, Jos G. W.

    2015-01-01

    Increased budget constraints and a continuous focus on improved quality require an efficient inpatient drug surveillance process. We describe a hospital-wide drug surveillance strategy consisting of a multidisciplinary evaluation of drug surveillance activities and using clinical decision support to

  13. Associating Drugs, Targets and Clinical Outcomes into an Integrated Network Affords a New Platform for Computer-Aided Drug Repurposing.

    Science.gov (United States)

    Oprea, Tudor I; Nielsen, Sonny Kim; Ursu, Oleg; Yang, Jeremy J; Taboureau, Olivier; Mathias, Stephen L; Kouskoumvekaki, Lrene; Sklar, Larry A; Bologa, Cristian G

    2011-03-14

    Finding new uses for old drugs is a strategy embraced by the pharmaceutical industry, with increasing participation from the academic sector. Drug repurposing efforts focus on identifying novel modes of action, but not in a systematic manner. With intensive data mining and curation, we aim to apply bio- and cheminformatics tools using the DRUGS database, containing 3,837 unique small molecules annotated on 1,750 proteins. These are likely to serve as drug targets and antitargets (i.e., associated with side effects, SE). The academic community, the pharmaceutical sector and clinicians alike could benefit from an integrated, semantic-web compliant computer-aided drug repurposing (CADR) effort, one that would enable deep data mining of associations between approved drugs (D), targets (T), clinical outcomes (CO) and SE. We report preliminary results from text mining and multivariate statistics, based on 7,684 approved drug labels, ADL (Dailymed) via text mining. From the ADL corresponding to 988 unique drugs, the "adverse reactions" section was mapped onto 174 SE, then clustered via principal component analysis into a 5x5 self-organizing map that was integrated into a Cytoscape network of SE-D-T-CO. This type of data can be used to streamline drug repurposing and may result in novel insights that can lead to the identification of novel drug actions.

  14. Non-invasive radiotracer imaging as a tool for drug development.

    Science.gov (United States)

    Gibson, R E; Burns, H D; Hamill, T G; Eng, W S; Francis, B E; Ryan, C

    2000-07-01

    Non-Invasive Radiotracer Imaging (NIRI) uses either short-lived positron-emitting isotopes, such as 11C and 18F, for Positron Emis ion Tomography (PET) or single photon emitting nuclides, e.g., 123I, which provide images using planar imaging or Single-Photon Emission Computed Tomography (SPECT). These high-resolution imaging modalities provide anatomical distribution and localization of radiolabeled drugs, which can be used to generate real time receptor occupancy and off-rate studies in humans. This can be accomplished by either isotopically labeling a potential new drug (usually with 11C), or indirectly by studying how the unlabelled drug inhibits specific radioligand binding in vivo. Competitive blockade studies can be accomplished using a radiolabeled analogue which binds to the site of interest, rather than a radiolabeled version of the potential drug. Imaging, particularly PET imaging, can be used to demonstrate the effect of a drug through a biochemical marker of processes such as glucose metabolism or blood flow. NIRI as a development tool in the pharmaceutical industry is gaining increased acceptance as its unique ability to provide such critical information in human subjects is recognized. This section will review recent examples that illustrate the utility of NIRI, principally PET, in drug development, and the potential of imaging advances in the development of cancer drugs and gene therapy. Finally, we provide a brief overview of the design of new radiotracers for novel targets.

  15. NMR clinical imaging and spectroscopy: Its impact on nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    1990-02-02

    This is a collection of four papers describing aspects of past and future use of nuclear magnetic resonance as a clinical diagnostic tool. The four papers are entitled (1) What Does NMR Offer that Nuclear Medicine Does Not by Jerry W. Froelich, (2) Oncological Imaging: Now, Future and Impact Jerry W. Froelich, (3) Magnetic Resonance Spectroscopy/Spectroscopic Imaging and Nuclear Medicine: Past, Present and Future by H. Cecil Charles, and (4) MR Cardiology: Now, Future and Impact by Robert J. Herfkens.

  16. NMR clinical imaging and spectroscopy: Its impact on nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    1990-02-02

    This is a collection of four papers describing aspects of past and future use of nuclear magnetic resonance as a clinical diagnostic tool. The four papers are entitled (1) What Does NMR Offer that Nuclear Medicine Does Not? by Jerry W. Froelich, (2) Oncological Imaging: Now, Future and Impact Jerry W. Froelich, (3) Magnetic Resonance Spectroscopy/Spectroscopic Imaging and Nuclear Medicine: Past, Present and Future by H. Cecil Charles, and (4) MR Cardiology: Now, Future and Impact by Robert J. Herfkens.

  17. Imaging of Cells and Nanoparticles : Implications for Drug Delivery to the Brain

    NARCIS (Netherlands)

    Stojanov, Katica; Zuhorn, Inge S.; Dierckx, Rudi A. J. O.; de Vries, Erik F. J.

    2012-01-01

    A major challenge in the development of central nervous system drugs is to obtain therapeutic effective drug concentrations inside the brain. Many potentially effective drugs have never reached clinical application because of poor brain penetration. Currently, devices are being developed that may im

  18. First-in-human clinical trials of imaging devices: an example from optical imaging.

    Science.gov (United States)

    Gibbs-Strauss, Summer L; Rosenberg, Mireille; Clough, Barbara L; Troyan, Susan L; Frangioni, John V

    2009-01-01

    Clinical translation of scientific discoveries is often the long-term goal of academic medical research. However, this goal is not always realized due to the complicated path between bench research and clinical use. In this review, we outline the fundamental steps required for first-in-human testing of a new imaging device, and use the FLARE() (Fluorescence-Assisted Resection and Exploration) near-infrared fluorescence optical imaging platform as an example.

  19. High-Throughput 3D Tumor Spheroid Screening Method for Cancer Drug Discovery Using Celigo Image Cytometry.

    Science.gov (United States)

    Kessel, Sarah; Cribbes, Scott; Déry, Olivier; Kuksin, Dmitry; Sincoff, Eric; Qiu, Jean; Chan, Leo Li-Ying

    2016-06-01

    Oncologists have investigated the effect of protein or chemical-based compounds on cancer cells to identify potential drug candidates. Traditionally, the growth inhibitory and cytotoxic effects of the drugs are first measured in 2D in vitro models, and then further tested in 3D xenograft in vivo models. Although the drug candidates can demonstrate promising inhibitory or cytotoxicity results in a 2D environment, similar effects may not be observed under a 3D environment. In this work, we developed an image-based high-throughput screening method for 3D tumor spheroids using the Celigo image cytometer. First, optimal seeding density for tumor spheroid formation was determined by investigating the cell seeding density of U87MG, a human glioblastoma cell line. Next, the dose-response effects of 17-AAG with respect to spheroid size and viability were measured to determine the IC50 value. Finally, the developed high-throughput method was used to measure the dose response of four drugs (17-AAG, paclitaxel, TMZ, and doxorubicin) with respect to the spheroid size and viability. Each experiment was performed simultaneously in the 2D model for comparison. This detection method allowed for a more efficient process to identify highly qualified drug candidates, which may reduce the overall time required to bring a drug to clinical trial.

  20. Clinical study of cutaneous drug eruptions in 200 patients

    Directory of Open Access Journals (Sweden)

    Raksha M

    2008-01-01

    Full Text Available Two hundred patients (112 males and 88 females with cutaneous drug eruption were studied. The aim was to recognize the offending drug, to evaluate mortality and morbidity, educate the patient and avoid self-administration and readministration of drugs. Fixed drug eruption was the commonest reaction, seen in 61 patients; other reactions being urticaria and angioedema, morbilliform rash in 37, pruritus in 25, Stevens Johnson Syndrome (SJS in 6, purpura in 6, exfoliative dermatitis in 5, photosensitivity in 5, toxic epidermal necrolysis in 2, acneiform eruption in 3, erythema multiforme in 2. Maximum patients belonged to the age group 41-50, followed by 21-30 and 31-40 years. The youngest was 1 year old and the oldest was 80 years old. Period of development of lesion after intake of drug varied from 1 day to 45 days. Cotrimoxazole was the commonest drug, in 26 cases; followed by Ibuprofen in 20 cases.

  1. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    Science.gov (United States)

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  2. Comparison of pharmaceutical formulations: ATR-FTIR spectroscopic imaging to study drug-carrier interactions.

    Science.gov (United States)

    Ewing, Andrew V; Biggart, Gordon D; Hale, Carwyn R; Clarke, Graham S; Kazarian, Sergei G

    2015-11-10

    Attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopic imaging has been used in combination with UV detection to study the release of a model poorly water-soluble drug, indomethacin, when formulated with selected drug carriers. Firstly, formulations of indomethacin and nicotinamide in varying weight ratios were studied since novel tablet dosage forms containing multi-drugs are of industrial interest. The in situ spectroscopic imaging measurements of the dissolving tablets showed that as the loading of indomethacin was increased, the rate of drug release changed from one that expressed first-order drug release to one which showed zero-order drug release. Two drug release mechanisms have been identified from the recorded spectroscopic images and UV dissolution profiles. To further validate these mechanisms, specific formulations containing the model drug and two other excipients, urea and mannitol, were studied. The formulations with urea showed similar first-order release, indicative of the drug-carrier interactions. Whereas, the indomethacin/mannitol formulations showed a zero-order release curve explained by disintegration of the tablet. ATR-FTIR spectroscopic imaging provided highly chemically specific information as well as the spatial distribution of the components during the dissolution process which has demonstrated the potential of this combined analytical setup to determine the mechanisms of drug release.

  3. Clinical outcomes of the inclusion of the therapeutic drug monitoring report in the electronic clinical record

    Directory of Open Access Journals (Sweden)

    Marina Sáez Belló

    2016-12-01

    Full Text Available Objectives: To assess the inclusion of the Therapeutic Drug Monitoring Report (TDMR in the Electronic Clinical Record (ECR. Method: An observational ambispective cohort study with a duration of 149 days: PRE (retrospective, 49 days with the TDMR printed in paper, and POST (prospective, 100 days with the TDMR included in the ECR. Exclusion criteria: Patients not hospitalized, applications for Therapeutic Drug Monitoring by Critical Care and Neonatal Units, as well as monitoring with an objective other than dose adjustment. Variables: Number of TDMRs prepared, number of patients admitted with TDMR, time of delay for treatment adjustment, defined as the number of adjustments made to the treatment within over or under 24 hours from the time of TDMR preparation, and medication errors (MEs associated with said delay, as well as the degree of acceptance of the TDMR. Results: 690 TDMRs were conducted in 391 patients, 339 in PRE (n = 206 and 351 in POST (n = 185. The number of treatment modifications made in under 24 hours increased from 73.9% in PRE to 87.3% in POST [RR = 1.2 (CI95% = 0.97-1.43. We identified 35 patients with ME, 9.7% of them in PRE and 8.1% in POST (RR = 0.84 (CI95% = 0.44-1.58]. The degree of acceptance of the pharmacist recommendation increased from 53.3% in PRE to 68.3% in POST [RR = 1.3 (CI95% = 1.02- 1.62]. Conclusions: The inclusion of the Therapeutic Drug Monitoring Report (TDMR in the Electronic Clinical Record increases the degree of acceptance of recommendations, and may reduce the delay in treatment modifications, reducing MEs and improving the process quality in terms of efficacy and safety

  4. Recommendations for imaging tumor response in neurofibromatosis clinical trials.

    Science.gov (United States)

    Dombi, Eva; Ardern-Holmes, Simone L; Babovic-Vuksanovic, Dusica; Barker, Fred G; Connor, Steve; Evans, D Gareth; Fisher, Michael J; Goutagny, Stephane; Harris, Gordon J; Jaramillo, Diego; Karajannis, Matthias A; Korf, Bruce R; Mautner, Victor; Plotkin, Scott R; Poussaint, Tina Y; Robertson, Kent; Shih, Chie-Schin; Widemann, Brigitte C

    2013-11-19

    Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these tumors have become available. Due to differences in disease manifestations and the natural history of NF-related tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria in Solid Tumors] and bidimensional/World Health Organization) have limited applicability. No standardized response criteria for benign NF tumors exist. The goal of the Tumor Measurement Working Group of the REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) committee is to propose consensus guidelines for the evaluation of imaging response in clinical trials for NF tumors. Currently used imaging endpoints, designs of NF clinical trials, and knowledge of the natural history of NF-related tumors, in particular PN and VS, were reviewed. Consensus recommendations for response evaluation for future studies were developed based on this review and the expertise of group members. MRI with volumetric analysis is recommended to sensitively and reproducibly evaluate changes in tumor size in clinical trials. Volumetric analysis requires adherence to specific imaging recommendations. A 20% volume change was chosen to indicate a decrease or increase in tumor size. Use of these criteria in future trials will enable meaningful comparison of results across studies. The proposed imaging response evaluation guidelines, along with validated clinical outcome measures, will maximize the ability to identify potentially active agents for patients with NF and benign tumors.

  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. Diffusion Tensor Imaging: Exploring the Motor Networks and Clinical Applications

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Sung Soo; Lee, Seung Koo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2011-11-15

    With the advances in diffusion magnetic resonance (MR) imaging techniques, diffusion tensor imaging (DTI) has been applied to a number of neurological conditions because DTI can demonstrate microstructures of the brain that are not assessable with conventional MR imaging. Tractography based on DTI offers gross visualization of the white matter fiber architecture in the human brain in vivo. Degradation of restrictive barriers and disruption of the cytoarchitecture result in changes in the diffusion of water molecules in various pathological conditions, and these conditions can also be assessed with DTI. Yet many factors may influence the ability to apply DTI clinically, so these techniques have to be used with a cautious hand.

  7. Body packing: a review of general background, clinical and imaging aspects.

    Science.gov (United States)

    Berger, Ferco H; Nieboer, Koenraad H; Goh, Gerard S; Pinto, Antonio; Scaglione, Mariano

    2015-01-01

    To avoid detection at border crossings or airport customs, drug trafficking is increasingly performed by intra-corporeal concealment. Body packers may ingest packets of varying size and containing varying drugs (mostly cocaine, heroin and cannabis) mixed with other compounds, while body pushers will insert packets in the rectum or vaginal cavity. Body packing may lead to potential life-threatening complications with acute overdose syndromes after packet rupture and intestinal obstruction with possible ensuing bowel rupture being the most significant complications. Physicians including radiologists should be aware of the capabilities of imaging techniques to screen for presence of drug packets as well as the potential complications. Although conventional radiography has long been and still is the most important imaging modality for screening for presence of intestinal packets, the better test characteristics in conjunction with the decreasing radiation exposure, will likely render computed tomography (CT) more important in the future. For imaging of symptomatic patients, CT already is the modality of choice. Besides these modalities, ultrasound and magnetic resonance imaging will be discussed in this paper, together with more general background and clinical information.

  8. Clinical Drug Development in Epilepsy Revisited: A Proposal for a New Paradigm Streamlined Using Extrapolation

    OpenAIRE

    Wadsworth, Ian; Jaki, Thomas; Sills, Graeme J; Appleton, Richard; Cross, J Helen; Marson, Anthony G; Martland, Tim; McLellan, Ailsa; Smith, Philip E. M.; Pellock, John M; Hampson, Lisa V.

    2016-01-01

    Data from clinical trials in adults, extrapolated to predict benefits in paediatric patients, could result in fewer or smaller trials being required to obtain a new drug licence for paediatrics. This article outlines the place of such extrapolation in the development of drugs for use in paediatric epilepsies. Based on consensus expert opinion, a proposal is presented for a new paradigm for the clinical development of drugs for focal epilepsies. Phase I data should continue to be collected in ...

  9. The effect of the European Clinical Trials Directive on published drug research in anaesthesia.

    Science.gov (United States)

    Walker, E; Hankins, M C; White, S M

    2009-09-01

    The clinical indications for anaesthetic drugs are developed through peer-reviewed publication of clinical trials. We performed a bibliometric analysis of all human research papers reported in nine general anaesthesia journals over 6 years (n = 6489), to determine any effects of the 2004 European Clinical Trials Directive on reported drug research in anaesthesia originating from Europe and the United Kingdom. We found 89% studies involved patients and 11% volunteers. Of 3234 (50%) drug studies, 96% were phase IV (post-marketing) trials. Worldwide, the number of research papers fell by 3.6% (p European Clinical Trials Directive (5% Europe, 18% United Kingdom), and drug research papers fell by 12% (p European drug research, particularly that originating from the United Kingdom. We suggest a number of measures researchers could take in response, and we propose a simplification of the application process for phase IV clinical trials, emphasising patient risk assessment.

  10. [Combination analysis of new drug discovery with "Xiaohe Silian" method and traditional Chinese medicine clinical pharmacy].

    Science.gov (United States)

    Liu, Yang; Zhai, Hua-Qiang; Xiang, Jia-Mei; Wang, Jing-Juan; Zhao, Bao-Sheng; Wang, Gang; Dong, Hong-Huan; Ouyang, Guo-Qing

    2014-07-01

    With the kernel of efficacy, "Xiaohe Silian" was a pattern and method for new drug discovery which was constituted with "metabolism-efficacy, toxicity-efficacy, quality-efficacy and structure-efficacy". Its connotation was in keeping with traditional Chinese medicine (TCM) clinical pharmacy. This paper systematically summarized the research method of new drug discovery practice process for TCM. To avoid western drug like in TCM new drug discovery, we carried out combination analysis with TCM clinical pharmacy. The correlation analysis between basic elements of "Xiaohe Silian(n) and TCM clinical pharmacy was studied to guarantee this method could integrate closely with TCM clinic from all angles. Hence, this method aimed to provide a new method for TCM new drug discovery on the basis of TCM clinical pharmacy with insisting on holistic view of multicomponent study, kinetic view of metabolic process when the curative effect occurred and molecular material view of quality control and structure-activity exposition.

  11. Early Diagnosis and Prediction of Anticancer Drug-induced Cardiotoxicity: From Cardiac Imaging to "Omics" Technologies.

    Science.gov (United States)

    Madonna, Rosalinda

    2017-07-01

    Heart failure due to antineoplastic therapy remains a major cause of morbidity and mortality in oncological patients. These patients often have no prior manifestation of disease. There is therefore a need for accurate identification of individuals at risk of such events before the appearance of clinical manifestations. The present article aims to provide an overview of cardiac imaging as well as new "-omics" technologies, especially with regard to genomics and proteomics as promising tools for the early detection and prediction of cardiotoxicity and individual responses to antineoplastic drugs. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Identification of Anti-Persister Activity against Uropathogenic Escherichia coli from a Clinical Drug Library

    OpenAIRE

    2015-01-01

    Uropathogenic E. coli is a major cause of urinary tract infections (UTIs), but current antibiotics do not always effectively clear the persistent infection. To identify drugs that eliminate uropathogenic E. coli persisters, we screened a clinical drug library consisting of 1524 compounds using high throughput drug exposure assay in 96-well plates. Bacterial survival was assessed by growth on LB plates. We identified 14 drug candidates (tosufloxacin, colistin, sparfloxacin, moxifloxacin and ga...

  13. Clinical pharmacokinetics of antimicrobial drugs in cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J

    The disposition of many drugs in cystic fibrosis is abnormal compared with healthy individuals. In general, changes include an increased volume of distribution expressed in liters per kg bodyweight for highly hydrophilic drugs such as aminoglycosides, and, to a lesser extent, for penicillins and

  14. Preclinical and clinical pharmacology of oral anticancer drugs

    NARCIS (Netherlands)

    Oostendorp, R.L.

    2009-01-01

    Nowadays, more than 25% of all anticancer drugs are developed as oral formulations. Oral administration of drugs has several advantages over intravenous (i.v.) administration. It will on average be more convenient for patients, because they can take oral medication themselves, there is no need for

  15. Preclinical and clinical pharmacology of oral anticancer drugs

    NARCIS (Netherlands)

    Oostendorp, R.L.

    2009-01-01

    Nowadays, more than 25% of all anticancer drugs are developed as oral formulations. Oral administration of drugs has several advantages over intravenous (i.v.) administration. It will on average be more convenient for patients, because they can take oral medication themselves, there is no need for f

  16. Personalized Medicine : Pharmacogenetic Testing in Drug Development and Clinical Practice

    NARCIS (Netherlands)

    van der Baan, F.H.

    2012-01-01

    For drugs that are registered on the market, efficacy was proven on a population level. However, on an individual level, most drugs have a different effect in different patients. They may fail to work in some patients or cause serious side effects. Pharmacogenetic research studies the contribution o

  17. Development of multifunctional nanoparticles for targeted drug delivery and noninvasive imaging of therapeutic effect.

    Science.gov (United States)

    Sajja, Hari Krishna; East, Michael P; Mao, Hui; Wang, Y Andrew; Nie, Shuming; Yang, Lily

    2009-03-01

    Nanotechnology is a multidisciplinary scientific field undergoing explosive development. Nanometer-sized particles offer novel structural, optical and electronic properties that are not attainable with individual molecules or bulk solids. Advances in nanomedicine can be made by engineering biodegradable nanoparticles such as magnetic iron oxide nanoparticles, polymers, dendrimers and liposomes that are capable of targeted delivery of both imaging agents and anticancer drugs. This leads toward the concept and possibility of personalized medicine for the potential of early detection of cancer lesions, determination of molecular signatures of the tumor by noninvasive imaging and, most importantly, molecular targeted cancer therapy. Increasing evidence suggests that the nanoparticles, whose surface contains a targeting molecule that binds to receptors highly expressed in tumor cells, can serve as cancer image contrast agents to increase sensitivity and specificity in tumor detection. In comparison with other small molecule contrast agents, the advantage of using nanoparticles is their large surface area and the possibility of surface modifications for further conjugation or encapsulation of large amounts of therapeutic agents. Targeted nanoparticles ferry large doses of therapeutic agents into malignant cells while sparing the normal healthy cells. Such multifunctional nanodevices hold the promise of significant improvement of current clinical management of cancer patients. This review explores the development of nanoparticles for enabling and improving the targeted delivery of therapeutic agents, the potential of nanomedicine, and the development of novel and more effective diagnostic and screening techniques to extend the limits of molecular diagnostics providing point-of-care diagnosis and more personalized medicine.

  18. Clinical factors predict surgical outcomes in pediatric MRI-negative drug-resistant epilepsy.

    Science.gov (United States)

    Arya, Ravindra; Leach, James L; Horn, Paul S; Greiner, Hansel M; Gelfand, Michael; Byars, Anna W; Arthur, Todd M; Tenney, Jeffrey R; Jain, Sejal V; Rozhkov, Leonid; Fujiwara, Hisako; Rose, Douglas F; Mangano, Francesco T; Holland, Katherine D

    2016-10-01

    Lack of a potentially epileptogenic lesion on brain magnetic resonance imaging (MRI) is a poor prognostic marker for epilepsy surgery. We present a single-center series of childhood-onset MRI-negative drug-resistant epilepsy (DRE) and analyze surgical outcomes and predictors. Children with MRI-negative DRE who had resective surgery from January 2007 to December 2013 were identified using an institutional database. Relevant clinical, neurophysiological, imaging, and surgical data was extracted. The primary outcome measure was seizure freedom. Predictors of seizure freedom were obtained using multivariate logistic regression. Out of 47 children with MRI-negative DRE, 12 (25.5%) were seizure free (International League Against Epilepsy [ILAE] outcome class I), after mean follow-up of 2.75 (±1.72) years. Seizure-free proportion was significantly higher in patients with single seizure semiology and concordant ictal EEG (50.0% vs. 15.2%, p=0.025). Multivariate analysis using only non-invasive pre-surgical data showed that children with daily seizures (OR 0.02, 95% CIseizures (OR 0.72, 95% CI 0.52-0.99) were less likely to be seizure-free. Also, each additional anti-epileptic drug (AED) tried before surgery decreased the probability of seizure-free outcome (OR 0.16, 95% CI 0.04-0.63). Repeat multivariate analysis after including surgical variables found no additional significant predictors of seizure-freedom. Cortical dysplasia (ILAE type IB) was the commonest histopathology. Surgical outcomes in children with MRI-negative DRE are determined by clinical factors including seizure frequency, age of onset of seizures, and number of failed AEDs. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  19. Clinical relevance of sirolimus drug interactions in transplant patients.

    Science.gov (United States)

    Sádaba, B; Campanero, M A; Quetglas, E G; Azanza, J R

    2004-12-01

    Sirolimus, a new immunosuppressant drug; is metabolized by cytochrome P450 3A4 (CYP3A4) and is a substrate of the P-glycoprotein drug efflux pump. The CYP3A4/P-glycoprotein system is mainly localized in the liver and intestine. It is responsible for the severe first pass metabolism of sirolimus with a low bioavailability. Drugs like voriconazole, itraconazole, fluconazole, and erytrhomycin may decrease the metabolic activity of this enzymatic system. This report documents in five patients that coadministration of these antimicrobials with sirolimus increases the blood concentrations of the immunosuppressant. The dose-normalized trough blood concentration showed a mean increase of sevenfold with the coadministration of these drugs. It is essential to monitor the blood sirolimus concentrations and to adjust the sirolimus doses before and after coadministration of these drugs.

  20. New receptor targeted drugs : pharmaceutical aspects and molecular imaging

    NARCIS (Netherlands)

    Lub-de Hooge, Marjolijn Nicolette

    2006-01-01

    A new generation of innovative receptor targeted drugs rapidly enters the market. However, since these drugs target a specific receptor, they are not of value for all cancer patients, but only for specific tumor types or a subset within a tumor type. This makes it increasingly important to select

  1. General issues and precautions in the design for clinical trials of investigational new drugs.

    Science.gov (United States)

    Hu, Liang-ping; Bao, Xiao-lei

    2011-02-01

    The general problems existing in the clinical trials of investigational new drugs involve some key aspects such as the guiding principles, research designs, quality controls and statistical analyses. This paper explores the eight general issues in the clinical trials of investigational new drugs and presents precautionary measures with high operability. Research on the clinical trials of investigational new drugs is a complex project, which should be carried out strictly according to the policies, laws, criteria and operating rules set by related agencies. The neglect of research designs and data analyses will lead clinical trials to failure.

  2. Feasibility of poly(ethylene glycol) derivatives as diagnostic drug carriers for tumor imaging.

    Science.gov (United States)

    Kanazaki, Kengo; Sano, Kohei; Makino, Akira; Yamauchi, Fumio; Takahashi, Atsushi; Homma, Tsutomu; Ono, Masahiro; Saji, Hideo

    2016-03-28

    Poly(ethylene glycol) (PEG) is an artificial but biocompatible hydrophilic polymer that has been widely used in clinical products. To evaluate the feasibility of using PEG derivative itself as a tumor imaging carrier via an enhanced permeability and retention (EPR) effect, we prepared indium-111-labeled PEG ((111)In-DTPA-PEG) and indocyanine green (ICG)-labeled PEG (ICG-PEG) with PEG molecular weights of 5-40kDa and investigated their in vivo biodistribution in colon26 tumor-bearing mice. Thereafter, single-photon emission computed tomography (SPECT) and photoacoustic (PA) imaging studies were performed. The in vivo biodistribution studies demonstrated increased tumor uptake and a prolongation of circulation half-life as the molecular weight of PEG increased. Although the observed differences in in vivo biodistribution were dependent on the labeling method ((111)In or ICG), the tumor-to-normal tissue ratios were comparable. Because PEG-based probes with a molecular weight of 20kDa (PEG20) showed a preferable biodistribution (highest accumulation among tissues excised and relatively high tumor-to-blood ratios), an imaging study using (111)In-DTPA-PEG20 and ICG-PEG20 was performed. Colon26 tumors inoculated in the right shoulder were clearly visualized by SPECT 24h after administration. Furthermore, PA imaging using ICG-PEG20 also detected tumor regions, and the detected PA signals increased in proportion with the injected dose. These results suggest that PEG derivatives (20kDa) serve as robust diagnostic drug carriers for tumor imaging. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. 21 CFR 312.40 - General requirements for use of an investigational new drug in a clinical investigation.

    Science.gov (United States)

    2010-04-01

    ... new drug in a clinical investigation. 312.40 Section 312.40 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Administrative Actions § 312.40 General requirements for use of an investigational new drug in...

  4. COMPUTER DYNAMICS SIMULATION OF DRUG DEPENDENCE THROUGH ARTIFICIAL NEURONAL NETWORK: PEDAGOGICAL AND CLINICAL IMPLICATIONS

    Directory of Open Access Journals (Sweden)

    G. SANTOS

    2008-05-01

    Full Text Available To develop and to evaluate the efficiency of a software able to simulate a virtual patient at different stages of addition was the main goal and challenge of this work. We developed the software in Borland™ Delphi  5®  programming language. Techniques of artificial intelligence, neuronal networks and expert systems, were responsible for modeling the neurobiological structures and mechanisms of the interaction with the drugs used. Dynamical simulation and  hypermedia were designed to increase the software’s interactivity which was able to show graphical information from virtual instrumentation and from realistic functional magnetic resonance imaging display. Early, the program was designed to be used by undergraduate students to improve their neurophysiologic learn, based not only in an interaction of membrane receptors with drugs, but in such a large behavioral simulation. The experimental manipulation of the software was accomplished by: i creating a virtual patient from a normal mood to a behavioral addiction, increasing gradatively: alcohol, opiate or cocaine doses. ii designing an approach to treat the patient, to get total or partial remission of behavioral disorder by combining psychopharmacology and psychotherapy. Integration of dynamic simulation with hypermedia and artificial intelligence has been able to point out behavioral details as tolerance, sensitization and level of addiction to drugs of abuse and so on, turned into a potentially useful tool in the development of teaching activities on several ways, such as education as well clinical skills, in which it could assist patients, families and health care to improve and test their knowledge and skills about different faces supported by drugs dependency. Those features are currently under investigation.

  5. MR imaging and clinical findings of spontaneous spinal epidural hematoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sam Soo [Seoul City Boramae Hospital, Seoul (Korea, Republic of); Han, Moon Hee; Kim, Hyun Beom [College of Medicine, Seoul National University, Seoul (Korea, Republic of)] [and others

    2000-01-01

    To describe the MR imaging and clinical findings of spontaneous spinal epidural hematoma. The MR and clinical findings in six patients (M:F=3D4:2;adult:child=3D3:3) with spontaneous spinal epidural hematoma were reviewed. Five patients without any predisposing factor which might cause the condition and one with acute myelogenous leukemia were included. Emergency surgery was performed in two patients, and the other four were managed conservatively. The epidural lesion involved between three and seven vertebrae (mean:4.5), and relative to the spinal cord was located in the posterior-lateral (n=3D4), anterior (n=3D1), or right lateral (n=3D1) area. The hematoma was isointense (n=3D1) or hyperintense (n=3D5) with spinal cord on T1-weighted images, and hypointense (n=3D2) or hyperintense (n=3D4) on T2-weighted images. It was completely absorbed in four of five patients who underwent follow-up MR imaging, but not changed in one. The clinical outcome of these patients was complete recovery (n=3D4), spastic cerebral palsy (n=3D1), or unknown (n=3D1). Because of the lesion's characteristic signal intensity; MR imaging is very useful in the diagnosis and evaluation of spontaneous spinal epidural hematoma. (author)

  6. Recent advances in medical imaging: anatomical and clinical applications.

    Science.gov (United States)

    Grignon, Bruno; Mainard, Laurence; Delion, Matthieu; Hodez, Claude; Oldrini, Guillaume

    2012-10-01

    The aim of this paper was to present an overview of the most important recent advances in medical imaging and their potential clinical and anatomical applications. Dramatic changes have been particularly observed in the field of computed tomography (CT) and magnetic resonance imaging (MRI). Computed tomography (CT) has been completely overturned by the successive development of helical acquisition, multidetector and large area-detector acquisition. Visualising brain function has become a new challenge for MRI, which is called functional MRI, currently based principally on blood oxygenation level-dependent sequences, which could be completed or replaced by other techniques such as diffusion MRI (DWI). Based on molecular diffusion due to the thermal energy of free water, DWI offers a spectrum of anatomical and clinical applications, ranging from brain ischemia to visualisation of large fibrous structures of the human body such as the anatomical bundles of white matter with diffusion tensor imaging and tractography. In the field of X-ray projection imaging, a new low-dose device called EOS has been developed through new highly sensitive detectors of X-rays, allowing for acquiring frontal and lateral images simultaneously. Other improvements have been briefly mentioned. Technical principles have been considered in order to understand what is most useful in clinical practice as well as in the field of anatomical applications. Nuclear medicine has not been included.

  7. Drug utilization in clinical conditions: an update on its essentials

    Directory of Open Access Journals (Sweden)

    Ashok Kumar

    2013-08-01

    Full Text Available Drug utilization studies may be defined as studies of the marketing, distribution, prescription and use of drugs in a society, with special emphasis on the resulting medical, social and economic consequences. Drug utilization studies can provide highly valuable information, at a reasonable price, on the costs and effects (harmful and beneficial of drugs. Such studies make available much useful information including indirect data on morbidity, the pharmaceutical component of the treatment cost of an illness, therapeutic compliance, the incidence of adverse reactions, the effectiveness of drug consumption and the choice of comparators. This information can be of great use in the subsequent elaboration of pharmacoeconomy studies, or in the selection of problematic areas in which these studies may be applied. Pharmacoeconomy studies, in turn, can be used to discover the economic repercussions of inappropriate prescribing and to quantify the cost effectiveness of various therapeutic interventions. The use of drug utilization studies in conjunction with pharmacoeconornic analysis can result in more cost effective utilization of medicines and a better utilization of pharmacoeconomy methods, both of which contribute to a more rational use of drugs. [Int J Res Med Sci 2013; 1(4.000: 320-325

  8. Clinical features and management of intoxication due to hallucinogenic drugs.

    Science.gov (United States)

    Leikin, J B; Krantz, A J; Zell-Kanter, M; Barkin, R L; Hryhorczuk, D O

    1989-01-01

    Hallucinogenic drugs are unique in that they produce the desired hallucinogenic effects at what are considered non-toxic doses. The hallucinogenic drugs can be categorised into 4 basic groups: indole alkaloid derivatives, piperidine derivatives, phenylethylamines and the cannabinols. The drugs reviewed include lysergic acid diethylamide (LSD), phencyclidine (PCP), cocaine, amphetamines, opiates, marijuana, psilocybin, mescaline, and 'designer drugs.' Particularly noteworthy is that each hallucinogen produces characteristic behavioural effects which are related to its serotonergic, dopaminergic or adrenergic activity. Cocaine produces simple hallucinations, PCP can produce complex hallucinations analogous to a paranoid psychosis, while LSD produces a combination of hallucinations, pseudohallucinations and illusions. Dose relationships with changes in the quality of the hallucinatory experience have been described with amphetamines and, to some extent, LSD. Flashbacks have been described with LSD and alcohol. Management of the intoxicated patient is dependent on the specific behavioural manifestation elicited by the drug. The principles involve differentiating the patient's symptoms from organic (medical or toxicological) and psychiatric aetiologies and identifying the symptom complex associated with the particular drug. Panic reactions may require treatment with a benzodiazepine or haloperidol. Patients with LSD psychosis may require an antipsychotic. Patients exhibiting prolonged drug-induced psychosis may require a variety of treatments including ECT, lithium and l-5-hydroxytryptophan.

  9. Clinical applications of imaging biomarkers. Part 1. The neuroradiologist's perspective

    OpenAIRE

    Smith, E T S

    2011-01-01

    This article is concerned with the application and usage in clinical practice of techniques of detection and measurement of imaging biomarkers. Some commentaries in the article derive from a literature search and include summaries of recently published material compiled and linked to each other by extensive use of the text contained in the material examined.

  10. Matching the Clinical Question to the Appropriate Imaging Procedure: What a Cardiologist Wants from Cardiac Imaging

    Directory of Open Access Journals (Sweden)

    S. Wann

    2007-05-01

    Full Text Available In modern medicine, we too often become enamored with technology and lose focus on the reason for per-forming a diagnostic study. Cardiac imaging may have advanced to point of replacing the physical ex-amination, but there is still no substitute for thought-ful planning of a diagnostic approach based on a hier-archy of clinical data, an appreciation of the pre-test likelihood of disease, realistic expectation from vari-ous imaging procedures, and a rational plan for utiliz-ing the information gained. Team work is required to effectively utilize all the capabilities of the modern medical environment. Communication is essential if patients are to receive the best care. As the power and complexity of imag-ing has increase, so has its over-utilization. This lec-ture will focus on maximizing useful diagnostic yield, while minimizing redundancy and excessive costs. While evidence based medical practice is ideally based on controlled randomized trials to show im-proved patient outcomes. Medical imaging has his-torically developed by improving the quality of im-ages, comparing new to existing technologist. Exam-ples will be given of applications of various imaging techniques to common clinical problems, pointing out areas where true evidence is lacking. Appropriate imaging in these situations must be defined by con-sensus of expert opinion. A variety of clinical vi-gnettes will be presented.

  11. Local anesthetics: dentistry's most important drugs, clinical update 2006.

    Science.gov (United States)

    Malamed, Stanley F

    2006-12-01

    Local anesthetics are the safest most effective drugs in medicine for the control and management of pain. They also represent the most important drugs in dentistry. Today, dentistry has a spectrum of local anesthetics that permit pain control to be tailored to the specific needs of the patient: short-, intermediate-, and long-acting drugs. Bupivacaine has become a standard part of the armamentarium for postsurgical pain control while articaine has become the second-most used local anesthetic in the United States since its introduction in 2000. Despite an increase in anecdotal reports of paresthesia since articaine's introduction there is yet, no supporting scientific evidence.

  12. Normal feline brain: clinical anatomy using magnetic resonance imaging.

    Science.gov (United States)

    Mogicato, G; Conchou, F; Layssol-Lamour, C; Raharison, F; Sautet, J

    2012-04-01

    The purpose of this study was to provide a clinical anatomy atlas of the feline brain using magnetic resonance imaging (MRI). Brains of twelve normal cats were imaged using a 1.5 T magnetic resonance unit and an inversion/recovery sequence (T1). Fourteen relevant MRI sections were chosen in transverse, dorsal, median and sagittal planes. Anatomic structures were identified and labelled using anatomical texts and Nomina Anatomica Veterinaria, sectioned specimen heads, and previously published articles. The MRI sections were stained according to the major embryological and anatomical subdivisions of the brain. The relevant anatomical structures seen on MRI will assist clinicians to better understand MR images and to relate this neuro-anatomy to clinical signs. © 2011 Blackwell Verlag GmbH.

  13. A cascade classifier for diagnosis of melanoma in clinical images.

    Science.gov (United States)

    Sabouri, P; GholamHosseini, H; Larsson, T; Collins, J

    2014-01-01

    Computer aided diagnosis of medical images can help physicians in better detecting and early diagnosis of many symptoms and therefore reducing the mortality rate. Realization of an efficient mobile device for semi-automatic diagnosis of melanoma would greatly enhance the applicability of medical image classification scheme and make it useful in clinical contexts. In this paper, interactive object recognition methodology is adopted for border segmentation of clinical skin lesion images. In addition, performance of five classifiers, KNN, Naïve Bayes, multi-layer perceptron, random forest and SVM are compared based on color and texture features for discriminating melanoma from benign nevus. The results show that a sensitivity of 82.6% and specificity of 83% can be achieved using a single SVM classifier. However, a better classification performance was achieved using a proposed cascade classifier with the sensitivity of 83.06% and specificity of 90.05% when performing ten-fold cross validation.

  14. Live cell in vitro and in vivo imaging applications: accelerating drug discovery.

    Science.gov (United States)

    Isherwood, Beverley; Timpson, Paul; McGhee, Ewan J; Anderson, Kurt I; Canel, Marta; Serrels, Alan; Brunton, Valerie G; Carragher, Neil O

    2011-04-04

    Dynamic regulation of specific molecular processes and cellular phenotypes in live cell systems reveal unique insights into cell fate and drug pharmacology that are not gained from traditional fixed endpoint assays. Recent advances in microscopic imaging platform technology combined with the development of novel optical biosensors and sophisticated image analysis solutions have increased the scope of live cell imaging applications in drug discovery. We highlight recent literature examples where live cell imaging has uncovered novel insight into biological mechanism or drug mode-of-action. We survey distinct types of optical biosensors and associated analytical methods for monitoring molecular dynamics, in vitro and in vivo. We describe the recent expansion of live cell imaging into automated target validation and drug screening activities through the development of dedicated brightfield and fluorescence kinetic imaging platforms. We provide specific examples of how temporal profiling of phenotypic response signatures using such kinetic imaging platforms can increase the value of in vitro high-content screening. Finally, we offer a prospective view of how further application and development of live cell imaging technology and reagents can accelerate preclinical lead optimization cycles and enhance the in vitro to in vivo translation of drug candidates.

  15. Imaging of cystic fibrosis lung disease and clinical interpretation

    Energy Technology Data Exchange (ETDEWEB)

    Wielpuetz, M.O.; Eichinger, M.; Kauczor, H.U. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology with Nuclear Medicine; Biederer, J. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Gross-Gerau Community Hospital (Germany). Radiologie Darmstadt; Wege, S. [Heidelberg University Hospital (Germany). Dept. of Pulmonology and Respiratory Medicine; Stahl, M.; Sommerburg, O. [Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Div. of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center; Mall, M.A. [Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Div. of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center; Heidelberg University Hospital (Germany). Dept. of Translational Pulmonology; Puderbach, M. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology with Nuclear Medicine; Hufeland Hospital, Bad Langensalza (Germany). Dept. of Diagnostic and Interventional Radiology

    2016-09-15

    Progressive lung disease in cystic fibrosis (CF) is the life-limiting factor of this autosomal recessive genetic disorder. Increasing implementation of CF newborn screening allows for a diagnosis even in pre-symptomatic stages. Improvements in therapy have led to a significant improvement in survival, the majority now being of adult age. Imaging provides detailed information on the regional distribution of CF lung disease, hence longitudinal imaging is recommended for disease monitoring in the clinical routine. Chest X-ray (CXR), computed tomography (CT) and magnetic resonance imaging (MRI) are now available as routine modalities, each with individual strengths and drawbacks, which need to be considered when choosing the optimal modality adapted to the clinical situation of the patient. CT stands out with the highest morphological detail and has often been a substitute for CXR for regular severity monitoring at specialized centers. Multidetector CT data can be post-processed with dedicated software for a detailed measurement of airway dimensions and bronchiectasis and potentially a more objective and precise grading of disease severity. However, changing to CT was inseparably accompanied by an increase in radiation exposure of CF patients, a young population with high sensitivity to ionizing radiation and lifetime accumulation of dose. MRI as a cross-sectional imaging modality free of ionizing radiation can depict morphological hallmarks of CF lung disease at lower spatial resolution but excels with comprehensive functional lung imaging, with time-resolved perfusion imaging currently being most valuable.

  16. Motion Compensated Ultrasound Imaging Allows Thermometry and Image Guided Drug Delivery Monitoring from Echogenic Liposomes

    Science.gov (United States)

    Ektate, Kalyani; Kapoor, Ankur; Maples, Danny; Tuysuzoglu, Ahmet; VanOsdol, Joshua; Ramasami, Selvarani; Ranjan, Ashish

    2016-01-01

    Ultrasound imaging is widely used both for cancer diagnosis and to assess therapeutic success, but due to its weak tissue contrast and the short half-life of commercially available contrast agents, it is currently not practical for assessing motion compensated contrast-enhanced tumor imaging, or for determining time-resolved absolute tumor temperature while simultaneously reporting on drug delivery. The objectives of this study were to: 1) develop echogenic heat sensitive liposomes (E-LTSL) and non-thermosensitive liposomes (E-NTSL) to enhance half-life of contrast agents, and 2) measure motion compensated temperature induced state changes in acoustic impedance and Laplace pressure of liposomes to monitor temperature and doxorubicin (Dox) delivery to tumors. LTSL and NTSL containing Dox were co-loaded with an US contrast agent (perfluoropentane, PFP) using a one-step sonoporation method to create E-LTSL and E-NTSL. To determine temperature induced intensity variation with respect to the state change of E-LTSL and E-NTSL in mouse colon tumors, cine acquisition of 20 frames/second for about 20 min (or until wash out) at temperatures of 42°C, 39.5°C, and 37°C was performed. A rigid rotation and translation was applied to each of the “key frames” to adjust for any gross motion that arose due to motion of the animal or the transducer. To evaluate the correlation between ultrasound (US) intensity variation and Dox release at various temperatures, treatment (5 mg Dox/kg) was administered via a tail vein once tumors reached a size of 300-400 mm3, and mean intensity within regions of interest (ROIs) defined for each sample was computed over the collected frames and normalized in the range of [0,1]. When the motion compensation technique was applied, a > 2-fold drop in standard deviation in mean image intensity of tumor was observed, enabling a more robust estimation of temporal variations in tumor temperatures for 15-20 min. due to state change of E-LTSL and E

  17. Digital subtraction peripheral angiography using image stacking: initial clinical results.

    Science.gov (United States)

    Kump, K S; Sachs, P B; Wilson, D L

    2001-07-01

    Using clinically acquired x-ray angiography image sequences, we compared three algorithms for creating a single diagnostic quality image that combined input images containing flowing contrast agent. These image-stacking algorithms were: maximum opacity with the minimum gray-scale value across time recorded at each spatial location, (REC) recursive temporal filtering followed by a maximum opacity operation, and (AMF) an approximate matched filter consisting of a convolution with a kernel approximating the matched filter followed by a maximum opacity operation. Eighteen clinical exams of the peripheral arteries of the legs were evaluated. AMF gave 2.7 times greater contrast to noise ratio than the single best subtraction image and 1.3 times improvement over REC, the second best stacking algorithm. This is consistent with previous simulations showing that AMF performs nearly equal to the optimal result from matched filtering without the well-known limitations. For example, unlike matched filtering, AMF filter coefficients were obtained automatically using an image-processing algorithm. AMF effectively brought out small collateral arteries, otherwise difficult to see, without degrading artery sharpness or stenosis grading. Comparing results using reduced and full contrast agent volumes demonstrated that contrast agent load could be reduced to one-third of the conventional amount with AMF processing. By simulating reduced x-ray exposures on clinical exams, we determined that x-ray exposure could be reduced by 80% with AMF processing. We conclude that AMF is a promising, potential technique for reducing contrast agent load and for improving vessel visibility, both very important characteristics for vascular imaging.

  18. The Food and Drug Administration and pragmatic clinical trials of marketed medical products.

    Science.gov (United States)

    Anderson, Monique L; Griffin, Joseph; Goldkind, Sara F; Zeitler, Emily P; Wing, Liz; Al-Khatib, Sana M; Sherman, Rachel E

    2015-10-01

    Pragmatic clinical trials can help answer questions of comparative effectiveness for interventions routinely used in medical practice. Pragmatic clinical trials may examine outcomes of one or more marketed medical products, and they are heterogeneous in design and risk. The Food and Drug Administration is charged with protecting the rights, safety, and welfare of individuals enrolled in clinical investigations, as well as assuring the integrity of the data upon which approval of medical products is made. The Food and Drug Administration has broad jurisdiction over drugs and medical devices (whether or not they are approved for marketing), and as such, clinical investigations of these products are subject to applicable Food and Drug Administration regulations. While many pragmatic clinical trials will meet the criteria for an exemption from the requirements for an investigational new drug application or investigational device exemption, in general, all clinical investigations of medical products that fall under Food and Drug Administration jurisdiction must adhere to regulations for informed consent and review by an institutional review board. We are concerned that current Food and Drug Administration requirements for obtaining individual informed consent may deter or delay the conduct of pragmatic clinical trials intended to develop reliable evidence of comparative safety and effectiveness of approved medical products that are regulated by the Food and Drug Administration. Under current regulations, there are no described mechanisms to alter or waive informed consent to make it less burdensome or more practicable for low-risk pragmatic clinical trials. We recommend that the Food and Drug Administration establish a risk-based approach to obtaining informed consent in pragmatic clinical trials that would facilitate the conduct of pragmatic clinical trials without compromising the protection of enrolled individuals or the integrity of the resulting data.

  19. Expert committee to formulate policy and guidelines for approval of new drugs, clinical trials and banning of drugs-comments.

    Science.gov (United States)

    Ghooi, Ravindra B

    2014-07-01

    All is not well with the clinical research industry. Instances of scientific misconduct by investigators, cutting corners by sponsors, irregularities by regulators, have brought a bad name to the industry. These however form a small part of the clinical research done in this country. The US FDA has conducted over 40 audits, and not made any major observations, suggesting that the clinical research in India is by and large above board. Regulators have amended trial rules recently which have cost the industry dear. A committee appointed to formulate the policy and guidelines for approval of new drugs, clinical trials and banning of the drugs has made 25 recommendations of which most are either superfluous or not likely produce the desired effect. Clubbing banning of the drugs with approval of new drugs and clinical trials also does not make sense, since the mechanisms involved are totally different. Barring a few, most recommendations are counterproductive and should be rejected outright. It is time we learnt that appointment of a committee is not the best way to solve a problem.

  20. Therapeutic Drug Monitoring of Venlafaxine in an Everyday Clinical Setting

    DEFF Research Database (Denmark)

    Hansen, Morten Rix; Kuhlmann, Ida Berglund; Pottegård, Anton

    2017-01-01

    Venlafaxine is a commonly used antidepressant agent. We aimed to provide detailed information on the associations between venlafaxine dose and concentrations of venlafaxine, by patient age and sex. From a therapeutic drug monitoring (TDM) database located at Odense University Hospital, Denmark, we......, and initiation of venlafaxine therapy in the elderly should be made cautiously and supported by drug measurements. This article is protected by copyright. All rights reserved....

  1. Evaluation of popular drug information resources on clinically useful and actionable pharmacogenomic information*†

    Science.gov (United States)

    Chang, Jennifer S.; Pham, Duyen-Anh; Dang, Maithao T.; Lu, Yiting; VanOsdol, Sheri

    2016-01-01

    Background Pharmacogenomics is the study of how genes affect a person's response to drugs. This descriptive study assessed whether popular drug information resources provide clinically useful pharmacogenomic (PGx) information. Methods Four resources (package inserts, Lexicomp, Micromedex 2.0, and Epocrates) were evaluated for information about twenty-seven drugs. Results There was wide variability of PGx information. Whereas Lexicomp included relevant PGx biomarker information for all 27 drugs, Epocrates did in less than 50% of the drugs. None of the resources had monographs that fully incorporated Clinical Pharmacogenomics Implementation Consortium (CPIC) recommendations in more than 30% of the drugs. Conclusion Lexicomp appears to be most useful PGx drug information resource, but none of the resources are sufficient. PMID:26807054

  2. [Exploration and demonstration study on drug combination from clinical real world].

    Science.gov (United States)

    Xie, Yan-ming; Wang, Lian-xin; Wang, Yong-yan

    2014-09-01

    Drug combination is extensive in the clinical real world,which is an important part and the inherent requirements of the post-marketing evaluation of traditional Chinese medicine (TCM). The key issues and technology include multi-domain and multi-disciplinary such as the rationality, efficacy and safety evaluation of combination drug starting from clinical real world, study on component in vivo and mechanism of combination drug, the risk/benefit assessment and cost-benefit evaluation of combination drug and so on. The topic has been studied as clinical demonstration on combination therapy of variety of diseases such as coronary heart disease, stroke, insomnia, depression, hepatitis, herpes zoster, psoriasis and ectopic pregnancy. Meanwhile, multi-disciplinary dynamic innovation alliance of clinical drug combination has been presented, which can promote the academic development and improving service ability and level of TCM.

  3. Find, Fight, Follow: Ultrasound triggered image-guided drug delivery

    NARCIS (Netherlands)

    Sanches, P.G.; Gruell, H.; Steinbach, O.C.

    2012-01-01

    The integration of therapeutic interventions with diagnostic imaginghas been recognized as one of the next technological developments that will have a major impact on medical treatments. Therapeutic applications using ultrasound, for example thermal ablation, hyperthermia or ultrasound induced drug

  4. New developments in the treatment of drug-resistant tuberculosis: clinical utility of bedaquiline and delamanid

    Directory of Open Access Journals (Sweden)

    Brigden G

    2015-10-01

    Full Text Available Grania Brigden,1 Cathy Hewison,2 Francis Varaine21Access Campaign, Médecins Sans Frontières, Geneva, Switzerland; 2Medical Department, Médecins Sans Frontières, Paris, France Abstract: The current treatment for drug-resistant tuberculosis (TB is long, complex, and associated with severe and life-threatening side effects and poor outcomes. For the first time in nearly 50 years, there have been two new drugs registered for use in multidrug-resistant TB (MDR-TB. Bedaquiline, a diarylquinoline, and delamanid, a nitromidoxazole, have received conditional stringent regulatory approval and have World Health Organization interim policy guidance for their use. As countries improve and scale up their diagnostic services, increasing number of patients with MDR-TB and extensively drug-resistant TB are identified. These two new drugs offer a real opportunity to improve the outcomes of these patients. This article reviews the evidence for these two new drugs and discusses the clinical questions raised as they are used outside clinical trial settings. It also reviews the importance of the accompanying drugs used with these new drugs. It is important that barriers hindering the use of these two new drugs are addressed and that the existing clinical experience in using these drugs is shared, such that their routine-use programmatic conditions is scaled up, ensuring maximum benefit for patients and countries battling the MDR-TB crisis. Keywords: MDR-TB, XDR-TB, tuberculosis drugs, group 5 drugs

  5. Magnetic resonance imaging for prostate cancer clinical application

    Institute of Scientific and Technical Information of China (English)

    Bing Li; Yong Du; Hanfeng Yang; Yayong Huang; Jun Meng; Dongmei Xiao

    2013-01-01

    As prostate cancer is a biologically heterogeneous disease for which a variety of treatment options are available,the major objective of prostate cancer imaging is to achieve more precise disease characterization.In clinical practice,magnetic resonance imaging (MRI) is one of the imaging tools for the evaluation of prostate cancer,the fusion of MRI or dynamic contrast-enhanced MRI (DCE-MRI) with magnetic resonance spectroscopic imaging (MRSI) is improving the evaluation of cancer location,size,and extent,while providing an indication of tumor aggressiveness.This review summarizes the role of MRI in the application of prostate cancer and describes molecular MRI techniques (including MRSI and DCE-MRI)for aiding prostate cancer management.

  6. 78 FR 55728 - Society of Clinical Research Associates-Food and Drug Administration: Food and Drug...

    Science.gov (United States)

    2013-09-11

    ... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical trial... Expects in a Pharmaceutical Clinical Trial; (4) Medical Device Aspects of Clinical Research; (5)...

  7. Inner ear barriers to nanomedicine-augmented drug delivery and imaging

    Directory of Open Access Journals (Sweden)

    Jing Zou

    2016-12-01

    Full Text Available There are several challenges to inner ear drug delivery and imaging due to the existence of tight biological barriers to the target structure and the dense bone surrounding it. Advances in imaging and nanomedicine may provide knowledge for overcoming the existing limitations to both the diagnosis and treatment of inner ear diseases. Novel techniques have improved the efficacy of drug delivery and targeting to the inner ear, as well as the quality and accuracy of imaging this structure. In this review, we will describe the pathways and biological barriers of the inner ear regarding drug delivery, the beneficial applications and limitations of the imaging techniques available for inner ear research, the behavior of engineered nanomaterials in inner ear applications, and future perspectives for nanomedicine-based inner ear imaging.

  8. Multifunctional magnetic silica nanotubes for MR imaging and targeted drug delivery.

    Science.gov (United States)

    Huang, Liang; Ao, Lijiao; Wang, Wei; Hu, Dehong; Sheng, Zonghai; Su, Wu

    2015-03-04

    A multifunctional drug delivery vehicle consisting of a tubular shaped silica host, a compact superparamagnetic iron oxide nanoparticle layer and a hyaluronic acid surface coating was developed as a theranostic platform, for in vivo MR imaging and magnetically guided/cancer targeted drug delivery.

  9. Clinical relevance of the small intestine as an organ of drug elimination: drug-fruit juice interactions.

    Science.gov (United States)

    Paine, Mary F; Oberlies, Nicholas H

    2007-02-01

    Most drugs are taken orally. For those intended to act systemically, a significant fraction of the dose can be eliminated during its first passage through a sequence of organs before entry into the general circulation. For some drugs, the degree of first-pass elimination can be large enough such that oral bioavailability is significantly reduced, with the consequent potential for a reduced clinical response. Of these first-pass eliminating organs, the small intestine and liver are the most commonly implicated, in part because they express the highest levels of drug-metabolizing enzymes. For several drugs whose major route of elimination occurs via CYP3A-mediated metabolism, the extent of first-pass metabolism in the small intestine can rival that in the liver. As such, alterations in enteric CYP3A activity alone can significantly influence oral bioavailability. The most extensively studied xenobiotic shown to inhibit only enteric CYP3A is grapefruit juice, the consequences of which can be clinically significant. Although much information has been gained regarding the grapefruit juice effect, progress in the relatively understudied area of drug-diet interactions continues to be sluggish and reactive. In stark contrast, the potential for drug-drug interactions involving any new therapeutic agent must be evaluated, prospectively, before market introduction. To prospectively elucidate mechanisms underlying drug-diet interactions, a multidisciplinary, translational research approach is required, which capitalizes on the collective expertise of drug metabolism scientists and natural products chemists. Such an approach would allow proper between-study comparisons, and ultimately provide conclusive information as to whether specific dietary substances can be taken safely with certain medications.

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

    Science.gov (United States)

    Kieler-Ferguson, Heidi M; Fréchet, Jean M J; Szoka, Francis C

    2013-01-01

    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.

  11. Evaluating drug delivery with salt formation: Drug disproportionation studied in situ by ATR-FTIR imaging and Raman mapping.

    Science.gov (United States)

    Ewing, Andrew V; Wray, Patrick S; Clarke, Graham S; Kazarian, Sergei G

    2015-01-01

    Two different vibrational spectroscopic approaches, ATR-FTIR spectroscopic imaging and Raman mapping, were used to investigate the components within a tablet containing an ionised drug during dissolution experiments. Delivering certain drugs in their salt form is a method that can be used to improve the bioavailability and dissolution of the poorly aqueous soluble materials. However, these ionised species have a propensity to covert back to their thermodynamically favourable free acid or base forms. Dissolution experiments of the ionised drug in different aqueous media resulted in conversion to the more poorly soluble free acid form, which is detrimental for controlled drug release. This study investigates the chemical changes occurring to formulations containing a development ionised drug (37% by weight), in different aqueous pH environments. Firstly, dissolution in a neutral medium was studied, showing that there was clear release of ionised monosodium form of the drug from the tablet as it swelled in the aqueous medium. There was no presence of any drug in the monohydrate free acid form detected in these experiments. Dissolution in an acidic (0.1M HCl) solution showed disproportionation forming the free acid form. Disproportionation occurred rapidly upon contact with the acidic solution, initially resulting in a shell of the monohydrate free acid form around the tablet edges. This slowed ingress of the solution into the tablet before full conversion of the ionised form to the free acid form was characterised in the spectroscopic data.

  12. Acoustic characterization of ultrasound contrast microbubbles and echogenic liposomes: Applications to imaging and drug-delivery

    Science.gov (United States)

    Paul, Shirshendu

    Micron- to nanometer - sized ultrasound agents, like encapsulated microbubbles and echogenic liposomes (ELIPs), are being actively developed for possible clinical implementations in diagnostic imaging and ultrasound mediated drug/gene delivery. The primary objective of this thesis is to characterize the acoustic behavior of and the ultrasound-mediated contents release from these contrast agents for developing multi-functional ultrasound contrast agents. Subharmonic imaging using contrast microbubbles can improve image quality by providing a higher signal to noise ratio. However, the design and development of contrast microbubbles with favorable subharmonic behavior requires accurate mathematical models capable of predicting their nonlinear dynamics. To this goal, 'strain-softening' viscoelastic interfacial models of the encapsulation were developed and subsequently utilized to simulate the dynamics of encapsulated microbubbles. A hierarchical two-pronged approach of modeling --- a model is applied to one set of experimental data to obtain the model parameters (material characterization), and then the model is validated against a second independent experiment --- is demonstrated in this thesis for two lipid coated (SonazoidRTM and DefinityRTM) and a few polymer (polylactide) encapsulated microbubbles. The proposed models were successful in predicting several experimentally observed behaviors e.g., low subharmonic thresholds and "compression-only" radial oscillations. Results indicate that neglecting the polydisperse size distribution of contrast agent suspensions, a common practice in the literature, can lead to inaccurate results. In vitro experimental investigation of the dependence of subharmonic response from these microbubbles on the ambient pressure is also in conformity with the recent numerical investigations, showing both increase or decrease under appropriate excitation conditions. Experimental characterization of the ELIPs and polymersomes was performed

  13. Drug-drug interactions in patients treated for cancer : a prospective study on clinical interventions

    NARCIS (Netherlands)

    van Leeuwen, R. W. F.; Jansman, F. G. A.; van den Bemt, P. M. L. A.; de Man, F.; Piran, F.; Vincenten, I.; Jager, A.; Rijneveld, A. W.; Brugma, J. D.; Mathijssen, R. H. J.; van Gelder, T.

    Background: Drug-drug interactions (DDIs) are of major concern in oncology, since cancer patients typically take many concomitant medications. Retrospective studies have been conducted to determine the prevalence of DDIs. However, prospective studies on DDIs needing interventions in cancer patients

  14. Drug-drug interactions as a determinant of elevated lithium serum levels in daily clinical practice

    NARCIS (Netherlands)

    Wilting, [No Value; Movig, KL; Moolenaar, M; Hekster, YA; Brouwers, [No Value; Heerdink, ER; Nolen, WA; Egberts, AC

    2005-01-01

    Objective: Lithium is a drug with a narrow therapeutic window. Concomitantly used medication is a potentially influencing factor of lithium serum concentrations. We conducted a multicentre retrospective case-control study with the aim of investigating lithium-related drug interactions as determinant

  15. Drug-drug interactions as a determinant of elevated lithium serum levels in daily clinical practice.

    NARCIS (Netherlands)

    Wilting, I.; Movig, K.L.L.; Moolenaar, M.; Hekster, Y.A.; Brouwers, J.R.B.J.; Heerdink, E.R.; Nolen, W.A.; Egberts, A.C.G.

    2005-01-01

    OBJECTIVE: Lithium is a drug with a narrow therapeutic window. Concomitantly used medication is a potentially influencing factor of lithium serum concentrations. We conducted a multicentre retrospective case-control study with the aim of investigating lithium-related drug interactions as determinant

  16. Clinical, Pharmacokinetic, and In Vitro Studies to Support Bioequivalence of Ophthalmic Drug Products.

    Science.gov (United States)

    Choi, Stephanie H; Lionberger, Robert A

    2016-07-01

    For ophthalmic drug products, the determination of bioequivalence can be challenging, as drug concentrations at the site of action cannot always be measured. The FDA has recommended a variety of studies that can be used to demonstrate bioequivalence for different ophthalmic drug products. Product-specific bioequivalence recommendations for 28 ophthalmic products have been posted on FDA's website as of May 2016, outlining the specific tests which should be performed to demonstrate bioequivalence. The type of study that can be used to demonstrate bioequivalence depends on the drug product's active pharmaceutical ingredient(s), dosage form, indication, site of action, mechanism of action, and scientific understanding of drug release/drug availability and drug product characteristics. This article outlines the FDA's current guidance on studies to demonstrate bioequivalence through clinical endpoint studies, pharmacokinetic studies, and in vitro studies for generic ophthalmic drug products.

  17. Digital management and regulatory submission of medical images from clinical trials: role and benefits of the core laboratory

    Science.gov (United States)

    Robbins, William L.; Conklin, James J.

    1995-10-01

    Medical images (angiography, CT, MRI, nuclear medicine, ultrasound, x ray) play an increasingly important role in the clinical development and regulatory review process for pharmaceuticals and medical devices. Since medical images are increasingly acquired and archived digitally, or are readily digitized from film, they can be visualized, processed and analyzed in a variety of ways using digital image processing and display technology. Moreover, with image-based data management and data visualization tools, medical images can be electronically organized and submitted to the U.S. Food and Drug Administration (FDA) for review. The collection, processing, analysis, archival, and submission of medical images in a digital format versus an analog (film-based) format presents both challenges and opportunities for the clinical and regulatory information management specialist. The medical imaging 'core laboratory' is an important resource for clinical trials and regulatory submissions involving medical imaging data. Use of digital imaging technology within a core laboratory can increase efficiency and decrease overall costs in the image data management and regulatory review process.

  18. Clinical trials information in drug development and regulation : existing systems and standards

    NARCIS (Netherlands)

    Valkenhoef, Gert van; Tervonen, Tommi; Brock, Bert de; Hillege, Hans

    2012-01-01

    Clinical trials provide pivotal evidence on drug efficacy and safety. The evidence, information from clinical trials, is currently used by regulatory decision makers in marketing authorization decisions, but only in an implicit manner. For clinical trials information to be used in a transparent and

  19. Identification of drug-related problems by a clinical pharmacist in addition to computerized alerts

    NARCIS (Netherlands)

    R.J. Zaal (Rianne); M.M.P.M. Jansen (Mark M. P.); M. Duisenberg-Van Essenberg (Marjolijn); C.C. Tijssen (Cees); J.A. Roukema; P.M.L.A. van den Bemt (Patricia)

    2013-01-01

    textabstractBackground Both clinical pharmacists and computerized physician order entry systems with clinical decision support (CPOE/CDSS) can reduce drug-related problems (DRPs). However, the contribution of a clinical pharmacist in addition to CPOE/CDSS has not been established in a prospective st

  20. Clinical applications of diffusion imaging in the spine.

    Science.gov (United States)

    Tanenbaum, Lawrence N

    2013-05-01

    As in the brain, the sensitivity of diffusion-weighted imaging (DWI) to ischemic damage in the spinal cord may provide early identification of infarction. Diffusion anisotropy may enhance the detection and understanding of damage to the long fiber tracts with clinical implications for diseases such as multiple sclerosis and amyotrophic lateral sclerosis and may also yield insight into damage that occurs with spondylotic and traumatic myelopathy. This article reviews the basis for DWI for the evaluation of the spinal cord, osseous, and soft tissues of the spine and reviews the imaging appearance of a variety of disease states.

  1. Nuclear Breast Imaging: Clinical Results and Future Directions.

    Science.gov (United States)

    Berg, Wendie A

    2016-02-01

    Interest in nuclear breast imaging is increasing because of technical improvements in dedicated devices that allow the use of relatively low doses of radiotracers with high sensitivity for even small breast cancers. For women with newly diagnosed cancer, primary chemotherapy is often recommended, and improved methods of assessing treatment response are of interest. With widespread breast density notification, functional rather than anatomic methods of screening are of increasing interest as well. For a cancer imaging technology to be adopted, several criteria must be met that will be discussed: evidence of clinical benefit with minimal harm, standardized interpretive criteria, direct biopsy guidance, and acceptable cost-effectiveness.

  2. Use of artificial neural networks in drug and explosive detection through tomographic images with thermal neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Francisco J.O.; Crispim, Verginia R.; Silva, Ademir X., E-mail: fferreira@ien.gov.b, E-mail: verginia@con.ufri.b, E-mail: ademir@con.ufri.b [Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear

    2009-07-01

    The artificial neural network technique was used to identify drugs and plastic explosives, from a tomography composed by a set of six neutrongraphic projections obtained in real time. Bidimensional tomographic images of samples of drugs, explosives and other materials, when digitally processed, yield the characteristic spectra of each type of material. The information contained in those spectra was then used for ANN training, the best images being obtained when the multilayer perceptron model, the back-propagation training algorithm and the Cross-validation interruption criterion were used. ANN showed to be useful in forecasting presence of drugs and explosives hitting a rate of success above 97 %. (author)

  3. Lipoproteins and lipoprotein mimetics for imaging and drug delivery.

    Science.gov (United States)

    Thaxton, C Shad; Rink, Jonathan S; Naha, Pratap C; Cormode, David P

    2016-11-15

    Lipoproteins are a set of natural nanoparticles whose main role is the transport of fats within the body. While much work has been done to develop synthetic nanocarriers to deliver drugs or contrast media, natural nanoparticles such as lipoproteins represent appealing alternatives. Lipoproteins are biocompatible, biodegradable, non-immunogenic and are naturally targeted to some disease sites. Lipoproteins can be modified to act as contrast agents in many ways, such as by insertion of gold cores to provide contrast for computed tomography. They can be loaded with drugs, nucleic acids, photosensitizers or boron to act as therapeutics. Attachment of ligands can re-route lipoproteins to new targets. These attributes render lipoproteins attractive and versatile delivery vehicles. In this review we will provide background on lipoproteins, then survey their roles as contrast agents, in drug and nucleic acid delivery, as well as in photodynamic therapy and boron neutron capture therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Clinical features, MRI brain, and MRS abnormalities of drug-naïve neurologic Wilson′s disease

    Directory of Open Access Journals (Sweden)

    Satyabrata Pulai

    2014-01-01

    Full Text Available Background: Magnetic resonance imaging (MRI helps in the diagnosis of neurologic Wilson′s disease (WD. The literature regarding MR spectroscopy (MRS and diffusion-weighted imaging (DWI in WD is limited. Objectives: To evaluate the clinical features and neuroimaging findings in drug-naοve neurologic WD and to find correlation between clinical stage and disease duration with different imaging findings. Materials and Methods: The study subjects included consecutive and follow-up neurologic WD patients attending movement disorder clinic. The initial clinical and MRI features before commencement of chelation therapy were noted. Of 78 patients, 34 underwent DWI study and MRS was done in 38 patients and in 32 control subjects. Results: Dystonia, dysarthria, tremor, and behavioral abnormality were common presenting features. All patients had MRI abnormality with major affection of basal ganglia. The clinical severity and anatomical extent of MRI abnormalities were positively correlated (P < 0.001; r s = 0.709. Presence of diffusion restriction was inversely related to duration of disease (P < 0.001; r s = 0.760. WD patients had reduced N-acetylaspartate/creatine (Cr and choline (Cho/Cr ratio (P < 0.001 as compared with control subjects in MRS study. Conclusion: Dystonia, dysarthria and tremor are common neurological features of WD. In this study, MRI abnormalities were positively correlated with disease severity; diffusion restriction was inversely correlated with the duration of the disease process. MRS was also a sensitive tool for diagnosing patient of neurologic WD.

  5. Outcome Measures for Clinical Drug Trials in Autism

    OpenAIRE

    Aman, Michael G; Novotny, Sherie; Samango-Sprouse, Carole; Lecavalier, Luc; Leonard, Elizabeth; Gadow, Kenneth D.; King, Bryan H; Pearson, Deborah A.; Gernsbacher, Morton Ann; Chez, Michael

    2004-01-01

    This paper identifies instruments and measures that may be appropriate for randomized clinical trials in participants with autism spectrum disorders (ASDs). The Clinical Global Impressions scale was recommended for all randomized clinical trials. At this point, however, there is no “perfect” choice of outcome measure for core features of autism, although we will discuss five measures of potential utility. Several communication instruments are recommended, based in part on suitability across t...

  6. Definition of variables required for comprehensive description of drug dosage and clinical pharmacokinetics.

    Science.gov (United States)

    Medem, Anna V; Seidling, Hanna M; Eichler, Hans-Georg; Kaltschmidt, Jens; Metzner, Michael; Hubert, Carina M; Czock, David; Haefeli, Walter E

    2017-05-01

    Electronic clinical decision support systems (CDSS) require drug information that can be processed by computers. The goal of this project was to determine and evaluate a compilation of variables that comprehensively capture the information contained in the summary of product characteristic (SmPC) and unequivocally describe the drug, its dosage options, and clinical pharmacokinetics. An expert panel defined and structured a set of variables and drafted a guideline to extract and enter information on dosage and clinical pharmacokinetics from textual SmPCs as published by the European Medicines Agency (EMA). The set of variables was iteratively revised and evaluated by data extraction and variable allocation of roughly 7% of all centrally approved drugs. The information contained in the SmPC was allocated to three information clusters consisting of 260 variables. The cluster "drug characterization" specifies the nature of the drug. The cluster "dosage" provides information on approved drug dosages and defines corresponding specific conditions. The cluster "clinical pharmacokinetics" includes pharmacokinetic parameters of relevance for dosing in clinical practice. A first evaluation demonstrated that, despite the complexity of the current free text SmPCs, dosage and pharmacokinetic information can be reliably extracted from the SmPCs and comprehensively described by a limited set of variables. By proposing a compilation of variables well describing drug dosage and clinical pharmacokinetics, the project represents a step forward towards the development of a comprehensive database system serving as information source for sophisticated CDSS.

  7. Development of photoacoustic imaging technology overlaid on ultrasound imaging and its clinical application

    Science.gov (United States)

    Ishihara, Miya; Tsujita, Kazuhiro; Horiguchi, Akio; Irisawa, Kaku; Komatsu, Tomohiro; Ayaori, Makoto; Hirasawa, Takeshi; Kasamatsu, Tadashi; Hirota, Kazuhiro; Tsuda, Hitoshi; Ikewaki, Katsunori; Asano, Tomohiko

    2015-03-01

    Purpose: Photoacoustic imaging (PAI) enables one to visualize the distribution of hemoglobin and acquire a map of microvessels without using contrast agents. The purpose of our study is to develop a clinically applicable PAI system integrated with a clinical ultrasound (US) array system with handheld PAI probes providing coregistered PAI and US images. Clinical research trials were performed to evaluate the performance and feasibility of clinical value. Materials and Methods: We developed two types of handheld PAI probes: a linear PAI probe combining a conventional linear-array US probe with optical illumination and a transrectal ultrasonography (TRUS)-type PAI probe. We performed experiments with Japanese white rabbits and conducted clinical research trials of urology and vascular medicine with the approval of the medical human ethics committee of the National Defense Medical College. Results: We successfully acquired high-dynamic-range images of the vascular network ranging from capillaries to landmark arteries and identified the femoral vein, deep femoral vein, and great saphenous vein of rabbits. These major vessels in the rabbits groin are surrounded with microvessels connected to each other. Periprostatic microvessels were monitored during radical prostatectomy for localized prostate cancer and they were colocalized with nerve fibers, and their distribution was consistent with the corresponding PAI. The TRUS-type PAI probe clearly demonstrated the location and extent of the neurovascular bundle (NVB) better than does TRUS alone. Conclusions: The system, which can obtain a PAI, a US image, and a merged image, was innovatively designed so that medical doctors can easily find the location without any prior knowledge or extended skills to analyze the obtained images. Our pilot feasibility study confirms that PAI could be an imaging modality useful in the screening study and diagnostic biopsy.

  8. Drug Dose Adjustment in Dialysis Patients Admitted in Clinics Other Than Internal Medicine.

    Science.gov (United States)

    Solak, Yalcin; Biyik, Zeynep; Gaipov, Abduzhappar; Kayrak, Mehmet; Ciray, Hilal; Cizmecioglu, Ahmet; Tonbul, Halil Zeki; Turk, Suleyman

    2016-01-01

    Many drugs that are administered during hospitalization are metabolized or excreted through kidneys, consequently require dosage adjustment. We aimed to investigate inappropriate prescription of drugs requiring renal dose adjustment (RDA) in various surgical and medical inpatient clinics. We retrospectively determined dialysis patients hospitalized between January 2007 and December 2010. Inpatient clinics, including cardiology, pulmonary medicine, neurology, infectious diseases (medical clinics) and cardiovascular surgery, orthopedics, general surgery, obstetrics and gynecology, and neurosurgery (surgical clinics), were screened via electronic database. Total and RDA medications were determined. RDA drugs correctly adjusted to creatinine clearance were labeled as RDA-A (appropriate), otherwise as RDA-I (inappropriate). Renal doses of RDA medications were based on the "American College of Physicians Drug Prescribing in Renal Failure, fifth Edition." Two hundred seventeen hospitalization records of 172 dialysis patients (92 men and 80 women) were included in the analysis. Mean age of patients was 59.4 ± 14.6 years, and the mean hospitalization duration was 8.5 ± 7.8 days. In total, 247 (84.3%, percentage in drugs requiring dose adjustment) and 175 (46.2%) drugs have been inadequately dosed in surgical and medical clinics, respectively. The percentage of patients to whom at least 1 RDA-I drug was ordered was 92% and 91.4% for surgical and medical clinics, respectively (P > 0.05). Nephrology consultation numbers were 8 (7.1%) in surgical and 32 (30.4%) in medical clinics. The most common RDA-I drugs were aspirin and famotidine. A significant portion of RDA drugs was ordered inappropriately both in surgical and medical clinics. Nephrology consultation rate was very low. Measures to increase physician awareness are required to improve results.

  9. Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis

    DEFF Research Database (Denmark)

    Rocca, Maria A; Amato, Maria P; De Stefano, Nicola

    2015-01-01

    that causes clinical symptoms to trigger. Findings on cortical reorganisation support the contribution of brain plasticity and cognitive reserve in limiting cognitive deficits. The development of clinical and imaging biomarkers that can monitor disease development and treatment response is crucial to allow......In patients with multiple sclerosis (MS), grey matter damage is widespread and might underlie many of the clinical symptoms, especially cognitive impairment. This relation between grey matter damage and cognitive impairment has been lent support by findings from clinical and MRI studies. However......, many aspects of cognitive impairment in patients with MS still need to be characterised. Standardised neuropsychological tests that are easy to administer and sensitive to disease-related abnormalities are needed to gain a better understanding of the factors affecting cognitive performance in patients...

  10. A Nanostructured Matrices Assessment to Study Drug Distribution in Solid Tumor Tissues by Mass Spectrometry Imaging

    Science.gov (United States)

    Giordano, Silvia; Pifferi, Valentina; Morosi, Lavinia; Morelli, Melinda; Falciola, Luigi; Cappelletti, Giuseppe; Visentin, Sonja; Licandro, Simonetta A.; Frapolli, Roberta; Zucchetti, Massimo; Pastorelli, Roberta; Brunelli, Laura; D’Incalci, Maurizio; Davoli, Enrico

    2017-01-01

    The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all cells in an adequate enough concentration to eradicate the tumor. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) is one of the most promising imaging techniques that enables the simultaneous visualization of multiple compounds inside tissues. The choice of a suitable matrix constitutes a critical aspect during the development of a MALDI-MSI protocol since the matrix ionization efficiency changes depending on the analyte structure and its physico-chemical properties. The objective of this study is the improvement of the MALDI-MSI technique in the field of pharmacology; developing specifically designed nanostructured surfaces that allow the imaging of different drugs with high sensitivity and reproducibility. Among several nanomaterials, we tested the behavior of gold and titanium nanoparticles, and halloysites and carbon nanotubes as possible matrices. All nanomaterials were firstly screened by co-spotting them with drugs on a MALDI plate, evaluating the drug signal intensity and the signal-to-noise ratio. The best performing matrices were tested on control tumor slices, and were spotted with drugs to check the ion suppression effect of the biological matrix. Finally; the best nanomaterials were employed in a preliminary drug distribution study inside tumors from treated mice. PMID:28336905

  11. Acoustically active liposome-nanobubble complexes for enhanced ultrasonic imaging and ultrasound-triggered drug delivery.

    Science.gov (United States)

    Nguyen, An T; Wrenn, Steven P

    2014-01-01

    Ultrasound is well known as a safe, reliable imaging modality. A historical limitation of ultrasound, however, was its inability to resolve structures at length scales less than nominally 20 µm, which meant that classical ultrasound could not be used in applications such as echocardiography and angiogenesis where one requires the ability to image small blood vessels. The advent of ultrasound contrast agents, or microbubbles, removed this limitation and ushered in a new wave of enhanced ultrasound applications. In recent years, the microbubbles have been designed to achieve yet another application, namely ultrasound-triggered drug delivery. Ultrasound contrast agents are thus tantamount to 'theranostic' vehicles, meaning they can do both therapy (drug delivery) and imaging (diagnostics). The use of ultrasound contrast agents as drug delivery vehicles, however, is perhaps less than ideal when compared to traditional drug delivery vehicles (e.g., polymeric microcapsules and liposomes) which have greater drug carrying capacities. The drawback of the traditional drug delivery vehicles is that they are not naturally acoustically active and cannot be used for imaging. The notion of a theranostic vehicle is sufficiently intriguing that many attempts have been made in recent years to achieve a vehicle that combines the echogenicity of microbubbles with the drug carrying capacity of liposomes. The attempts can be classified into three categories, namely entrapping, tethering, and nesting. Of these, nesting is the newest-and perhaps the most promising.

  12. Positron emission tomography molecular imaging of dopaminergic system in drug addiction.

    Science.gov (United States)

    Hou, Haifeng; Tian, Mei; Zhang, Hong

    2012-05-01

    Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction remains unclear. Positron emission tomography (PET) is the first technology used for the direct measurement of components of the dopaminergic system in the living human brain. In this article, we reviewed the major findings of PET imaging studies on the involvement of DA in drug addiction, especially in heroin addiction. Furthermore, we summarized PET radiotracers that have been used to study the role of DA in drug addiction. To investigate presynaptic function in drug addiction, PET tracers have been developed to measure DA synthesis and transport. For the investigation of postsynaptic function, several radioligands targeting dopamine one (D1) receptor and dopamine two (D2) receptor are extensively used in PET imaging studies. Moreover, we also summarized the PET imaging findings of heroin addiction studies, including heroin-induced DA increases and the reinforcement, role of DA in the long-term effects of heroin abuse, DA and vulnerability to heroin abuse and the treatment implications. PET imaging studies have corroborated the role of DA in drug addiction and increase our understanding the mechanism of drug addiction.

  13. Breast imaging with SoftVue: initial clinical evaluation

    Science.gov (United States)

    Duric, Neb; Littrup, Peter; Li, Cuiping; Roy, Olivier; Schmidt, Steven; Cheng, Xiaoyang; Seamans, John; Wallen, Andrea; Bey-Knight, Lisa

    2014-03-01

    We describe the clinical performance of SoftVue, a breast imaging device based on the principles of ultrasound tomography. Participants were enrolled in an IRB-approved study at Wayne State University, Detroit, MI. The main research findings indicate that SoftVue is able to image the whole uncompressed breast up to cup size H. Masses can be imaged in even the densest breasts with the ability to discern margins and mass shapes. Additionally, it is demonstrated that multi-focal disease can also be imaged. The system was also tested in its research mode for additional imaging capabilities. These tests demonstrated the potential for generating tissue stiffness information for the entire breast using through-transmission data. This research capability differentiates SoftVue from the other whole breast systems on the market. It is also shown that MRI-like images can be generated using alternative processing of the echo data. Ongoing research is focused on validating and quantifying these findings in a larger sample of study participants and quantifying SoftVue's ability to differentiate benign masses from cancer.

  14. Clinical Pharmacokinetic Interactions between Herbal Supplements and Anticancer Drugs

    NARCIS (Netherlands)

    Goey, A.K.L.

    2013-01-01

    In cancer treatment the response to chemotherapy is often characterized by a wide interpatient variability. The increasing popularity of herbal supplements among cancer patients may contribute to this phenomenon. Since these supplements may affect drug metabolizing cytochrome P450 (CYP) enzymes, pla

  15. Clinical Pharmacokinetic Interactions between Herbal Supplements and Anticancer Drugs

    NARCIS (Netherlands)

    Goey, A.K.L.|info:eu-repo/dai/nl/315030135

    2013-01-01

    In cancer treatment the response to chemotherapy is often characterized by a wide interpatient variability. The increasing popularity of herbal supplements among cancer patients may contribute to this phenomenon. Since these supplements may affect drug metabolizing cytochrome P450 (CYP) enzymes, pla

  16. Clinical Pharmacokinetic Interactions between Herbal Supplements and Anticancer Drugs

    NARCIS (Netherlands)

    Goey, A.K.L.

    2013-01-01

    In cancer treatment the response to chemotherapy is often characterized by a wide interpatient variability. The increasing popularity of herbal supplements among cancer patients may contribute to this phenomenon. Since these supplements may affect drug metabolizing cytochrome P450 (CYP) enzymes,

  17. Predicting clinical relevance of grapefruit-drug interactions: a complicated process.

    Science.gov (United States)

    Bailey, D G

    2017-04-01

    Grapefruit juice interacts with a number of drugs. This commentary provides feedback on a previously proposed approach for predicting clinically relevant interactions with grapefruit juice based on the average inherent oral bioavailability (F) and magnitude of increase in bioavailability with other CYP3A inhibitors of the drug. Additional factors such as variability of the magnitude of the pharmacokinetic interaction among individuals, product monograph cautionary statements and vulnerability of the patient population should be considered. A flow diagram is provided that should improve prediction of the pharmacokinetic interaction and clinical relevance for affected drugs and that recommends different courses of action for patient management. Forecasting the clinical importance of a particular drug interaction with grapefruit can be improved through consideration of additional readily available drug regulatory information. © 2016 John Wiley & Sons Ltd.

  18. [3D imaging benefits in clinical pratice of orthodontics].

    Science.gov (United States)

    Frèrejouand, Emmanuel

    2016-12-01

    3D imaging possibilities raised up in the last few years in the orthodontic field. In 2016, it can be used for diagnosis improvement and treatment planning by using digital set up combined to CBCT. It is relevant for orthodontic mechanic updating by creating visible or invisible customised appliances. It forms the basis of numerous scientific researches. The author explains the progress 3D imaging brings to diagnosis and clinics but also highlights the requirements it creates. The daily use of these processes in orthodontic clinical practices needs to be regulated regarding the benefit/risk ratio and the patient satisfaction. The command of the digital work flow created by these technics requires habits modifications from the orthodontist and his staff. © EDP Sciences, SFODF, 2016.

  19. Smart Cancer Cell Targeting Imaging and Drug Delivery System by Systematically Engineering Periodic Mesoporous Organosilica Nanoparticles.

    Science.gov (United States)

    Lu, Nan; Tian, Ying; Tian, Wei; Huang, Peng; Liu, Ying; Tang, Yuxia; Wang, Chunyan; Wang, Shouju; Su, Yunyan; Zhang, Yunlei; Pan, Jing; Teng, Zhaogang; Lu, Guangming

    2016-02-10

    The integration of diagnosis and therapy into one nanoplatform, known as theranostics, has attracted increasing attention in the biomedical areas. Herein, we first present a cancer cell targeting imaging and drug delivery system based on engineered thioether-bridged periodic mesoporous organosilica nanoparticles (PMOs). The PMOs are stably and selectively conjugated with near-infrared fluorescence (NIRF) dye Cyanine 5.5 (Cy5.5) and anti-Her2 affibody on the outer surfaces to endow them with excellent NIRF imaging and cancer targeting properties. Also, taking the advantage of the thioether-group-incorporated mesopores, the release of chemotherapy drug doxorubicin (DOX) loaded in the PMOs is responsive to the tumor-related molecule glutathione (GSH). The drug release percentage reaches 84.8% in 10 mM of GSH solution within 24 h, which is more than 2-fold higher than that without GSH. In addition, the drug release also exhibits pH-responsive, which reaches 53.6% at pH 5 and 31.7% at pH 7.4 within 24 h. Confocal laser scanning microscopy and flow cytometry analysis demonstrate that the PMOs-based theranostic platforms can efficiently target to and enter Her2 positive tumor cells. Thus, the smart imaging and drug delivery nanoplatforms induce high tumor cell growth inhibition. Meanwhile, the Cy5.5 conjugated PMOs perform great NIRF imaging ability, which could monitor the intracellular distribution, delivery and release of the chemotherapy drug. In addition, cell viability and histological assessments show the engineered PMOs have good biocompatibility, further encouraging the following biomedical applications. Over all, the systemically engineered PMOs can serve as a novel cancer cell targeting imaging and drug delivery platform with NIRF imaging, GSH and pH dual-responsive drug release, and high tumor cell targeting ability.

  20. Ability of online drug databases to assist in clinical decision-making with infectious disease therapies

    OpenAIRE

    Jebrock Jennifer; Clauson Kevin A; Zapantis Antonia; Polen Hyla H; Paris Mark

    2008-01-01

    Abstract Background Infectious disease (ID) is a dynamic field with new guidelines being adopted at a rapid rate. Clinical decision support tools (CDSTs) have proven beneficial in selecting treatment options to improve outcomes. However, there is a dearth of information on the abilities of CDSTs, such as drug information databases. This study evaluated online drug information databases when answering infectious disease-specific queries. Methods Eight subscription drug information databases: A...

  1. In Vitro Evaluation of Theranostic Polymeric Micelles for Imaging and Drug Delivery in Cancer

    Directory of Open Access Journals (Sweden)

    Rajiv Kumar, Apurva Kulkarni, Dattatri K Nagesha, Srinivas Sridhar

    2012-01-01

    Full Text Available For the past decade engineered nanoplatforms have seen a momentous progress in developing a multimodal theranostic formulation which can be simultaneously used for imaging and therapy. In this report we describe the synthesis and application of theranostic phospholipid based polymeric micelles for optical fluorescence imaging and controlled drug delivery. CdSe quantum dots (QDs and anti-cancer drug, doxorubicin (Dox, were co-encapsulated into the hydrophobic core of the micelles. The micelles are characterized using optical spectroscopy for characteristic absorbance and fluorescence features of QDs and Dox. TEM and DLS studies yielded a size of <50 nm for the micellar formulations with very narrow size distribution. A sustained release of the drug was observed from the co-encapsulated micellar formulation. In vitro optical fluorescence imaging and cytotoxicity studies with HeLa cell line demonstrated the potential of these micellar systems as efficient optical imaging and therapeutic probes.

  2. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    Science.gov (United States)

    Wang, Taejun; Jang, Won Hyuk; Lee, Seunghun; Yoon, Calvin J.; Lee, Jun Ho; Kim, Bumju; Hwang, Sekyu; Hong, Chun-Pyo; Yoon, Yeoreum; Lee, Gilgu; Le, Viet-Hoan; Bok, Seoyeon; Ahn, G.-One; Lee, Jaewook; Gho, Yong Song; Chung, Euiheon; Kim, Sungjee; Jang, Myoung Ho; Myung, Seung-Jae; Kim, Myoung Joon; So, Peter T. C.; Kim, Ki Hean

    2016-06-01

    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence.

  3. Clinics in diagnostic imaging (82). Lesser trochanter metastasis.

    Science.gov (United States)

    Peh, W C G; Muttarak, M

    2003-02-01

    A 73-year-old woman who had previous mastectomy for breast carcinoma presented with persistent pain over the left hip area for two to three months. Pelvic radiograph showed an expanded osteolytic lesion involving the lesser trochanter of the left femur, with adjacent ill-defined destructive changes. She subsequently developed a displaced pathological fracture through the lesser trochanteric metastasis. The clinical features and pathophysiology of bone metastases are discussed. The role of imaging, with additional illustrative examples, is emphasised.

  4. Clinical safety of magnetic resonance imaging in patients with implanted SynchroMed EL infusion pumps

    Energy Technology Data Exchange (ETDEWEB)

    Diehn, Felix E.; Wood, Christopher P.; Watson, Robert E.; Hunt, Christopher H. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Mauck, William D. [Mayo Clinic, Department of Anesthesiology, Rochester, MN (United States); Burke, Michelle M. [Mayo Clinic, Department of Psychiatry and Psychology, Rochester, MN (United States)

    2011-02-15

    Patients with implanted SynchroMed spinal infusion pumps (Medtronic, Inc., Minneapolis, MN) routinely undergo magnetic resonance imaging at our institution. In August 2008, Medtronic issued an urgent medical device correction report regarding several pumps. Because of the rare potential ''for a delay in the return of proper drug infusion'' and ''for a delay in the logging of motor stall events,'' ''a patient's pump must be interrogated after MRI exposure in order to confirm proper pump functionality.'' This is particularly important in patients receiving intrathecal baclofen, for whom a delay in return of proper pump infusion could lead to life-threatening baclofen withdrawal syndrome. The objective of this report is to present our experience and protocol of performing magnetic resonance imaging in patients with implanted SynchroMed EL pumps. We retrospectively reviewed records of 86 patients with implanted SynchroMed EL spinal infusion pumps who underwent 112 examinations on 1.5-T magnetic resonance imaging scanners from September 1, 1998 to July 7, 2004. No SynchroMed EL pumps were damaged by magnetic resonance imaging, and the programmable settings remained unchanged in all patients. Our data suggest that SynchroMed EL pump malfunction is indeed rare after routine clinical 1.5-T magnetic resonance imaging examinations. However, based on the Medtronic correction report, we perform pump interrogation before and after imaging. (orig.)

  5. Physician adherence to hypertension treatment guidelines and drug acquisition costs of antihypertensive drugs at the cardiac clinic: a pilot study.

    Science.gov (United States)

    Abdulameer, Shaymaa Abdalwahed; Sahib, Mohanad Naji; Aziz, Noorizan Abd; Hassan, Yahaya; Alrazzaq, Hadeer Akram Abdul; Ismail, Omar

    2012-01-01

    Prescribing pattern surveys are one of the pharmacoepidemiological techniques that provide an unbiased picture of prescribing habits. Prescription surveys permit the identification of suboptimal prescribing patterns for further evaluation. The aims of this study were to determine the prescribing trend, adherence of the prescribers to the guideline, and the impact of drug expenditure on drug utilization at the cardiac clinic of Penang Hospital, Malaysia. This was a cross-sectional study. Demographic data of the patients, diagnoses and the drugs prescribed were recorded. The average drug acquisition costs (ADAC) were calculated for each antihypertensive drug class on a daily and annual basis. Adherence to the guideline was calculated as a percentage of the total number of patients. A total of 313 individuals fulfilled the inclusion criteria. The average age of the study population was 59.30 ± 10.35 years. The mean number of drugs per prescription in the study was 2.09 ± 0.78. There were no significant differences in the demographic data. Antihypertensive drugs were used in monotherapy and polytherapy in 20.8% and 79.2% of the patients, respectively. Adherence to the guideline regarding prescription occurred in 85.30% of the patients. The lowest priced drug class was diuretics and the highest was angiotensin-receptor blockers. In conclusion, the total adherence to the guideline was good; the adherence percentage only slightly decreased with a co-existing comorbidity (such as diabetes mellitus). The use of thiazide diuretics was encouraged because they are well tolerated and inexpensive, and perindopril was still prescribed for diabetic patients since it is relatively cheap (generic drug) and its daily dosage is beneficial.

  6. 75 FR 8968 - Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability

    Science.gov (United States)

    2010-02-26

    ... current thinking on adaptive design clinical trials for drugs and biologics. It does not create or confer... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Adaptive Design Clinical... entitled ``Adaptive Design Clinical Trials for Drugs and Biologics.'' The draft guidance provides...

  7. Clinical rules in hospital pharmacy practice to prevent adverse drug events

    NARCIS (Netherlands)

    Rommers, Mirjam Kristien

    2014-01-01

    Adverse drug events (ADEs) refer to any injury from the use of a drug. ADEs occur frequently in hospitalized patients and a substantial proportion are considered preventable. A method to prevent ADEs is computerized physician order entry (CPOE) combined with a clinical decision support system

  8. Electroporation for drug and gene delivery in the clinic: doctors go electric

    DEFF Research Database (Denmark)

    Gehl, J.

    2008-01-01

    Electroporation is a unique system for drug and gene delivery, as it is possible to very specifically target certain tissues within the body with whatever drug, gene, isotope, or other product is desired in a specific situation. An increasing number of clinical trials are being launched, and soph...

  9. Simulated drug administration : An emerging tool for teaching clinical pharmacology during anesthesiology training

    NARCIS (Netherlands)

    Struys, M. M. R. F.; De Smet, T.; Mortier, E. P.

    A thorough understanding of the dose-response relationship is required for optimizing the efficacy of anesthetics while minimizing adverse drug effects.(1) Nowadays, except for the inhaled anesthetics (for which end-tidal concentrations can be measured online), most of the drugs used in clinical

  10. Clinical rules in hospital pharmacy practice to prevent adverse drug events

    NARCIS (Netherlands)

    Rommers, Mirjam Kristien

    2014-01-01

    Adverse drug events (ADEs) refer to any injury from the use of a drug. ADEs occur frequently in hospitalized patients and a substantial proportion are considered preventable. A method to prevent ADEs is computerized physician order entry (CPOE) combined with a clinical decision support system (CDSS)

  11. Simulated drug administration : An emerging tool for teaching clinical pharmacology during anesthesiology training

    NARCIS (Netherlands)

    Struys, M. M. R. F.; De Smet, T.; Mortier, E. P.

    2008-01-01

    A thorough understanding of the dose-response relationship is required for optimizing the efficacy of anesthetics while minimizing adverse drug effects.(1) Nowadays, except for the inhaled anesthetics (for which end-tidal concentrations can be measured online), most of the drugs used in clinical ane

  12. Iliac vein compression syndrome: Clinical, imaging and pathologic findings

    Institute of Scientific and Technical Information of China (English)

    Katelyn; N; Brinegar; Rahul; A; Sheth; Ali; Khademhosseini; Jemianne; Bautista; Rahmi; Oklu

    2015-01-01

    May-Thurner syndrome(MTS) is the pathologic compression of the left common iliac vein by the right common iliac artery, resulting in left lower extremity pain, swelling, and deep venous thrombosis. Though this syndrome was first described in 1851, there are currently no standardized criteria to establish the diagnosis of MTS. Since MTS is treated by a wide array of specialties, including interventional radiology, vascular surgery, cardiology, and vascular medicine, the need for an established diagnostic criterion is imperative in order to reduce misdiagnosis and inappropriate treatment. Although MTS has historically been diagnosed by the presence of pathologic features, the use of dynamic imaging techniques has led to a more radiologic based diagnosis. Thus, imaging plays an integral part in screening patients for MTS, and the utility of a wide array of imaging modalities has been evaluated. Here, we summarize the historical aspects of the clinical features of this syndrome. We then provide a comprehensive assessment of the literature on the efficacy of imaging tools available to diagnose MTS. Lastly, we provide clinical pearls and recommendations to aid physicians in diagnosing the syndrome through the use of provocative measures.

  13. Drug eruptions: An 8-year study including 106 inpatients at a dermatology clinic in Turkey

    Directory of Open Access Journals (Sweden)

    Fatma Akpinar

    2012-01-01

    Full Text Available Background: Few clinical studies are found in the literature about patients hospitalized with a diagnosis of cutaneous drug eruption. Aims: To determine the clinical types of drug eruptions and their causative agents in a hospital-based population. Materials and Methods: This retrospective study was performed in the Dermatology Department of Haseki General Hospital. Through 1751 patients hospitalized in this department between 2002 and 2009, inpatients diagnosed as drug eruption were evaluated according to WHO causality definitions. 106 patients composed of probable and possible cases of cutaneous drug eruptions were included in this study. Results: Seventy one females and 35 males were evolved. Mean age was 44.03±15.14. Duration between drug intake and onset of reaction varied from 5 minutes to 3 months. The most common clinical type was urticaria and/or angioedema in 48.1% of the patients, followed by maculopapular rash in 13.2%, and drug rash with eosinophilia and systemic symptoms in 8.5%. Drugs most frequently associated with cutaneous drug eruptions were antimicrobial agents in 40.5% of the patients, followed by antipyretic/anti-inflammatory analgesics in 31.1%, and antiepileptics in 11.3%. Conclusion: Urticaria and/or angioedema and maculopapular rash comprised majority of the drug eruptions. Rare reactions such as acute generalized exanthematous pustulosis, sweet syndrome, oral ulceration were also found. Antimicrobial agents and antipyretic/anti-inflammatory analgesics were the most commonly implicated drugs. Infrequently reported adverse reactions to myorelaxant agents, newer cephalosporins and fluoroquinolones were also detected. We suppose that studies on drug eruptions should continue, because the pattern of consumption of drugs is changing in every country at different periods and many new drugs are introduced on the market continuously.

  14. Spinal cord ischemia: aetiology, clinical syndromes and imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Weidauer, Stefan [Frankfurt Univ., Sankt Katharinen Hospital Teaching Hospital, Frankfurt am Main (Germany). Dept. of Neurology; Hattingen, Elke; Berkefeld, Joachim [Frankfurt Univ., Frankfurt am Main (Germany). Inst. of Neuroradiology; Nichtweiss, Michael

    2015-03-01

    The purpose of this study was to analyse MR imaging features and lesion patterns as defined by compromised vascular territories, correlating them to different clinical syndromes and aetiological aspects. In a 19.8-year period, clinical records and magnetic resonance imaging (MRI) features of 55 consecutive patients suffering from spinal cord ischemia were evaluated. Aetiologies of infarcts were arteriosclerosis of the aorta and vertebral arteries (23.6 %), aortic surgery or interventional aneurysm repair (11 %) and aortic and vertebral artery dissection (11 %), and in 23.6 %, aetiology remained unclear. Infarcts occurred in 38.2 % at the cervical and thoracic level, respectively, and 49 % of patients suffered from centromedullar syndrome caused by anterior spinal artery ischemia. MRI disclosed hyperintense pencil-like lesion pattern on T2WI in 98.2 %, cord swelling in 40 %, enhancement on post-contrast T1WI in 42.9 % and always hyperintense signal on diffusion-weighted imaging (DWI) when acquired. The most common clinical feature in spinal cord ischemia is a centromedullar syndrome, and in contrast to anterior spinal artery ischemia, infarcts in the posterior spinal artery territory are rare. The exclusively cervical location of the spinal sulcal artery syndrome seems to be a likely consequence of anterior spinal artery duplication which is observed preferentially here. (orig.)

  15. Chest wall tuberculosis - A clinical and imaging experience

    Directory of Open Access Journals (Sweden)

    Shabnam Bhandari Grover

    2011-01-01

    Full Text Available Aims: Tuberculous infection of the thoracic cage is rare and is difficult to discern clinically or on radiographs. This study aims to describe the common sites and the imaging appearances of chest wall tuberculosis. Materials and Methods: A retrospective review of the clinical and imaging records of 12 confirmed cases of thoracic cage tuberculosis (excluding that of the spine, seen over the last 7 years, was performed. Imaging studies available included radiographs, ultrasonographies (USGs, and computed tomography (CT scans. Pathological confirmation was obtained in all cases. Results: All patients had clinical signs and symptoms localized to the site of involvement, whether it was the sternum, sternoclavicular joints, or ribs. CT scan revealed sternal destruction in three patients and osteolytic lesions with sclerosis of the articular surfaces of the sternoclavicular joints in two patients. In five patients with rib lesions, USG elegantly demonstrated the bone destruction underlying the cold abscess. All cases were confirmed to be of tuberculous origin by pathology studies of the aspirated/curetted material, obtained by CT / USG guidance. Conclusions: Tuberculous etiology should be considered for patients presenting with atypical sites of skeletal inflammation. CT scan plays an important role in the evaluation of these patients. However, the use of USG for demonstrating rib destruction in a chest wall cold abscess has so far been under-emphasized, as has been the role of CT and USG guided aspiration in confirming the aetiology.

  16. Clinical benefits of diffusion tensor imaging in hydrocephalus.

    Science.gov (United States)

    Ben-Sira, Liat; Goder, Noam; Bassan, Haim; Lifshits, Shlomi; Assaf, Yaniv; Constantini, Shlomi

    2015-08-01

    OBJECT The object of this study was to use diffusion tensor imaging (DTI) to evaluate and characterize white matter changes in hydrocephalus. METHODS The authors performed a retrospective analysis of DTI in a cohort of patients with hydrocephalus (n = 35), 19 of whom had both pre- and postsurgical imaging studies. These patient's DTI values were compared with values extracted from age-dependent trend lines computed from a healthy subject group (n = 70, age span 14 months-14 years). Several DTI parameters in different regions of interest (ROIs) were evaluated to find the most sensitive parameters for clinical decision making in hydrocephalus. RESULTS Compared with healthy controls, patients with active hydrocephalus had a statistically significant change in all DTI parameters. The most sensitive and specific DTI parameter for predicting hydrocephalus was axial diffusivity (λ1) measured at the level of the corona radiata. Diffusion tensor imaging parameters correlated with several conventional radiological parameters in the assessment of hydrocephalus but were not superior to them. There was no convincing correlation between clinical disease severity and DTI parameters. When examining the pre- and postsurgical effect, it was found that DTI may be a sensitive tool for estimating tissue improvement. CONCLUSIONS This large-cohort study with a multidisciplinary approach combining clinical, neurological, radiological, and multiple DTI parameters revealed the most sensitive DTI parameters for identifying hydrocephalus and suggested that they may serve as an important tool for the disorder's quantitative radiological assessment.

  17. Monitoring of early warning indicators for HIV drug resistance in antiretroviral therapy clinics in Zimbabwe.

    Science.gov (United States)

    Dzangare, J; Gonese, E; Mugurungi, O; Shamu, T; Apollo, T; Bennett, D E; Kelley, K F; Jordan, M R; Chakanyuka, C; Cham, F; Banda, R M

    2012-05-01

    Monitoring human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) can help national antiretroviral treatment (ART) programs to identify clinic factors associated with HIVDR emergence and provide evidence to support national program and clinic-level adjustments, if necessary. World Health Organization-recommended HIVDR EWIs were monitored in Zimbabwe using routinely available data at selected ART clinics between 2007 and 2009. As Zimbabwe's national ART coverage increases, improved ART information systems are required to strengthen routine national ART monitoring and evaluation and facilitate scale-up of HIVDR EWI monitoring. Attention should be paid to minimizing loss to follow-up, supporting adherence, and ensuring clinic-level drug supply continuity.

  18. Army Drug Development Program. Phase I. Clinical Testing.

    Science.gov (United States)

    1980-03-01

    ingestion of each formulation. Various symptoms occured - "twitching", "fuzzy spots on ceiling", "feeling hot" and " bad dreams" - which could not be...Counter, Model S. Scientific Product diluents were used for diluting the blood samples ( Isotonic Buffered Saline; Automated Lysing and Hemoglobin Reagent...1), and at 6 a.m. will drink 360 ml of Sustacal (Mead Johnson product), containing a total of 360 calories. The drug will be administered at 8 a.m

  19. Antiretroviral salvage therapy for multiclass drug-resistant HIV-1-infected patients: from clinical trials to daily clinical practice.

    Science.gov (United States)

    Imaz, Arkaitz; Falcó, Vicenç; Ribera, Esteban

    2011-01-01

    Drug resistance is one of the key problems in the management of long-term HIV-1-infected patients. Due to cross-resistance patterns within classes, broad resistance to the three original antiretroviral classes can develop in some patients, mainly those with extensive antiretroviral treatment experience and multiple treatment failures. Triple-class-resistant HIV-1 infection has been associated with a higher risk of clinical progression and death. Additionally, it increases the probability of transmission of multidrug-resistant HIV-1 strains. Over the last years, the availability of new antiretroviral agents against novel targets (integrase inhibitors and CCR5 antagonists), and new drugs within old classes (nonnucleoside reverse transcriptase inhibitors and protease inhibitors) has opened a range of new therapeutic options for patients with multiclass drug-resistant HIV-1 infection and scarce therapeutic options with previous drugs. In randomized clinical trials, each of these new drugs has shown exceptional efficacy results, especially in patients who received other fully active drugs in the regimen. Indeed, in nonrandomized trials and observational studies, unprecedented rates of virologic suppression similar to those obtained in naive patients have been achieved when three of the currently available new drugs were combined, even in heavily experienced patients who had no viable salvage options with the previous classes. Thus, the goal of suppression and maintenance (plasma HIV-1 RNA infection. Treatment failure can still occur, however, and the management of patients with multidrug-resistant HIV-1 infection remains a challenge. Clinicians are encouraged to optimize use of the new drugs to obtain better control of HIV infection while avoiding emergence of new resistance-associated mutations. The aim of this article is to summarize current knowledge on the management of salvage therapy for patients with multidrug-resistant HIV-1 infection by analyzing the evidence

  20. Literature based drug interaction prediction with clinical assessment using electronic medical records: novel myopathy associated drug interactions.

    Directory of Open Access Journals (Sweden)

    Jon D Duke

    Full Text Available Drug-drug interactions (DDIs are a common cause of adverse drug events. In this paper, we combined a literature discovery approach with analysis of a large electronic medical record database method to predict and evaluate novel DDIs. We predicted an initial set of 13197 potential DDIs based on substrates and inhibitors of cytochrome P450 (CYP metabolism enzymes identified from published in vitro pharmacology experiments. Using a clinical repository of over 800,000 patients, we narrowed this theoretical set of DDIs to 3670 drug pairs actually taken by patients. Finally, we sought to identify novel combinations that synergistically increased the risk of myopathy. Five pairs were identified with their p-values less than 1E-06: loratadine and simvastatin (relative risk or RR = 1.69; loratadine and alprazolam (RR = 1.86; loratadine and duloxetine (RR = 1.94; loratadine and ropinirole (RR = 3.21; and promethazine and tegaserod (RR = 3.00. When taken together, each drug pair showed a significantly increased risk of myopathy when compared to the expected additive myopathy risk from taking either of the drugs alone. Based on additional literature data on in vitro drug metabolism and inhibition potency, loratadine and simvastatin and tegaserod and promethazine were predicted to have a strong DDI through the CYP3A4 and CYP2D6 enzymes, respectively. This new translational biomedical informatics approach supports not only detection of new clinically significant DDI signals, but also evaluation of their potential molecular mechanisms.

  1. Raman spectroscopy towards clinical application: drug monitoring and pathogen identification.

    Science.gov (United States)

    Neugebauer, Ute; Rösch, Petra; Popp, Jürgen

    2015-12-01

    Raman spectroscopy is a label-free method that measures quickly and contactlessly, providing detailed information from the sample, and has proved to be an ideal tool for medical and life science research. In this review, recent advances of the technique towards drug monitoring and pathogen identification by the Jena Research Groups are reviewed. Surface-enhanced Raman spectroscopy (SERS) and ultraviolet resonance Raman spectroscopy in hollow-core optical fibres enable the detection of drugs at low concentrations as shown for the metabolites of the immunosuppressive drug 6-mercaptopurine as well as antimalarial agents. Furthermore, Raman spectroscopy can be used to characterise pathogenic bacteria in infectious diseases directly from body fluids, making time-consuming cultivation processes dispensable. Using the example of urinary tract infection, it is shown how bacteria can be identified from patients' urine samples within <1 h. The methods cover both single-cell analysis and dielectrophoretic capturing of bacteria in suspension. The latter method could also be used for fast (<3.5 h) identification of antibiotic resistance as shown exemplarily for vancomycin-resistant enterococci. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  2. Rapid interferometric imaging of printed drug laden multilayer structures

    DEFF Research Database (Denmark)

    Sandler, Niklas; Kassamakov, Ivan; Ehlers, Henrik

    2014-01-01

    /and active pharmaceutical ingredients (API) adhere to each other. This is crucial in order to have predetermined drug release profiles. We also demonstrate non-invasive measurement of a polymer structure in a microfluidic channel. It shown that traceable interferometric 3D microscopy is a viable technique......The developments in printing technologies allow fabrication of micron-size nano-layered delivery systems to personal specifications. In this study we fabricated layered polymer structures for drug-delivery into a microfluidic channel and aimed to interferometrically assure their topography...... and adherence to each other. We present a scanning white light interferometer (SWLI) method for quantitative assurance of the topography of the embedded structure. We determined rapidly in non-destructive manner the thickness and roughness of the structures and whether the printed layers containing polymers or...

  3. Rapid interferometric imaging of printed drug laden multilayer structures

    DEFF Research Database (Denmark)

    Sandler, Niklas; Kassamakov, Ivan; Ehlers, Henrik

    2014-01-01

    /and active pharmaceutical ingredients (API) adhere to each other. This is crucial in order to have predetermined drug release profiles. We also demonstrate non-invasive measurement of a polymer structure in a microfluidic channel. It shown that traceable interferometric 3D microscopy is a viable technique......The developments in printing technologies allow fabrication of micron-size nano-layered delivery systems to personal specifications. In this study we fabricated layered polymer structures for drug-delivery into a microfluidic channel and aimed to interferometrically assure their topography...... and adherence to each other. We present a scanning white light interferometer (SWLI) method for quantitative assurance of the topography of the embedded structure. We determined rapidly in non-destructive manner the thickness and roughness of the structures and whether the printed layers containing polymers or...

  4. [Evaluating the maturity of IT-supported clinical imaging and diagnosis using the Digital Imaging Adoption Model : Are your clinical imaging processes ready for the digital era?

    Science.gov (United States)

    Studzinski, J

    2017-06-01

    The Digital Imaging Adoption Model (DIAM) has been jointly developed by HIMSS Analytics and the European Society of Radiology (ESR). It helps evaluate the maturity of IT-supported processes in medical imaging, particularly in radiology. This eight-stage maturity model drives your organisational, strategic and tactical alignment towards imaging-IT planning. The key audience for the model comprises hospitals with imaging centers, as well as external imaging centers that collaborate with hospitals. The assessment focuses on different dimensions relevant to digital imaging, such as software infrastructure and usage, workflow security, clinical documentation and decision support, data exchange and analytical capabilities. With its standardised approach, it enables regional, national and international benchmarking. All DIAM participants receive a structured report that can be used as a basis for presenting, e.g. budget planning and investment decisions at management level.

  5. MR imaging of model drug distribution in simulated vitreous

    Directory of Open Access Journals (Sweden)

    Stein Sandra

    2015-09-01

    Full Text Available The in vitro and in vivo characterization of intravitreal injections plays an important role in developing innovative therapy approaches. Using the established vitreous model (VM and eye movement system (EyeMoS the distribution of contrast agents with different molecular weight was studied in vitro. The impact of the simulated age-related vitreal liquefaction (VL on drug distribution in VM was examined either with injection through the gel phase or through the liquid phase. For comparison the distribution was studied ex vivo in the porcine vitreous. The studies were performed in a magnetic resonance (MR scanner. As expected, with increasing molecular weight the diffusion velocity and the visual distribution of the injected substances decreased. Similar drug distribution was observed in VM and in porcine eye. VL causes enhanced convective flow and faster distribution in VM. Confirming the importance of the injection technique in progress of VL, injection through gelatinous phase caused faster distribution into peripheral regions of the VM than following injection through liquefied phase. VM and MR scanner in combination present a new approach for the in vitro characterization of drug release and distribution of intravitreal dosage forms.

  6. Rapid interferometric imaging of printed drug laden multilayer structures.

    Science.gov (United States)

    Sandler, Niklas; Kassamakov, Ivan; Ehlers, Henrik; Genina, Natalja; Ylitalo, Tuomo; Haeggstrom, Edward

    2014-01-01

    The developments in printing technologies allow fabrication of micron-size nano-layered delivery systems to personal specifications. In this study we fabricated layered polymer structures for drug-delivery into a microfluidic channel and aimed to interferometrically assure their topography and adherence to each other. We present a scanning white light interferometer (SWLI) method for quantitative assurance of the topography of the embedded structure. We determined rapidly in non-destructive manner the thickness and roughness of the structures and whether the printed layers containing polymers or/and active pharmaceutical ingredients (API) adhere to each other. This is crucial in order to have predetermined drug release profiles. We also demonstrate non-invasive measurement of a polymer structure in a microfluidic channel. It shown that traceable interferometric 3D microscopy is a viable technique for detailed structural quality assurance of layered drug-delivery systems. The approach can have impact and find use in a much broader setting within and outside life sciences.

  7. Building blocks for a clinical imaging informatics environment.

    Science.gov (United States)

    Kohli, Marc D; Warnock, Max; Daly, Mark; Toland, Christopher; Meenan, Chris; Nagy, Paul G

    2014-04-01

    Over the past 20 years, imaging informatics has been driven by the widespread adoption of radiology information and picture archiving and communication and speech recognition systems. These three clinical information systems are commonplace and are intuitive to most radiologists as they replicate familiar paper and film workflow. So what is next? There is a surge of innovation in imaging informatics around advanced workflow, search, electronic medical record aggregation, dashboarding, and analytics tools for quality measures (Nance et al., AJR Am J Roentgenol 200:1064-1070, 2013). The challenge lies in not having to rebuild the technological wheel for each of these new applications but instead attempt to share common components through open standards and modern development techniques. The next generation of applications will be built with moving parts that work together to satisfy advanced use cases without replicating databases and without requiring fragile, intense synchronization from clinical systems. The purpose of this paper is to identify building blocks that can position a practice to be able to quickly innovate when addressing clinical, educational, and research-related problems. This paper is the result of identifying common components in the construction of over two dozen clinical informatics projects developed at the University of Maryland Radiology Informatics Research Laboratory. The systems outlined are intended as a mere foundation rather than an exhaustive list of possible extensions.

  8. The image schema and innate archetypes: theoretical and clinical implications.

    Science.gov (United States)

    Merchant, John

    2016-02-01

    Based in contemporary neuroscience, Jean Knox's 2004 JAP paper 'From archetypes to reflective function' honed her position on image schemas, thereby introducing a model for archetypes which sees them as 'reliably repeated early developmental achievements' and not as genetically inherited, innate psychic structures. The image schema model is used to illustrate how the analyst worked with a patient who began life as an unwanted pregnancy, was adopted at birth and as an adult experienced profound synchronicities, paranormal/telepathic phenomena and visions. The classical approach to such phenomena would see the intense affectivity arising out of a ruptured symbiotic mother-infant relationship constellating certain archetypes which set up the patient's visions. This view is contrasted with Knox's model which sees the archetype an sich as a developmentally produced image schema underpinning the emergence of later imagery. The patient's visions can then be understood to arise from his psychoid body memory related to his traumatic conception and birth. The contemporary neuroscience which supports this view is outlined and a subsequent image schema explanation is presented. Clinically, the case material suggests that a pre-birth perspective needs to be explored in all analytic work. Other implications of Knox's image schema model are summarized.

  9. Appendiceal mucocele: clinical and imaging features of 14 cases.

    Science.gov (United States)

    Malya, F Umit; Hasbahceci, M; Serter, A; Cipe, G; Karatepe, O; Kocakoc, E; Muslumanoglu, M

    2014-01-01

    Appendiceal mucocele as a cystic dilatation filled with mucinous material is a very rare disease of the appendix vermiformis. Its preoperative diagnosis is still acking behind common use of imaging techniques. Retrospective analysis of the patients with a pathological diagnosis of appendiceal mucocele with regard to clinical and imaging features. The study group included 14 patients with a mean age of 51 years (range from 17 to 82 years). Predominant symptoms were pain and feeling of fullness in the right iliac fossa in 9(64%) and 5 (36%) patients, respectively. For imaging purposes, use of computed tomography resulted in preoperative diagnosis of appendiceal mucocele in half of the patients(50%). 93% of the cases underwent appendectomy, and righth emicolectomy was performed in one patient (7%). Mucocele and cystadenoma were detected in 11 (79%) and 3 (21%)patients, respectively. Presence of acute appendicitis and coloncarcinoma were confirmed afterwards histologically in 4 (29%)and one (7%) patients, respectively. Despite the common use of imaging studies,preoperative diagnosis of appendiceal mucocele is still not possible in most of the cases. During surgical treatment,which is tailored according to imaging and intraoperative findings, precautionary measures to avoid intraperitoneal rupture and dissemination should be taken. Celsius.

  10. Drug-induced immune thrombocytopenia: incidence, clinical features, laboratory testing, and pathogenic mechanisms.

    Science.gov (United States)

    Curtis, Brian R

    2014-01-01

    Drug-induced immune thrombocytopenia (DIIT) is a relatively uncommon adverse reaction caused by drug-dependent antibodies (DDAbs) that react with platelet membrane glycoproteins only when the implicated drug is present. Although more than 100 drugs have been associated with causing DIIT, recent reviews of available data show that carbamazepine, eptifibatide, ibuprofen, quinidine, quinine, oxaliplatin, rifampin, sulfamethoxazole, trimethoprim, and vancomycin are probably the most frequently implicated. Patients with DIIT typically present with petechiae, bruising, and epistaxis caused by an acute, severe drop in platelet count (often to transfusion refractoriness, and must be differentiated by temporal association of exposure to a candidate drug with an acute, severe drop in platelet count. Treatment consists of immediate withdrawal of the implicated drug. Criteria for strong evidence of DIIT include (1) exposure to candidate drug-preceded thrombocytopenia; (2) sustained normal platelet levels after discontinuing candidate drug; (3) candidate drug was only drug used before onset of thrombocytopenia or other drugs were continued or reintroduced after resolution of thrombocytopenia, and other causes for thrombocytopenia were excluded; and (4) reexposure to the candidate drug resulted in recurrent thrombocytopenia. Flow cytometry testing for DDAbs can be useful in confirmation of a clinical diagnosis, and monoclonal antibody enzyme-linked immunosorbent assay testing can be used to determine the platelet glycoprotein target(s), usually GPIIb/IIIa or GPIb/IX/V, but testing is not widely available. Several pathogenic mechanisms for DIIT have been proposed, including hapten, autoantibody, neoepitope, drug-specific, and quinine-type drug mechanisms. A recent proposal suggests weakly reactive platelet autoantibodies that develop greatly increased affinity for platelet glycoprotein epitopes through bridging interactions facilitated by the drug is a possible mechanism for the

  11. Clinical evaluation of irreversible image compression: analysis of chest imaging with computed radiography.

    Science.gov (United States)

    Ishigaki, T; Sakuma, S; Ikeda, M; Itoh, Y; Suzuki, M; Iwai, S

    1990-06-01

    To implement a picture archiving and communication system, clinical evaluation of irreversible image compression with a newly developed modified two-dimensional discrete cosine transform (DCT) and bit-allocation technique was performed for chest images with computed radiography (CR). CR images were observed on a cathode-ray-tube monitor in a 1,024 X 1,536 matrix. One original and five reconstructed versions of the same images with compression ratios of 3:1, 6:1, 13:1, 19:1, and 31:1 were ranked according to quality. Test images with higher spatial frequency were ranked better than those with lower spatial frequency and the acceptable upper limit of the compression ratio was 19:1. In studies of receiver operating characteristics for scoring the presence or absence of nodules and linear shadows, the images with a compression ratio of 25:1 showed a statistical difference as compared with the other images with a compression ratio of 20:1 or less. Both studies show that plain CR chest images with a compression ratio of 10:1 are acceptable and, with use of an improved DCT technique, the upper limit of the compression ratio is 20:1.

  12. 'Ready-access' CT imaging for an orthopaedic trauma clinic.

    LENUS (Irish Health Repository)

    Cawley, D

    2011-03-01

    \\'Ready-Access\\' to CT imaging facilities in Orthopaedic Trauma Clinics is not a standard facility. This facility has been available at the regional trauma unit, in Merlin Park Hospital, Galway for the past four years. We reviewed the use of this facility over a 2-year period when 100 patients had CT scans as part of their trauma clinic assessment. The rate of CT scan per clinic was 0.6. The mean waiting time for a CT scan was 30 minutes. 20 (20%) new fractures were confirmed, 33 (33%) fractures were out-ruled, 25 (25%) fractures demonstrated additional information and 8 (8%) had additional fractures. 20 (20%) patients were discharged and 12 (12%) patients were admitted as a result of the CT scan. It adds little time and cost to CT scanning lists.

  13. Uremic Encephalopathy: MR Imaging Findings and Clinical Correlation.

    Science.gov (United States)

    Kim, D M; Lee, I H; Song, C J

    2016-09-01

    Uremic encephalopathy is a metabolic disorder in patients with renal failure. The purpose of this study was to describe the MR imaging findings of uremic encephalopathy. This study retrospectively reviewed MR imaging findings in 10 patients with clinically proved uremic encephalopathy between May 2005 and December 2014. Parameters evaluated were lesion location and appearance; MR signal intensity of the lesions on T1WI, T2WI, and T2 fluid-attenuated inversion recovery images; the presence or absence of restricted diffusion on diffusion-weighted images and apparent diffusion coefficient maps; and the reversibility of documented signal-intensity abnormalities on follow-up MR imaging. MR imaging abnormalities accompanying marked elevation of serum creatinine (range, 4.3-11.7 mg/dL) were evident in the 10 patients. Nine patients had a history of chronic renal failure with expansile bilateral basal ganglia lesions, and 1 patient with acute renal failure had reversible largely cortical lesions. Two of 6 patients with available arterial blood gas results had metabolic acidosis. All basal ganglia lesions showed expansile high signal intensity (lentiform fork sign) on T2WI. Varied levels of restricted diffusion and a range of signal intensities on DWI were evident and were not correlated with serum Cr levels. All cortical lesions demonstrated high signal intensity on T2WI. Four patients with follow-up MR imaging after hemodialysis showed complete resolution of all lesions. The lentiform fork sign is reliable in the early diagnosis of uremic encephalopathy, regardless of the presence of metabolic acidosis. Cytotoxic edema and/or vasogenic edema on DWI/ADC maps may be associated with uremic encephalopathy. © 2016 by American Journal of Neuroradiology.

  14. Pre-clinical functional Magnetic Resonance Imaging Part I: The kidney.

    Science.gov (United States)

    Zöllner, Frank G; Kalayciyan, Raffi; Chacón-Caldera, Jorge; Zimmer, Fabian; Schad, Lothar R

    2014-12-01

    The prevalence of chronic kidney disease (CKD) is increasing worldwide. In Europe alone, at least 8% of the population currently has some degree of CKD. CKD is associated with serious comorbidity, reduced life expectancy, and high economic costs; hence, the early detection and adequate treatment of kidney disease is important. Pre-clinical research can not only give insights into the mechanisms of the various kidney diseases but it also allows for investigating the outcome of new drugs developed to treat kidney disease. Functional magnetic resonance imaging provides non-invasive access to tissue and organ function in animal models. Advantages over classical animal research approaches are numerous: the same animal might be repeatedly imaged to investigate a progress or a treatment of disease over time. This has also a direct impact on animal welfare and the refinement of classical animal experiments as the number of animals in the studies might be reduced. In this paper, we review current state of the art in functional magnetic resonance imaging with a focus on pre-clinical kidney imaging. Copyright © 2014. Published by Elsevier GmbH.

  15. Pre-clinical functional magnetic resonance imaging. Pt. I. The kidney

    Energy Technology Data Exchange (ETDEWEB)

    Zoellner, Frank G.; Kalayciyan, Raffi; Chacon-Caldera, Jorge; Zimmer, Fabian; Schad, Lothar R. [Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine

    2014-07-01

    The prevalence of chronic kidney disease (CKD) is increasing worldwide. In Europe alone, at least 8% of the population currently has some degree of CKD. CKD is associated with serious comorbidity, reduced life expectancy, and high economic costs; hence, the early detection and adequate treatment of kidney disease is important. Pre-clinical research can not only give insights into the mechanisms of the various kidney diseases but it also allows for investigating the outcome of new drugs developed to treat kidney disease. Functional magnetic resonance imaging provides non-invasive access to tissue and organ function in animal models. Advantages over classical animal research approaches are numerous: the same animal might be repeatedly imaged to investigate a progress or a treatment of disease over time. This has also a direct impact on animal welfare and the refinement of classical animal experiments as the number of animals in the studies might be reduced. In this paper, we review current state of the art in functional magnetic resonance imaging with a focus on pre-clinical kidney imaging.

  16. Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Leach, M.O.; Orton, M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Research UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Morgan, B. [Univ. of Leicester, College of Medicine, Biological Sciences and Psychology, Leicester (United Kingdom); Tofts, P.S. [Brighton and Sussex Medical School, Univ. of Sussex, Clinical Imaging Sciences Centre, Sussex (United Kingdom); Buckley, D.L. [University of Leeds, Division of Medical Physics, Leeds (United Kingdom); Huang, W. [Oregon Health and Science Univ., Advanced Imaging Research Centre, Portland, OR (United States); Horsfield, M.A. [Medical Physics Section, Leicester Royal Infirmary, Dept. of Cardiovascular Sciences, Leicester (United Kingdom); Chenevert, T.L. [Univ. of Michigan Health System, Ann Arbor, MI (United States); Collins, D.J. [Royal Marsden Hospital NHS Foundation Trust, Cancer Research UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Jackson, A. [Univ. of Manchester, Wolfson Molecular Imaging Centre, Withington, Manchester, M20 3LJ (United Kingdom); Lomas, D. [Univ. of Cambridge, Dept. of Radiology, Cambridge (United Kingdom); Whitcher, B. [Unit 2 Greenways Business Park, Mango Solutions, Chippenham (United Kingdom); Clarke, L. [Cancer Imaging Program, Imaging Technology Development Branch, Rockville, MD (United States); Plummer, R. [Univ. of Newcastle Upon Tyne, The Medical School, Medical Oncology, Northern Inst. for Cancer Research, Newcastle Upon Tyne (United Kingdom); Judson, I. [Royal Marsden Hospital, Sutton, Surrey (United Kingdom); Jones, R. [Beatson West of Scotland Cancer Centre, Glasgow (United Kingdom); Alonzi, R. [Mount Vernon Cancer Centre, Northwood (United Kingdom); Brunner, T. [Gray Inst. for Radiation, Oncology and Biology, Oxford (United Kingdom); Koh, D.M. [Royal Marsden NHS Foundation Trust, Diagnostic Radiology, Sutton, Surrey (United Kingdom)] [and others

    2012-07-15

    Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. (orig.)

  17. Measurement of drug-target engagement in live cells by two-photon fluorescence anisotropy imaging.

    Science.gov (United States)

    Vinegoni, Claudio; Fumene Feruglio, Paolo; Brand, Christian; Lee, Sungon; Nibbs, Antoinette E; Stapleton, Shawn; Shah, Sunil; Gryczynski, Ignacy; Reiner, Thomas; Mazitschek, Ralph; Weissleder, Ralph

    2017-07-01

    The ability to directly image and quantify drug-target engagement and drug distribution with subcellular resolution in live cells and whole organisms is a prerequisite to establishing accurate models of the kinetics and dynamics of drug action. Such methods would thus have far-reaching applications in drug development and molecular pharmacology. We recently presented one such technique based on fluorescence anisotropy, a spectroscopic method based on polarization light analysis and capable of measuring the binding interaction between molecules. Our technique allows the direct characterization of target engagement of fluorescently labeled drugs, using fluorophores with a fluorescence lifetime larger than the rotational correlation of the bound complex. Here we describe an optimized protocol for simultaneous dual-channel two-photon fluorescence anisotropy microscopy acquisition to perform drug-target measurements. We also provide the necessary software to implement stream processing to visualize images and to calculate quantitative parameters. The assembly and characterization part of the protocol can be implemented in 1 d. Sample preparation, characterization and imaging of drug binding can be completed in 2 d. Although currently adapted to an Olympus FV1000MPE microscope, the protocol can be extended to other commercial or custom-built microscopes.

  18. Anti-Hepatitis B Virus Drugs in Clinical and Preclinical Development

    Institute of Scientific and Technical Information of China (English)

    Gui-feng WANG; Li-ping SHI; Jian-ping ZUO

    2008-01-01

    Up to date, there are two types of drugs approved to treat hepatitis B: interferons and nucleos (t) ide analogues. However, the therapies are limited in the clinical context because of the negative side effects of interferon-α and the development of substantial viral resistance to nucleos (t) idic inhibitors. Therefore, new drugs with novel structures and mechanisms are needed. In this article, the drugs approved by FDA or the European Commission for treating chronic hepatitis B virus infection, as well as those under clinical trials, and several compounds in preclinical studies are reviewed. Additionally, some potential targets and strategies to combat chronic hepatitis B virus infection are discussed.

  19. Biotech injectable drugs: clinical applications and financial effects.

    Science.gov (United States)

    Vogenberg, F Randy; Young, Coleen

    2004-07-01

    Biotechnology-derived injectable medications raise complex issues with respect to access and administration for both manufacturers and payers. In addition, biotech injectables rarely fit within traditional prescription drug benefit design structures, thereby creating inequities in reimbursement and access that can undermine a health benefit plan's goals.Benefit-design changes focusing on short-term solutions can exacerbate such situations. Employers, insurers, and managed care organizations need to consider innovative benefit-plan designs to effectively address issues that are associated with biotech medications.Actuarial models, such as the Reimbursement model described in this article, can help to provide the options analyses and decision-making support that are required.

  20. Doxorubicin liposome-loaded microbubbles for contrast imaging and ultrasound-triggered drug delivery.

    Science.gov (United States)

    Escoffre, Jean-Michel; Mannaris, Christophoros; Geers, Bart; Novell, Anthony; Lentacker, Ine; Averkiou, Michalakis; Bouakaz, Ayache

    2013-01-01

    Targeted drug delivery under image guidance is gaining more interest in the drug-delivery field. The use of microbubbles as contrast agents in diagnostic ultrasound provides new opportunities in noninvasive image-guided drug delivery. In the present study, the imaging and therapeutic properties of novel doxorubicin liposome-loaded microbubbles are evaluated. The results showed that at scanning settings (1.7 MHz and mechanical index 0.2), these microbubbles scatter sufficient signal for nonlinear ultrasound imaging and can thus be imaged in real time and be tracked in vivo. In vitro therapeutic evaluation showed that ultrasound at 1 MHz and pressures up to 600 kPa in combination with the doxorubicin liposomeloaded microbubbles induced 4-fold decrease of cell viability compared with treatment with free doxorubicin or doxorubicin liposome-loaded microbubbles alone. The therapeutic effectiveness is correlated to an ultrasound-triggered release of doxorubicin from the liposomes and an enhanced uptake of the free doxorubicin by glioblastoma cells. The results obtained demonstrate that the combination of ultrasound and the doxorubicin liposome-loaded microbubbles can provide a new method of noninvasive image-guided drug delivery.

  1. Potential drug-drug and drug-disease interactions in prescriptions for ambulatory patients over 50 years of age in family medicine clinics in Mexico City

    Directory of Open Access Journals (Sweden)

    Torres-Arreola Laura del Pilar

    2007-09-01

    Full Text Available Abstract Background In Mexico, inappropriate prescription of drugs with potential interactions causing serious risks to patient health has been little studied. Work in this area has focused mainly on hospitalized patients, with only specific drug combinations analyzed; moreover, the studies have not produced conclusive results. In the present study, we determined the frequency of potential drug-drug and drug-disease interactions in prescriptions for ambulatory patients over 50 years of age, who used Mexican Institute of Social Security (IMSS family medicine clinics. In addition, we aimed to identify the associated factors for these interactions. Methods We collected information on general patient characteristics, medical histories, and medication (complete data. The study included 624 ambulatory patients over 50 years of age, with non-malignant pain syndrome, who made ambulatory visits to two IMSS family medicine clinics in Mexico City. The patients received 7-day prescriptions for non-opioid analgesics. The potential interactions were identified by using the Thompson Micromedex program. Data were analyzed using descriptive, bivariate and multiple logistic regression analyses. Results The average number of prescribed drugs was 5.9 ± 2.5. About 80.0% of patients had prescriptions implying one or more potential drug-drug interactions and 3.8% of patients were prescribed drug combinations with interactions that should be avoided. Also, 64.0% of patients had prescriptions implying one or more potential drug disease interactions. The factors significantly associated with having one or more potential interactions included: taking 5 or more medicines (adjusted Odds Ratio (OR: 4.34, 95%CI: 2.76–6.83, patient age 60 years or older (adjusted OR: 1.66, 95% CI: 1.01–2.74 and suffering from cardiovascular diseases (adjusted OR: 7.26, 95% CI: 4.61–11.44. Conclusion The high frequency of prescription of drugs with potential drug interactions showed in

  2. The pharmacokinetic/pharmacodynamic pipeline: translating anticancer drug pharmacology to the clinic.

    Science.gov (United States)

    Zhou, Qingyu; Gallo, James M

    2011-03-01

    Progress in an understanding of the genetic basis of cancer coupled to molecular pharmacology of potential new anticancer drugs calls for new approaches that are able to address key issues in the drug development process, including pharmacokinetic (PK) and pharmacodynamic (PD) relationships. The incorporation of predictive preclinical PK/PD models into rationally designed early-stage clinical trials offers a promising way to relieve a significant bottleneck in the drug discovery pipeline. The aim of the current review is to discuss some considerations for how quantitative PK and PD analyses for anticancer drugs may be conducted and integrated into a global translational effort, and the importance of examining drug disposition and dynamics in target tissues to support the development of preclinical PK/PD models that can be subsequently extrapolated to predict pharmacologic characteristics in patients. In this article, we describe three different physiologically based (PB) PK modeling approaches, i.e., the whole-body PBPK model, the hybrid PBPK model, and the two-pore model for macromolecules, as well as their applications. General conclusions are that greater effort should be made to generate more clinical data that could validate scaled preclinical PB-PK/PD tumor-based models and, thus, stimulate a framework for preclinical to clinical translation. Finally, given the innovative techniques to measure tissue drug concentrations and associated biomarkers of drug responses, development of predictive PK/PD models will become a standard approach for drug discovery and development.

  3. Clinical analysis of 275 cases of acute drug-induced liver disease

    Institute of Scientific and Technical Information of China (English)

    LI Lei; JIANG Wei; WANG Jiyao

    2007-01-01

    In order to analyze the causative drugs,clinical manifestation and pathological characteristics of the patients with acute drug-induced liver disease,from January 2000 to December 2005,275 cases diagnosed as acute druginduced liver diseases according to Maria Criterion and hospitalized in Zhongshan Hospital of Fudan University were retrospectively reviewed.Each was determined by drug history,clinical symptoms and signs,laboratory tests and therapeutic effects.In 41 cases,the diagnosis was confirmed by liver biopsy.The proportion of acute drug-induced liver disease among all of the acute liver injuries was annually increased.The most common drugs which induced acute liver injuries were traditional Chinese herb medicine (23.3 %,64/275 cases),antineoplastics (15.3%,42/275),hormones and other immunosuppressant agents (13.8%,38/275),antihypertensive drugs and other cardiovascular drugs (10.2 %,28/275),NSAIDs (8.7%,24/275) respectively.Hepatocellular injury was the predominant type in these cases (132 cases,48%).The principal clinical manifestation included nausea (54.8%),fatigue (50.2%),jaundice (35.6%).27.9% patients were asymptomatic.Most patients were cured with good prognosis.The total effective rate was 94.2% after treatment.The clinicians should pay attention to the prevention,diagnosis and therapy of drug-induced liver disease.

  4. Identification of possible adverse drug reactions in clinical notes

    DEFF Research Database (Denmark)

    Warrer, Pernille; Jensen, Peter Bjødstrup; Aagaard, Lise

    2015-01-01

    and stomach ulcer associated with liraglutide. Of the unlabeled ADRs, 13 (87%) were associated with "other blood glucose lowering medications," the remaining 2 (13%) with "DDP-4 inhibitors." Conclusion: Clinical notes could potentially reveal unlabeled ADRs associated with prescribed medicines and sufficient...... information is generally available for causality assessment. However, manual review of clinical notes is too time-consuming for routine use and hence there is a need for developing information technology (IT) tools for automatic screening of patient records with the purpose to detect information about...

  5. Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

    Directory of Open Access Journals (Sweden)

    Maarten Janssen

    2014-03-01

    Full Text Available Osteoarthritis (OA is a big burden of disease worldwide and one of the most common causes of disability in the adult population. Currently applied therapies consist of physical therapy, oral medication, intra-articular injections, and surgical interventions, with the main goal being to reduce pain and improve function and quality of life. Intra-articular (IA administration of drugs has potential benefits in OA treatment because it minimizes systemic bioavailability and side effects associated with oral administration of drugs without compromising the therapeutic effect in the joint. However, IA drug residence time is short and there is a clinical need for a vehicle that is able to provide a sustained release long enough for IA therapy to fulfill its promise. This review summarizes the use of different polymeric systems and the incorporated drugs for IA drug delivery in the osteoarthritic joint with a primary focus on clinical needs and opportunities.

  6. 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.

  7. Deciphering the clinical effect of drugs through large-scale data integration

    DEFF Research Database (Denmark)

    Kjærulff, Sonny Kim

    . This work demonstrates the power of a strategy that uses clinical data mining in association with chemical biology in order to reduce the search space and aid identification of novel drug actions. The second article described in chapter 3 outlines a high confidence side-effect-drug interaction dataset. We...... chemical biology database. ChemProt integrates different chemical-protein annotation resources for disease-associated proteins and protein-protein interaction data. ChemProt is developed to assist in silico evaluation of environmental chemicals, natural products and approved drugs, as well as to aid......-effect data have been implemented. Chapter 3 presents two articles that showcase the application of systems chemical biology approaches to understand and model drug side-effect data. The first approach applies machine learning methods to cluster side-effects, drugs, proteins and clinical outcomes in networks...

  8. Drug-drug interactions among recently hospitalised patients--frequent but mostly clinically insignificant

    DEFF Research Database (Denmark)

    Glintborg, Bente; Andersen, Stig Ejdrup; Dalhoff, Kim

    2005-01-01

    involved over-the-counter products (aspirin and ginkgo biloba). Of the 52 drugs involved in potential class 2 interactions, 50 had been used for more than 1 month. According to the hospital case notes, none of the potential class 2 interactions had actually caused adverse effects. CONCLUSION: Although...

  9. Towards clinical use of a laser-induced microjet system aimed at reliable and safe drug delivery.

    Science.gov (United States)

    Jang, Hun-jae; Yu, Hyeonju; Lee, Seonggeun; Hur, Eugene; Kim, Yoonkwan; Lee, Seol-Hoon; Kang, Naegyu; Yoh, Jack J

    2014-05-01

    An Er:YAG laser with 2940-nm wavelength and 250-μs pulse duration is used to generate a microjet that is ejected at ∼50 m/s in air. The strength of the microjet depends on the bubble dynamics from the beam-water interaction within the driving chamber as well as the discharging of the drug solution underneath the elastic membrane that separates the drug from the driving liquid. The jet characteristics, such as velocity, volume, and level of atomization, are obtained by high-speed camera images taken at 42,000 fps. The enhancements in jet volume (dosage) and repeated jet generation, which are aimed at making the injector suitable for general clinical applications, are achieved. The generation of repeated microjets is achieved with the help of a stepping motor that provides a uniform pressure within the drug reservoir before an ejection occurs through a micro nozzle. Also, two types of human growth hormones are used for monitoring any potential thermal damage to the drug solution due to a repeated laser ablation when driving the microjet. We provide strong evidence to support that the drugs, as they are injected to porcine skins, are free of the damage associated with the present delivery method.

  10. Hounsfield unit recovery in clinical cone beam CT images of the thorax acquired for image guided radiation therapy

    Science.gov (United States)

    Slot Thing, Rune; Bernchou, Uffe; Mainegra-Hing, Ernesto; Hansen, Olfred; Brink, Carsten

    2016-08-01

    A comprehensive artefact correction method for clinical cone beam CT (CBCT) images acquired for image guided radiation therapy (IGRT) on a commercial system is presented. The method is demonstrated to reduce artefacts and recover CT-like Hounsfield units (HU) in reconstructed CBCT images of five lung cancer patients. Projection image based artefact corrections of image lag, detector scatter, body scatter and beam hardening are described and applied to CBCT images of five lung cancer patients. Image quality is evaluated through visual appearance of the reconstructed images, HU-correspondence with the planning CT images, and total volume HU error. Artefacts are reduced and CT-like HUs are recovered in the artefact corrected CBCT images. Visual inspection confirms that artefacts are indeed suppressed by the proposed method, and the HU root mean square difference between reconstructed CBCTs and the reference CT images are reduced by 31% when using the artefact corrections compared to the standard clinical CBCT reconstruction. A versatile artefact correction method for clinical CBCT images acquired for IGRT has been developed. HU values are recovered in the corrected CBCT images. The proposed method relies on post processing of clinical projection images, and does not require patient specific optimisation. It is thus a powerful tool for image quality improvement of large numbers of CBCT images.

  11. STUDIES ON ANTIBACTERIAL EFFECT OF APAMARGA (ACHYRANTHES ASPERA ON MULTI-DRUG RESISTANT CLINICAL ISOLATES

    Directory of Open Access Journals (Sweden)

    Patil Usha

    2013-04-01

    Full Text Available Recent reports on emergence of multidrug resistant bacteria are cause of concern in medical world. Several ayurvedic drugs have been proved to contain the antimicrobial activity. Literature on effect of ayurvedic drugs on multidrug resistant bacterial pathogens is limited. Present study reports the antimicrobial effect of Achyranthes aspera (Apamarga crude extracts on the clinical isolates of multidrug resistant bacteria. The drug was evaluated by using phytochemical tests. Crude extracts of aqueous, methanol, ethanol and chloroform was prepared. Antibacterial activity against clinically isolated multidrug resistant bacteria belonging to groups of bacillus, citrobacter, E.coli, klebsiella, proteus and salmonella was tested. The drug showed highest efficacy against Bacillus organism while least effectiveness on Proteus spp bacteria. Results of the study conclude that the medicinal plant A. aspera might be useful against multidrug resistance in pathogens of clinical importance.

  12. Multidrug resistance in oncology and beyond : from imaging of drug efflux pumps to cellular drug targets

    NARCIS (Netherlands)

    Nagengast, Wouter B; Oude Munnink, Thijs H; Dijkers, Eli; Hospers, Geesiena; Brouwers, Adrienne H; Schröder, Carolien P; Lub-de Hooge, Marjolijn; de Vries, Elisabeth G E

    2010-01-01

    Resistance of tumor cells to several structurally unrelated classes of natural products, including anthracyclines, taxanes, and epipodophyllotoxines, is often referred as multidrug resistance (MDR). This is associated with ATP-binding cassette transporters, which function as drug efflux pumps such a

  13. Cyclotrons and positron emission tomography radiopharmaceuticals for clinical imaging.

    Science.gov (United States)

    Saha, G B; MacIntyre, W J; Go, R T

    1992-07-01

    Positron emission tomography (PET) requires positron-emitting radionuclides that emit 511-keV photons detectable by PET imagers. Positron-emitting radionuclides are commonly produced in charged particle accelerators, eg, linear accelerators or cyclotrons. The most widely available radiopharmaceuticals for PET imaging are carbon-11-, nitrogen-13-, and oxygen-15-labeled compounds, many of which, either in their normal state or incorporated in other compounds, serve as physiological tracers. Other useful PET radiopharmaceuticals include fluorine-18-, bromine-75-, gallium-68 (68Ga)-, rubidium-82 (82Rb)-, and copper-62 (62Cu)-labeled compounds. Many positron emitters have short half-lives and thus require on-site cyclotrons for application, and others (68Ga, 82Rb, and 62Cu) are available from radionuclides generators using relatively long-lived parent radionuclides. This review is divided into two sections: cyclotrons and PET radiopharmaceuticals for clinical imaging. In the cyclotron section, the principle of operation of the cyclotron, types of cyclotrons, medical cyclotrons, and production of radionuclides are discussed. In the section on PET radiopharmaceuticals, the synthesis and clinical use of PET radiopharmaceuticals are described.

  14. Outcome Measures for Clinical Drug Trials in Autism

    Science.gov (United States)

    Aman, Michael G.; Novotny, Sherie; Samango-Sprouse, Carole; Lecavalier, Luc; Leonard, Elizabeth; Gadow, Kenneth D.; King, Bryan H.; Pearson, Deborah A.; Gernsbacher, Morton Ann; Chez, Michael

    2015-01-01

    This paper identifies instruments and measures that may be appropriate for randomized clinical trials in participants with autism spectrum disorders (ASDs). The Clinical Global Impressions scale was recommended for all randomized clinical trials. At this point, however, there is no “perfect” choice of outcome measure for core features of autism, although we will discuss five measures of potential utility. Several communication instruments are recommended, based in part on suitability across the age range. In trials where the intention is to alter core features of ASDs, adaptive behavior scales are also worthy of consideration. Several “behavior complexes” common to ASDs are identified, and instruments are recommended for assessment of these. Given the prevalence of cognitive impairment in ASDs, it is important to assess any cognitive effects, although cognitive data from ASD randomized clinical trials, thus far, are minimal. Guidance from trials in related pharmacologic areas and behavioral pharmacology may be helpful. We recommend routine elicitation of side effects, height and weight, vital signs, and (in the case of antipsychotics) extrapyramidal side-effects assessment. It is often appropriate to include laboratory tests and assessments for continence and sleep pattern. PMID:14999174

  15. An overview of clinical and commercial impact of drug delivery systems.

    Science.gov (United States)

    Anselmo, Aaron C; Mitragotri, Samir

    2014-09-28

    Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems.

  16. High-Resolution Imaging of Dendrimers Used in Drug Delivery via Scanning Probe Microscopy

    Directory of Open Access Journals (Sweden)

    Lifang Shi

    2011-01-01

    Full Text Available Dendrimers and telodendrimer micelles represent two new classes of vehicles for drug delivery that have attracted much attention recently. Their structural characterization at the molecular and submolecular level remains a challenge due to the difficulties in reaching high resolution when imaging small particles in their native media. This investigation offers a new approach towards this challenge, using scanning tunneling microscopy (STM and atomic force microscopy (AFM. By using new sample preparation protocols, this work demonstrates that (a intramolecular features such as drug molecules and dendrimer termini can be resolved; and (b telodendrimer micelles can be immobilized on the surface without compromising structural integrity, and as such, high resolution AFM imaging may be performed to attain 3D information. This high-resolution structural information should enhance our knowledge of the nanocarrier structure and nanocarrier-drug interaction and, therefore, facilitate design and optimization of the efficiency in drug delivery.

  17. Application of electron paramagnetic resonance (EPR) spectroscopy and imaging in drug delivery research - chances and challenges.

    Science.gov (United States)

    Kempe, Sabine; Metz, Hendrik; Mäder, Karsten

    2010-01-01

    Electron Paramagnetic Resonance (EPR) spectroscopy is a powerful technique to study chemical species with unpaired electrons. Since its discovery in 1944, it has been widely used in a number of research fields such as physics, chemistry, biology and material and food science. This review is focused on its application in drug delivery research. EPR permits the direct measurement of microviscosity and micropolarity inside drug delivery systems (DDS), the detection of microacidity, phase transitions and the characterization of colloidal drug carriers. Additional information about the spatial distribution can be obtained by EPR imaging. The chances and also the challenges of in vitro and in vivo EPR spectroscopy and imaging in the field of drug delivery are discussed.

  18. Ultrasound mediated destruction of multifunctional microbubbles for image guided delivery of oxygen and drugs.

    Science.gov (United States)

    Chang, Shufang; Si, Ting; Zhang, Shiwu; Merrick, Mark A; Cohn, David E; Xu, Ronald X

    2016-01-01

    We synthesized multifunctional activatible microbubbles (MAMs) for ultrasound mediated delivery of oxygen and drugs with both ultrasound and fluorescence imaging guidance. Oxygen enriched perfluorocarbon (PFC) compound was encapsulated in liposome microbubbles (MBs) by a modified emulsification process. DiI dye was loaded as a model drug. The ultrasound targeted microbubble destruction (UTMD) process was guided by both ultrasonography and fluorescence imaging modalities. The process was validated in both a dialysis membrane tube model and a porcine carotid artery model. Our experiment results show that the UTMD process effectively facilitates the controlled delivery of oxygen and drug at the disease site and that the MAM agent enables ultrasound and fluorescence imaging guidance of the UTMD process. The proposed MAM agent can be potentially used for UTMD-mediated combination therapy in hypoxic ovarian cancer.

  19. Evaluation of new drugs in daily clinical practice : anti-TNFα in rheumatoid arthritis patients

    NARCIS (Netherlands)

    Kievit, Wietske

    2008-01-01

    The objective of this thesis was to explore the value and the validity of data collected in daily clinical practice for drug evaluation and cost-effectiveness studies, using data collected on TNFa blocking agents in rheumatoid arthritis. First, the need for and value of information from daily clinic

  20. How can we improve the pre-clinical development of drugs for stroke?

    NARCIS (Netherlands)

    Sena, Emily; van der Worp, H. Bart; Howells, David; Macleod, Malcolm

    2007-01-01

    The development of stroke drugs has been characterized by success in animal studies and subsequent failure in clinical trials. Animal studies might have overstated efficacy, or clinical trials might have understated efficacy; in either case we need to better understand the reasons for failure. Techn

  1. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, Hebert Alberto; Sala, Evis; Hricak, Hedvig [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Grimm, Jan [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York (United States); Donati, Olivio F. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. (orig.)

  2. The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?

    OpenAIRE

    Blumenfeld, P; Pfeffer, R M; Symon, Z; Den, R B; Dicker, A.P.; Raben, D.; Lawrence, Y R

    2014-01-01

    Background: The clinical development of new drugs with radiation appears to be limited. We hypothesised that phase I clinical trials with radiation therapy (RT) are initiated too late into a new drug's lifetime, impeding the ability to complete RT–drug development programmes before patent expiration. Methods: We identified novel drug–radiation phase I combination trials performed between 1980 and 2012 within the PubMed and ClinicalTrials.gov databases. Data gathered for each drug included: da...

  3. Clinical Application of Magnetic Resonance Imaging in Management of Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Jeon-Hor Chen

    2013-01-01

    Full Text Available Neoadjuvant chemotherapy (NAC, also termed primary, induction, or preoperative chemotherapy, is traditionally used to downstage inoperable breast cancer. In recent years it has been increasingly used for patients who have operable cancers in order to facilitate breast-conserving surgery, achieve better cosmetic outcome, and improve prognosis by reaching pathologic complete response (pCR. Many studies have demonstrated that magnetic resonance imaging (MRI can assess residual tumor size after NAC, and that provides critical information for planning of the optimal surgery. NAC also allows for timely adjustment of administered drugs based on response, so ineffective regimens could be terminated early to spare patients from unnecessary toxicity while allowing other effective regimens to work sooner. This review article summarizes the clinical application of MRI during NAC. The use of different MR imaging methods, including dynamic contrast-enhanced MRI, proton MR spectroscopy, and diffusion-weighted MRI, to monitor and evaluate the NAC response, as well as how changes of parameters measured at an early time after initiation of a drug regimen can predict final treatment outcome, are reviewed. MRI has been proven a valuable tool and will continue to provide important information facilitating individualized image-guided treatment and personalized management for breast cancer patients undergoing NAC.

  4. 77 FR 49448 - Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...

    Science.gov (United States)

    2012-08-16

    ... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical trial... Pharmaceutical Clinical Trial; (3) Medical Device Aspects of Clinical Research; (4) Adverse Event...

  5. NEW ANTIARRHYTHMIC DRUG FOR THE TREATMENT OF ATRIAL FIBRILLATION. STUDY DATA, CLINICAL GUIDELINES, REGULATORY AGENCY RECOMMENDATIONS

    Directory of Open Access Journals (Sweden)

    S. Yu. Martsevich

    2011-01-01

    Full Text Available The main objectives and strategies for treatment of atrial fibrillation (AF, one of the most common cardiac arrhythmia, are seen. A combination of strategies for heart rate control in patients with atrial fibrillation receiving rhythm-controling therapy is preferred at present, according to current guidelines. Amiodarone, one of the most effective anti-arrhythmic drugs with an extensive evidence base, remains the drug of reserve because of serious side effects. A new drug, dronedarone, has electrophysiological properties attributable to all four classes of antiarrhythmic drugs. According to meta-analysis of randomized clinical trials dronedarone is inferior to amiodarone in prevention of AF recurrences, but it is superior to amiodaron in safety. However , in 2011 dronedarone was included in the Food and Drug Administration (FDA list of drugs that require further analysis in connection with appearance of the new information about its safety.

  6. Functional imaging in oncology. Clinical applications. Vol. 2

    Energy Technology Data Exchange (ETDEWEB)

    Luna, Antonio [Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Radiology; MRI Health Time Group, Jaen (Spain); Vilanova, Joan C. [Girona Univ. (Spain). Clinica Girona - Hospital Sta. Caterina; Hygino da Cruz, L. Celso Jr. (ed.) [CDPI and IRM, Rio de Janeiro (Brazil). Dept. of Radiology; Rossi, Santiago E. [Centro de Diagnostico, Buenos Aires (Argentina)

    2014-06-01

    Easy-to-read manual on new functional imaging techniques in oncology. Explains current clinical applications and outlines future avenues. Includes numerous high-quality illustrations to highlight the major teaching points. In the new era of functional and molecular imaging, both currently available imaging biomarkers and biomarkers under development are expected to lead to major changes in the management of oncological patients. This two-volume book is a practical manual on the various imaging techniques capable of delivering functional information on cancer, including diffusion MRI, perfusion CT and MRI, dual-energy CT, spectroscopy, dynamic contrast-enhanced ultrasonography, PET, and hybrid modalities. This second volume considers the applications and benefits of these techniques in a wide range of tumor types, including their role in diagnosis, prediction of treatment outcome, and early evaluation of treatment response. Each chapter addresses a specific malignancy and is written by one or more acclaimed experts. The lucid text is complemented by numerous high-quality illustrations that highlight key features and major teaching points.

  7. Left-sided gallbladder: Its clinical significance and imaging presentations

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To assess the importance of preoperative diagnosis and presentation of left-sided gallbladder using ultrasound (US), CT and angiography.METHODS: Retrospective review of 1482 patients who underwent enhanced CT scanning was performed. Left-sided gallbladder was diagnosed if a right-sided ligamentum teres was present. The image presentations on US, CT and angiography were also reviewed.RESULTS: Left-sided gallbladder was diagnosed in nine patients. The associated abnormalities on CT imaging included portal vein anomalies, absence of umbilical portion of the portal vein in the left lobe of the liver,club-shaped portal vein in the right lobe of the liver, and difficulty in identifying segment Ⅳ. Angiography in six of nine patients demonstrated abnormal portal venous system (trifurcation type in four of six patients). The main hepatic arteries followed the portal veins in all six patients. The segment Ⅳ artery was identified in four of six patients using angiography, although segment Ⅳ was difficult to define on CT imaging. Hepatectomy was performed in three patients with concomitant liver tumor and the diagnosis of left-sided gallbladder was confirmed intraoperatively.CONCLUSION: Left-sided gallbladder is an important clinical entity in hepatectomy due to its associated portal venous and biliary anomalies. It should be considered in US, CT and angiography images that demonstrate no definite segment IV, absence of umbilical portion of the portal vein in the left lobe, and club-shaped right anterior portal vein.

  8. Adverse drug reaction suggests by a clinical vignette

    Directory of Open Access Journals (Sweden)

    Finestone AJ

    2011-07-01

    Full Text Available Albert J FinestoneTemple University School of Medicine, Philadelphia, PA, USAI had a three-lobe pneumonia and toxic encephalopathy in 2004. A lumbar puncture did not show meningitis. Magnetic resonance imaging showed a macroadenoma of the pituitary gland. Prolactin level was significantly elevated, making the diagnosis a functioning prolactinoma requiring treatment. Initially, I was treated with the dopamineagonist cabergoline, which is also used in much larger doses to treat Parkinsonism. Recent reports have indicated heart valve damage in Parkinsonism patients treated with ergot-derived dopamine-receptor agonists.

  9. Multimodality imaging in cranial blastomycosis, a great mimicker: Case-based illustration with review of clinical and imaging findings

    Directory of Open Access Journals (Sweden)

    Puneet S Kochar

    2016-01-01

    Full Text Available We describe the clinical, laboratory, and imaging data of three patients who are proven cases of blastomycosis with cranial involvement. In this review, we discuss the imaging features of cranial blastomycosis with relevant clinical case examples including computed tomography (CT, magnetic resonance imaging (MRI, and advanced MR imaging techniques like magnetic resonance spectroscopy (MRS and MR perfusion. Literature is reviewed for modern-day diagnosis and treatment of this fatal intracranial infection, if not diagnosed promptly and managed effectively.

  10. Clinical Application of Image-Based CFD for Cerebral Aneurysms.

    Science.gov (United States)

    Cebral, Jr; Mut, F; Sforza, D; Löhner, R; Scrivano, E; Lylyk, P; Putman, Cm

    2011-07-01

    During the last decade, the convergence of medical imaging and computational modeling technologies has enabled tremendous progress in the development and application of image-based computational fluid dynamics modeling of patient-specific blood flows. These techniques have been used for studying the basic mechanisms involved in the initiation and progression of vascular diseases, for studying possible ways to improve the diagnosis and evaluation of patients by incorporating hemodynamics information to the anatomical data typically available, and for the development of computational tools that can be used to improve surgical and endovascular treatment planning. However, before these technologies can have a significant impact on the routine clinical practice, it is still necessary to demonstrate the connection between the extra information provided by the models and the natural progression of vascular diseases and the outcome of interventions. This paper summarizes some of our contributions in this direction, focusing in particular on cerebral aneurysms.

  11. Patellofemoral pain, instability, and arthritis. Clinical presentation, imaging, and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Zaffagnini, Stefano [Laboratorio di Biomeccanica, Bologna (Italy). Istituti Ortopedici Rizzoli; Dejour, David [Lyon-Ortho-Clinic (France). Knee Surgery Orthopaedic Dept.; Arendt, Elizabeth A. (eds.) [Minnesota Univ., Minneapolis, MN (United States). Dept. of Orthopaedics

    2010-07-01

    Despite numerous studies, a lack of consensus still exists over many aspects of patellofemoral pain, instability, and arthritis. This book adopts an evidence-based approach to assess each of these topics in depth. The book reviews general features of clinical examination and global evaluation techniques including the use of different imaging methods, e.g. x-rays, CT, MRI, stress x-rays, and bone scan. Various conservative and surgical treatment approaches for each of the three presentations - pain, instability, and arthritis - are then explained and assessed. Postoperative management and options in the event of failed surgery are also evaluated. Throughout, careful attention is paid to the literature in an attempt to establish the level of evidence for the efficacy of each imaging and treatment method. It is hoped that this book will serve as an informative guide for the practitioner when confronted with disorders of the patellofemoral joint. (orig.)

  12. Simultaneous magnetically directed drug convection and MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yathindranath, V; Hegmann, T [Department of Chemistry, University of Manitoba, Winnipeg, MB, R3T 2N2 (Canada); Van Lierop, J [Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB, R3T 2N2 (Canada); Potter, K; Fowler, C B [DVBIC/DCoE AFIP, Traumatic Brain Injury Research Center, Department of Biophysics, Rockville, MD 20850 (United States); Moore, D F, E-mail: johan@physics.umanitoba.c [Defense and Veterans Brain Injury Center, Walter Reed Army Medical Center, Washington, DC 20307 (United States)

    2009-10-07

    Superparamagnetic iron oxide nanoparticles (IO NPs) are of interest for their usefulness in biomedical applications. In this work, we have synthesized iron oxide nanocomposites surface-modified with different biocompatible polymers. Bovine serum albumin (BSA) was physisorbed onto these IO NPs along with an excipient during freeze-drying. The mass transport of the protein attached to the iron oxide core-shell nanoparticles (IO cs-NPs) under a gradient magnetic field of an MRI instrument was observed in vitro and in an egg as a model system for a biological fluid. From the in vitro experiments in agarose gels, it was observed that the protein gets separated from the core during mass transport for some cs-IO, but co-migration was observed for PEG-modified IO cs-NPs. These experiments demonstrated proof-of-concept for the use of IO cs-NPs in magnetically directed drug convection.

  13. Toward an evaluation of an integrated clinical imaging system: identifying clinical benefits.

    Science.gov (United States)

    Kaplan, B; Lundsgaarde, H P

    1996-09-01

    Integrated clinical imaging systems can provide the foundation for future computer-based patient record systems as recommended by the Institute of Medicine. However, documenting the benefits of such systems is difficult. This paper reports an evaluation of a clinical imaging system that is integrated with an on-line electronic patient record. The evaluation used interviews and observations to identify what physicians thought were the benefits of this system. Reported benefits may be classified into patient care benefits, educational benefits, and productivity and cost-reduction benefits Physicians said that the imaging system provided patient care benefits by: improving clinical communication and decision making, making care more patient-based, reducing the number of procedures and patient risks, and improving record keeping. Educational benefits they reported included: improving communication, providing broad "real" experience, and improving supervision. These benefits may be reflected in increased productivity and cost reduction by increasing time savings, reducing clerical work, improving morale, and reducing the costs of care. The approach described in this study was valuable in identifying potential benefits of a clinical information system. The findings point the way to realization of benefits for other systems, and, ultimately, for computer-based patient records.

  14. Physician adherence to hypertension treatment guidelines and drug acquisition costs of antihypertensive drugs at the cardiac clinic: a pilot study

    Directory of Open Access Journals (Sweden)

    Abdulameer SA

    2012-01-01

    Full Text Available Shaymaa Abdalwahed Abdulameer1, Mohanad Naji Sahib1, Noorizan Abd Aziz1,2, Yahaya Hassan1,2, Hadeer Akram Abdul AlRazzaq1, Omar Ismail31School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia; 2Faculty of Pharmacy, Universiti Teknologi MARA (UiTM, 42300 Puncak Alam, Selangor, Malaysia; 3Hospital Pulau Pinang, 10900, Penang, MalaysiaAbstract: Prescribing pattern surveys are one of the pharmacoepidemiological techniques that provide an unbiased picture of prescribing habits. Prescription surveys permit the identification of suboptimal prescribing patterns for further evaluation. The aims of this study were to determine the prescribing trend, adherence of the prescribers to the guideline, and the impact of drug expenditure on drug utilization at the cardiac clinic of Penang Hospital, Malaysia. This was a cross-sectional study. Demographic data of the patients, diagnoses and the drugs prescribed were recorded. The average drug acquisition costs (ADAC were calculated for each antihypertensive drug class on a daily and annual basis. Adherence to the guideline was calculated as a percentage of the total number of patients. A total of 313 individuals fulfilled the inclusion criteria. The average age of the study population was 59.30 ± 10.35 years. The mean number of drugs per prescription in the study was 2.09 ± 0.78. There were no significant differences in the demographic data. Antihypertensive drugs were used in monotherapy and polytherapy in 20.8% and 79.2% of the patients, respectively. Adherence to the guideline regarding prescription occurred in 85.30% of the patients. The lowest priced drug class was diuretics and the highest was angiotensin-receptor blockers. In conclusion, the total adherence to the guideline was good; the adherence percentage only slightly decreased with a co-existing comorbidity (such as diabetes mellitus. The use of thiazide diuretics was encouraged because they are well tolerated and

  15. A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials

    Science.gov (United States)

    Eleuteri, C.; Olla, S.; Veroni, C.; Umeton, R.; Mechelli, R.; Romano, S.; Buscarinu, Mc.; Ferrari, F.; Calò, G.; Ristori, G.; Salvetti, M.; Agresti, C.

    2017-04-01

    There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects. We then characterized the effects of these compounds on OPC proliferation and differentiation in mouse glial cultures, and on myelination and remyelination in organotypic cultures. Three molecules, edaravone, 5-methyl-7-methoxyisoflavone and lovastatin, gave positive results in all screening tiers. We validated the results by retesting independent stocks of the compounds, analyzing their purity, and performing dose-response curves. To identify the chemical features that may be modified to enhance the compounds’ activity, we tested chemical analogs and identified, for edaravone, the functional groups that may be essential for its activity. Among the selected remyelinating candidates, edaravone appears to be of strong interest, also considering that this drug has been approved as a neuroprotective agent for acute ischemic stroke and amyotrophic lateral sclerosis in Japan.

  16. Long-term drug survival and clinical effectiveness of etanercept treatment in patients with ankylosing spondylitis in daily clinical practice

    NARCIS (Netherlands)

    Arends, S.; Brouwer, Liesbeth; Efde, Monique; van der Veer, E.; Bootsma, H.; Wink, F.; Spoorenberg, A.

    2017-01-01

    Objective Randomised controlled trials and open-label extension studies have demonstrated the clinical efficacy and safety of tumour necrosis factor-alpha (TNF-alpha) blocking therapy in pre-selected study patients with ankylosing spondylitis (AS). Our aim was to investigate the 7-year drug survival

  17. Long-term drug survival and clinical effectiveness of etanercept treatment in patients with ankylosing spondylitis in daily clinical practice

    NARCIS (Netherlands)

    Arends, Suzanne; Brouwer, Elisabeth; Efde, Monique; van der Veer, Eveline; Bootsma, Hendrika; Wink, Freke; Spoorenberg, Johanna

    2017-01-01

    OBJECTIVES: Randomised controlled trials and open-label extension studies have demonstrated the clinical efficacy and safety of tumour necrosis factor-alpha (TNF-α) blocking therapy in pre-selected study patients with ankylosing spondylitis (AS). Our aim was to investigate the 7-year drug survival a

  18. Schizencephaly: clinical and imaging features in 30 infantile cases.

    Science.gov (United States)

    Denis, D; Chateil, J F; Brun, M; Brissaud, O; Lacombe, D; Fontan, D; Flurin, V; Pedespan, J

    2000-12-01

    Schizencephaly is an uncommon structural disorder of cerebral cortical development, characterized by congenital clefts spanning the cerebral hemispheres from the pial surface to the lateral ventricles and lined by cortical gray matter. Either an antenatal environmental incident or a genetic origin could be responsible for this lesion which occurs between the third and fourth month of gestation. We report the clinical and cranial imaging features of 30 children, of whom 15 had unilateral and 15 had bilateral lesions. Their ages at the time of the first presentation ranged from 1 month to 10 years. They were thoroughly studied from clinical, epileptical, imaging and electroencephalographic (EEG) viewpoints. Five patients were investigated by cranial computed tomography (CT), eight by cranial magnetic resonance (MR) imaging, and 17 by both methods. The clinical features consisted of mild hemiparesis in 17 cases (57%), 12/17 were related to a unilateral phenotype (80% of all unilateral forms) and 5/17 to a bilateral phenotype. A tetraparesis was present in nine cases, all of which were due to a bilateral cleft. Bilateral forms were significantly associated with tetraparesis, whereas unilateral forms were associated with hemiparesis. Mental retardation was observed in 17 cases (57%), and was observed significantly more often in bilateral clefts (80%). When both hemispheres are involved, an absence of reorganization of the brain function between the two hemispheres leads to severe mental deficits, in addition to the cerebral anomaly itself. Eleven patients had seizures (seven from unilateral and three from bilateral forms). The degree of malformation was not related to the severity of epilepsy. Migration disorders, such as dysplasia or heterotopia, were observed in 30% of cases and are also important etiopathogenetic factors. The septum pellucidum was absent in 13 cases (43%), with septo-optical dysplasia in two cases. Corpus callosum dysgenesis was noted in 30% of cases

  19. Exploiting the Metal-Chelating Properties of the Drug Cargo for In Vivo Positron Emission Tomography Imaging of Liposomal Nanomedicines

    DEFF Research Database (Denmark)

    Edmonds, Scott; Volpe, Alessia; Shmeeda, Hilary;

    2016-01-01

    The clinical value of current and future nanomedicines can be improved by introducing patient selection strategies based on noninvasive sensitive whole-body imaging techniques such as positron emission tomography (PET). Thus, a broad method to radiolabel and track preformed nanomedicines...... such as liposomal drugs with PET radionuclides will have a wide impact in nanomedicine. Here, we introduce a simple and efficient PET radiolabeling method that exploits the metal-chelating properties of certain drugs (e.g., bisphosphonates such as alendronate and anthracyclines such as doxorubicin) and widely used...... ionophores to achieve excellent radiolabeling yields, purities, and stabilities with 89Zr, 52Mn, and 64Cu, and without the requirement of modification of the nanomedicine components. In a model of metastatic breast cancer, we demonstrate that this technique allows quantification of the biodistribution...

  20. The economics of functional magnetic resonance imaging: clinical and research.

    Science.gov (United States)

    Yousem, David M

    2014-11-01

    It is difficult to justify maintaining a clinical functional magnetic resonance imaging (fMRI) program based solely on revenue generation. The use of fMRI is, therefore, based mostly in patient care considerations, leading to better outcomes. The high costs of the top-of-the-line equipment, hardware, and software needed for state-of-the-art fMRI and the time commitment by multiple professionals are not adequately reimbursed at a representative rate by current payor schemes for the Current Procedure Terminology codes assigned.

  1. Imaging and clinical characteristics of sporadic Creutzfeldt-Jakob disease

    Directory of Open Access Journals (Sweden)

    HAN Shun-chang

    2013-04-01

    Full Text Available Five patients with sporadic Creutzfeldt-Jakob disease (sCJD presented rapidly progressive dementia which were subacute onset from 1 to 4 months. Among these cases, periodic synchronous discharge (PSD of electroencephalography (EEG was seen in 2 patients. Besides, 4 patients obtained positive results in cerebrospinal fluid (CSF analysis for 14-3-3 protein. The cranial MRI examination showed symmetrical or asymmetrical colored-ribbon-shaped high signals in cerebral cortex or basal ganglia by diffusion weighted imaging (DWI, suggesting that DWI had high sensitivity and specificity for the diagnosis of sCJD as a preferred method in the clinical examination of sCJD.

  2. Primary hyperoxaluria: spectrum of clinical and imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Strauss, Sara B.; Levin, Terry L. [Children' s Hospital of Montefiore Medical Center, Division of Pediatric Radiology, Department of Radiology, Bronx, NY (United States); Waltuch, Temima; Kaskel, Frederick [Children' s Hospital at Montefiore Medical Center, Division of Pediatric Nephrology, Bronx, NY (United States); Bivin, William [Allegheny General Hospital, Department of Pathology, Pittsburgh, PA (United States)

    2017-01-15

    Primary hyperoxaluria is a rare autosomal recessive inborn error of metabolism with three known subtypes. In primary hyperoxaluria type 1, the most common of the subtypes, a deficiency in the hepatic enzymes responsible for the metabolism of glycoxylate to glycine, leads to excessive levels of glyoxylate, which is converted to oxalate. The resultant elevation in serum and urinary oxalate that characterizes primary hyperoxaluria leads to calcium oxalate crystal deposition in multiple organ systems (oxalosis). We review the genetics, pathogenesis, variable clinical presentation and course of this disease as well as its treatment. Emphasis is placed on the characteristic imaging findings before and after definitive treatment with combined liver and renal transplantation. (orig.)

  3. Interplay between Mutations and Efflux in Drug Resistant Clinical Isolates of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Miguel Viveiros

    2017-04-01

    Full Text Available Numerous studies show efflux as a universal bacterial mechanism contributing to antibiotic resistance and also that the activity of the antibiotics subject to efflux can be enhanced by the combined use of efflux inhibitors. Nevertheless, the contribution of efflux to the overall drug resistance levels of clinical isolates of Mycobacterium tuberculosis is poorly understood and still is ignored by many. Here, we evaluated the contribution of drug efflux plus target-gene mutations to the drug resistance levels in clinical isolates of M. tuberculosis. A panel of 17 M. tuberculosis clinical strains were characterized for drug resistance associated mutations and antibiotic profiles in the presence and absence of efflux inhibitors. The correlation between the effect of the efflux inhibitors and the resistance levels was assessed by quantitative drug susceptibility testing. The bacterial growth/survival vs. growth inhibition was analyzed through the comparison between the time of growth in the presence and absence of an inhibitor. For the same mutation conferring antibiotic resistance, different MICs were observed and the different resistance levels found could be reduced by efflux inhibitors. Although susceptibility was not restored, the results demonstrate the existence of a broad-spectrum synergistic interaction between antibiotics and efflux inhibitors. The existence of efflux activity was confirmed by real-time fluorometry. Moreover, the efflux pump genes mmr, mmpL7, Rv1258c, p55, and efpA were shown to be overexpressed in the presence of antibiotics, demonstrating the contribution of these efflux pumps to the overall resistance phenotype of the M. tuberculosis clinical isolates studied, independently of the genotype of the strains. These results showed that the drug resistance levels of multi- and extensively-drug resistant M. tuberculosis clinical strains are a combination between drug efflux and the presence of target-gene mutations, a reality

  4. Unenhanced MR Imaging in adults with clinically suspected acute appendicitis

    DEFF Research Database (Denmark)

    Chabanova, Elizaveta; Balslev, Ingegerd; Achiam, Michael;

    2011-01-01

    PURPOSE: The purpose of the study was to evaluate unenhanced Magnetic Resonance Imaging (MRI) for the diagnosis of appendicitis or another surgery-requiring condition in an adult population scheduled for emergency appendectomy based on a clinical diagnosis of suspected acute appendicitis. MATERIALS...... radiologists and one surgeon independent of each other and compared with surgical and pathological records. RESULTS: According to the surgical and histopathological findings 30 of 48 patients (63%) had acute appendicitis. Of the remaining 18 patients, 4 patients had no reasons for the clinical symptoms and 14...... patients had other pathology. For the three reviewers the performance of MRI in the diagnosis of acute appendicitis showed the following sensitivity, specificity and accuracy ranges: 83-93%, 50-83% and 77-83%. Moderate (kappa=0.51) and fair (kappa=0.31) interobserver agreements in the MR diagnosis of acute...

  5. Bimelic Hirayama Disease: Clinical Dilemma Solved by Imaging

    Directory of Open Access Journals (Sweden)

    Shalabh Jain

    2013-01-01

    Full Text Available Hirayama disease (juvenile muscular atrophy of distal upper extremity is a cervical myelopathy predominantly affecting adolescent males. It is characterized by progressive muscular weakness and atrophy of unilateral or asymmetrically bilateral distal upper limbs. We report a case of an 18-year-male painter, who presented with gradually progressive, symmetrical bilateral weakness of hands and forearm for the last two years. On the basis of clinical examination, a provisional diagnosis of lower motor neuron type of symmetrical distal weakness due to heavy metal intoxication was kept. However, imaging studies helped in making a definitive diagnosis of Hirayama disease. The patient was advised cervical collar, and there was no progression in symptoms after six months of followup. Due to the rarity of bilateral symmetrical involvement in Hirayama disease, it remains obscured or unsuspected clinically, and MRI plays a pivotal role in diagnosis.

  6. Functional Imaging of Breast Tissue and Clinical Application

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A novel approach to image hemoglobin concentration(ΔDhb) and oxygen saturation (ΔDoxy) of breast tissue is presented. The scenograph of dual-wavelength (760 and 850 nm) near infrared lights through breast tissue is acquired by high sensitive charge coupled device (CCD) camera. The evaluation criterion of the difference of ΔDhb and ΔDoxy between detected and referenced breast tissue can be obtained by a calculation formula without complicate caculation. This approach is applied to clinic detection in breast tissue. The ongoing clinical experiments indicate that malignant tumor usually exhibits characterize of "higher ΔDhb and lower ΔDoxy", while benign lesion often shows "lower ΔDhb and higher ΔDoxy" or other characters. So it is useful to assist the diagnosis of breast disease.

  7. MR imaging assessment of clinical problems in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Narvaez, Jose A.; Roca, Yolanda; Aguilera, Carlos [Department of CT and MR Imaging, Hospital Duran i Reynals, Universitaria de Bellvitge, Barcelona (Spain); Narvaez, Javier [Department of Medicine, Delfos Medical Center, Barcelona (Spain)

    2002-07-01

    Although MR imaging has been increasingly recognized as a useful tool in the diagnosis of early rheumatoid arthritis (RA) and in the assessment of disease activity, these applications have not yet been usually included in the routine management of this condition. Our goal is to review the current role of MRI in the everyday clinical management of patients with RA. The usefulness of MRI in the evaluation of articular and para-articular changes in specific locations, mainly the craniocervical region and the temporomandibular joint, are reviewed. Clinical problems derived from local extra-articular involvement, such as tenosynovitis, ''rice-bodies'' bursitis, and Baker's cyst rupture, are also described. Finally, we also review the value of MRI in evaluation of some complications of RA such as tendinous rupture, osteonecrosis, stress fracture, and septic arthritis/osteomyelitis. (orig.)

  8. Time-course mass spectrometry imaging for depicting drug incorporation into hair.

    Science.gov (United States)

    Kamata, Tooru; Shima, Noriaki; Sasaki, Keiko; Matsuta, Shuntaro; Takei, Shiori; Katagi, Munehiro; Miki, Akihiro; Zaitsu, Kei; Nakanishi, Toyofumi; Sato, Takako; Suzuki, Koichi; Tsuchihashi, Hitoshi

    2015-06-01

    In order to investigate the incorporation of drugs into hair, matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MS/MS) imaging was performed on the longitudinal sections of single scalp hair shafts sampled from volunteers after a single oral administration of methoxyphenamine (MOP), a noncontrolled analogue of methamphetamine. Hair specimens were collected by plucking out with the roots intact, and these specimens were prepped by an optimized procedure based on freeze-sectioning to detect the drug inside the hair shaft and hair root. Time-course changes in the imaging results, with confirmatory quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for each 1-mm segment of single hair strands, revealed a substantial concentration of the drug first onto the hair bulbs after ingestion, while only a small portion appeared to be incorporated into the hair matrix, forming a 2-3 mm distinctive drug band with tailing. Comparable amount of the drug also appeared to be incorporated into the keratinized hair shaft in the upper dermis zone, forming another distinct drug band of about 2 mm, which both moved toward the distal side, following the strand's growth rate. These findings provide forensically crucial information: there are two major drug incorporation sites, at least for MOP, which cause overlap of the recordings and deteriorates its chronological resolution down to about 11 days or perhaps longer.

  9. Therapeutic drug monitoring in epilepsy clinic: a multi-disciplinary approach

    Directory of Open Access Journals (Sweden)

    Sunee Lertsinudom

    2014-12-01

    Full Text Available Epilepsy is a common public health problem and needs multi-disciplinary treatment. Therapeutic drug monitoring (TDM is one of step of the multi-disciplinary treatment in epilepsy at Epilepsy clinic, Khon Kaen University (Thailand. The TDM service has been established since 2008. Here, we aimed to study the roles of TDM order and epilepsy control. This is a prospective descriptive study in which data collection was done from January 1 to December 31, 2010, the period when pharmacists took part in assessing the appropriateness in measurement and interpretation of TDM in order to provide suggestions for physicians. The 112 patients under study had an average age of 38.21±15.36 years; 254 samples were collected for therapeutic drug monitoring; phenytoin was submitted mostly for drug monitoring at 46.46%; 44.49% of sub-missions for drug level monitoring were made owing to a suspected sub-therapeutic level. Associations were found between reasons of sending samples for drug level monitoring and the measured drug levels, i.e., 66.67% of drug levels found was so low that they were undetectable in sample for patients’ compliance investigation and 38.94% of the drug levels were found to be sub-therapeutic as for the case where submission of samples was done because of suspected sub-therapeutic level, 40% of the cases were found to be in toxicity range in the cases with suspected over-therapeutic levels and monitoring levels, 58.25% were found to be within the therapeutic range. Pharmacists used the interpreted results in patients’ care by recommending physicians to monitor therapeutic drug closely, to adjust the dosage of drugs, and to recommend checking patients’ compliance in their use of drugs at 56.5, 38.9, and 4.3%, respectively. Physicians’ responses were found to be absolute follow, partial follow and not follow at 77.95, 11.03, and 7.48%, respectively. In conclusion, associations were found between reasons of TDM order and measured drug

  10. Traceable working standards with SI units of radiance for characterizing the measurement performance of investigational clinical NIRF imaging devices

    Science.gov (United States)

    Zhu, Banghe; Rasmussen, John C.; Litorja, Maritoni; Sevick-Muraca, Eva M.

    2017-03-01

    All medical devices for Food and Drug market approval require specifications of performance based upon International System of Units (SI) or units derived from SI for reasons of traceability. Recently, near-infrared fluorescence (NIRF) imaging devices of a variety of designs have emerged on the market and in investigational clinical studies. Yet the design of devices used in the clinical studies vary widely, suggesting variable device performance. Device performance depends upon optimal excitation of NIRF imaging agents, rejection of backscattered excitation and ambient light, and selective collection of fluorescence emanating from the fluorophore. There remains no traceable working standards with SI units of radiance to enable prediction that a given molecular imaging agent can be detected in humans by a given NIRF imaging device. Furthermore, as technologies evolve and as NIRF imaging device components change, there remains no standardized means to track device improvements over time and establish clinical performance without involving clinical trials, often costly. In this study, we deployed a methodology to calibrate luminescent radiance of a stable, solid phantom in SI units of mW/cm2/sr for characterizing the measurement performance of ICCD and IsCMOS camera based NIRF imaging devices, such as signal-to-noise ratio (SNR) and contrast. The methodology allowed determination of superior SNR of the ICCD over the IsCMOS system; comparable contrast of ICCD and IsCMOS depending upon binning strategies.

  11. Clinical practice guidelines for translating pharmacogenomic knowledge to bedside. Focus on anticancer drugs.

    Directory of Open Access Journals (Sweden)

    José A G Agúndez

    2014-08-01

    Full Text Available The development of clinical practice recommendations or guidelines for the clinical use of pharmacogenomics data is an essential issue for improving drug therapy, particularly for drugs with high toxicity and/or narrow therapeutic index such as anticancer drugs. Although pharmacogenomic-based recommendations have been formulated for over 40 anticancer drugs, the number of clinical practice guidelines available is very low. The guidelines already published indicate that pharmacogenomic testing is useful for patient selection, but final dosing adjustment should be carried out on the basis of clinical or analytical parameters rather than on pharmacogenomic information.Patient selection may seem a modest objective, but it constitutes a crucial improvement with regard to the pre-pharmacogenomics situation and it saves patients’ lives. However we should not overstate the current power of pharmacogenomics. At present the pharmacogenomics of anticancer drugs is not sufficiently developed for dose adjustments based on pharmacogenomics only, and no current guidelines recommend such adjustments without considering clinical and/or analytical parameters.

  12. Differential expression of putative drug resistance genes in Mycobacterium tuberculosis clinical isolates.

    Science.gov (United States)

    González-Escalante, Laura; Peñuelas-Urquides, Katia; Said-Fernández, Salvador; Silva-Ramírez, Beatriz; Bermúdez de León, Mario

    2015-12-01

    Understanding drug resistance in Mycobacterium tuberculosis requires an integrated analysis of strain lineages, mutations and gene expression. Previously, we reported the differential expression of esxG, esxH, infA, groES, rpmI, rpsA and lipF genes in a sensitive M. tuberculosis strain and in a multidrug-resistant clinical isolate. Here, we have evaluated the expression of these genes in 24 clinical isolates that belong to different lineages and have different drug resistance profiles. In vitro, growth kinetics analysis showed no difference in the growth of the clinical isolates, and thus drug resistance occurred without a fitness cost. However, a quantitative reverse transcription PCR analysis of gene expression revealed high variability among the clinical isolates, including those with similar drug resistance profiles. Due to the complexity of gene regulation pathways and the wide diversity of M. tuberculosis lineages, the use of gene expression as a molecular signature for drug resistance is not straightforward. Therefore, we recommend that the expression of M. tuberculosis genes be performed individually, and baseline expression levels should be verified among several different clinical isolates, before any further applications of these findings.

  13. Sinusitis and intracranial sepsis: the CT imaging and clinical presentation

    Energy Technology Data Exchange (ETDEWEB)

    Saxton, V.J. [Dept. of Radiology, Royal Children`s Hospital, Melbourne (Australia); Boldt, D.W. [Dept. of Radiology, Royal Children`s Hospital, Melbourne (Australia); Shield, L.K. [Dept. of Neurology, Royal Children`s Hospital, Melbourne (Australia)

    1995-11-01

    The CT imaging and clinical presentation in 14 children with coexistent intracranial sepsis and sinusitis were reviewed. A routine CT head scan (10-mm thick semi-axial slices through the cranium done before and after intravenous contrast medium administration) was found to be an inadequate initial investigation as the intracranial collection was missed in four patients and the abnormal sinuses not shown in six. In half the children the dagnosis of sinusitis was unsuspected at the time of admission. The dominant clinical features were fever, intense headache and facial swelling in early adolescent males. In this clinical setting we recommend: (1) The routine scan is extended through the frontal and ethmoidal sinuses and photographed at a window level and width showing both bone detail and air/soft tissue interfaces; (2) direct coronal projections are performed through the anterior cranial fossa if no collection is seen on the routine study; (3) an early repeat scan within 48 h if the initial study shows no intracranial pathology but the fronto-ethomoidal sinuses are abnormal and there is a high clinical supicion of intracranial sepsis; and (4) in the presence of intracranial sepsis the vault is viewed at bone window settings to exclude cranial osteomyelitis. (orig.)

  14. Organic-Inorganic Hybrid Hollow Mesoporous Organosilica Nanoparticles for Efficient Ultrasound-Based Imaging and Controlled Drug Release

    Directory of Open Access Journals (Sweden)

    Xiaoqin Qian

    2014-01-01

    Full Text Available A novel anticancer drug delivery system with contrast-enhanced ultrasound-imaging performance was synthesized by a typical hard-templating method using monodispersed silica nanoparticles as the templates, which was based on unique molecularly organic/inorganic hybrid hollow periodic mesoporous organosilicas (HPMOs. The highly dispersed HPMOs show the uniform spherical morphology, large hollow interior, and well-defined mesoporous structures, which are very beneficial for ultrasound-based theranostics. The obtained HPMOs exhibit excellent performances in contrast-enhanced ultrasonography both in vitro and in vivo and can be used for the real-time determination of the progress of lesion tissues during the chemotherapeutic process. Importantly, hydrophobic paclitaxel- (PTX- loaded HPMOs combined with ultrasound irradiation show fast ultrasound responsiveness for controlled drug release and higher in vitro and in vivo tumor inhibition rates compared with free PTX and PTX-loaded HPMOs, which is due to the enhanced ultrasound-triggered drug release and ultrasound-induced cavitation effect. Therefore, the achieved novel HPMOs-based nanoparticle systems will find broad application potentials in clinically ultrasound-based imaging and auxiliary tumor chemotherapy.

  15. «Dallas Buyers Club (2013» clinical research with drugs for the AIDS epidemic 80

    Directory of Open Access Journals (Sweden)

    Marian de HAAN-BOSCH

    2015-07-01

    Full Text Available Dallas Buyers Club (2013, inspired by true events, tells the story of Ron Woodroof, a middle?aged elec? trician from Dallas (Texas, who is diagnosed with AIDS in 1985. With few treatment options, he estab? lishes the Dallas Buyers Club in order to provide unapproved drugs to the AIDS community. This results in constant business travels, disputes with the FDA and problems with the law and the IRS. The article analyzes the buyers’ clubs phenomenon in the US, the drugs cited in the film and the clinical trial with zidovudine shown in the movie. The film could be useful as a teaching tool providing an introduction to the AIDS epidemic, clinical research and drug development, bioethics of human research and the agen? cies that regulate drug approval and their availability. Finally, the article presents a possible guideline for the use of the film in a teaching environment.

  16. Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

    DEFF Research Database (Denmark)

    Zielinski, Daniel C.; Filipp, F. V.; Bordbar, A.

    2015-01-01

    Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways...... dysregulated by drugs are linked to the development of side effects. We show such dysregulated metabolic pathways contain genes with sequence variants affecting side effect incidence, play established roles in pathophysiology, have significantly altered activity in corresponding diseases, are susceptible...... to metabolic inhibitors and are effective targets for therapeutic nutrient supplementation. Our results indicate that metabolic dysregulation represents a common mechanism underlying side effect pathogenesis that is distinct from the role of metabolism in drug clearance. We suggest that elucidating...

  17. How the Probability and Potential Clinical Significance of Pharmacokinetically Mediated Drug-Drug Interactions Are Assessed in Drug Development: Desvenlafaxine as an Example

    Science.gov (United States)

    Nichols, Alice I.; Preskorn, Sheldon H.

    2015-01-01

    Objective: The avoidance of adverse drug-drug interactions (DDIs) is a high priority in terms of both the US Food and Drug Administration (FDA) and the individual prescriber. With this perspective in mind, this article illustrates the process for assessing the risk of a drug (example here being desvenlafaxine) causing or being the victim of DDIs, in accordance with FDA guidance. Data Sources/Study Selection: DDI studies for the serotonin-norepinephrine reuptake inhibitor desvenlafaxine conducted by the sponsor and published since 2009 are used as examples of the systematic way that the FDA requires drug developers to assess whether their new drug is either capable of causing clinically meaningful DDIs or being the victim of such DDIs. In total, 8 open-label studies tested the effects of steady-state treatment with desvenlafaxine (50–400 mg/d) on the pharmacokinetics of cytochrome (CYP) 2D6 and/or CYP 3A4 substrate drugs, or the effect of CYP 3A4 inhibition on desvenlafaxine pharmacokinetics. The potential for DDIs mediated by the P-glycoprotein (P-gp) transporter was assessed in in vitro studies using Caco-2 monolayers. Data Extraction: Changes in area under the plasma concentration-time curve (AUC; CYP studies) and efflux (P-gp studies) were reviewed for potential DDIs in accordance with FDA criteria. Results: Desvenlafaxine coadministration had minimal effect on CYP 2D6 and/or 3A4 substrates per FDA criteria. Changes in AUC indicated either no interaction (90% confidence intervals for the ratio of AUC geometric least-squares means [GM] within 80%–125%) or weak inhibition (AUC GM ratio 125% to desvenlafaxine (AUC GM ratio of 143%). Desvenlafaxine was not a substrate (efflux ratio 250 μM) of P-gp. Conclusions: A 2-step process based on FDA guidance can be used first to determine whether a pharmacokinetically mediated interaction occurs and then to assess the potential clinical significance of the DDI. In the case of the drug tested in this series of studies

  18. Nanoparticles for Biomedical Imaging: Fundamentals of Clinical Translation

    Directory of Open Access Journals (Sweden)

    Hak Soo Choi

    2010-11-01

    Full Text Available Because of their large size compared to small molecules and their multifunctionality, nanoparticles (NPs hold promise as biomedical imaging, diagnostic, and theragnostic agents. However, the key to their success hinges on a detailed understanding of their behavior after administration into the body. NP biodistribution, target binding, and clearance are complex functions of their physicochemical properties in serum, which include hydrodynamic diameter, solubility, stability, shape and flexibility, surface charge, composition, and formulation. Moreover, many materials used to construct NPs have real or potential toxicity or may interfere with other medical tests. In this review, we discuss the design considerations that mediate NP behavior in the body and the fundamental principles that govern clinical translation. By analyzing those nanomaterials that have already received regulatory approval, most of which are actually therapeutic agents, we attempt to predict which types of NPs hold potential as diagnostic agents for biomedical imaging. Finally, using quantum dots as an example, we provide a framework for deciding whether an NP-based agent is the best choice for a particular clinical application.

  19. Prevalence and type of drug-drug interactions involving antiretrovirals in patients attending a specialist outpatient clinic in Kampala, Uganda

    Directory of Open Access Journals (Sweden)

    K Seden

    2012-11-01

    Full Text Available Scale-up of HIV services in countries such as Uganda has resulted in a rapid increase in facilities offering antiretrovirals (ARVs and an increase in healthcare workers trained to deliver care. Consequently, evaluating medication safety is increasingly important in these settings. Data from developed countries suggest that drug-drug interactions (DDIs involving ARVs are common, occurring at rates of 14–58%. Few data are available from low resource settings, however a study of 996 Kenyan patients found that 33.5% were at risk of clinically significant DDIs. We evaluated the prevalence and type of ARV DDIs and the patients most at risk in an African outpatient setting. A random sample of patients taking current ARVs and accessing care at the Infectious Diseases Institute, Makerere University, Kampala was selected from the clinic database. The most recent prescription for each patient was screened for DDIs using www.hiv-druginteractions.org. Clinical significance of DDIs was assessed by two of us using a previously developed technique evaluating: likelihood of interaction, therapeutic index of affected drug and severity of potential adverse effect. From 1000 consecutive patients 99.6% were taking≥1 co-medication alongside their ARV regimen (mean 1.89. 24.5% had≥1 potential DDI, with a total of 335 DDIs observed. Of these, 255 DDIs were considered clinically significant, affecting 18.8% of patients. Only 0.3% of DDIs involved a contraindicated combination. There was a higher rate of potential DDIs observed in patients taking TB treatment (p=0.0047, who were WHO stage 3 or 4 (p=0.001, or patients taking ≥2 co-medications alongside ARVs (p<0.0001 (Fishers exact test. Patient age, gender, CD4 count and weight did not affect risk for DDIs. Co-medications commonly associated with potential DDIs were antibiotics (6.2% of 1000 patients, anthelminthics (4.6% and antifungals (3.5%. Potential DDIs involving ARVs occur at similar rates in resource

  20. Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer's Disease

    OpenAIRE

    Francesco Panza; Vincenzo Solfrizzi; Davide Seripa; Imbimbo, Bruno P.; Madia Lozupone; Andrea Santamato; Chiara Zecca; Maria Rosaria Barulli; Antonello Bellomo; Alberto Pilotto; Antonio Daniele; Antonio Greco; Giancarlo Logroscino

    2016-01-01

    The failure of several Phase II/III clinical trials in Alzheimer’s disease (AD) with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized f...

  1. Penicillin allergy evaluation: experience from a drug allergy clinic in an Arabian Gulf Country, Kuwait

    OpenAIRE

    Al-Ahmad, Mona; Rodriguez Bouza, Tito; Arifhodzic, Nermina

    2014-01-01

    Background Hypersensitivity to penicillin has been studied worldwide, but data regarding patterns of sensitization in Arabian Gulf countries are scarce. Objective To describe the patterns of penicillin hypersensitivity during a 6-year study in Kuwait in terms of demographics, type of the culprit drug, in vivo and in vitro allergy testing. Methods One hundred and twenty-four patients referred to the drug allergy clinic for penicillin allergy were fully evaluated by skin prick and intradermal t...

  2. Imaging of a clinically relevant stroke model: glucose hypermetabolism revisited.

    Science.gov (United States)

    Arnberg, Fabian; Grafström, Jonas; Lundberg, Johan; Nikkhou-Aski, Sahar; Little, Philip; Damberg, Peter; Mitsios, Nicholas; Mulder, Jan; Lu, Li; Söderman, Michael; Stone-Elander, Sharon; Holmin, Staffan

    2015-03-01

    Ischemic stroke has been shown to cause hypermetabolism of glucose in the ischemic penumbra. Experimental and clinical data indicate that infarct-related systemic hyperglycemia is a potential therapeutic target in acute stroke. However, clinical studies aiming for glucose control in acute stroke have neither improved functional outcome nor reduced mortality. Thus, further studies on glucose metabolism in the ischemic brain are warranted. We used a rat model of stroke that preserves collateral flow. The animals were analyzed by [2-(18)F]-2-fluoro-2-deoxy-d-glucose positron emission tomography or magnetic resonance imaging during 90-minute occlusion of the middle cerebral artery and during 60 minutes after reperfusion. Results were correlated to magnetic resonance imaging of cerebral blood flow, diffusion of water, lactate formation, and histological data on cell death and blood-brain barrier breakdown. We detected an increased [2-(18)F]-2-fluoro-2-deoxy-d-glucose uptake within ischemic regions succumbing to infarction and in the peri-infarct region. Magnetic resonance imaging revealed impairment of blood flow to ischemic levels in the infarct and a reduction of cerebral blood flow in the peri-infarct region. Magnetic resonance spectroscopy revealed lactate in the ischemic region and absence of lactate in the peri-infarct region. Immunohistochemical analyses revealed apoptosis and blood-brain barrier breakdown within the infarct. The increased uptake of [2-(18)F]-2-fluoro-2-deoxy-d-glucose in cerebral ischemia most likely reflects hypermetabolism of glucose meeting increased energy needs of ischemic and hypoperfused brain tissue, and it occurs under both anaerobic and aerobic conditions measured by local lactate production. Infarct-related systemic hyperglycemia could serve to facilitate glucose supply to the ischemic brain. Glycemic control by insulin treatment could negatively influence this mechanism. © 2015 American Heart Association, Inc.

  3. Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice.

    Science.gov (United States)

    Isbister, Geoffrey K; Page, Colin B

    2013-07-01

    There has been an increasing focus on drug induced QT prolongation including research on drug development and QT prolongation, following the removal of drugs due to torsades de pointes (TdP). Although this has improved our understanding of drug-induced QT prolongation there has been much less research aimed at helping clinicians assess risk in individual patients with drug induced QT prolongation. This review will focus on assessment of drug-induced QT prolongation in clinical practice using a simple risk assessment approach. Accurate measurement of the QT interval is best done manually, and not using the measurement of standard ECG machines. Correction for heart rate (HR) using correction formulae such as Bazett's is often inaccurate. These formulae underestimate and overestimate the duration of cardiac repolarization at low and high heart rates, respectively. Numerous cut-offs have been suggested as an indicator of an abnormal QT, but are problematic in clinical practice. An alternative approach is the QT nomogram which is a plot of QT vs. HR. The nomogram has an 'at risk' line and QT-HR pairs above this line have been shown in a systematic study to be associated with TdP and the line is more sensitive and specific than Bazett's QTc of 440 ms or 500 ms. Plotting the QT-HR pair for patients on drugs suspected or known to cause QT prolongation allows assessment of the QT interval based on normal population QT variability. This risk assessment then allows the safer commencement of drugs therapeutically or management of drug induced effects in overdose. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  4. Spatial mapping of drug delivery to brain tissue using hyperspectral spatial frequency-domain imaging

    Science.gov (United States)

    Singh-Moon, Rajinder P.; Roblyer, Darren M.; Bigio, Irving J.; Joshi, Shailendra

    2014-09-01

    We present an application of spatial frequency-domain imaging (SFDI) to the wide-field imaging of drug delivery to brain tissue. Measurements were compared with values obtained by a previously validated variation of diffuse reflectance spectroscopy, the method of optical pharmacokinetics (OP). We demonstrate a cross-correlation between the two methods for absorption extraction and drug concentration determination in both experimental tissue phantoms and freshly extracted rodent brain tissue. These methods were first used to assess intra-arterial (IA) delivery of cationic liposomes to brain tissue in Sprague Dawley rats under transient cerebral hypoperfusion. Results were found to be in agreement with previously published experimental data and pharmacokinetic models of IA drug delivery. We then applied the same scheme to evaluate IA mitoxantrone delivery to glioma-bearing rats. Good correlation was seen between OP and SFDI determined concentrations taken from normal and tumor averaged sites. This study shows the feasibility of mapping drug/tracer distributions and encourages the use of SFDI for spatial imaging of tissues for drug/tracer-tagged carrier deposition and pharmacokinetic studies.

  5. Clinical applications of drug desensitization in the Asia-Pacific region.

    Science.gov (United States)

    Thong, Bernard Yu-Hor

    2011-04-01

    Drug desensitization is the induction, within hours to days, of a temporary state of tolerance to a drug which the patient has developed a hypersensitivity reaction to. It may be used for IgE and non-IgE mediated allergic reactions, and certain non-allergic reactions. The indication for desensitization is where no alternative medications are available for the treatment of that condition, and where the benefits of desensitization outweigh the risks. Desensitization is a therapeutic modality for drug allergy (similar to allergen specific immunotherapy for allergic rhinitis and insect venom anaphylaxis). In contrast, the drug provocation test is a diagnostic modality used to confirm or refute the diagnosis of drug allergy. This review discusses the clinical applications of desensitization for the treatment of common infectious, metabolic and cardiovascular diseases, and oncological conditions in the Asia-Pacific region.

  6. Investigation of drug distribution in tablets using surface enhanced Raman chemical imaging.

    Science.gov (United States)

    Firkala, Tamás; Farkas, Attila; Vajna, Balázs; Farkas, István; Marosi, György

    2013-03-25

    This paper reports the first application of surface enhanced Raman chemical imaging on pharmaceutical tablets containing the active ingredient (API) in very low concentrations. Taking advantage of the extremely intensive Raman signals in the presence of silver colloids, image aquisition time was radically decreased. Moreover, the investigation of drug distribution below the detection limit of regular micro-Raman spectrometry was made feasible. The characteristics of different manufacturing technologies could be revealed at very low API concentrations by using chemometric methods for processing and evaluating the large number of varying spectra provided with this imaging method.

  7. Consumption of psychiatric drugs by patients of medical and surgical clinics in a general hospital

    Directory of Open Access Journals (Sweden)

    Flavio Hiroshi Shirama

    2013-07-01

    Full Text Available PURPOSES: to identify the prevalence of the use of psychiatric drugs among patients admitted to medical and surgical clinics of a general hospital, and also the factors related to the consumption of this type of medication. METHOD: this is a transversal, descriptive, correlational study with quantitative analysis. For the collection of data, there was use of structured interviews and also reference to medical files. RESULTS: there was confirmation of a high prevalence of users of psychiatric drugs, which was associated to the female sex, to people who do not practice Roman Catholicism, and admittance to the clinic not covered by the Single Health System (Sistema Único de Saúde - SUS, as well as the presence of common mental disorders. Benzodiazepine drugs were the most commonly used psychiatric drugs. Among the total number of users, there has been the identification of patients who were not aware that they were receiving such medication. Doctors who are not psychiatrists were responsible for most prescriptions of psychiatric drugs. CONCLUSIONS: this signals the need to prepare health professionals to deal with psychological and social problems commonly found in clinical practice, in order to promote the rational use of psychiatric drugs.

  8. High-throughput imaging: Focusing in on drug discovery in 3D.

    Science.gov (United States)

    Li, Linfeng; Zhou, Qiong; Voss, Ty C; Quick, Kevin L; LaBarbera, Daniel V

    2016-03-01

    3D organotypic culture models such as organoids and multicellular tumor spheroids (MCTS) are becoming more widely used for drug discovery and toxicology screening. As a result, 3D culture technologies adapted for high-throughput screening formats are prevalent. While a multitude of assays have been reported and validated for high-throughput imaging (HTI) and high-content screening (HCS) for novel drug discovery and toxicology, limited HTI/HCS with large compound libraries have been reported. Nonetheless, 3D HTI instrumentation technology is advancing and this technology is now on the verge of allowing for 3D HCS of thousands of samples. This review focuses on the state-of-the-art high-throughput imaging systems, including hardware and software, and recent literature examples of 3D organotypic culture models employing this technology for drug discovery and toxicology screening.

  9. The biopharmaceutics risk assessment roadmap for optimizing clinical drug product performance.

    Science.gov (United States)

    Selen, Arzu; Dickinson, Paul A; Müllertz, Anette; Crison, John R; Mistry, Hitesh B; Cruañes, Maria T; Martinez, Marilyn N; Lennernäs, Hans; Wigal, Tim L; Swinney, David C; Polli, James E; Serajuddin, Abu T M; Cook, Jack A; Dressman, Jennifer B

    2014-11-01

    The biopharmaceutics risk assessment roadmap (BioRAM) optimizes drug product development and performance by using therapy-driven target drug delivery profiles as a framework to achieve the desired therapeutic outcome. Hence, clinical relevance is directly built into early formulation development. Biopharmaceutics tools are used to identify and address potential challenges to optimize the drug product for patient benefit. For illustration, BioRAM is applied to four relatively common therapy-driven drug delivery scenarios: rapid therapeutic onset, multiphasic delivery, delayed therapeutic onset, and maintenance of target exposure. BioRAM considers the therapeutic target with the drug substance characteristics and enables collection of critical knowledge for development of a dosage form that can perform consistently for meeting the patient's needs. Accordingly, the key factors are identified and in vitro, in vivo, and in silico modeling and simulation techniques are used to elucidate the optimal drug delivery rate and pattern. BioRAM enables (1) feasibility assessment for the dosage form, (2) development and conduct of appropriate "learning and confirming" studies, (3) transparency in decision-making, (4) assurance of drug product quality during lifecycle management, and (5) development of robust linkages between the desired clinical outcome and the necessary product quality attributes for inclusion in the quality target product profile.

  10. Evidence behind FDA alerts for drugs with adverse cardiovascular effects: implications for clinical practice.

    Science.gov (United States)

    Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen

    2014-01-01

    The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications.

  11. Antibacterial effect of Allium sativum cloves and Zingiber officinale rhizomes against multiple-drug resistant clinical pathogens

    Directory of Open Access Journals (Sweden)

    Ponmurugan Karuppiah

    2012-08-01

    Conclusions: Natural spices of garlic and ginger possess effective anti-bacterial activity against multi-drug clinical pathogens and can be used for prevention of drug resistant microbial diseases and further evaluation is necessary.

  12. Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging

    Science.gov (United States)

    Horcajada, Patricia; Chalati, Tamim; Serre, Christian; Gillet, Brigitte; Sebrie, Catherine; Baati, Tarek; Eubank, Jarrod F.; Heurtaux, Daniela; Clayette, Pascal; Kreuz, Christine; Chang, Jong-San; Hwang, Young Kyu; Marsaud, Veronique; Bories, Phuong-Nhi; Cynober, Luc; Gil, Sophie; Férey, Gérard; Couvreur, Patrick; Gref, Ruxandra

    2010-02-01

    In the domain of health, one important challenge is the efficient delivery of drugs in the body using non-toxic nanocarriers. Most of the existing carrier materials show poor drug loading (usually less than 5wt% of the transported drug versus the carrier material) and/or rapid release of the proportion of the drug that is simply adsorbed (or anchored) at the external surface of the nanocarrier. In this context, porous hybrid solids, with the ability to tune their structures and porosities for better drug interactions and high loadings, are well suited to serve as nanocarriers for delivery and imaging applications. Here we show that specific non-toxic porous iron(III)-based metal-organic frameworks with engineered cores and surfaces, as well as imaging properties, function as superior nanocarriers for efficient controlled delivery of challenging antitumoural and retroviral drugs (that is, busulfan, azidothymidine triphosphate, doxorubicin or cidofovir) against cancer and AIDS. In addition to their high loadings, they also potentially associate therapeutics and diagnostics, thus opening the way for theranostics, or personalized patient treatments.

  13. Lumbar spinal imaging in radicular pain and related conditions. Understanding diagnostic images in a clinical context

    Energy Technology Data Exchange (ETDEWEB)

    Wilmink, Jan T. [University Hospital Maastricht (Netherlands). Dept. Radiology

    2010-07-01

    There is general agreement that lumbosacral nerve root compression is a prime factor in the pathogenesis of sciatica and neurogenic claudication, although humoral and vascular factors certainly play a role as well. This book focuses on imaging of the various ways in which nerve root compression can come about, and assessing which anatomic features are reliably associated with the occurrence of radicular pain, as opposed to morphologic findings which are probably coincidental. After a discussion of the nature of radicular pain and related symptoms, spinal imaging techniques and options are reviewed, with emphasis on the role of MR myelography in assessing the condition of the intradural nerve roots. A chapter on normal topographic, sectional, and functional (dynamic) radiologic anatomy is followed by a presentation on pathologic anatomy, addressing the various mechanisms of nerve root compression. In the chapter on pre- and postoperative imaging, features which may help to predict the evolution of the symptoms are discussed, with an eye to selecting candidates for surgical treatment. This is followed by a discussion of the role and limitations of imaging studies in various adverse postoperative conditions. In illustrations involving patient studies, imaging features are linked where possible to the clinical symptoms and history of the individuals involved. (orig.)

  14. Quantitative imaging biomarkers: the application of advanced image processing and analysis to clinical and preclinical decision making.

    Science.gov (United States)

    Prescott, Jeffrey William

    2013-02-01

    The importance of medical imaging for clinical decision making has been steadily increasing over the last four decades. Recently, there has also been an emphasis on medical imaging for preclinical decision making, i.e., for use in pharamaceutical and medical device development. There is also a drive towards quantification of imaging findings by using quantitative imaging biomarkers, which can improve sensitivity, specificity, accuracy and reproducibility of imaged characteristics used for diagnostic and therapeutic decisions. An important component of the discovery, characterization, validation and application of quantitative imaging biomarkers is the extraction of information and meaning from images through image processing and subsequent analysis. However, many advanced image processing and analysis methods are not applied directly to questions of clinical interest, i.e., for diagnostic and therapeutic decision making, which is a consideration that should be closely linked to the development of such algorithms. This article is meant to address these concerns. First, quantitative imaging biomarkers are introduced by providing definitions and concepts. Then, potential applications of advanced image processing and analysis to areas of quantitative imaging biomarker research are described; specifically, research into osteoarthritis (OA), Alzheimer's disease (AD) and cancer is presented. Then, challenges in quantitative imaging biomarker research are discussed. Finally, a conceptual framework for integrating clinical and preclinical considerations into the development of quantitative imaging biomarkers and their computer-assisted methods of extraction is presented.

  15. Clinical application of functional magnetic resonance imaging in China

    Institute of Scientific and Technical Information of China (English)

    MA Lin

    2006-01-01

    @@ Functional magnetic resonance imaging (fMRI)has been widely used in basic research in the past decade, and more clinically in recent years.Unlike conventional MRI that demonstrates the anatomy and morphology of the brain, fMRI provides the functional information of the brain, including neuronal activation, perfusion, diffusion, metabolism,and fiber connection. Since the publication of the pioneer study by Ogawa et al1 in 1990, blood oxygenation level dependent (BOLD) technique has been adopted by neuroscientists and psychologists in research into the mechanisms of motion, vision,hearing, language, memory, and functions of the brain. Soon after, clinical studies with BOLD technique were conducted in some fields like surgery (surgical planning). In China, however, basic and clinical studies on fMRI in the early years were limited by the shortage of funding, difficulty in integrating personnel of different disciplines from different institutions, and long-term use of MR scanners. In recent years, the studies on fMRI in this country have been flourishing as the conditions are greatly improved, and the number of published papers has increased because more and more radiologists and clinicians are involved.

  16. Hemicrania Continua: Functional Imaging and Clinical Features With Diagnostic Implications.

    Science.gov (United States)

    Sahler, Kristen

    2013-04-10

    This review focuses on summarizing 2 pivotal articles in the clinical and pathophysiologic understanding of hemicrania continua (HC). The first article, a functional imaging project, identifies both the dorsal rostral pons (a region associated with the generation of migraines) and the posterior hypothalamus (a region associated with the generation of cluster and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing [SUNCT]) as active during HC. The second article is a summary of the clinical features seen in a prospective cohort of HC patients that carry significant diagnostic implications. In particular, they identify a wider range of autonomic signs than what is currently included in the International Headache Society criteria (including an absence of autonomic signs in a small percentage of patients), a high frequency of migrainous features, and the presence of aggravation and/or restlessness during attacks. Wide variations in exacerbation length, frequency, pain description, and pain location (including side-switching pain) are also noted. Thus, a case is made for widening and modifying the clinical diagnostic criteria used to identify patients with HC.

  17. Clinical Pharmacology of Alpha-1 Blockers Improving Drug-profile through Novel Formulations.

    Science.gov (United States)

    Nerurkar, Rajan P; Ved, Jignesh K

    2014-09-01

    Clinical pharmacology is an essential consideration in chronic therapies, and may play a significant role in modifying the pharmacological characteristics of drug formulations. Improvement in drug formulations may ensure their safe and effective use over a period of time. This has been particularly observed with α-1 adrenergic blockers in hypertension management. Advancements in formulations like prazosin GITS, have resulted in improvement in tolerability profile and smoother, more effective blood pressure control, which reasonably translate into improvement in patient compliance and better clinical outcomes.

  18. Identifying the mechanisms of drug release from amorphous solid dispersions using MRI and ATR-FTIR spectroscopic imaging.

    Science.gov (United States)

    Punčochová, Kateřina; Ewing, Andrew V; Gajdošová, Michaela; Sarvašová, Nina; Kazarian, Sergei G; Beránek, Josef; Štěpánek, František

    2015-04-10

    The dissolution mechanism of a poorly aqueous soluble drug from amorphous solid dispersions was investigated using a combination of two imaging methods: attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging and magnetic resonance imaging (MRI). The rates of elementary processes such as water penetration, polymer swelling, growth and erosion of gel layer, and the diffusion, release and in some cases precipitation of drug were evaluated by image analysis. The results from the imaging methods were compared with drug release profiles obtained by classical dissolution tests. The study was conducted using three polymeric excipients (soluplus, polyvinylpyrrolidone - PVP K30, hydroxypropylmethyl cellulose - HPMC 100M) alone and in combination with a poorly soluble drug, aprepitant. The imaging methods were complementary: ATR-FTIR imaging enabled a qualitative observation of all three components during the dissolution experiments, water, polymer and drug, including identifying structural changes from the amorphous form of drug to the crystalline form. The comparison of quantitative MRI data with drug release profiles enabled the different processes during dissolution to be established and the rate-limiting step to be identified, which - for the drug-polymer combinations investigated in this work - was the drug diffusion through the gel layer rather than water penetration into the tablet.

  19. Application of concave microwells to pancreatic tumor spheroids enabling anticancer drug evaluation in a clinically relevant drug resistance model.

    Directory of Open Access Journals (Sweden)

    Sang-Eun Yeon

    Full Text Available Intrinsic drug resistance of pancreatic ductal adenocarcinoma (PDAC warrants studies using models that are more clinically relevant for identifying novel resistance mechanisms as well as for drug development. Tumor spheroids (TS mimic in vivo tumor conditions associated with multicellular resistance and represent a promising model for efficient drug screening, however, pancreatic cancer cells often fail to form spheroids using conventional methods such as liquid overlay. This study describes the induction of TS of human pancreatic cancer cells (Panc-1, Aspc-1, Capan-2 in concave polydimethylsiloxane (PDMS microwell plates and evaluation of their usefulness as an anticancer efficacy test model. All three cell lines showed TS formation with varying degree of necrosis inside TS. Among these, Panc-1 spheroid with spherical morphology, a rather rough surface, and unique adhesion structures were successfully produced with no notable necrosis in concave microwell plates. Panc-1 TS contained growth factors or enzymes such as TGF-β1, CTGF, and MT1-MMP, and extracellular matrix proteins such as collagen type I, fibronectin, and laminin. Panc-1 cells grown as TS showed changes in stem cell populations and in expression levels of miRNAs that may play roles in chemoresistance. Visualization of drug penetration and detection of viability indicators, such as Ki-67 and MitoSOX, were optimized for TS for quantitative analysis. Water-soluble tetrazolium (MTS and acid phosphatase (APH assays were also successfully optimized. Overall, we demonstrated that concave PDMS microwell plates are a novel platform for preparation of TS of weakly aggregating cells and that Panc-1 spheroids may represent a novel three-dimensional model for anti-pancreatic cancer drug screening.

  20. Application of concave microwells to pancreatic tumor spheroids enabling anticancer drug evaluation in a clinically relevant drug resistance model.

    Science.gov (United States)

    Yeon, Sang-Eun; No, Da Yoon; Lee, Sang-Hoon; Nam, Suk Woo; Oh, Il-Hoan; Lee, Jaehwi; Kuh, Hyo-Jeong

    2013-01-01

    Intrinsic drug resistance of pancreatic ductal adenocarcinoma (PDAC) warrants studies using models that are more clinically relevant for identifying novel resistance mechanisms as well as for drug development. Tumor spheroids (TS) mimic in vivo tumor conditions associated with multicellular resistance and represent a promising model for efficient drug screening, however, pancreatic cancer cells often fail to form spheroids using conventional methods such as liquid overlay. This study describes the induction of TS of human pancreatic cancer cells (Panc-1, Aspc-1, Capan-2) in concave polydimethylsiloxane (PDMS) microwell plates and evaluation of their usefulness as an anticancer efficacy test model. All three cell lines showed TS formation with varying degree of necrosis inside TS. Among these, Panc-1 spheroid with spherical morphology, a rather rough surface, and unique adhesion structures were successfully produced with no notable necrosis in concave microwell plates. Panc-1 TS contained growth factors or enzymes such as TGF-β1, CTGF, and MT1-MMP, and extracellular matrix proteins such as collagen type I, fibronectin, and laminin. Panc-1 cells grown as TS showed changes in stem cell populations and in expression levels of miRNAs that may play roles in chemoresistance. Visualization of drug penetration and detection of viability indicators, such as Ki-67 and MitoSOX, were optimized for TS for quantitative analysis. Water-soluble tetrazolium (MTS) and acid phosphatase (APH) assays were also successfully optimized. Overall, we demonstrated that concave PDMS microwell plates are a novel platform for preparation of TS of weakly aggregating cells and that Panc-1 spheroids may represent a novel three-dimensional model for anti-pancreatic cancer drug screening.

  1. Hounsfield unit recovery in clinical cone beam CT images of the thorax acquired for image guided radiation therapy

    DEFF Research Database (Denmark)

    Thing, Rune Slot; Bernchou, Uffe; Mainegra-Hing, Ernesto

    2016-01-01

    A comprehensive artefact correction method for clinical cone beam CT (CBCT) images acquired for image guided radiation therapy (IGRT) on a commercial system is presented. The method is demonstrated to reduce artefacts and recover CT-like Hounsfield units (HU) in reconstructed CBCT images of five ...

  2. Causality Assessment in Premarketing Drug Clinical Trials: Regulatory Evolution in the USA and Ongoing Concerns.

    Science.gov (United States)

    Goldman, Stephen A

    2016-10-01

    Since 1993, how to assess the causality of serious adverse events in premarketing drug clinical trials has undergone sustained regulatory evolution in the USA. In that year, an investigational drug study for chronic hepatitis B virus infection was emergently stopped after a patient suddenly exhibited hepatic failure and lactic acidosis, which later developed, along with pancreatitis and peripheral neuropathy, in several others after drug discontinuation. Five patients eventually died, including three despite emergency liver transplantation. The drug's multisystem toxicity was not predicted by preclinical animal studies, with grave injury to human mitochondria subsequently implicated. A concerned US Food and Drug Administration (FDA) created a task force whose findings would have a lasting impact on the agency's thinking. In 1994, the FDA proposed to amend its investigational new drug reporting requirements largely based on task force recommendations for ways to enhance the likelihood that sponsors and investigators would consider investigational agents as a possible cause of serious adverse events mimicking the underlying disease or concomitant drug toxicity. Then, in its 1997 final rule for expedited safety reporting requirements for drugs and biologics, the FDA advised sponsors that such reporting of serious, unexpected clinical trial cases would be expected when "there is a reasonable suspected causal relationship between the investigational product and the adverse event (i.e., the causal relationship cannot be ruled out)." This last clause was codified into the suspected adverse drug reaction definition in the FDA's 2003 safety reporting requirements for drugs and biologics proposed rule. The negatively received suspected adverse drug reaction and proposed causality standard were not adopted in the FDA's 2010 finalized investigational new drug safety reporting regulations, the agency stating that "'reasonable possibility' means there is evidence to suggest a

  3. SIMulation of Medication Error induced by Clinical Trial drug labeling: the SIMME-CT study.

    Science.gov (United States)

    Dollinger, Cecile; Schwiertz, Vérane; Sarfati, Laura; Gourc-Berthod, Chloé; Guédat, Marie-Gabrielle; Alloux, Céline; Vantard, Nicolas; Gauthier, Noémie; He, Sophie; Kiouris, Elena; Caffin, Anne-Gaelle; Bernard, Delphine; Ranchon, Florence; Rioufol, Catherine

    2016-06-01

    To assess the impact of investigational drug labels on the risk of medication error in drug dispensing. A simulation-based learning program focusing on investigational drug dispensing was conducted. The study was undertaken in an Investigational Drugs Dispensing Unit of a University Hospital of Lyon, France. Sixty-three pharmacy workers (pharmacists, residents, technicians or students) were enrolled. Ten risk factors were selected concerning label information or the risk of confusion with another clinical trial. Each risk factor was scored independently out of 5: the higher the score, the greater the risk of error. From 400 labels analyzed, two groups were selected for the dispensing simulation: 27 labels with high risk (score ≥3) and 27 with low risk (score ≤2). Each question in the learning program was displayed as a simulated clinical trial prescription. Medication error was defined as at least one erroneous answer (i.e. error in drug dispensing). For each question, response times were collected. High-risk investigational drug labels correlated with medication error and slower response time. Error rates were significantly 5.5-fold higher for high-risk series. Error frequency was not significantly affected by occupational category or experience in clinical trials. SIMME-CT is the first simulation-based learning tool to focus on investigational drug labels as a risk factor for medication error. SIMME-CT was also used as a training tool for staff involved in clinical research, to develop medication error risk awareness and to validate competence in continuing medical education. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

  4. Novel approach to in vitro drug susceptibility assessment of clinical strains of Leishmania spp.

    Science.gov (United States)

    Fernández, Olga; Diaz-Toro, Yira; Valderrama, Liliana; Ovalle, Clemencia; Valderrama, Mabel; Castillo, Harry; Perez, Mauricio; Saravia, Nancy Gore

    2012-07-01

    Resistance to antimonial drugs has been documented in Leishmania isolates transmitted in South America, Europe, and Asia. The frequency and distribution of resistance to these and other antileishmanial drugs are unknown. Technical constraints have limited the assessment of drug susceptibility of clinical strains of Leishmania. Susceptibility of experimentally selected lines and 130 clinical strains of Leishmania panamensis, L. braziliensis, and L. guyanensis to meglumine antimoniate and miltefosine was determined on the basis of parasite burden and percentage of infected U-937 human macrophages. Reductions of infection at single predefined concentrations of meglumine antimoniate and miltefosine and 50% effective doses (ED(50)s) were measured and correlated. The effects of 34°C and 37°C incubation temperatures and different parasite-to-host cell ratios on drug susceptibility were evaluated at 5, 10, and 20 parasites/cell. Reduction of the intracellular burden of Leishmania amastigotes in U-937 cells exposed to the predefined concentrations of meglumine antimoniate or miltefosine discriminated sensitive and experimentally derived resistant Leishmania populations and was significantly correlated with ED(50) values of clinical strains (for meglumine antimoniate, ρ = -0.926 and P < 0.001; for miltefosine, ρ = -0.906 and P < 0.001). Incubation at 37°C significantly inhibited parasite growth compared to that at 34°C in the absence of antileishmanial drugs and resulted in a significantly lower ED(50) in the presence of drugs. Susceptibility assessment was not altered by the parasite-to-cell ratio over the range evaluated. In conclusion, measurement of the reduction of parasite burden at a single predetermined drug concentration under standardized conditions provides an efficient and reliable strategy for susceptibility evaluation and monitoring of clinical strains of Leishmania.

  5. Stereomicroscopic imaging technique for the quantification of cold flow in drug-in-adhesive type of transdermal drug delivery systems.

    Science.gov (United States)

    Krishnaiah, Yellela S R; Katragadda, Usha; Khan, Mansoor A

    2014-05-01

    Cold flow is a phenomenon occurring in drug-in-adhesive type of transdermal drug delivery systems (DIA-TDDS) because of the migration of DIA coat beyond the edge. Excessive cold flow can affect their therapeutic effectiveness, make removal of DIA-TDDS difficult from the pouch, and potentially decrease available dose if any drug remains adhered to pouch. There are no compendial or noncompendial methods available for quantification of this critical quality attribute. The objective was to develop a method for quantification of cold flow using stereomicroscopic imaging technique. Cold flow was induced by applying 1 kg force on punched-out samples of marketed estradiol DIA-TDDS (model product) stored at 25°C, 32°C, and 40°C/60% relative humidity (RH) for 1, 2, or 3 days. At the end of testing period, dimensional change in the area of DIA-TDDS samples was measured using image analysis software, and expressed as percent of cold flow. The percent of cold flow significantly decreased (p < 0.001) with increase in size of punched-out DIA-TDDS samples and increased (p < 0.001) with increase in cold flow induction temperature and time. This first ever report suggests that dimensional change in the area of punched-out samples stored at 32°C/60%RH for 2 days applied with 1 kg force could be used for quantification of cold flow in DIA-TDDS. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. Comparison of clinical features between primary and drug-induced sleep-related eating disorder

    Directory of Open Access Journals (Sweden)

    Komada Y

    2016-05-01

    Full Text Available Yoko Komada,1 Yoshikazu Takaesu,2 Kentaro Matsui,3 Masaki Nakamura,3 Shingo Nishida,3 Meri Kanno,3,† Akira Usui,3 Yuichi Inoue1,3 1Department of Somnology, 2Department of Psychiatry, Tokyo Medical University, 3Japan Somnology Center, Institute of Neuropsychiatry, Tokyo, Japan †Meri Kanno passed away on March 1, 2016 Purpose: The aim of this study was to ascertain the clinical characteristics of drug-induced sleep-related eating disorder (SRED. Patients and methods: We retrospectively reviewed the medical records of 30 patients with primary SRED (without any comorbid sleep disorders and who were not taking any possible causative medications, and ten patients with drug-induced SRED (occurrence of SRED episodes after starting nightly medication of sedative drugs, which completely resolved after dose reduction or discontinuation of the sedatives. Results: All patients with drug-induced SRED took multiple types of sedatives, such as benzodiazepines or benzodiazepine receptor agonists. Clinical features of drug-induced SRED compared with primary SRED were as follows: higher mean age of onset (40 years old in drug-induced SRED vs 26 years old in primary SRED, significantly higher rate of patients who had total amnesia during most of their SRED episodes (75.0% vs 31.8%, significantly lower rate of comorbidity of night eating syndrome (0% vs 63.3%, and significantly lower rate of history of sleepwalking (10.0% vs 46.7%. Increased doses of benzodiazepine receptor agonists may be responsible for drug-induced SRED. Conclusion: The clinical features of drug-induced SRED were different from those of primary SRED, possibly reflecting differences in the underlying mechanisms between these two categories of SREDs. Keywords: nocturnal eating syndrome, night eating, eating disorder, hypnotics, amnesia, sleepwalking, benzodiazepine

  7. Clinical trial of a new technique for drugs of abuse testing: a new possible sampling technique.

    Science.gov (United States)

    Skoglund, Charlotte; Hermansson, Ulric; Beck, Olof

    2015-01-01

    Exhaled breath has recently been proposed as a matrix for drug testing. This study aims to further explore, develop and validate exhaled breath as a safe and effective non-invasive method for drug testing in a clinical setting. Self-reported drug use was recorded and drug testing was performed by mass spectrometry and immunochemical methods using breath, plasma and urine samples from 45 individuals voluntarily seeking treatment for recreational drug use. Cannabis was the most prevalent drug detected by any method. Urine sampling detected most cases. The exhaled breath technique was less sensitive (73%) than plasma analysis for detection of cannabis uses but captures a more recent drug intake than both plasma and urine. Exhaled breath was the preferred specimen to donate according to interview data of the participants. Testing illicit drugs with the exhaled breath sampling technique is a sufficient, non-invasive and safe alternative and complement to plasma and/or urine sampling. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Preclinical imaging and translational animal models of cancer for accelerated clinical implementation of nanotechnologies and macromolecular agents.

    Science.gov (United States)

    De Souza, Raquel; Spence, Tara; Huang, Huang; Allen, Christine

    2015-12-10

    The majority of animal models of cancer have performed poorly in terms of predicting clinical performance of new therapeutics, which are most often first evaluated in patients with advanced, metastatic disease. The development and use of metastatic models of cancer may enhance clinical translatability of preclinical studies focused on the development of nanotechnology-based drug delivery systems and macromolecular therapeutics, potentially accelerating their clinical implementation. It is recognized that the development and use of such models are not without challenge. Preclinical imaging tools offer a solution by allowing temporal and spatial characterization of metastatic lesions. This paper provides a review of imaging methods applicable for evaluation of novel therapeutics in clinically relevant models of advanced cancer. An overview of currently utilized models of oncology in small animals is followed by image-based development and characterization of visceral metastatic cancer models. Examples of imaging tools employed for metastatic lesion detection, evaluation of anti-tumor and anti-metastatic potential and biodistribution of novel therapies, as well as the co-development and/or use of imageable surrogates of response, are also discussed. While the focus is on development of macromolecular and nanotechnology-based therapeutics, examples with small molecules are included in some cases to illustrate concepts and approaches that can be applied in the assessment of nanotechnologies or macromolecules.

  9. Clinical and operational value of the extensively drug-resistant tuberculosis definition.

    Science.gov (United States)

    Migliori, G B; Besozzi, G; Girardi, E; Kliiman, K; Lange, C; Toungoussova, O S; Ferrara, G; Cirillo, D M; Gori, A; Matteelli, A; Spanevello, A; Codecasa, L R; Raviglione, M C

    2007-10-01

    Currently, no information is available on the effect of resistance/susceptibility to first-line drugs different from isoniazid and rifampicin in determining the outcome of extensively drug-resistant tuberculosis (XDR-TB) patients, and whether being XDR-TB is a more accurate indicator of poor clinical outcome than being resistant to all first-line anti-tuberculosis (TB) drugs. To investigate this issue, a large series of multidrug-resistant TB (MDR-TB) and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation during the period 1999-2006 were analysed. Drug-susceptibility testing for first- and second-line anti-TB drugs, quality assurance and treatment delivery was performed according to World Health Organization recommendations in all study sites. Out of 4,583 culture-positive TB cases analysed, 361 (7.9%) were MDR and 64 (1.4%) were XDR. XDR-TB cases had a relative risk (RR) of 1.58 to have an unfavourable outcome compared with MDR-TB cases resistant to all first-line drugs (isoniazid, rifampicin ethambutol, streptomycin and, when tested, pyrazinamide), and an RR of 2.61 compared with "other" MDR-TB cases (those susceptible to at least one first-line anti-TB drug among ethambutol, pyrazinamide and streptomycin, regardless of resistance to the second-line drugs not defining XDR-TB). The emergence of extensively drug-resistant tuberculosis confirms that problems in tuberculosis management are still present in Europe. While waiting for new tools which will facilitate management of extensively drug-resistant tuberculosis, accessibility to quality diagnostic and treatment services should be urgently ensured and adequate public health policies should be rapidly implemented to prevent further development of drug resistance.

  10. Nonclinical Evaluations of Small-Molecule Oncology Drugs: Integration into Clinical Dose Optimization and Toxicity Management.

    Science.gov (United States)

    Dambach, Donna M; Simpson, Natalie E; Jones, Thomas W; Brennan, Richard J; Pazdur, Richard; Palmby, Todd R

    2016-06-01

    Multidisciplinary approaches that incorporate nonclinical pharmacologic and toxicologic characterization of small-molecule oncology drugs into clinical development programs may facilitate improved benefit-risk profiles and clinical toxicity management in patients. The performance of the current nonclinical safety-testing scheme was discussed, highlighting current strengths and areas for improvement. While current nonclinical testing appears to predict the clinical outcome where the prevalence of specific adverse effects are high, nonclinical testing becomes less reliable for predicting clinical adverse effects that occur infrequently, as with some kinase inhibitors. Although adverse effects associated with kinase inhibitors can often be predicted on the basis of target biology, drugs can be promiscuous and inhibit targets with poorly defined function and associated risks. Improvements in adverse effect databases and better characterization of the biologic activities of drug targets may enable better use of computational modeling approaches in predicting adverse effects with kinase inhibitors. Assessing safety of a lead candidate in parallel with other drug properties enables incorporation of a molecule's best features during chemical design, eliminates the worst molecules early, and permits timely investigation/characterization of toxicity mechanisms for identified liabilities. A safety lead optimization and candidate identification strategy that reduces intrinsic toxicity and metabolic risk and enhances selectivity can deliver selective kinase inhibitors that demonstrate on-target adverse effects identified nonclinically. Integrating clinical and nonclinical data during drug development can facilitate better identification and management of oncology drugs. Follow-up nonclinical studies may be used to better understand the risks in a given patient population and minimize or manage these risks more appropriately. Clin Cancer Res; 22(11); 2618-22. ©2016 AACR SEE ALL

  11. Laboratory tests in the clinical risk management of potential drug-drug interactions: a cross-sectional study using drug-dispensing data from 100 Dutch community pharmacies.

    Science.gov (United States)

    Geerts, Arjen F J; De Koning, Fred H P; De Smet, Peter A G M; Van Solinge, Wouter W; Egberts, Toine C G

    2009-01-01

    Patient safety and the life cycle of a drug are negatively influenced by the still increasing occurrence of potential drug-drug interactions (DDIs). Clinical risk management of potential DDIs is required in patients using drugs to influence the benefit-risk profile positively. Information about laboratory test results, in particular, may be useful in the assessment of potential DDIs for the individual patient. The objective of this study was to examine the frequency and nature of laboratory tests required for the assessment of the clinical relevance of potential DDIs in Dutch community pharmacies. In addition, the nature and clinical relevance of these potential DDIs is analysed. All patients from 100 Dutch community pharmacies using, according to dispensing information, two or more drugs concomitantly on a specified date (Wednesday, 4 April 2007), were included (n = 223,019). The anonymous dispensing data of the included patients were analysed against a list of DDIs requiring laboratory tests for the assessment of their clinical relevance. The number of patients at risk for these potential DDIs with severe adverse reactions was calculated. The frequency of potential DDIs requiring laboratory tests were stratified by age, sex and degree of polypharmacy. Of the included patients, 24.4% had one or more potential DDIs (n = 54,427). In 9.0% of the included patients, one or more laboratory tests for the assessment of clinical relevance of the potential DDI were required (n = 19,968). The frequency of DDIs requiring laboratory tests increased with increasing age and number of drugs, but was not related to sex. The most commonly required laboratory tests were for renal function (42.2%), electrolytes (20.1%) and coagulation (13.1%). The percentage of patients at risk for potential DDIs requiring laboratory tests with adverse reaction category F (serious, irrecoverable disablement or death) was 2.5%; category E (increased risk of failure of life-saving therapy) was 0

  12. Cue-Induced Craving to Paraphernalia and Drug Images in Opioid Dependence

    Science.gov (United States)

    McHugh, R. Kathryn; Fulciniti, Francesca; Mashhoon, Yasmin; Weiss, Roger D.

    2016-01-01

    Background and Objectives Stimuli that are repeatedly paired with substance use, such as drug paraphernalia, can themselves elicit drug craving. The aim of this study was to examine whether particular cue types elicit greater craving responses than others among individuals with opioid dependence. Methods Participants seeking inpatient treatment for opioid dependence were recruited for a study of cue-induced craving. This sample (N=50), included 25 primary heroin users, 20 primary prescription opioid users, and 5 users of heroin and prescription opioids equally. Participants completed a cue reactivity task, in which images of drug-related stimuli were presented on a computer screen, each followed by a question assessing state drug craving. Results Overall, participants reported higher craving following paraphernalia stimuli relative to drug stimuli. However, this was moderated by opioid type; there was significantly higher craving in response to images of paraphernalia cues in the heroin group, and higher craving in response to drug cues in the prescription opioid group. Discussion and Conclusions These findings highlight potential differences in cue reactivity to opioid paraphernalia and drug cues, which appears to be moderated by drug type. Scientific Significance Cue-induced craving is an important factor in relapse. This study adds further to the literature on cue-induced craving in opioid dependence, suggesting that craving may vary based on both cue type and opioid type. Future studies designed to discriminate the impact of substance of abuse, route of administration, and cue type will help to further understand cue-induced craving in this population. PMID:26848719

  13. Juvenile idiopathic arthritis: clinically relevant imaging in diagnosis and monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Southwood, Tauny [Birmingham Children' s Hospital NHS Foundation Trust, Department of Rheumatology, Birmingham (United Kingdom)

    2008-06-15

    The role of plain radiographs in monitoring the disease process in JIA is being increasingly superseded by MRI. The use of ultrasound by clinicians is contentious, but has the potential to corroborate and supplement the clinical impression of individual joint inflammation and it can be very useful for localising intra-articular treatment at the bedside. There are exciting developments in MRS technology which may eventually allow in vivo evaluation of the acute inflammatory process, measurement of early responses to treatment and detection of residual inflammation. The aim of this article is to describe a clinician's view of the current role of imaging in the diagnosis and monitoring of JIA. (orig.)

  14. SLAP lesions: Anatomy, clinical presentation, MR imaging diagnosis and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Debra [University of California San Diego, Department of Radiology, 200 W. Arbor Drive, San Diego, CA 92103 (United States); VA Healthcare System San Diego, Department of Radiology, 3350 La Jolla Village Drive, La Jolla, CA 92161 (United States); MedRay Imaging and Fraser Health Authority, Vancouver, BC (Canada)], E-mail: cbchung@ucsd.edu; Mohana-Borges, Aurea; Borso, Maya; Chung, Christine B. [University of California San Diego, Department of Radiology, 200 W. Arbor Drive, San Diego, CA 92103 (United States); VA Healthcare System San Diego, Department of Radiology, 3350 La Jolla Village Drive, La Jolla, CA 92161 (United States)

    2008-10-15

    ABSTRACT: Superior labral anterior posterior (SLAP) tears are an abnormality of the superior labrum usually centered on the attachment of the long head of the biceps tendon. Tears are commonly caused by repetitive overhead motion or fall on an outstretched arm. SLAP lesions can lead to shoulder pain and instability. Clinical diagnosis is difficult thus imaging plays a key diagnostic role. The normal anatomic variability of the capsulolabral complex can make SLAP lesions a diagnostic challenge. Concurrent shoulder injuries are often present including rotator cuff tears, cystic changes or marrow edema in the humeral head, capsular laxity, Hill-Sachs or Bankart lesion. The relevant anatomy, capsulolabral anatomic variants, primary and secondary findings of SLAP tears including MR arthrography findings, types of SLAP lesions and a practical approach to labral lesions are reviewed.

  15. Test Sample for the Spatially Resolved Quantification of Illicit Drugs on Fingerprints Using Imaging Mass Spectrometry.

    Science.gov (United States)

    Muramoto, Shin; Forbes, Thomas P; van Asten, Arian C; Gillen, Greg

    2015-01-01

    A novel test sample for the spatially resolved quantification of illicit drugs on the surface of a fingerprint using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and desorption electrospray ionization mass spectrometry (DESI-MS) was demonstrated. Calibration curves relating the signal intensity to the amount of drug deposited on the surface were generated from inkjet-printed arrays of cocaine, methamphetamine, and heroin with a deposited-mass ranging nominally from 10 pg to 50 ng per spot. These curves were used to construct concentration maps that visualized the spatial distribution of the drugs on top of a fingerprint, as well as being able to quantify the amount of drugs in a given area within the map. For the drugs on the fingerprint on silicon, ToF-SIMS showed great success, as it was able to generate concentration maps of all three drugs. On the fingerprint on paper, only the concentration map of cocaine could be constructed using ToF-SIMS and DESI-MS, as the signals of methamphetamine and heroin were completely suppressed by matrix and substrate effects. Spatially resolved quantification of illicit drugs using imaging mass spectrometry is possible, but the choice of substrates could significantly affect the results.

  16. Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-11-1-0639 TITLE: Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval PRINCIPAL...SEP 2014 – 29 SEP 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-1-0639 Development of Pain Endpoint Models for Use in Prostate Cancer...standard methods for measuring pain palliation and pain progression in prostate cancer clinical trials that are feasible, methodologically rigorous, and

  17. Evaluation of drug delivery profiles in geometric three-layered tablets with various mechanical properties, in vitro-in vivo drug release, and Raman imaging.

    Science.gov (United States)

    Choi, Du Hyung; Kim, Ki Hyun; Park, Jun Sang; Jeong, Seong Hoon; Park, Kinam

    2013-12-28

    Even though various multi-layered tablets have been developed for sustained release formulations, evaluations of mechanical properties during dissolution with drug release and imaging in the tablets have been limited. A novel geometric system consisting of an inner immediate release layer and two extended release barrier layers with swellable hydrophilic polymers was suggested as a once-a-day formulation. To evaluate drug release mechanisms with geometric properties, various mechanical characteristics during swelling were investigated to comprehend the relationship among in vitro drug release, human pharmacokinetics, and geometric characteristics. Imaging of drug movement was also studied in real-time using Raman spectroscopy. Drug delivery in the tablets might be divided into three processes through the geometric properties. When exposed to aqueous environments, the drug in the mid-layer was released until wrapped by the swollen barrier layers. Then, the drug in the mid-layer was mainly delivered to the barrier layers and a small amount of the drug was delivered to the contact region of the swollen barrier layers. Finally, the delivered drug to the barrier layers was consistently released out in response to the characteristics of the polymer of the barrier layers. Using Raman spectroscopy, these processes were confirmed in real-time analysis. Moreover, in vitro drug release profiles and human pharmacokinetics showed consistent results suggesting that drug release might be dependent on the various geometric properties and be modified consistently during the formulation development. © 2013.

  18. Clinical imaging guidelines part 2: Risks, benefits, barriers, and solutions.

    Science.gov (United States)

    Malone, James; del Rosario-Perez, Maria; Van Bladel, Lodewijk; Jung, Seung Eun; Holmberg, Ola; Bettmann, Michael A

    2015-02-01

    A recent international meeting was convened by two United Nations bodies to focus on international collaboration on clinical appropriateness/referral guidelines for use in medical imaging. This paper, the second of 4 from this technical meeting, addresses barriers to the successful development/deployment of clinical imaging guidelines and means of overcoming them. It reflects the discussions of the attendees, and the issues identified are treated under 7 headings: ■ Practical Strategy for Development and Deployment of Guidelines; ■ Governance Arrangements and Concerns with Deployment of Guidelines; ■ Finance, Sustainability, Reimbursement, and Related Issues; ■ Identifying Benefits and Radiation Risks from Radiological Examinations; ■ Information Given to Patients and the Public, and Consent Issues; ■ Special Concerns Related to Pregnancy; and ■ The Research Agenda. Examples of topics identified include the observation that guideline development is a global task and there is no case for continuing it as the project of the few professional organizations that have been brave enough to make the long-term commitment required. Advocacy for guidelines should include the expectations that they will facilitate: (1) better health care delivery; (2) lower cost of that delivery; with (3) reduced radiation dose and associated health risks. Radiation protection issues should not be isolated; rather, they should be integrated with the overall health care picture. The type of dose/radiation risk information to be provided with guidelines should include the uncertainty involved and advice on application of the precautionary principle with patients. This principle may be taken as an extension of the well-established medical principle of "first do no harm." Copyright © 2015. Published by Elsevier Inc.

  19. Osseous metastases of chordoma: imaging and clinical findings

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Connie; Torriani, Martin; Bredella, Miriam [Massachusetts General Hospital, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States); Chebib, Ivan [Massachusetts General Hospital, Department of Pathology, Boston, MA (United States)

    2017-03-15

    To describe the imaging and clinical characteristics of chordoma osseous metastases (COM). Our study was IRB approved and HIPAA compliant. A retrospective search of our pathology database for pathology-proven COM yielded 15 patients who had undergone MRI, CT, bone scan, and/or FDG-PET/CT. The imaging and clinical features of the COMs were recorded. A control group of age and gender matched chordoma patients without osseous metastasis was evaluated. The COM mean maximal dimension was 6.4 ± 4.0 cm. The majority (60%) of patients had one lesion. Extra-osseous soft tissue component was present in 85% and was larger than intra-osseous component in 76%. On MRI the lesions were heterogeneous but predominantly T2 hyperintense with hypointense septae, and with variable enhancement. On CT the lesions were typically destructive or permeative; calcifications were rare. The extent of the soft tissue component was isodense to muscle on CT and therefore better evaluated on MRI. COM was in a body part contiguous to the site of the primary tumor. Compared to the controls, COM patients were more likely to have local recurrence (P = 0.0009) and positive resection margins (P = 0.002). At 1 year, 33% of COM patients were deceased and 13% had progressive metastases. COM are associated with large extra-osseous soft tissue components, which are better visualized by MRI. They are often located in a body part contiguous to the site of the primary tumor, portend poor prognosis, and are associated with positive resection margins and local recurrence. (orig.)

  20. Fourier transform infared spectroscopic imaging for the identification of concealed drug residue particles and fingerprints

    Science.gov (United States)

    Ricci, Camilla; Chan, K. L. Andrew; Kazarian, Sergei G.

    2006-09-01

    Conventional FTIR spectroscopy and microscopy has been widely used in forensic science. New opportunities exist to obtain rapid chemical images and to enhance the sensitivity of detection of trace materials using attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy coupled with a focal-plane array (FPA) detector. In this work, the sensitivity of ATR-FTIR spectroscopic imaging using three different kinds of ATR crystals (Ge coupled with an infrared microscope, ZnSe and diamond) and resulting in three different optical arrangements for the detection of model drug particles is discussed. Model systems of ibuprofen and paracetamol particles having a size below 32 micrometers have been prepared by sieving. The sensitivity level in the three different approaches has been compared and it has been found that both micro and macro-ATR imaging methods have proven to be a promising techniques for the identification of concealed drug particles. To demonstrate the power and applicability of FTIR chemical imaging to forensic research, various examples are discussed. This includes investigation of the changes of chemical nature of latent fingerprint residue under controlled conditions of humidity and temperature studied by ATR-FTIR imaging. This study demonstrates the potential of spectroscopic imaging for visualizing the chemical changes of fingerprints.

  1. Nanotechnology-based drug delivery systems for Alzheimer's disease management: Technical, industrial, and clinical challenges.

    Science.gov (United States)

    Wen, Ming Ming; El-Salamouni, Noha S; El-Refaie, Wessam M; Hazzah, Heba A; Ali, Mai M; Tosi, Giovanni; Farid, Ragwa M; Blanco-Prieto, Maria J; Billa, Nashiru; Hanafy, Amira S

    2017-01-10

    Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes. Despite extensive research, literature screening revealed that clinical activities involving NTDDS application in research for AD are lagging compared to NTDDS for other diseases such as cancers. The industrial perspectives, processability, and cost/benefit ratio of using NTDDS for AD treatment are usually overlooked. Moreover, active and passive immunization against AD are by far the mostly studied alternative AD therapies because conventional oral drug therapy is not yielding satisfactorily results. NTDDS of approved drugs appear promising to transform this research from 'paper to clinic' and raise hope for AD sufferers and their caretakers. This review summarizes the recent studies conducted on NTDDS for AD treatment, with a primary focus on the industrial perspectives and processability. Additionally, it highlights the ongoing clinical trials for AD management.

  2. Effect of cardiac drugs on imaging studies with thallous chloride Tl 201

    Energy Technology Data Exchange (ETDEWEB)

    Waschek, J.; Hinkle, G.; Basmadjian, G.; Allen, E.W.; Ice, R.

    1981-11-01

    The effects of commonly used cardiac drugs on cardiac imaging with thallium-201-labeled thallous chloride were studied. This retrospective study included 62 men ranging in age from 37 to 70 years who had cardiac imaging attempted with thallium during an eight-month period. Seven drugs were being used by at least eight patients each--propranolol, nitroglycerin ointment, isosorbide dinitrate, digoxin, hydrochlorothiazide, potassium chloride, and quinidine. Myocardial-to-background (M/Bk) ratios were calculated for each patient. No drug consistently affected the M/Bk ratios. The lowest M/Bk ratio was found in patients receiving digoxin, but there was no significant difference between the M/Bk ratios for patients taking digoxin (1.38 +/- 0.16) and those not taking digoxin (1.45 +/- 0.10) (0.05 less than p less than 0.10, Student's t test). It is concluded that the drugs studied do not affect cardiac imaging with thallous chloride Tl 201.

  3. Clinical types of spinocerebellar degeneration and evaluation with MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kojima, Shigeyuki (Chiba Univ. (Japan). School of Medicine)

    1993-12-01

    Eighty one patients with the clinical diagnosis of non-hereditary spinocerebellar degeneration were examined by magnetic resonance imaging (MRI). The MRI findings were subdivided into non-cerebellar atrophy, cerebellar atrophy without and with apparent enlargement of the fourth ventricle as a result of atrophy of the middle or superior cerebellar peduncles. The first pattern of non-cerebellar atrophy included ataxias such as Friendreich's ataxia and Machado-Joseph disease (MJD; type II). In the patients with MJD, atrophy of the brainstem was frequently recognized. The second pattern largely included late cortical cerebellar atrophy and hereditary ataxia of Holmes type. The third pattern was subdivided further into atrophies of the middle and superior cerebellar peduncles. The pattern of the former included olivo-ponto-cerebellar atrophy (OPCA) and hereditary ataxia of Menzel type, and the pattern of the latter included MJD and dentato-rubro-pallido-luysian atrophy (DRPLA). In the patients with OPCA and hereditary ataxia of Menzel type, increased signal intensity on T2-weighted image was always observed in the transverese pontine fibers, middle cerebellar peduncles. In several patients with MJD and DRPLA, atrophy of both cerebellar peduncles was demonstrated, but abnormal signal intensity was not observed in the pontocerebellar areas. (author).

  4. DGIdb 2.0: mining clinically relevant drug-gene interactions.

    Science.gov (United States)

    Wagner, Alex H; Coffman, Adam C; Ainscough, Benjamin J; Spies, Nicholas C; Skidmore, Zachary L; Campbell, Katie M; Krysiak, Kilannin; Pan, Deng; McMichael, Joshua F; Eldred, James M; Walker, Jason R; Wilson, Richard K; Mardis, Elaine R; Griffith, Malachi; Griffith, Obi L

    2016-01-01

    The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that consolidates disparate data sources describing drug-gene interactions and gene druggability. It provides an intuitive graphical user interface and a documented application programming interface (API) for querying these data. DGIdb was assembled through an extensive manual curation effort, reflecting the combined information of twenty-seven sources. For DGIdb 2.0, substantial updates have been made to increase content and improve its usefulness as a resource for mining clinically actionable drug targets. Specifically, nine new sources of drug-gene interactions have been added, including seven resources specifically focused on interactions linked to clinical trials. These additions have more than doubled the overall count of drug-gene interactions. The total number of druggable gene claims has also increased by 30%. Importantly, a majority of the unrestricted, publicly-accessible sources used in DGIdb are now automatically updated on a weekly basis, providing the most current information for these sources. Finally, a new web view and API have been developed to allow searching for interactions by drug identifiers to complement existing gene-based search functionality. With these updates, DGIdb represents a comprehensive and user friendly tool for mining the druggable genome for precision medicine hypothesis generation.

  5. Clinical pharmacokinetic/pharmacodynamic and physiologically based pharmacokinetic modeling in new drug development: the capecitabine experience.

    Science.gov (United States)

    Blesch, Karen S; Gieschke, Ronald; Tsukamoto, Yuko; Reigner, Bruno G; Burger, Hans U; Steimer, Jean-Louis

    2003-05-01

    Preclinical studies, along with Phase I, II, and III clinical trials demonstrate the pharmacokinetics, pharmacodynamics, safety and efficacy of a new drug under well controlled circumstances in relatively homogeneous populations. However, these types of studies generally do not answer important questions about variability in specific factors that predict pharmacokinetic and pharmacodynamic (PKPD) activity, in turn affecting safety and efficacy. Semi-physiological and clinical PKPD modeling and simulation offer the possibility of utilizing data obtained in the laboratory and the clinic to make accurate characterizations and predictions of PKPD activity in the target population, based on variability in predictive factors. Capecitabine is an orally administered pro-drug of 5-fluorouracil (5-FU), designed to exploit tissue-specific differences in metabolic enzyme activities in order to enhance efficacy and safety. It undergoes extensive metabolism in multiple physiologic compartments, and presents particular challenges for predicting pharmacokinetic and pharmacodynamic activity in humans. Clinical and physiologically based pharmacokinetic (PBPK) and pharmacodynamic models were developed to characterize the activity of capecitabine and its metabolites, and the clinical consequences under varying physiological conditions such as creatinine clearance or activity of key metabolic enzymes. The results of the modeling investigations were consistent with capecitabine's rational design as a triple pro-drug of 5-FU. This paper reviews and discusses the PKPD and PBPK modeling approaches used in capecitabine development to provide a more thorough understanding of what the key predictors of its PBPK activity are, and how variability in these predictors may affect its PKPD, and ultimately, clinical outcomes.

  6. Cryo-sectioning of mice for whole-body imaging of drugs and metabolites with desorption electrospray ionization mass spectrometry imaging - a simplified approach

    DEFF Research Database (Denmark)

    Okutan, Seda; Hansen, Harald S; Janfelt, Christian

    2016-01-01

    bodyweight which is comparable to the normal prescribed human dose. The simultaneous imaging of endogenous and exogenous compounds facilitates registration of the drug images to certain organs in the body by colored-overlay of the two types of images. The method represents a relatively low-cost approach...

  7. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems

    Directory of Open Access Journals (Sweden)

    Kaur R

    2013-01-01

    Full Text Available Randeep Kaur, Ildiko BadeaDrug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaAbstract: Detonation nanodiamonds (NDs are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.Keywords: dispersion, surface functionalization, toxicity, carriers, fluorescence, light scattering

  8. Multimodal Imaging of Nanocomposite Microspheres for Transcatheter Intra-Arterial Drug Delivery to Liver Tumors

    Science.gov (United States)

    Kim, Dong-Hyun; Li, Weiguo; Chen, Jeane; Zhang, Zhuoli; Green, Richard M.; Huang, Sui; Larson, Andrew C.

    2016-01-01

    A modern multi-functional drug carrier is critically needed to improve the efficacy of image-guided catheter-directed approaches for the treatment of hepatic malignancies. For this purpose, a nanocomposite microsphere platform was developed for selective intra-arterial transcatheter drug delivery to liver tumors. In our study, continuous microfluidic methods were used to fabricate drug-loaded multimodal MRI/CT visible microspheres that included both gold nanorods and magnetic clusters. The resulting hydrophilic, deformable, and non-aggregated microspheres were mono-disperse and roughly 25 um in size. Sustained drug release and strong MRI T2 and CT contrast effects were achieved with the embedded magnetic nano-clusters and radiopaque gold nanorods. The microspheres were successfully infused through catheters selectively placed within the hepatic artery in rodent models and subsequent distribution in the targeted liver tissues and hepatic tumors confirmed with MRI and CT imaging. These multimodal nanocomposite drug carriers should be ideal for selective intra-arterial catheter-directed administration to liver tumors while permitting MRI/CT visualization for patient-specific confirmation of tumor-targeted delivery. PMID:27405824

  9. [Drug users' quality of life, self-esteem and self-image].

    Science.gov (United States)

    Silveira, Camila da; Meyer, Carolina; Souza, Gabriel Renaldo de; Ramos, Manoella de Oliveira; Souza, Melissa de Carvalho; Monte, Fernanda Guidarini; Guimarães, Adriana Coutinho de Azevedo; Parcias, Sílvia Rosane

    2013-07-01

    This cross-sectional study aimed to investigate the quality of life, self-esteem and self-image among drug users of São José Institute in São José in the State of Santa Catarina. The accessibility sample was comprised of 100 male patients with a mean age of 43.0 ± 10.7, who had studied for a mean period of 8.4 ± 3.7 years. 48% of them were married and had been hospitalized or treated for a minimum period of seven days. When the participants were not hospitalized they lived with wives and children (23%), were married (48%), employed (72%), were part of income level B (58%), had done something they regret in their lives (57%) and perceived their health as good (57%). Regarding quality of life, the highest scores were found in the environmental domain (65%) and the lowest scores were in the psychological domain (58%). All patients were taking medication and had low self-esteem and self-image (77% and 96% respectively). The absence of interference of the quality of life on self-esteem and self-image of the drug users was observed by means of logistic regression. Positive quality of life did not interfere in changes in low self-esteem and self-image of drug users.

  10. Zika viral polymerase inhibition using anti-HCV drugs both in market and under clinical trials.

    Science.gov (United States)

    Elfiky, Abdo A

    2016-12-01

    In the last few months, a new Zika virus (ZIKV) outbreak evolved in America. In accordance, World Health Organization (WHO) in February 2016 declared it as Public Health Emergency of International Concern (PHEIC). ZIKV infection was reported in more than 60 countries and the disease was spreading since 2007 but with little momentum. Many antiviral drugs are available in market or in laboratories under clinical trials, could affect ZIKV infection. In silico docking study were performed on the ZIKV polymerase to test some of Hepatitis C Virus (HCV) drugs (approved and in clinical trials). The results show potency of almost all of the studied compounds on ZIKV polymerase and hence inhibiting the propagation of the disease. In addition, the study suggested two nucleotide inhibitors (IDX-184 and MK0608) that may be tested as drugs against ZIKV infection. J. Med. Virol. 88:2044-2051, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. SMART drug delivery systems: Back to the future vs. clinical reality

    NARCIS (Netherlands)

    Lammers, T.G.G.M.

    2013-01-01

    Recent advances in nanotechnology and material science have re-ignited interest in drug delivery research. Arguably, however, hardly any of the systems developed and strategies proposed are really relevant for shaping the future (clinical) face of the nanomedicine field. Consequently, as outlined in

  12. Struggles in prescribing : determinants of psychotropic drug use in multiple clinical settings

    NARCIS (Netherlands)

    Stolker, J.J.

    2002-01-01

    The main objectives of this thesis were to establish the prevalence of psychotropic drug use as well as possible determinants associated with its use in multiple clinical settings: psychiatric admission wards, an intensive care unit and two settings for the intellectually disabled. In this

  13. Total Protein Profile and Drug Resistance in Candida albicans Isolated from Clinical Samples

    Directory of Open Access Journals (Sweden)

    Kamal Uddin Zaidi

    2016-01-01

    Full Text Available This study was done to assess the antifungal susceptibility of clinical isolates of Candida albicans and to evaluate its total protein profile based on morphological difference on drug resistance. Hundred and twenty clinical isolates of C. albicans from various clinical specimens were tested for susceptibility against four antifungal agents, namely, fluconazole, itraconazole, amphotericin B, and ketoconazole. A significant increase of drug resistance in clinical isolates of C. albicans was observed. The study showed 50% fluconazole and itraconazole resistance at 32 μg mL−1 with a MIC50 and MIC90 values at 34 and 47 and 36 and 49 μg mL−1, respectively. All isolates were sensitive to amphotericin B and ketoconazole. The SDS-PAGE protein profile showed a prevalent band of ~52.5 kDa, indicating overexpression of gene in 72% strains with fluconazole resistance. Since the opportunistic infections of Candida spp. are increasing along with drug resistance, the total protein profile will help in understanding the evolutionary changes in drug resistance and also to characterize them.

  14. Clinical drug development using dynamic biomarkers to enable personalized health care in Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Bihlet, Asger R; Karsdal, Morten A; Bay-Jensen, Anne-Christine;

    2015-01-01

    already in the clinical development of new compounds could offer a solution. In this review, we discuss past successes and failures in drug development and biomarker research in COPD. We describe research in COPD phenotypes, and the required characteristics of a suitable biomarker for identifying patients...

  15. New developments in the clinical use of drug-coated balloon catheters in peripheral arterial disease

    Directory of Open Access Journals (Sweden)

    Naghi J

    2016-06-01

    Full Text Available Jesse Naghi, Ethan A Yalvac, Ali Pourdjabbar, Lawrence Ang, John Bahadorani, Ryan R Reeves, Ehtisham Mahmud, Mitul Patel Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California, San Diego, CA, USA Abstract: Peripheral arterial disease (PAD involving the lower extremity is a major source of morbidity and mortality. Clinical manifestations of PAD span the spectrum from lifestyle limiting claudication to ulceration and gangrene leading to amputation. Advancements including balloon angioplasty, self-expanding stents, drug-eluting stents, and atherectomy have resulted in high technical success rates for endovascular therapy in patients with PAD. However, these advances have been limited by somewhat high rates of clinical restenosis and clinically driven target lesion revascularization. The recent introduction of drug-coated balloon technology shows promise in limiting neointimal hyperplasia induced by vascular injury after endovascular therapies. This review summarizes the contemporary clinical data in the emerging area of drug-coated balloons. Keywords: drug-coated balloons, endovascular, percutaneous transluminal angioplasty, paclitaxel, peripheral arterial disease

  16. Struggles in prescribing : determinants of psychotropic drug use in multiple clinical settings

    NARCIS (Netherlands)

    Stolker, J.J.

    2002-01-01

    The main objectives of this thesis were to establish the prevalence of psychotropic drug use as well as possible determinants associated with its use in multiple clinical settings: psychiatric admission wards, an intensive care unit and two settings for the intellectually disabled. In this thesis,

  17. Current role of anticholinergic drugs in the treatment of asthma : Key messages for clinical practice

    NARCIS (Netherlands)

    Pizzichini, Marcia M. M.; Kerstjens, Huib A. M.; Pizzichini, Emilio

    2015-01-01

    Anticholinergic bronchodilators such as tiotropium, a potent long-acting drug, are central to the symptomatic treatment of chronic obstructive pulmonary disease. Its role in asthma treatment has been recently investigated. This review critically evaluates documented evidence of clinical trials and a

  18. SMART drug delivery systems: Back to the future vs. clinical reality

    NARCIS (Netherlands)

    Lammers, Twan Gerardus Gertudis Maria

    2013-01-01

    Recent advances in nanotechnology and material science have re-ignited interest in drug delivery research. Arguably, however, hardly any of the systems developed and strategies proposed are really relevant for shaping the future (clinical) face of the nanomedicine field. Consequently, as outlined in

  19. The biological and clinical activity of anti-malarial drugs in autoimmune disorders.

    Science.gov (United States)

    Taherian, Elham; Rao, Anshul; Malemud, Charles J; Askari, Ali D

    2013-01-01

    Chloroquine and hydroxychloroquine are 4-aminoquinoline compounds commonly employed as anti-malarial drugs. Chloroquine and its synthetic analogue, hydroxychloroquine also belong to the disease-modifying anti-rheumatic drug class because these drugs are immunosuppressive. The immunosuppressive activity of chloroquine and hydroxychloroquine is likely to account for their capacity to reduce T-cell and B-cell hyperactivity as well as pro-inflammatory cytokine gene expression. This review evaluated experimental and clinical trials results as well as clinical response data relative to the use of chloroquine and/or hydroxychloroquine as first-line medical therapies in systemic lupus erythematosus, rheumatoid arthritis, primary Sjogren's syndrome, the anti-phospholipid syndrome and in the treatment of sarcoidosis. A primary outcomes measure in these clinical trials was the extent to which chloroquine and/or hydroxychloroquine reduced disease progression or exacerbations and/or the use and dosage of corticosteroids. The relative efficacy of chloroquine and hydroxychloroquine in modifying the clinical course of these autoimmune disorders is balanced against evidence that these drugs induce adverse effects which may reduce their use and effectiveness in the therapy of autoimmune disorders.

  20. Maternal Drug Abuse History, Maltreatment, and Functioning in a Clinical Sample of Urban Children

    Science.gov (United States)

    Onigu-Otite, Edore C.; Belcher, Harolyn M. E.

    2012-01-01

    Objective: This study examined the association between maternal drug abuse history, maltreatment exposure, and functioning, in a clinical sample of young children seeking therapy for maltreatment. Methods: Data were collected on 91 children, mean age 5.3 years (SD 1.0). The Preschool and Early Childhood Functional Assessment Scales (PECFAS) was…